GERADO POR INTELIGÊNCIA ARTIFICIAL
A neurodegeneração que leva à doença de Parkinson (DP) e à doença de Alzheimer (DA) tornou-se um grande fardo para a ... (Ver mais)
GERADO POR INTELIGÊNCIA ARTIFICIAL
A neurodegeneração que leva à doença de Parkinson (DP) e à doença de Alzheimer (DA) tornou-se um grande fardo para a saúde globalmente. Os tratamentos atuais visam principalmente controlar os sintomas e não existem terapias disponíveis na prática clínica para prevenir a neurodegeneração ou induzir a reparação neuronal. Assim, a demanda por pesquisas inovadoras para os dois distúrbios é imperativa. Esta revisão de literatura tem como objetivo fornecer uma coleção de trabalhos publicados sobre PD e AD e o uso atual do sistema endocanabinoide (SEC) como um potencial alvo terapêutico para a neurodegeneração. DP é frequentemente tratada com L-DOPA e estimulação cerebral profunda. Técnicas recentes de modificação genética e remodelação, como CRISPR por meio de células-tronco embrionárias humanas e células-tronco pluripotentes induzidas, têm mostrado estratégias promissoras para a medicina personalizada. DA, caracterizada por depósitos extracelulares de placas senis de β-amiloide e emaranhados neurofibrilares de proteína tau, usa frequentemente potencializadores da colina acetiltransferase como terapêutica. O SEC está sendo estudado, atualmente, como alvo terapêutico para DP e DA, onde a superexpressão de receptores SEC exerce neuroproteção contra DP e reduz a neuroinflamação em DA. Os canabinoides delta-9-tetra-hidrocanabinol (Δ9-THC) e canabidiol (CBD) da planta Cannabis sativa têm demonstrado neuroproteção em modelos animais de DP e DA, mas provocaram efeitos tóxicos em pacientes quando administrados diretamente. Portanto, sugere-se entender a cascata molecular precisa após o tratamento com canabinoides, concentrando-se especialmente na expressão gênica para identificar alvos terapêuticos para prevenir e reparar a neurodegeneração.
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Dialogues in Clinical Neuroscience -
Revisão -
2017
Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a "soft" ... (Ver mais)
Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a "soft" drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (toward a higher proportion of Δ9-THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use.
Terpenes are the primary constituents of essential oils and are responsible for the aroma characteristics of cannabis. Together with the cannabinoids, te ... (Ver mais)
Terpenes are the primary constituents of essential oils and are responsible for the aroma characteristics of cannabis. Together with the cannabinoids, terpenes illustrate synergic and/or entourage effect and their interactions have only been speculated in for the last few decades. Hundreds of terpenes are identified that allude to cannabis sensory attributes, contributing largely to the consumers experiences and market price. They also enhance many therapeutic benefits, especially as aromatherapy. To shed light on the importance of terpenes in the cannabis industry, the purpose of this review is to morphologically describe sources of cannabis terpenes and to explain the biosynthesis and diversity of terpene profiles in different cannabis chemovars.
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Journal of Neuroimmune Pharmacology -
Revisão -
2018
Cannabis is the most commonly used substance of abuse in the United States after alcohol and tobacco. With a recent increase in the rates of cannabis use ... (Ver mais)
Cannabis is the most commonly used substance of abuse in the United States after alcohol and tobacco. With a recent increase in the rates of cannabis use disorder (CUD) and a decrease in the perceived risk of cannabis use, it is imperative to assess the addictive potential of cannabis. Here we evaluate cannabis use through the neurobiological model of addiction proposed by Koob and Volkow. The model proposes that repeated substance abuse drives neurobiological changes in the brain that can be separated into three distinct stages, each of which perpetuates the cycle of addiction. Here we review previous research on the acute and long-term effects of cannabis use on the brain and behavior, and find that the three-stage framework of addiction applies to CUD in a manner similar to other drugs of abuse, albeit with some slight differences. These findings highlight the urgent need to conduct research that elucidates specific neurobiological changes associated with CUD in humans.
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Journal of Thoracic Oncology -
Revisão -
2018
The cannabis plant and its derivatives have been exploited for centuries for recreational and medicinal purposes, with millions of regular users around t ... (Ver mais)
The cannabis plant and its derivatives have been exploited for centuries for recreational and medicinal purposes, with millions of regular users around the world. The recreational use of cannabis is reflective of its neuropsychiatric effects, such as anxiolysis and euphoria. However, cannabis appears to have an emerging therapeutic role, especially in chronic disease and as an adjunct to cancer treatment. Increasing evidence supports cannabis in the management of chemotherapy-induced nausea and vomiting (CINV) and for pain management; however, studies are limited, particularly by difficulties associated with standardized dosing estimates and inability to accurately assess biologic activities of compounds in cannabis and derivative products. Smoking cannabis has not been proved to be a risk factor in the development of lung cancer, but the data are limited by small studies, misclassification due to self-reporting of use, small numbers of heavy cannabis smokers, and confounding of the risk associated with known causative agents for lung cancer (such as parallel chronic tobacco use). Cannabis and its biologically effective derivatives warrant additional research, ideally, controlled trials in which the cannabidiol and the delta-9-tetrahydrocabinol strength and use are controlled and documented.
Cannabis use disorder (CUD) is an underappreciated risk of using cannabis that affects ~10% of the 193 million cannabis users worldwide. The individual a ... (Ver mais)
Cannabis use disorder (CUD) is an underappreciated risk of using cannabis that affects ~10% of the 193 million cannabis users worldwide. The individual and public health burdens are less than those of other forms of drug use, but CUD accounts for a substantial proportion of persons seeking treatment for drug use disorders owing to the high global prevalence of cannabis use. Cognitive behavioural therapy, motivational enhancement therapy and contingency management can substantially reduce cannabis use and cannabis-related problems, but enduring abstinence is not a common outcome. No pharmacotherapies have been approved for cannabis use or CUD, although a number of drug classes (such as cannabinoid agonists) have shown promise and require more rigorous evaluation. Treatment of cannabis use and CUD is often complicated by comorbid mental health and other substance use disorders. The legalization of non-medical cannabis use in some high-income countries may increase the prevalence of CUD by making more potent cannabis products more readily available at a lower price. States that legalize medical and non-medical cannabis use should inform users about the risks of CUD and provide information on how to obtain assistance if they develop cannabis-related mental and/or physical health problems.
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British Journal of Clinical Pharmacology -
Revisão -
2018
The therapeutic application of cannabis is attracting substantial public and clinical interest. The cannabis plant has been described as a veritable ‘tre ... (Ver mais)
The therapeutic application of cannabis is attracting substantial public and clinical interest. The cannabis plant has been described as a veritable ‘treasure trove’, producing more than 100 different cannabinoids, although the focus to date has been on the psychoactive molecule delta-9-tetraydrocannabinol (THC) and cannabidiol (CBD). Other numerous secondary metabolites of cannabis, the terpenes, some of which share the common intermediary geranyl diphosphate (GPP) with the cannabinoids, are hypothesized to contribute synergistically to their therapeutic benefits, an attribute that has been described as the ‘entourage effect’. The effective delivery of such a complex multicomponent pharmaceutical relies upon the stable genetic background and standardized growth of the plant material, particularly if the raw botanical product in the form of the dried pistillate inflorescence (flos) is the source. Following supercritical CO2 extraction of the inflorescence (and possibly bracts), the secondary metabolites can be blended to provide a specific ratio of major cannabinoids (THC : CBD) or individual cannabinoids can be isolated, purified and supplied as the pharmaceutical. Intensive breeding strategies will provide novel cultivars of cannabis possessing elevated levels of specific cannabinoids or other secondary metabolites.
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Schizophrenia Bulletin -
Meta análise -
2016
Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic r ... (Ver mais)
Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/ amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs
Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties. Despite being the foundation of a multi-billion ... (Ver mais)
Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties. Despite being the foundation of a multi-billion dollar global industry, scientific knowledge and research on cannabis is lagging behind compared to other high-value crops. This is largely due to legal restrictions that have prevented many researchers from studying cannabis, its products, and their effects in humans. Cannabis resin contains hundreds of different terpene and cannabinoid metabolites. Many of these metabolites have not been con- clusively identified. Our understanding of the genomic and biosynthetic systems of these metabolites in can- nabis, and the factors that affect their variability, is rudimentary. As a consequence, there is concern about lack of consistency with regard to the terpene and cannabinoid composition of different cannabis ‘strains’. Likewise, claims of some of the medicinal properties attributed to cannabis metabolites would benefit from thorough scientific validation
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Revista Médica de Chile -
Revisão -
2017
Cannabis sativa (marihuana) is considered an illicit drug due to its psychoactive properties. Recently, the Chilean government opened to the use cannabis ... (Ver mais)
Cannabis sativa (marihuana) is considered an illicit drug due to its psychoactive properties. Recently, the Chilean government opened to the use cannabis in the symptomatic treatment of some patients. The biological effects of cannabis render it useful for the complementary treatment of specific clinical situations such as chronic pain. We retrieved scientific information about the analgesic properties of cannabis, using it as a safe drug. The drug may block or inhibit the transmission of nervous impulses at different levels, an effect associated with pain control. Within this context and using adequate doses, forms and administration pathways, it can be used for chronic pain management, considering its effectiveness and low cost. It could also be considered as an alternative in patients receiving prolonged analgesic therapies with multiple adverse effects.
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British Journal of Pharmacology -
Revisão -
2011
Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recentl ... (Ver mais)
Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, a-pinene, linalool, b-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL-1 . They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.
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PLOS ONE -
Teste controlado randomizado -
2021
Importance There is a pressing need for development of novel pharmacology for the treatment of Posttraumatic Stress Disorder (PTSD). Given increasing u ... (Ver mais)
Importance There is a pressing need for development of novel pharmacology for the treatment of Posttraumatic Stress Disorder (PTSD). Given increasing use of medical cannabis among US military veterans to self-treat PTSD, there is strong public interest in whether cannabis may be a safe and effective treatment for PTSD. Objective The aim of the present study was to collect preliminary data on the safety and potential efficacy of three active concentrations of smoked cannabis (i.e., High THC = approximately 12% THC and < 0.05% CBD; High CBD = 11% CBD and 0.50% THC; THC+CBD = approximately 7.9% THC and 8.1% CBD, and placebo = < 0.03% THC and < 0.01% CBD) compared to placebo in the treatment of PTSD among military veterans. Methods The study used a double-blind, cross-over design, where participants were randomly assigned to receive three weeks of either active treatment or placebo in Stage 1 (N = 80), and then were re-randomized after a 2-week washout period to receive one of the other three active treatments in Stage 2 (N = 74). The primary outcome measure was change in PTSD symptom severity from baseline to end of treatment in Stage 1.Results
The study did not find a significant difference in change in PTSD symptom severity between
the active cannabis concentrations and placebo by the end of Stage 1. All three active concentrations of smoked cannabis were generally well tolerated.
Conclusions and relevance
The present study is the first randomized placebo-controlled trial of smoked cannabis for
PTSD. All treatment groups, including placebo, showed good tolerability and significant
improvements in PTSD symptoms during three weeks of treatment, but no active treatment
statistically outperformed placebo in this brief, preliminary trial. Additional well-controlled
and adequately powered studies with cannabis suitable for FDA drug development are
needed to determine whether smoked cannabis improves symptoms of PTSD.
Products derived from the plant Cannabis sativa are widely appreciated for their analgesic properties and are employed for the treatment of chronic neu ... (Ver mais)
Products derived from the plant Cannabis sativa are widely appreciated for their analgesic properties and are employed for the treatment of chronic neuropathic pain. Only nabiximols, a product composed of two extracts containing similar percentages of the two cannabinoids cannabidiol and delta-9-tetrahydrocannabinol, is approved by regulatory authorities for neuropathic pain and spasticity due to multiple sclerosis in many European countries and Canada. It is also included in pharmacovigilance systems monitoring the occurrence of adverse drug reactions. However, it is not the same for the great variety of other cannabis preparations widely used for medical purposes. This creates a situation characterized by insufficient knowledge of the safety of cannabis preparations and the impossibility of establishing a correct risk–benefit profile for their medical use in the treatment of chronic neuropathic pain. With the aim to explore this issue more deeply, we collected data on adverse reactions from published clinical studies reporting the use of cannabis for neuropathic relief.
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Current Opinion in Psychology -
Revisão -
2019
Laws regulating cannabis have changed radically in the U.S. and abroad. Historically, users smoked dried cannabis flowers that contained Δ9-tetrahydroc ... (Ver mais)
Laws regulating cannabis have changed radically in the U.S. and abroad. Historically, users smoked dried cannabis flowers that contained Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, as the principal product constituent. Coincident with cannabis legalization and increased interest in medicinal use of the plant, there is now an expansive retail cannabis marketplace with novel cannabis products, formulations, and methods of administration. In this review, we describe emergent cannabis product chemotypes (e.g. THC-dominant, CBD-dominant, balanced or hybrid with high concentrations of THC and CBD), product formulations (e.g. edibles, concentrates), and methods of administration (e.g. smoked, vaporized, orally ingested). Psychologists can play a pivotal role in studying the health impact of cannabis legalization and conducting research to inform product regulation.
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Brazilian Journal of Anesthesiology -
Revisão -
2022
For centuries, cannabis has been used with many different purposes, including medicinal use, usually bypassing any formal approval process. However, du ... (Ver mais)
For centuries, cannabis has been used with many different purposes, including medicinal use, usually bypassing any formal approval process. However, during the last decade, interest in cannabis in medicine has been increasing, and several countries, including the United States and Canada, have produced their own legislation about marihuana and cannabis-based medicines. Because of this, interest in research has been increasing and evidence about its medical effects is becoming necessary. We conducted a review examining the evidence of cannabis in pain. Cannabis had been shown to be useful in acute and chronic pain, however recently, these results have been controverted. Within the different types of chronic pain, it has a weak evidence for neuropathic, rheumatic pain, and headache, modest evidence for multiple sclerosis related pain, and as adjuvant therapy in cancer pain. There is no strong evidence to recommend cannabis in order to decrease opioids in patients with chronic use. Even though cannabis-based medications appear to be mostly safe, mild adverse effects are common; somnolence, sedation, amnesia, euphoric mood, hyperhidrosis, paranoia, and confusion may limit the use of cannabis in clinical practice. Risks have not been systematically analyzed. Special concern arises on how adverse effect might affect vulnerable population such as elderly patients. More research is needed in order to evaluate benefits and risks, as well as the ideal administration route and dosages. As cannabis use increases in several countries, answers to these questions might be coming soon.
Hemp (Cannabis sativa L.) is a herbaceous anemophilous plant that belongs to the Cannabinaceae family. The cannabis seed (hemp) has long been utilized ... (Ver mais)
Hemp (Cannabis sativa L.) is a herbaceous anemophilous plant that belongs to the Cannabinaceae family. The cannabis seed (hemp) has long been utilized as a food source and is commercially important as an edible oil source. In this review, the positive and negative health effects of cannabis, the relationship between cannabis and various diseases, and the use of cannabis in various food products have been discussed. In addition, the scientific literature on the potential use of cannabis and its derivatives as a dietary supplement for the prevention and treatment of inflammatory and chronic degenerative diseases in animals and humans has been reviewed. Cannabis is being developed as a key ingredient in a variety of food items, including bakery, confectionery, beverages, dairy, fruits, vegetables, and meat. Hemp seeds are high in readily digestible proteins, lipids, polyunsaturated fatty acids (PUFA), insoluble fiber, carbs, and favorable omega-6 PUFA acid to omega-3 PUFA ratio and have high nutritional value. The antioxidants of cannabis, such as polyphenols, help with anxiety, oxidative stress, and the risk of chronic illnesses, including cancer, neurological disorders, digestive problems, and skin diseases. Cannabis has been shown to have negative health impacts on the respiratory system, driving, and psychomotor functions, and the reproductive system. Overall, the purpose of this research is to stimulate more in-depth research on cannabis’s adaptation in various foods and for the treatment of chronic illnesses.
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Journal of Neuroimmune Pharmacology -
Informe -
2021
COVID-19 epidemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health efects that have included respiratory/pulm ... (Ver mais)
COVID-19 epidemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health efects that have included respiratory/pulmonary, cardiovascular, mental health and neurological consequences such as anxiety, depression, and substance use. Several efective vaccines have been developed and extensive eforts are underway to develop therapeutics to treat COVID-19. Cannabis and/or its product-cannabidiol (CBD) are being advertised for the treatment of COVID-19 associated mental/neurological complications and substance use disorders. However, research reviewed shows that there is insufcient data from clinical studies to support the use of cannabis or CBD for the treatment of COVID-19 associated mental health and neurological complications. Additional basic and clinical research is suggested to develop cannabis or cannabidiol for the treatment of mental health problems associated with coronavirus infection and or substance use disorders. In the meantime, it is important that the addiction physician/psychiatrist must caution while prescribing or recommending cannabis or CBD for treating such clinical indications.
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Australian Dental Journal -
Revisão -
2005
Cannabis, commonly known as marijuana, is themost frequently used illicit drug in Australia.Therefore, oral health care providers are likely toencounte ... (Ver mais)
Cannabis, commonly known as marijuana, is themost frequently used illicit drug in Australia.Therefore, oral health care providers are likely toencounter patients who are regular users. Anupward trend in cannabis use is occurring inAustralia, with 40 per cent of the population aged14 and above having used the drug. There are threemain forms of cannabis: marijuana, hash and hashoil, all of which contain the main psychoactiveconstituent delta-9-tetrahydrocannabinol (THC).Cannabis is most commonly smoked, however it canbe added to foods. THC from cannabis enters thebloodstream and exerts its effects on the body viainteraction with endogenous receptors. Cannabisaffects almost every system of the body, particularlythe cardiovascular, respiratory and immune systems.It also has acute and chronic effects on the mentalhealth of some users. Therefore, chronic abuse is aconcern because of its negative effects on generalphysical and mental health. Cannabis abusersgenerally have poorer oral health than non-users,with an increased risk of dental caries andperiodontal diseases. Cannabis smoke acts as acarcinogen and is associated with dysplastic changesand pre-malignant lesions within the oral mucosa.Users are also prone to oral infections, possibly dueto the immunosuppressive effects. Dental treatmenton patients intoxicated on cannabis can result in thepatient experiencing acute anxiety, dysphoria andpsychotic-like paranoiac thoughts. The use of localanaesthetic containing epinephrine may seriouslyprolong tachycardia already induced by an acutedose of cannabis. Oral health care providers shouldbe aware of the diverse adverse effects of cannabison general and oral health and incorporate questionsabout patients’ patterns of use in the medical history.
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Journal of Pain -
Teste controlado randomizado -
2013
We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of w ... (Ver mais)
We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive sideeffects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible
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International Journal of Molecular Sciences -
Revisão -
2020
Cannabidiol (CBD) is a non-intoxicating and generally well-tolerated constituent of cannabis which exhibits potential beneficial properties in a wide r ... (Ver mais)
Cannabidiol (CBD) is a non-intoxicating and generally well-tolerated constituent of cannabis which exhibits potential beneficial properties in a wide range of diseases, including cardiovascular disorders. Due to its complex mechanism of action, CBD may affect the cardiovascular system in different ways. Thus, we reviewed the influence of CBD on this system in health and disease to determine the potential risk of cardiovascular side effects during CBD use for medical and wellness purposes and to elucidate its therapeutic potential in cardiovascular diseases. Administration of CBD to healthy volunteers or animals usually does not markedly affect hemodynamic parameters. Although CBD has been found to exhibit vasodilatory and antioxidant properties in hypertension, it has not affected blood pressure in hypertensive animals. Hypotensive action of CBD has been mainly revealed under stress conditions. Many positive effects of CBD have been observed in experimental models of heart diseases (myocardial infarction, cardiomyopathy, myocarditis), stroke, neonatal hypoxic ischemic encephalopathy, sepsis-related encephalitis, cardiovascular complications of diabetes, and ischemia/reperfusion injures of liver and kidneys. In these pathological conditions CBD decreased organ damage and dysfunction, oxidative and nitrative stress, inflammatory processes and apoptosis, among others. Nevertheless, further clinical research is needed to recommend the use of CBD in the treatment of cardiovascular diseases.
Cannabis (Cannabis sativa L.) is one of the oldest cultivated plants purported to have unique medicinal properties. However, scientific research of can ... (Ver mais)
Cannabis (Cannabis sativa L.) is one of the oldest cultivated plants purported to have unique medicinal properties. However, scientific research of cannabis has been restricted by the Single Convention on Narcotic Drugs of 1961, an international treaty that prohibits the production and supply of narcotic drugs except under license. Legislation governing cannabis cultivation for research, medicinal and even recreational purposes has been relaxed recently in certain jurisdictions. As a result, there is now potential to accelerate cultivar development of this multi-use and potentially medically useful plant species by application of modern genomics technologies. Whilst genomics has been pivotal to our understanding of the basic biology and molecular mechanisms controlling key traits in several crop species, much work is needed for cannabis. In this review we provide a comprehensive summary of key cannabis genomics resources and their applications. We also discuss prospective applications of existing and emerging genomics technologies for accelerating the genetic improvement of cannabis.
Cannabis is an annual plant with a long history of use as food, feed, fiber, oil, medicine, and narcotics. Despite realizing its true value, it has not ... (Ver mais)
Cannabis is an annual plant with a long history of use as food, feed, fiber, oil, medicine, and narcotics. Despite realizing its true value, it has not yet found its true place. Cannabis has had a long history with many ups and downs, and now it is our turn to promote it. Cannabis contains approximately 600 identified and many yet unidentified potentially useful compounds. Cannabinoids, phenolic compounds, terpenoids, and alkaloids are some of the secondary metabolites present in cannabis. However, among a plethora of unique chemical compounds found in this plant, the most important ones are phytocannabinoids (PCs). Over hundreds of 21-22-carbon compounds exclusively produce in cannabis glandular hairs through either polyketide and or deoxyxylulose phosphate/methylerythritol phosphate (DOXP/MEP) pathways. Trans-∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD) are those that first come to mind while talking about cannabis. Nevertheless, despite the low concentration, cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinodiol (CBND), and cannabinidiol (CBDL) may have potentially some medical effects. PCs and endocannabinoids (ECs) mediate their effects mainly through CB1 and CB2 receptors. Despite all concerns regarding cannabis, nobody can ignore the use of cannabinoids as promising tonic, analgesic, antipyretic, antiemetic, anti-inflammatory, anti-epileptic, anticancer agents, which are effective for pain relief, depression, anxiety, sleep disorders, nausea and vomiting, multiple sclerosis, cardiovascular disorders, and appetite stimulation. The scientific community and public society have now increasingly accepted cannabis specifically hemp as much more than a recreational drug. There are growing demands for cannabinoids, mainly CBD, with many diverse therapeutic and nutritional properties in veterinary or human medicine. The main objective of this review article is to historically summarize findings concerning cannabinoids, mainly THC and CBD, towards putting these valuable compounds into food, feed and health baskets and current and future trends in the consumption of products derived from cannabis
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Neuropsychopharmacology -
Revisão -
2018
Cannabis use disorder (CUD) commonly occurs and carries a notable economic and functional burden at both individual and societal levels. While there ar ... (Ver mais)
Cannabis use disorder (CUD) commonly occurs and carries a notable economic and functional burden at both individual and societal levels. While there are no clearly efficacious medication treatments for CUD, 20 years of committed and high-quality research in the human laboratory and clinical settings have resulted in medications with demonstrated effectiveness in the treatment of cannabis withdrawal, the ability to reduce cannabis use, and results that point to promising future work. The current state of pharmacology research for CUD highlights the need to consider particular characteristics of patients, such as gender, impulsivity, and severity of cannabis use, when selecting a medication in the off-label treatment of CUD or cannabis withdrawal. As a field, the body of work also exposes some areas in need of improvement in study design, selection of outcome measures, interpretation of results, and the overall process of evaluating candidate medications. Coming to a consensus as a field and addressing these gaps in future research will likely lend itself to further advances in improving the lives of patients with CUD
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International Journal of Molecular Sciences -
Revisão -
2020
The Cannabis plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the e ... (Ver mais)
The Cannabis plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system. Cannabinoids affect the nervous system and play significant roles in the regulation of the immune system. While Cannabis is not yet registered as a drug, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries to authorize their clinical use. However, the data from basic and medical research dedicated to medical Cannabis is currently limited. A variety of pathological conditions involve dysregulation of the immune system. For example, in cancer, immune surveillance and cancer immuno-editing result in immune tolerance. On the other hand, in autoimmune diseases increased immune activity causes tissue damage. Immuno-modulating therapies can regulate the immune system and therefore the immune-regulatory properties of cannabinoids, suggest their use in the therapy of immune related disorders. In this contemporary review, we discuss the roles of the endocannabinoid system in immunity and explore the emerging data about the effects of cannabinoids on the immune response in different pathologies. In addition, we discuss the complexities of using cannabinoid-based treatments in each of these conditions.
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Complementary Therapies in Medicine -
Revisão -
2021
Objectives: It has been previously demonstrated that healthcare professionals would like additional education on medical cannabis. However, there has n ... (Ver mais)
Objectives: It has been previously demonstrated that healthcare professionals would like additional education on medical cannabis. However, there has not yet been a review of the status of medical cannabis curriculum for medical and allied healthcare trainees worldwide, even though future healthcare workers will be placed on the forefront of patient care and must be prepared to counsel patients. This study was designed to address this gap in knowledge. Design: A search syntax was generated and databases PubMed, ERIC, CINAHL, and Web of Science were searched for relevant articles. A grey literature search of Google Scholar, MedEd, Medline, and the Proquest Dissertations and Theses section was also performed. All titles and abstracts were screened. Selected articles were subsequently screened using predetermined inclusion and exclusion criteria. Results: Allied healthcare trainees lacked sufficient knowledge about medical cannabis and did not feel prepared to counsel patients on this subject. Additionally, they expressed a growing interest in medical cannabis and would like more standardized education on the topic. Finally, faculty and deans in various institutions agreed on the need to educate students on the subject, and aimed to implement courses on medical cannabis or expand their existing curricula. Conclusions: While the medical cannabis landscape is developing, medical and allied health students are not properly educated and knowledgeable on this emerging field of clinical care. The findings suggest that the implementation of competencies-based curricula on medical cannabis is essential for medical and allied healthcare trainees to have the appropriate level of knowledge to counsel and educate their patients.
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Journal of Otolaryngology - Head & Neck Surgery -
Revisão -
2021
Background: Cannabis has been rapidly legalized in North America; however, limited evidence exists around its side effects. Health Canada defines side ... (Ver mais)
Background: Cannabis has been rapidly legalized in North America; however, limited evidence exists around its side effects. Health Canada defines side effect as a harmful and unintended response to a health product. Given drug safety concerns, this studys purpose was to review the unintended side effects of cannabis in otolaryngology. Methods: The Preferred Reporting Items For Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR) protocol was used to conduct a scoping review of the MEDLINE, EMBASE, CINAHL, and CENTRAL databases. (PROSPERO: CRD42020153022). English studies in adults were included from inception to the end of 2019. In-vitro, animal, and studies with n < 5 were excluded. Primary outcome was defined as unintended side effects (defined as any Otolaryngology symptom or diagnosis) following cannabis use. Oxford Centre for Evidence-Based Medicine: Levels of Evidence and risk of bias using the Risk of Bias in randomized trials (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tools were assessed.. Two authors independently reviewed all studies; the senior author settled any discrepancies. Results: Five hundred and twenty-one studies were screened; 48 studies were analysed. Subspecialties comprised: Head and Neck (32), Otology (8), Rhinology (5), Airway (5), Laryngology (1). Cannabis use was associated with unintended tinnitus, vertigo, hearing loss, infection, malignancy, sinusitis, allergic rhinitis, thyroid dysfunction, and dyspnea. About half (54.1%) of studies showed increased side effects, or no change in symptoms following cannabis use. Oxford Levels of Evidence was 2-4 with substantial heterogeneity. Risk of bias assessment with RoB2 was low to high and ROBINS-1 was moderate to critical. Conclusion: This was the first comprehensive scoping review of unintended side effects of cannabis in Otolaryngology. The current literature is limited and lacks high-quality research Future randomized studies are needed to focus on therapeutic effects of cannabis in otolaryngology. Substantial work remains to guide clinicians to suggest safe, evidence-based choices for cannabis use
Cannabis abuse is a common phenomenon among adolescents. The dominant psychoactive substance in Cannabis sativa is tetrahydrocannabinol (THC). However, ... (Ver mais)
Cannabis abuse is a common phenomenon among adolescents. The dominant psychoactive substance in Cannabis sativa is tetrahydrocannabinol (THC). However, in the past 40 years the content of the psychoactive ingredient THC in most of the preparations is not constant but has increased due to other breeding and culturing conditions. THC acts as the endocannabinoids at CB1 and CB2 receptors but pharmacologically can be described as a partial (not a pure) agonist. Recent evidence shows that activation of the CB1 receptor by THC can diminish the production of neuronal growth factor in neurons and affect other signalling cascades involved in synapsis formation. Since these factors play an important role in the brain development and in the neuronal conversion processes during puberty, it seems reasonable that THC can affect the adolescent brain in another manner than the adult brain. Accordingly, in adolescent cannabis users structural changes were observed with loss of grey matter in certain brain areas. Moreover, recent studies show different effects of THC on adolescent and adult brains and on behaviour. These studies indicate that early THC abuse can result in neuropsychological deficits. This review gives an overview over the present knowledge in this field.
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Psychopharmacology Bulletin -
Revisão -
2021
Purpose of review: This comprehensive review discusses the adverse effects known today about marijuana, for either medical or recreational use. It revi ... (Ver mais)
Purpose of review: This comprehensive review discusses the adverse effects known today about marijuana, for either medical or recreational use. It reviews the role of cannabis in the treatment of chronic pain, cognitive and neurological adverse effects, special cases and addiction. Recent findings: Cannabinoids work through the endocannabinoids system and inhibit the release of GABA and glutamate in the brain, impact neuromodulation, as well as dopamine, acetylcholine and norepinephrine release. They affect reward, learning and pain. The use of cannabis is increasing nationally and world-wide for both recreational and medicinal purposes, however, there is relatively only low quality evidence to the efficacy and adverse effects of this. Cannabis and its derivatives may be used for treatment of chronic pain. They are via CB1 receptors that are thought to modulate nociceptive signals in the brain. CB2 receptors in the DRG likely affect pain integration in the afferent pathways, and peripherally CB2 also affects noradrenergic pathways influencing pain. A large proportion of users may see more than 50% of chronic pain alleviation compared with placebo. Cannabis affects cognition, most notably executive function, memory and attention, and may deteriorate the boundary between emotional and executive processing. Cannabis impairs memory in the short run, which become more significant with chronic use, and may also be accompanied by poorer effort, slower processing and impacted attention. It is generally believed that long-term use and earlier age are risk factor for neurocognitive deficits; neuroimaging studies have shown reduced hippocampal volume and density. Executive functions and memory are worse in adolescent users versus adults. Cannabis addiction is different and likely less common than other addictive substances, but up to 10% of users meet criteria for lifetime cannabis dependence. Addiction patterns may be linked to genetic and epigenetic differences. It is still unclear whether abstinence reverses patterns of addiction, and more research is required into this topic. Summary: Cannabis use has become more abundant for both medical and recreational use. It carries likely benefits in the form of analgesia, anti-emesis and improved appetite in chronic patients. The evidence reviewing adverse effects of this use are still limited, however, exiting data points to a clear link with neurocognitive deterioration, backed by loss of brain volume and density. Addiction is likely complex and variable, and no good data exists to support treatment at this point. It is becoming clear that use in earlier ages carries a higher risk for long-term deficits. As with any other drug, these risks should be considered alongside benefits prior to a decision on cannabis use.
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Journal of Ethnopharmacology -
Revisão -
2021
Ethnopharmacological relevance: Cannabis is one of the most versatile genera in terms of plant use and has been exploited by humans for millennia. Nowa ... (Ver mais)
Ethnopharmacological relevance: Cannabis is one of the most versatile genera in terms of plant use and has been exploited by humans for millennia. Nowadays, Cannabis is the centre of many scientific studies, most of them focusing on chemical composition and medicinal values. While new and varied applications are continuously being developed, the knowledge surrounding less common uses of the plant is slowly disappearing. Aim of the review: We have analysed diversity of global data of Cannabis traditional uses, to investigate if certain plant parts are significantly associated with particular Cannabis use. We wanted to uncover potential associations between the plant parts used for the treatment of different body systems and ailments. Materials and methods: We have analysed the extensive database of Cannabis traditional uses (CANNUSE). This database contains 2330 data entries of Cannabis ethnobotanical uses from over 40 countries across the world. The dataset was divided into five general groups based on the type of use: medicinal, alimentary, psychoactive, fibre and other uses. Given the abundance of human medicinal uses, detailed analysis was done on the subset of 1167 data entries. We analysed the relationship between 16 body system categories and ailments treated with Cannabis plant parts. We used a Pearsons chi-square and Fishers exact test, to determine which Cannabis parts are characteristic of treatment for specific ailments. Results: In this dataset, the majority of reports were represented by medicinal (75.41%), followed by psychoactive (8.35%) and alimentary (7.29%) use. The most commonly used plant parts were leaf (50.51%), seed (15.38%) and inflorescence (11.35%). We found that different Cannabis plant parts were significantly associated with different uses; the leaf was typically used for medicinal, seed for alimentary and inflorescence for psychoactive use. Regarding the human medicinal uses, most common were reports for treatments of the digestive system and nutritional disorders (17.66%), nervous system and mental disorders (16.24%), followed by pain and inflammations (12.21%). We found a significant relationship between the use of certain Cannabis parts and treatment of ailments and body systems categories; leaf was significantly associated with treatment of two categories: skin and subcutaneous tissue disorders and circulatory system and blood disorders; seed use was associated with musculoskeletal system disorders and traumas; while inflorescence use shows a statistical support for treatment of nervous system and mental disorders. Conclusion: Several pharmaceutical companies are intensely working on developing new drugs with isolated chemical compounds or crude extracts, almost exclusively from Cannabis inflorescences. However, our review revealed that use of leaf or seed in traditional medicine is often more important than use of inflorescence for the treatment of certain ailments. A review of traditional medicine provides a body of knowledge and an initial pathway to identify landraces and plant parts that could have an important role in future medicinal research. We are confident that traditional medicine still has a large potential for modern medicine. As more information on Cannabis diversity (genetics, biochemistry, and clinical studies) becomes available, ethnobotanical data are poised to be of much greater significance.
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Advances in Therapy -
Abordagem Prática -
2021
Although still not approved at the federal level for medical or adult recreational use, cannabis has been approved in the United States (USA) by indivi ... (Ver mais)
Although still not approved at the federal level for medical or adult recreational use, cannabis has been approved in the United States (USA) by individual states for both of these purposes. A total of 15 states now regulate cannabis for adult use and 36 states for medical use. In more recent years, cannabis has gained popularity for the treatment of chronic conditions, inflammatory bowel disease (IBD) being one of them. However, the exact role of cannabis in the treatment of IBD remains uncertain. While cannabis may help in some instances with symptom management, it has not been proven to help with inflammation or to fundamentally correct underlying disease processes. Additionally, along with the perceived symptom benefits of cannabis come concerning issues like dosing inconsistencies, dependence, and cannabinoid hyperemesis syndrome. In this review article, we explore the nuanced relationship between cannabis and the treatment of IBD by summarizing the current research. We also use clinical vignettes to discuss the more practical considerations surrounding its use.
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Scientific Reports -
Artigo Original -
2018
Recent surveys suggest that many parents are using illicit cannabis extracts in the hope of managing seizures in their children with epilepsy. In the c ... (Ver mais)
Recent surveys suggest that many parents are using illicit cannabis extracts in the hope of managing seizures in their children with epilepsy. In the current Australian study we conducted semi-structured interviews with families of children with diverse forms of epilepsy to explore their attitudes towards and experiences with using cannabis extracts. This included current or previous users of cannabis extracts to treat their child’s seizures (n = 41 families), and families who had never used (n = 24 families). For those using cannabis, extracts were analysed for cannabinoid content, with specific comparison of samples rated by families as “effective” versus those rated “ineffective”. Results showed that children given cannabis extracts tended to have more severe epilepsy historically and had trialled more anticonvulsants than those who had never received cannabis extracts. There was high variability in the cannabinoid content and profile of cannabis extracts rated as “effective”, with no clear differences between extracts perceived as “effective” and “ineffective”. Contrary to family’s expectations, most samples contained low concentrations of cannabidiol, while Δ9-tetrahydrocannabinol was present in nearly every sample. These findings highlight profound variation in the illicit cannabis extracts being currently used in Australia and warrant further investigations into the therapeutic value of cannabinoids in epilepsy.
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Frontiers in Public Health -
Artigo Original -
2021
With the medical use of cannabis permitted in Canada since 2001, patients seek to use this botanical drug to treat a range of medical conditions. Howev ... (Ver mais)
With the medical use of cannabis permitted in Canada since 2001, patients seek to use this botanical drug to treat a range of medical conditions. However, many healthcare practitioners express the need for further scientific evidence around the use of medical cannabis. This real-world evidence study aimed to address the paucity of scientific data by surveying newly registered medical cannabis patients, before beginning medical cannabis treatment, and at one follow up 6 weeks after beginning medical cannabis treatment. The goal was to collect data on efficacy, safety and cannabis product type information to capture the potential impact medical cannabis had on patient-reported quality of life (QOL) and several medical conditions over a 6-week period using validated questionnaires. The 214 participants were mainly male (58%) and 57% of the population was older than 50. The most frequently reported medical conditions were recurrent pain, post-traumatic stress disorder (PTSD), anxiety, sleep disorders [including restless leg syndrome (RLS)], and arthritis and other rheumatic disorders. Here we report that over 60% of our medical cannabis cohort self-reported improvements in their medical conditions. With the use of validated surveys, we found significant improvements in recurrent pain, PTSD, and sleep disorders after 6 weeks of medical cannabis treatment. Our findings from patients who reported arthritis and other rheumatic disorders are complex, showing improvements in pain and global activity sub-scores, but not overall changes in validated survey scores. We also report that patients who stated anxiety as their main medical condition did not experience significant changes in their anxiety after 6 weeks of cannabis treatment, though there were QOL improvements. While these results show that patients find cannabis treatment effective for a broad range of medical conditions, cannabis was not a remedy for all the conditions investigated. Thus, there is a need for future clinical research to support the findings we have reported. Additionally, while real-world evidence has not historically been utilized by regulatory bodies, we suggest changes in public policy surrounding cannabis should occur to reflect patient reported efficacy of cannabis from real-world studies due to the uniqueness of medical cannabiss path to legalization.
Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised ... (Ver mais)
Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabisbased antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.
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Monash Bioethics Review -
Artigo Original -
2021
This article situates the movement for the legalisation of medicinal cannabis within the bigger picture of the impetus toward recreational cannabis leg ... (Ver mais)
This article situates the movement for the legalisation of medicinal cannabis within the bigger picture of the impetus toward recreational cannabis legalisation. It describes the role played by children with epileptic syndromes in the medicinal cannabis law reform campaigns in the United Kingdom, and Queensland, New South Wales and Victoria in Australia. Noting the ‘rule of rescue’ and the prominence in media campaigns of children in Australian and English cases of parental disputation with clinicians about treatment for their children, it reviews whether paediatric epilepsy is a suitable test case for the legalisation of medicinal cannabis. Taking into account the vested commercial interests of Big Cannabis, the current medico-scientific knowledge of the efficacy of medicinal cannabis in controlling paediatric epileptic seizures, and issues of dignity, health privacy, and the enduring digital footprints of media coverage, the article commences discussion about the ethics of the media, parents, politicians and entrepreneurial doctors utilising parents’ testimonials about the effects of medicinal cannabis as part of the cannabis law reform movement.
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International Journal of Molecular Sciences -
Revisão -
2021
Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important ... (Ver mais)
Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.
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British Journal of Pharmacology -
Artigo Original -
2019
Numerous claims are made for cannabis therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence ... (Ver mais)
Numerous claims are made for cannabis therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both Δ9‐tetrahydrocannabinol (THC), variously reported to be pro‐ and anticonvulsant, and cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects of prolonged exposure to different THC/CBD cannabis extracts on seizure activity and associated measures of endocannabinoid (eCB) system signalling.Cannabis extract effects on in vivo neurological and behavioural responses, and on bioanalyte levels, were measured in rats and dogs. Extract effects on seizure activity were measured using electroencephalography telemetry in rats. eCB signalling was also investigated using radioligand binding in cannabis extract‐treated rats and treatment‐naïve rat, mouse, chicken, dog and human tissue.Prolonged exposure to cannabis extracts caused spontaneous, generalized seizures, subserved by epileptiform discharges in rats, but not dogs, and produced higher THC, but lower 11‐hydroxy‐THC (11‐OH‐THC) and CBD, plasma concentrations in rats versus dogs. In the same rats, prolonged exposure to cannabis also impaired cannabinoid type 1 receptor (CB1 receptorhttp://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=56)‐mediated signalling. Profiling CB1 receptor expression, basal activity, extent of activation and sensitivity to THC suggested interspecies differences in eCB signalling, being more pronounced in a species that exhibited cannabis extract‐induced seizures (rat) than one that did not (dog).Sustained cannabis extract treatment caused differential seizure, behavioural and bioanalyte levels between rats and dogs. Supporting radioligand binding data suggest species differences in eCB signalling. Interspecies variations may have important implications for predicting cannabis‐induced convulsions from animal models.
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The American Journal of Drug and Alcohol Abuse -
Revisão -
2020
Cannabis is the most widely used illicit substance worldwide, and legalization for recreational and medical purposes has substantially increased its av ... (Ver mais)
Cannabis is the most widely used illicit substance worldwide, and legalization for recreational and medical purposes has substantially increased its availability and use in the United States.Decades of research have suggested that recreational cannabis use confers risk for cognitive impairment across various domains, and structural and functional differences in the brain have been linked to early and heavy cannabis use.With substantial evidence for the role of the endocannabinoid system in neural development and understanding that brain development continues into early adulthood, the rising use of cannabis in adolescents and young adults raises major concerns. Yet some formulations of cannabinoid compounds are FDA-approved for medical uses, including applications in children.Potential effects on the trajectory of brain morphology and cognition, therefore, should be considered. The goal of this review is to update and consolidate relevant findings in order to inform attitudes and public policy regarding the recreational and medical use of cannabis and cannabinoid compounds.The findings point to considerations for age limits and guidelines for use.
Cannabis is legal for recreational and medical use in Canada. Our aim was to explore family experiences using medical cannabis for children with severe ... (Ver mais)
Cannabis is legal for recreational and medical use in Canada. Our aim was to explore family experiences using medical cannabis for children with severe conditions in the context of legalization.We conducted a qualitative study using semistructured interviews between April and July 2019. Participants were parents of children attending BC Children’s Hospital oncology or palliative care clinics, recruited through posters, emails or referral. Participants were included if they spoke English and their child used any type of cannabis for medical purposes. Interviews included open-ended questions about the child’s cannabis use. Interviews were recorded and transcribed, and thematic analysis was performed using qualitative description.Ten interviews were completed with 9 mothers and 1 mother–father pair. The age range of the children was 22 months to 16 years. The primary reasons for cannabis use were epilepsy (6 children) or chemotherapy management (4 children). Five major themes were identified. 1) Child and family context, and cannabis as a last resort: children were seen as severely ill; parents sought cannabis out of desperation and responsibility to their child. 2) Varied information sources informed decision-making: parents lacked resources from health care providers and sought support from social media, industry and other families. 3) Cannabis as an ambiguous medicine: cannabis was viewed as both a serious drug that doctors should prescribe and as a natural alternative health product, safe to pursue alone. 4) Perceived effects: parents perceived medical benefits with few concerns about adverse effects. 5) Legal and financial challenges: parents were willing to obtain cannabis despite high costs and uncertain legality.Parents of children with severe conditions pursued medical cannabis despite obstacles and needed unbiased information to access alone. Scientific investigation is needed to develop pediatric medical guidelines to inform decisions.
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International Journal of Environmental Research and Public Health -
Revisão -
2021
Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currentl ... (Ver mais)
Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission. This inefficacy of traditional AEDs, coupled with their undesirable side effect profile, has led to researchers considering alternative forms of treatment. Phytocannabinoids have long served as therapeutics with delta-9-THC (Δ9-THC) receiving extensive focus to determine its therapeutic potential. This focus on Δ9-THC has been to the detriment of analysing the plethora of other phytocannabinoids found in the cannabis plant. The overall aim of this review is to explore other novel phytocannabinoids and their place in epilepsy treatment. The current review intends to achieve this aim via an exploration of the molecular targets underlying the anticonvulsant capabilities of cannabidiol (CBD), cannabidavarin (CBDV), delta-9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG). Further, this review will provide an exploration of current pre-clinical and clinical data as it relates to the aforementioned phytocannabinoids and the treatment of epilepsy symptoms. With specific reference to epilepsy in young adult and adolescent populations, the exploration of CBD, CBDV, Δ9-THCV and CBG in both preclinical and clinical environments can guide future research and aid in the further understanding of the role of phytocannabinoids in epilepsy treatment. Currently, much more research is warranted in this area to be conclusive.
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Journal of the International Neuropsychological Society -
Artigo Original -
2021
ecent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’ anti-inflammatory propert ... (Ver mais)
ecent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’ anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.263 individuals were categorized into four groups: HIV− non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal-Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race/ethnicity, education, current CD4 count, and current tobacco use.HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = 0.015; p = 0.039), and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (p = 0.016; p = 0.036).Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.
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ACS Applied Materials & Interfaces -
Artigo Original -
2020
The therapeutic effect of the Cannabis plant largely depends on the presence and specific ratio of a spectrum of phytocannabinoids. Although prescripti ... (Ver mais)
The therapeutic effect of the Cannabis plant largely depends on the presence and specific ratio of a spectrum of phytocannabinoids. Although prescription of medicinal Cannabis for various conditions constantly grows, its consumption is mostly limited to oral or respiratory pathways, impeding its duration of action, bioavailability, and efficacy. Herein, a long-acting formulation in the form of melt-printed polymeric microdepots for full-spectrum cannabidiol (CBD)-rich extract administration is described. When injected subcutaneously in mice, the microdepots facilitate sustained release of the encapsulated extract over a two-week period. The prolonged delivery results in elevated serum levels of multiple, major and minor, phytocannabinoids for over 14 days, compared to Cannabis extract injection. A direct analysis of the microdepots retrieved from the injection site gives rise to an empirical model for the release kinetics of the phytocannabinoids as a function of their physical traits. As a proof of concept, we compare the long-term efficacy of a single administration of the microdepots to a single administration of Cannabis extract in a pentylenetetrazol-induced convulsion model. One week following administration, the microdepots reduce the incidence of tonic-clonic seizures by 40%, increase the survival rate by 50%, and the latency to first tonic-clonic seizures by 170%. These results suggest that a long-term full-spectrum Cannabis delivery system may provide new form of Cannabis administration and treatments.
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BMC Complementary Medicine and Therapies -
Revisão -
2020
Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical ... (Ver mais)
Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps. We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios.A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores.Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.
Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a ... (Ver mais)
Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.
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Frontiers in Pharmacology -
Artigo Original -
2020
For nearly a century, Cannabis has been stigmatized and criminalized across the globe, but in recent years, there has been a growing interest in Cannab ... (Ver mais)
For nearly a century, Cannabis has been stigmatized and criminalized across the globe, but in recent years, there has been a growing interest in Cannabis due to the therapeutic potential of phytocannabinoids. With this emerging interest in Cannabis, concerns have arisen about the possible contaminations of hemp with pesticides, heavy metals, microbial pathogens, and carcinogenic compounds during the cultivation, manufacturing, and packaging processes. This is of particular concern for those turning to Cannabis for medicinal purposes, especially those with compromised immune systems. This review aims to provide types of contaminants and examples of Cannabis contamination using case studies that elucidate the medical consequences consumers risk when using adulterated Cannabis products. Thus, it is imperative to develop universal standards for cultivation and testing of products to protect those who consume Cannabis.
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JAIDS Journal of Acquired Immune Deficiency Syndromes -
Artigo Original -
2021
Aging and HIV have adverse effects on the CNS, including increased inflammation and neural injury, and confer risk for neurocognitive impairment (NCI). ... (Ver mais)
Aging and HIV have adverse effects on the CNS, including increased inflammation and neural injury, and confer risk for neurocognitive impairment (NCI). Prior research suggests the non-acute neurocognitive effects of cannabis in the general population are adverse or null. However, in the context of aging and HIV, cannabis use may exert beneficial effects due to its anti-inflammatory properties. In the current study, we examined the independent and interactive effects of HIV and cannabis on NCI, and the potential moderation of these effects by age.Participants included 679 people living with HIV (PLHIV) and 273 people living without HIV (HIV−) (18-79 years old) who completed neurocognitive, neuromedical, and substance use assessments. NCI was defined as demographically-corrected global deficit score ≥0.5. Logistic regression models examined the effects of age, HIV, cannabis (history of cannabis substance use disorder and cannabis use in past year), and their two-way and three-way interactions on NCI.In logistic regression models, only a significant interaction of HIV X cannabis was detected (p=0.02). Among PLHIV, cannabis was associated with a lower proportion of NCI (OR=0.53, 95%CI=0.33–0.85), but not among HIV− individuals (p=0.40). These effects did not vary by age.Findings suggest cannabis exposure is linked to a lower odds of NCI in the context of HIV. A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for PLHIV. Further investigations are needed to refine the effects of dose, timing, and cannabis compound on this relationship, which could inform guidelines for cannabis use among populations vulnerable to cognitive decline.
To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regards to their relevance to epilepsy and other sele ... (Ver mais)
To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regards to their relevance to epilepsy and other selected neuropsychiatric disorders.We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology and data from studies with animal models and human subjects.Cannabis has been used to treat disease since ancient times. Δ9-THC is the major psychoactive ingredient and cannabidiol (CBD) is the major non-psychoactive ingredient in cannabis. Cannabis and Δ9-THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. Psychotropic effects of Δ9-THC limit tolerability. CBD is anticonvulsant in many acute animal models but there is limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of melastatin type 8 channel; the 5-HT1a receptor; the α3 and α1 glycine receptors; and the transient receptor potential of ankyrin type 1 channel. CBD has neuroprotective and anti-inflammatory effects. CBD appears to be well tolerated in humans but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ9-THC medical marijuana have claimed efficacy, but studies were not controlled.CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted.
Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex i ... (Ver mais)
Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship between the chemical composition of medical cannabis and the corresponding biological activity. In this study, we investigated 59 cannabis samples used by patients for medical reasons. The samples were subjected to extraction (microwave and supercritical carbon dioxide) and chemical analyses, and the resulting extracts were assayed in vitro using the CB1 and CB2 receptors. Using a partial least squares regression analysis, the chemical compositions of the extracts were then correlated to their corresponding cannabinoid receptor activities, thus generating predictive models that describe the receptor potency as a function of major phytocannabinoid content. Using the current dataset, meaningful models for CB1 and CB2 receptor agonism were obtained, and these reveal the insignificant relationships between the major phytocannabinoid content and receptor affinity for CB1 but good correlations between the two at CB2 receptors. These results also explain the anomalies between the receptor activities of pure phytocannabinoids and cannabis extracts. Furthermore, the models for CB1 and CB2 agonism in cannabis extracts predict the cannabinoid receptor activities of individual phytocannabinoids with reasonable accuracy. Here for the first time, we disclose a method to predict the relationship between the chemical composition, including phytocannabinoids, of cannabis extracts and cannabinoid receptor responses.
Cannabis is widely used for both recreational and medicinal purposes on a global scale. There is accumulating interest in the use of cannabis and its c ... (Ver mais)
Cannabis is widely used for both recreational and medicinal purposes on a global scale. There is accumulating interest in the use of cannabis and its constituents for athletic recovery, and in some instances, performance. Amidst speculation of potential beneficial applications, the effects of cannabis and its two most abundant constituents, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), remain largely un-investigated. The purpose of this review is to critically evaluate the literature describing the effects of whole cannabis, THC, and CBD, on athletic performance and recovery. While investigations of whole cannabis and THC have generally shown either null or detrimental effects on exercise performance in strength and aerobic-type activities, studies of sufficient rigor and validity to conclusively declare ergogenic or ergolytic potential in athletes are lacking. The ability of cannabis and THC to perturb cardiovascular homeostasis warrants further investigation regarding mechanisms by which performance may be affected across different exercise modalities and energetic demands. In contrast to cannabis and THC, CBD has largely been scrutinized for its potential to aid in recovery. The beneficial effects of CBD on sleep quality, pain, and mild traumatic brain injury may be of particular interest to certain athletes. However, research in each of these respective areas has yet to be thoroughly investigated in athletic populations. Elucidating the effects of whole cannabis, THC, and CBD is pertinent for both researchers and practitioners given the widespread use of these products, and their potential to interact with athletes’ performance and recovery.
Pediatric epilepsy, including treatment-resistant forms, has a major effect on the quality of life, morbidity, and mortality of affected children. Inte ... (Ver mais)
Pediatric epilepsy, including treatment-resistant forms, has a major effect on the quality of life, morbidity, and mortality of affected children. Interest has been growing in the use of medical cannabis as a treatment for pediatric epilepsy, yet there has been no comprehensive review of the benefits and harms of cannabis use in this population. In this systematic review, we will search for, synthesize, and assess the published and gray literature in order to provide usable and relevant information to parents, clinicians, and policy makers.We will perform a living systematic review of studies involving the use of cannabis to treat pediatric epilepsy. We will search the published and gray literature for studies involving children with any type of epilepsy taking any form of cannabis. Studies will be selected for inclusion by two independent reviewers. The primary outcome is seizure freedom. Secondary outcomes are seizure frequency, quality of life (child, caregiver), quality and quantity of sleep, status epilepticus, tonic-clonic seizures, death (all-cause, sudden unexpected death in epilepsy), gastrointestinal adverse events (diarrhea, vomiting), and visits to the emergency room. The quality of each included study will be assessed. If data are sufficient in quantity and sufficiently similar, we will conduct pairwise random-effects meta-analysis. We will repeat the literature search every 6 months to identify studies published after the previous search date. Sequential meta-analysis will be performed as necessary to update the review findings.Our review aims to provide a comprehensive and up-to-date summary of the available evidence to inform decisions about the use of cannabis in children with treatment-resistant epilepsy. The results of this review will be of use to parents, clinicians, and policy makers as they navigate this rapidly evolving area.
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Frontiers in Psychiatry -
Revisão -
2021
Cannabis is increasingly used by individuals with mental health diagnoses and often purported to treat anxiety and various other psychiatric symptoms. ... (Ver mais)
Cannabis is increasingly used by individuals with mental health diagnoses and often purported to treat anxiety and various other psychiatric symptoms. Yet support for using cannabis as a psychiatric treatment is currently limited by a lack of evidence from rigorous placebo-controlled studies. While regulatory hurdles and other barriers make clinical trials of cannabis challenging to conduct, addiction researchers have decades of experience studying cannabis use in human laboratory models. These include methods to control cannabis administration, to delineate clinical and mechanistic aspects of cannabis use, and to evaluate potential treatment applications for cannabis and its constituents. In this paper, we review these human laboratory procedures and describe how each can be applied to study cannabis use in patients with psychiatric disorders. Because anxiety disorders are among the most common psychiatric illnesses affecting American adults, and anxiety relief is also the most commonly-reported reason for medicinal cannabis use, we focus particularly on applying human laboratory models to study cannabis effects in individuals with anxiety and related disorders. Finally, we discuss how these methods can be integrated to study cannabis effects in other psychiatric conditions and guide future research in this area.
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Frontiers in Plant Science -
Artigo Original -
2021
Cannabis sativa L. is cultivated for its secondary metabolites, of which the cannabinoids have documented health benefits and growing pharmaceutical po ... (Ver mais)
Cannabis sativa L. is cultivated for its secondary metabolites, of which the cannabinoids have documented health benefits and growing pharmaceutical potential. Recent legal cannabis production in North America and Europe has been accompanied by an increase in reported findings for optimization of naturally occurring and synthetic cannabinoid production. Of the many environmental cues that can be manipulated during plant growth in controlled environments, cannabis cultivation with different lighting spectra indicates differential production and accumulation of medically important cannabinoids, including Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and cannabigerol (CBG), as well as terpenes and flavonoids. Ultraviolet (UV) radiation shows potential in stimulating cannabinoid biosynthesis in cannabis trichomes and pre-harvest or post-harvest UV treatment merits further exploration to determine if plant secondary metabolite accumulation could be enhanced in this manner. Visible LED light can augment THC and terpene accumulation, but not CBD. Well-designed experiments with light wavelengths other than blue and red light will provide more insight into light-dependent regulatory and molecular pathways in cannabis. Lighting strategies such as subcanopy lighting and varied light spectra at different developmental stages can lower energy consumption and optimize cannabis PSM production. Although evidence demonstrates that secondary metabolites in cannabis may be modulated by the light spectrum like other plant species, several questions remain for cannabinoid production pathways in this fast-paced and growing industry. In summarizing recent research progress on light spectra and secondary metabolites in cannabis, along with pertinent light responses in model plant species, future research directions are presented.
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Cannabis and Cannabinoid Research Journal -
Revisão -
2017
Headache disorders are common, debilitating, and, in many cases, inadequately managed by existing treatments. Although clinical trials of cannabis for ... (Ver mais)
Headache disorders are common, debilitating, and, in many cases, inadequately managed by existing treatments. Although clinical trials of cannabis for neuropathic pain have shown promising results, there has been limited research on its use, specifically for headache disorders. This review considers historical prescription practices, summarizes the existing reports on the use of cannabis for headache, and examines the preclinical literature exploring the role of exogenous and endogenous cannabinoids to alter headache pathophysiology. Currently, there is not enough evidence from well-designed clinical trials to support the use of cannabis for headache, but there are sufficient anecdotal and preliminary results, as well as plausible neurobiological mechanisms, to warrant properly designed clinical trials. Such trials are needed to determine short- and long-term efficacy for specific headache types, compatibility with existing treatments, optimal administration practices, as well as potential risks.
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Journal of Clinical Medicine -
Revisão -
2019
Older adults may benefit from cannabis treatment for various symptoms such as chronic pain, sleep difficulties, and others, that are not adequately con ... (Ver mais)
Older adults may benefit from cannabis treatment for various symptoms such as chronic pain, sleep difficulties, and others, that are not adequately controlled with evidence-based therapies. However, currently, there is a dearth of evidence about the efficacy and safety of cannabis treatment for these patients. This article aims to present a pragmatic treatment protocol for medical cannabis in older adults. We followed consecutive patients above 65 years of age prospectively who were treated with medical cannabis from April 2017 to October 2018. The outcomes included treatment adherence, global assessment of efficacy and adverse events after six months of treatment. During the study period, 184 patients began cannabis treatment, 63.6% were female, and the mean age was 81.2 ± 7.5 years (median age-82). After six months of treatment, 58.1% were still using cannabis. Of these patients, 33.6% reported adverse events, the most common of which were dizziness (12.1%) and sleepiness and fatigue (11.2%). Of the respondents, 84.8% reported some degree of improvement in their general condition. Special caution is warranted in older adults due to polypharmacy, pharmacokinetic changes, nervous system impairment, and increased cardiovascular risk. Medical cannabis should still be considered carefully and individually for each patient after a risk-benefit analysis and followed by frequent monitoring for efficacy and adverse events.
Cannabis legalization has increased its use. The incidence of acute pancreatitis (AP) and severe acute pancreatitis (SAP) has also increased. In this s ... (Ver mais)
Cannabis legalization has increased its use. The incidence of acute pancreatitis (AP) and severe acute pancreatitis (SAP) has also increased. In this study data on pancreatitis was obtained from two states before and after cannabis legalization and compared to two states without legalized cannabis. Data was extracted from State Inpatient Databases from the states of Colorado and Washington before recreational cannabis legalization (2011) and after legalization (2015). Arizona and Florida were used as the non-legalized cannabis states. Multivariable logistic regression models were fit for AP and SAP to determine a trend difference between legalized and non-legalized cannabis states.Cannabis use, AP and SAP increased in all states. The increase in AP and SAP was not significantly different between the states which legalized cannabis use and those which did not. Legalized cannabis states had lower charges for AP and SAP and shorter length of hospitalizations.The trend of AP and SAP increased during the study period, but this was not correlated to cannabis use. Cannabis users had lower hospitalization costs and hospital stay. The effect of other confounders such as cannabis dose and delivery methods, alcohol, tobacco, and others need to be studied further as use increases.
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Pharmaceuticals (Basel) -
Revisão -
2022
The antineoplastic effects of cannabis have been known since 1975. Since the identification of the components of the endogenous cannabinoid system (ECS ... (Ver mais)
The antineoplastic effects of cannabis have been known since 1975. Since the identification of the components of the endogenous cannabinoid system (ECS) in the 1990s, research into the potential of cannabinoids as medicine has exploded, including in anti-cancer research. However, nearly all of this research has been on adults. Physicians and governing bodies remain cautious in recommending the use of cannabis in children, since the ECS develops early in life and data about cannabis exposure in utero show negative outcomes. However, there exist many published cases of use of cannabis in children to treat pediatric epilepsy and chemotherapy-induced nausea and vomiting (CINV) that show both the safety and efficacy of cannabis in pediatric populations. Additionally, promising preclinical evidence showing that cannabis has anti-cancer effects on pediatric cancer warrants further investigation of cannabis’ use in pediatric cancer patients, as well as other populations of pediatric patients. This review aims to examine the evidence regarding the potential clinical utility of cannabis as an anti-cancer treatment in children by summarizing what is currently known about uses of medical cannabis in children, particularly regarding its anti-cancer potential.
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Journal of Cannabis Research -
Revisão -
2021
Chronic musculoskeletal pain (CMP) may lead to reduced physical function and is the most common cause of chronic non-cancer pain. Currently, the pharma ... (Ver mais)
Chronic musculoskeletal pain (CMP) may lead to reduced physical function and is the most common cause of chronic non-cancer pain. Currently, the pharmacotherapeutic options against CMP are limited and frequently consist of pain management with non-steroidal anti-inflammatories, gabapentinoids, or opioids, which carry major adverse effects. Although the effectiveness of medical cannabis (MC) for CMP still lacks solid evidence, several patients suffering from it are exploring this therapeutic option with their physicians.Little is known about patients’ perceptions of their MC treatment for CMP. We aimed to increase this knowledge, useful for healthcare professionals and patients considering this treatment, by conducting a scoping literature review, following guidance by Arksey and O’Malley, to describe the views and perceptions of adult patients who had consumed MC to relieve chronic CMP.Databases (PUBMED, EMBASE, Web of Science) and websites were searched using combinations of controlled and free vocabulary. All studies and study designs reporting on patients’ perceptions regarding MC against CMP were considered. Studies had to include adult patients reporting qualitatively or quantitatively, i.e., through questionnaires, on MC use to treat CMP or other non-cancer pain, since studies reporting exclusively on perceptions regarding CMP were very rare. Study characteristics were extracted and limitations of the study quality were assessed. The review includes patients’ demographic characteristics, patterns of MC use, perceived positive and negative effects, use of alcohol or other drugs, reported barriers to CM use, and funding sources of the studies.Participants of the 49 included studies reported that MC use helped them to reduce CMP and other chronic non-cancer pain, with only minor adverse effects, and some reported improved psychological well-being.
In the included studies, men represent between 18 and 88% of the subjects. The mean age of participants in these studies (42/49) varied between 28.4 and 62.8 years old. The most common route of administration is inhalation.MC users suffering from CMP or other chronic non-cancer pain perceived more benefits than harms. However, the information from these studies has several methodological limitations and results are exploratory. These user-reported experiences must thus be examined by well-designed and methodologically sound clinical or observational studies, particularly regarding CMP, where reports are very scarce.
Cannabis has been considered as a therapeutic strategy to control intractable epilepsy. Several cannabis components, especially cannabidiol (CBD), indu ... (Ver mais)
Cannabis has been considered as a therapeutic strategy to control intractable epilepsy. Several cannabis components, especially cannabidiol (CBD), induce antiseizure effects. However, additional information is necessary to identify the types of epilepsies that can be controlled by these components and the mechanisms involved in these effects. This review presents a summary of the discussion carried out during the 2nd Latin American Workshop on Neurobiology of Epilepsy entitled “Cannabinoid and epilepsy: myths and realities.” This event was carried out during the 10th Latin American Epilepsy Congress in San José de Costa Rica (September 28, 2018). The review focuses to discuss the use of CBD as a new therapeutic strategy to control drug‐resistant epilepsy. It also indicates the necessity to consider the evaluation of unconventional targets such as P‐glycoprotein, to explain the effects of CBD in drug‐resistant epilepsy.
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Pharmacology Research & Perspectives -
Artigo Original -
2021
The development of multidrug‐resistant bacteria has revealed the need for new antimicrobial compounds. Cannabis sativa preparations have a long history ... (Ver mais)
The development of multidrug‐resistant bacteria has revealed the need for new antimicrobial compounds. Cannabis sativa preparations have a long history of medical applications, including the treatment of infectious diseases. This review collects the information about the activity of C. sativa extracts and its main components (cannabinoids and terpenes) against pathogenic bacteria and fungus, to assess its potential using as antimicrobial agents.
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Journal of Cannabis Research -
Revisão -
2021
There is a worldwide interest in the use of Cannabis sativa for biomedicine purposes. Cannabis has ethnomedicinal usage as a natural medicine in Bangla ... (Ver mais)
There is a worldwide interest in the use of Cannabis sativa for biomedicine purposes. Cannabis has ethnomedicinal usage as a natural medicine in Bangladesh and cultivated during the British Empire period for revenues.Folk medicine practitioners (FMPs) from different districts of Bangladesh have been using Cannabis sativa, but until now there have not been any compiled studies particularly regarding this practice. Hence, this review is an effort to retrieve the traditional usage of Cannabis sativa as a phytomedicine from published ethnomedicinal studies.Information was searched by using the search terms “ethnomedicinal Cannabis sativa and Bangladesh”; “Bangladesh cannabaceae and ethnomedicinal survey”; “ganja, bhang and folk medicine Bangladesh”; “tetrahydrocannabinol (THC), cannabinoid and therapeutic, clinical trial”; and “cannabis and pharmacological/biological” and retrieved from ethnobotanical articles available on PubMed, Scopus, Science Direct, and Google Scholar databases. A search of the relevant scientific literature also was conducted to assess the efficacy of the ethnomedicinal usage of Cannabis sativa.While reviewing over 200 ethnomedicinal plants’ survey articles, we found that FMPs of Bangladesh from 12 different districts used Cannabis sativa to treat cited ailments like sleep-associated problems (n=5), neuropsychiatric and CNS problems (n=5), and infections and respiratory problems (n=5) followed by rheumatism, gastrointestinal, gynecological (n=4 each), cancer, sexual, and other ailments including hypertension, headache, itch, increases bile secretion, abortifacient, dandruff, fever, and urinary problems (n=1 each). There are a total of 15 formulations identified from the 11 out of 18 ethnomedicinal plant survey reports. The leaf was the main plant part used (53.8%), followed by root (23%), seed (7.7%) and flower, inflorescence, resin, and all parts 3.8% respectively.Sales and cultivation of Cannabis are illegal at present in Bangladesh, but the use of Cannabis sativa as a natural phytomedicine has been practiced traditionally by folk medicine practitioners of Bangladesh for many years and validated through relevant pharmacological justification. Although Cannabis sativa possesses ethnomedicinal properties in the folk medicine of Bangladesh, it is, furthermore, needed to conduct biological research to consolidate pharmacological justification about the prospects and challenges of Cannabis and cannabinoids’ use in Bangladesh as safer biomedicine in the future.
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Pharmacology Biochemistry and Behavior -
Revisão -
2021
The phytocannabinoid Δ9-tetrahydrocannabinol (THC) was isolated and synthesized in the 1960s. Since then, two synthetic cannabinoids (SCBs) targeting t ... (Ver mais)
The phytocannabinoid Δ9-tetrahydrocannabinol (THC) was isolated and synthesized in the 1960s. Since then, two synthetic cannabinoids (SCBs) targeting the cannabinoid 1 (CB1R) and 2 (CB2R) receptors were approved for medical use based on clinical safety and efficacy data: dronabinol (synthetic THC) and nabilone (synthetic THC analog). To probe the function of the endocannabinoid system further, hundreds of investigational compounds were developed; in particular, agonists with (1) greater CB1/2R affinity relative to THC and (2) full CB1/2R agonist activity. This pharmacological profile may pose greater risks for misuse and adverse effects relative to THC, and these SCBs proliferated in retail markets as legal alternatives to cannabis (e.g., novel psychoactive substances [NPS], “Spice,” “K2”). These SCBs were largely outlawed in the U.S., but blanket policies that placed all SCB chemicals into restrictive control categories impeded research progress into novel mechanisms for SCB therapeutic development. There is a concerted effort to develop new, therapeutically useful SCBs that target novel pharmacological mechanisms. This review highlights the potential therapeutic efficacy and safety considerations for unique SCBs, including CB1R partial and full agonists, peripherally-restricted CB1R agonists, selective CB2R agonists, selective CB1R antagonists/inverse agonists, CB1R allosteric modulators, endocannabinoid-degrading enzyme inhibitors, and cannabidiol. We propose promising directions for SCB research that may optimize therapeutic efficacy and diminish potential for adverse events, for example, peripherally-restricted CB1R antagonists/inverse agonists and biased CB1/2R agonists. Together, these strategies could lead to the discovery of new, therapeutically useful SCBs with reduced negative public health impact.
OPEN ACCESS -
Current Treatment Options in Psychiatry -
Revisão -
2020
This review summarizes (1) recent trends in delta-9-tetrahydrocannabionol [THC] and cannabidiol (CBD) content in cannabis products, (2) neurobiological ... (Ver mais)
This review summarizes (1) recent trends in delta-9-tetrahydrocannabionol [THC] and cannabidiol (CBD) content in cannabis products, (2) neurobiological correlates of cannabis use on the developing adolescent brain, (3) effects of cannabis on psychiatric symptoms and daily functioning in youth (i.e., academic performance, cognition, sleep and driving), (4) cannabis products used to relieve or treat medical issues in youth, and (5) available treatments for cannabis use disorder in adolescence.Despite marked increases in THC content and availability of cannabis, there has been a decline in perceived risk and an increase in use of THC extract products among youth in the United States. The primary psychiatric symptoms associated with cannabis use in youth are increased risk for addiction, depressive, and psychotic symptoms. Cannabis alters endocannabinoid system function which plays a central role in modulating the neurodevelopment of reward and stress systems. To date, few studies have examined neurobiological mechanisms underlying the psychiatric sequalae of cannabis exposure in youth. Adolescent cannabis exposure results in impaired cognition, sleep, and driving ability. There are very limited FDA-approved cannabinoid medications, none of them supporting their use for the treatment of psychiatric symptoms. Behavioral therapies are currently the mainstay of treating cannabis misuse, with no pharmacotherapies currently approved by the FDA for cannabis use disorder in youth.Here, we summarize the most up-to-date knowledge on the neurobiological psychiatric, and daily function effects of the most commonly used cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). We then review FDA approved medical use of cannabinoid treatments as well as pharmacological and psychological treatments for cannabis use disorder in youth. Our current understanding of the effects of cannabis on the developing brain and treatments for cannabis misuse in youth remain limited. Future research aimed at examining the neurobiological effects of cannabis, with objective measures of exposure, over the course of pediatric development and in relation to psychiatric symptoms are needed.
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Frontiers in Pharmacology -
Revisão -
2020
Cannabis extracts in oil are becoming increasingly available, and, during the last years, there has been growing public and scientific interest about t ... (Ver mais)
Cannabis extracts in oil are becoming increasingly available, and, during the last years, there has been growing public and scientific interest about therapeutic properties of these compounds for the treatment of several neurologic diseases, not just epilepsy. The discovered role of the endocannabinoid system in epileptogenesis has provided the basis to investigate the pharmacological use of exogenously produced cannabinoids, to treat epilepsy. Although, physicians show reluctance to recommend Cannabis extracts given the lack of high-quality safety available data, from literature data cannabidiol (CBD) results to be a promising and safe anticonvulsant drug with low side-effect. In particular, according to early studies, CBD can reduce the frequency of seizures and lead to improvements in quality of life in children affected by refractory epilepsy. So, for these reasons, the detailed study of the interactions between CBD and anticonvulsant drugs (AEDs) administered simultaneously in polytherapy, is arousing increasing interest, to clarify and to assess the incidence of adverse effects and the relation between dose escalation and quality of life measures. To date, in pediatric age, CBD efficacy and safety is not supported by well-designed trials and strong scientific evidence are not available. These studies are either retrospective or small-scale observational and only during the last years Class I evidence data for a pure form of CBD have been available, as demonstrated in placebo-controlled RCTs for patients affected by Lennox-Gastaut syndrome and Dravet syndrome. It is necessary to investigate CBD safety, pharmacokinetics and interaction with other AEDs alongside performing double-blinded placebo-controlled trials to obtain conclusive data on its efficacy and safety in the most frequent epilepsies in children, not just in the epileptic encephalopathy. This review was aimed to revise the available data to describe the scientific evidence for CBD in Pediatric Epilepsies.
To assess whether autistic and non-autistic adults differ in their cannabis and cannabidiol (CBD) use, their perceptions of cannabinoid products and th ... (Ver mais)
To assess whether autistic and non-autistic adults differ in their cannabis and cannabidiol (CBD) use, their perceptions of cannabinoid products and their cannabinoid-related support-seeking behaviours. Respondents to an online survey, who self-reported an autism-spectrum disorder diagnosis (autistic participants) or no issues relating to autism (controls). Exclusion criteria were: related/subclinical issues relating to autism, non-UK residence, under 16 years old. Propensity score matching was used to match autistic participants and controls on age, gender and ethnicity. The full-sample analysis included 269 participants and the propensity-matched sample analysis included 166 participants. Propensity-matched analysis was used for primary analysis and was considered robust if supported by triangulation with full-sample analysis.Autistic participants were more likely to have used CBD in the past 12 months compared with controls (OR=3.52, 95% CI 1.57 to 7.87, p=0.002). They used CBD on more days in the past 12 months (M=34, SD=93) compared with controls (M=17, SD=69, p=0.002). Autistic participants reported trusting the news and doctors less as sources of cannabinoid-related information than controls (p=0.024 and p=0.003, respectively). Autistic participants endorsed the following barriers to cannabinoid-related support seeking more than controls: ‘worrying they won’t understand me’ (OR=3.25, 95% CI 1.67 to 6.33, p<0.001), ‘going somewhere unfamiliar’ (OR=5.29, 95% CI 2.62 to 10.67, p<0.001) and ‘being in a crowded or chaotic place’ (OR=9.79, 95% CI 4.18 to 22.89, p<0.001).Results indicate a higher prevalence and frequency of CBD use, but not cannabis use, among autistic individuals compared with controls. Findings also suggest appropriate methods to disseminate cannabinoid-related support to autistic individuals, and indicate differences in the potential barriers autistic and non-autistic individuals may face when seeking cannabinoid-related support.Results indicate a higher prevalence and frequency of CBD use, but not cannabis use, among autistic individuals compared with controls. Findings also suggest appropriate methods to disseminate cannabinoid-related support to autistic individuals, and indicate differences in the potential barriers autistic and non-autistic individuals may face when seeking cannabinoid-related support.
Cannabis research has historically focused on the most prevalent cannabinoids. However, extracts with a broad spectrum of secondary metabolites may hav ... (Ver mais)
Cannabis research has historically focused on the most prevalent cannabinoids. However, extracts with a broad spectrum of secondary metabolites may have increased efficacy and decreased adverse effects compared to cannabinoids in isolation. Cannabis’s complexity contributes to the length and breadth of its historical usage, including the individual application of the leaves, stem barks, and roots, for which modern research has not fully developed its therapeutic potential. This study is the first attempt to profile secondary metabolites groups in individual plant parts comprehensively. We profiled 14 cannabinoids, 47 terpenoids (29 monoterpenoids, 15 sesquiterpenoids, and 3 triterpenoids), 3 sterols, and 7 flavonoids in cannabis flowers, leaves, stem barks, and roots in three chemovars available. Cannabis inflorescence was characterized by cannabinoids (15.77–20.37%), terpenoids (1.28–2.14%), and flavonoids (0.07–0.14%); the leaf by cannabinoids (1.10–2.10%), terpenoids (0.13–0.28%), and flavonoids (0.34–0.44%); stem barks by sterols (0.07–0.08%) and triterpenoids (0.05–0.15%); roots by sterols (0.06–0.09%) and triterpenoids (0.13–0.24%). This comprehensive profile of bioactive compounds can form a baseline of reference values useful for research and clinical studies to understand the “entourage effect” of cannabis as a whole, and also to rediscover therapeutic potential for each part of cannabis from their traditional use by applying modern scientific methodologies.
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Epilepsy & Behavior -
Relato de Caso -
2014
Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays and impaired quality of life. In these treatment-resistan ... (Ver mais)
Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child’s seizures. Nineteen responses met the inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy. The average number of anti-epileptic drugs (AEDs) tried before using cannabidiol-enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child’s seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25-60% seizure reduction. Other beneficial effects included increased alertness, better mood and improved sleep. Side effects included drowsiness and fatigue. Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children is not available. Objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated and efficacious at controlling seizures in this difficult-to-treat pediatric population.
OPEN ACCESS -
Medical Cannabis and Cannabinoids -
Revisão -
2021
Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, ... (Ver mais)
Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, various parts of the plant like leaf, flower, and seed were used for recreational as well as therapeutic purposes. The main chemical components of Cannabis sativa are termed as cannabinoids, among them the key psychoactive constituent is Δ-9-tetrahydrocannabinol and cannabidiol (CBD) as active nonpsychotic constituent. Upon doing extensive literature review, it was found that cannabis has been widely studied for a number of disorders. Very recently, a pure CBD formulation, named Epidiolex, got a green flag from both United States Food and Drug Administration and Drug Enforcement Administration for 2 rare types of epilepsies. This laid a milestone in medical cannabis research. This review intends to give a basic and extensive assessment, from past till present, of the ethnological, plant, chemical, pharmacological, and legal aspects of C. sativa. Further, this review contemplates the evidence the studies obtained of cannabis components on Alzheimers, Parkinsons, amyotrophic lateral sclerosis, multiple sclerosis, emesis, epilepsy, chronic pain, and cancer as a cytotoxic agent as well as a palliative therapy. The assessment in this study was done by reviewing in extensive details from studies on historical importance, ethnopharmacological aspects, and legal grounds of C. sativa from extensive literature available on the scientific databases, with a vision for elevating further pharmaceutical research to investigate its total potential as a therapeutic agent.
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Journal of Dual Diagnosis -
Revisão -
2021
Given the aging Baby Boomer generation, changes in cannabis legislation, and the growing acknowledgment of cannabis for its therapeutic potential, it i ... (Ver mais)
Given the aging Baby Boomer generation, changes in cannabis legislation, and the growing acknowledgment of cannabis for its therapeutic potential, it is predicted that cannabis use in the older population will escalate. It is, therefore, important to determine the interaction between the effects of cannabis and aging. The aim of this report is to describe the link between cannabis use and the aging brain. Our review of the literature found few and inconsistent empirical studies that directly address the impact of cannabis use on the aging brain. However, research focused on long-term cannabis use points toward cumulative effects on multimodal systems in the brain that are similarly affected during aging. Specifically, the effects of cannabis and aging converge on overlapping networks in the endocannabinoid, opioid, and dopamine systems that may affect functional decline particularly in the hippocampus and prefrontal cortex, which are critical areas for memory and executive functioning. To conclude, despite the limited current knowledge on the potential interactive effects between cannabis and aging, evidence from the literature suggests that cannabis and aging effects are concurrently present across several neurotransmitter systems. There is a great need for future research to directly test the interactions between cannabis and aging.
The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that ... (Ver mais)
The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients’ quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations.
OPEN ACCESS -
Frontiers in Pharmacology -
Revisão -
2022
Numerous existing full-spectrum cannabis extract products have been used in clinical trials for the treatment of various diseases. Despite their effica ... (Ver mais)
Numerous existing full-spectrum cannabis extract products have been used in clinical trials for the treatment of various diseases. Despite their efficacy, the clinical use of some of these full-spectrum cannabis extracts is limited by behavioral side effects such as cognitive dysfunction and impaired motor skills. To better understand what constitutes cannabis-induced behavioral effects, our objective was to identify a novel panel of blood-based metabolites that are predictive, diagnostic, and/or prognostic of behavioral effects.At 8 weeks of age, male rats were randomly assigned to groups and were gavage fed with full-spectrum cannabis extract (tetrahydrocannabinol/cannabidiol (THC/CBD) along with all other cannabis compounds, 15 mg/kg), broad-spectrum cannabis extract (CBD along with all other cannabis compounds, 15 mg/kg), or vehicle oil. Four hours after being gavage fed, behavioral assessments were determined using the open field test and the elevated plus maze. Following these assessments, serum was collected from all rats and the serum metabolites were identified and quantified by LC–MS/MS and 1H NMR spectroscopy.We found that only rats treated with full-spectrum cannabis extract exhibited behavioral changes. Compared to vehicle-treated and broad-spectrum extract–treated rats, full-spectrum extract–treated rats demonstrated higher serum concentrations of the amino acid phenylalanine and long-chain acylcarnitines, as well as lower serum concentrations of butyric acid and lysophosphatidylcholines. This unique metabolomic fingerprint in response to cannabis extract administration is linked to behavioral effects and may represent a biomarker profile of cannabis-induced behavioral changes. If validated, this work may allow a metabolomics-based decision tree that would aid in the rapid diagnosis of cannabis-induced behavioral changes including cognitive impairment.
OPEN ACCESS -
Frontiers in Pharmacology -
Revisão -
2020
Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects. Besides Δ9-tetrahydrocannabinol ... (Ver mais)
Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects. Besides Δ9-tetrahydrocannabinol that is the principal psychoactive constituent of Cannabis, cannabidiol (CBD) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for anti-inflammatory drug development for human pathologies where both the inflammation and oxidative stress (OS) play an important role to their etiology and progression. To this regard, Alzheimers disease (AD), Parkinsons disease (PD), the most common neurodegenerative disorders, are characterized by extensive oxidative damage to different biological substrates that can cause cell death by different pathways. Most cases of neurodegenerative diseases have a complex etiology with a variety of factors contributing to the progression of the neurodegenerative processes; therefore, promising treatment strategies should simultaneously target multiple substrates in order to stop and/or slow down the neurodegeneration. In this context, CBD, which interacts with the eCB system, but has also cannabinoid receptor-independent mechanism, might be a good candidate as a prototype for anti-oxidant drug development for the major neurodegenerative disorders, such as PD and AD. This review summarizes the multiple molecular pathways that underlie the positive effects of CBD, which may have a considerable impact on the progression of the major neurodegenerative disorders.
OPEN ACCESS -
American Journal of Men' s Health -
Revisão -
2019
Globally,
there is increasing usage
and legalization of cannabis.In addition to its reported therapeutic effects,
cannabis ... (Ver mais)
Globally,
there is increasing usage
and legalization of cannabis.In addition to its reported therapeutic effects,
cannabis has several health risks which are not clearly defined.Erectile dysfunction (ED) is the most common male sexual disorder
and there are plausible mechanisms linking cannabis use to ED.No attempt has been made to collate the literature on this topic.The aim of this review was to summarize the prevalence
and risk of ED in cannabis users compared to controls.A systematic review of major databases
from
inception to January 1,
2019,
without language restriction,
was undertaken to identify studies investigating cannabis use
and presence of ED.The analysis compared the prevalence of ED in cannabis users versus controls.Consequently,
the odds ratio (
OR
) with 95 % confidence intervals (CI) was calculated,
applying a random - effect model.Five case
– control studies were included with data
from
3,
395 healthy men,
1,
035 using cannabis (smoking)
and 2,
360 nonusers.The overall prevalence of ED in cannabis users was 69.1 % (95 % CI: 38.0 – 89.1),
whilst the correspondent figure in controls was 34.7 % (95 % CI: 20.3 – 52.7).The
OR of ED in cannabis users was almost four times that of controls (
OR = 3.83;
95 % CI: 1.30 – 11.28;
p =.02
),
even if characterized by high heterogeneity (I2 = 90 %)
and the prediction intervals overlapped 1.00 (95 % CI: 0.35 – 7.26).Data suggest that ED is twice as high in cannabis users compared to controls.Future longitudinal research is needed to confirm / refute this
and explore if a dose – response relationship between cannabis
and ED may be evident.
Alzheimer ’ s disease (AD) is a detrimental brain disorder characterized by a gradual cognitive decline
and neuronal deterioration.To date,
the trea ... (Ver mais)
Alzheimer ’ s disease (AD) is a detrimental brain disorder characterized by a gradual cognitive decline
and neuronal deterioration.To date,
the treatments available are effective only in the early stage of the disease.The AD etiology has not been completely revealed,
and investigating new pathological mechanisms is essential for developing effective
and safe drugs.The recreational
and pharmacological properties of marijuana are known for centuries,
but only recently the scientific community started to investigate the potential use of cannabinoids in AD therapy — sometimes with contradictory outcomes.Since the endocannabinoid system (ECS) is highly expressed in the hippocampus
and cortex,
cannabis use / abuse has often been associated with memory
and learning dysfunction in vulnerable individuals.However,
the latest findings in AD rodent models have shown promising effects of cannabinoids in reducing amyloid plaque deposition
and stimulating hippocampal neurogenesis.Beneficial effects on several dementia - related symptoms have also been reported in clinical trials
after
cannabinoid treatments.Accordingly,
future studies should address identifying the correct therapeutic dosage
and timing of treatment
from
the perspective of using cannabinoids in AD therapy.The present paper aims to summarize the potential
and limitations of cannabinoids as therapeutics for AD,
focusing on recent pre - clinical
and clinical evidence.
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2020
Alzheimer ’ s disease (AD),
considered the most common type of dementia,
is characterized by a progressive loss of memory,
visuospatial,
language ... (Ver mais)
Alzheimer ’ s disease (AD),
considered the most common type of dementia,
is characterized by a progressive loss of memory,
visuospatial,
language
and complex cognitive abilities.In addition,
patients often show comorbid depression
and aggressiveness.Aging is the major factor contributing to AD;
however,
the initial cause that triggers the disease is yet unknown.Scientific evidence demonstrates that AD,
especially the late onset of AD,
is not the result of a single event,
but rather it appears because of a combination of risk elements with the lack of protective ones.A major risk factor underlying the disease is neuroinflammation,
which can be activated by different situations,
including chronic pathogenic infections,
prolonged stress
and metabolic syndrome.Consequently,
many therapeutic strategies against AD have been designed to reduce neuro - inflammation,
with very promising results improving cognitive function in preclinical models of the disease.The literature is massive;
thus,
in this review we will revise the translational evidence of these early strategies focusing in anti - diabetic
and anti - inflammatory molecules
and discuss their therapeutic application in humans.Furthermore,
we review the preclinical
and clinical data of nutraceutical application against AD symptoms.Finally,
we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system
and the intestinal microbiota as neuroprotectors.This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD.
OPEN ACCESS -
Frontiers in Pharmacology -
Revisão -
2022
Medical use of cannabis has been receiving growing attention over the last few decades in modern medicine.As we know that the endocannabinoid system i ... (Ver mais)
Medical use of cannabis has been receiving growing attention over the last few decades in modern medicine.As we know that the endocannabinoid system is largely involved in neurological disorders,
we focused on the scientific rationale of medical cannabis in three neurological disorders: amyotrophic lateral sclerosis,
Parkinson ’ s disease,
and Alzheimer ’ s disease through pharmacological plausibility,
clinical studies,
and patients ’ view.Clinical studies (
randomized controlled trials,
open - label studies,
cohorts,
and casereports) exploring medical cannabis in these disorders show different results depending on the methods
and outcomes.Some show benefits on motor symptoms
and others on non - motor symptoms
and quality of life.Concerning patients ’ view,
several web surveys were collected,
highlighting the real use of cannabis to relieve symptoms of neurological disorders,
mostly outside a medical pathway.This anarchic use keeps questioning particularly in terms of risks: consumption of street cannabis,
drug – drug interactions with usual medical treatment,
consideration of medical history,
and adverse reactions (
psychiatric,
respiratory,
cardiovascular disorders,
etc.
),
underlining the importance of a medical supervision.To date,
most scientific data support the therapeutic potential of cannabis in neurological disorders.As far as patients
and patients ’ associations are calling for it,
there is an urgent need to manage clinical studies to provide stronger evidence
and secure medical cannabis use.
OPEN ACCESS -
The Journal of Neuroimmune Pharmacology -
Revisão -
2020
HIV infection
and drug use
intersect
epidemiologically,
and their combination can result in complex effects on brain
and behavior.The extent to w ... (Ver mais)
HIV infection
and drug use
intersect
epidemiologically,
and their combination can result in complex effects on brain
and behavior.The extent to which drugs affect the health of persons with HIV (PWH) depends on many factors including drug characteristics,
use patterns,
stage of HIV disease
and its treatment,
comorbid factors,
and age.To consider the range of drug effects,
we have selected two that are in common use by PWH: methamphetamine
and cannabis.We compare the effects of methamphetamine with those of cannabis,
to illustrate how substances may potentiate,
worsen,
or even buffer the effects of HIV on the CNS.Data
from
human,
animal,
and ex vivo studies provide insights into how these drugs have differing effects on the persistent inflammatory state that characterizes HIV infection,
including effects on viral replication,
immune activation,
mitochondrial function,
gut permeability,
blood brain barrier integrity,
glia
and neuronal signaling.Moving forward,
we consider how these mechanistic insights may inform interventions to improve brain outcomes in PWH.
OPEN ACCESS -
Frontiers in Pharmacology -
Revisão -
2022
Cannabinoids,
including those found in cannabis,
have shown promise as potential therapeutics for numerous health issues,
including pathological pa ... (Ver mais)
Cannabinoids,
including those found in cannabis,
have shown promise as potential therapeutics for numerous health issues,
including pathological pain
and diseases that produce an impact on neurological processing
and function.Thus,
cannabis use for medicinal purposes has become accepted by a growing majority.However,
clinical trials yielding satisfactory endpoints
and unequivocal proof that medicinal cannabis should be considered a frontline therapeutic for most examined central nervous system indications remains largely elusive.Although cannabis contains over 100 + compounds,
most preclinical
and clinical research with well - controlled dosing
and delivery methods utilize the various formulations of Δ9 - tetrahydrocannabinol (THC)
and cannabidiol (CBD),
the two most abundant compounds in cannabis.These controlled dosing
and delivery methods are in stark contrast to most clinical studies using whole plant cannabis products,
as few clinical studies using whole plant cannabis profile the exact composition,
including percentages of all compounds present within the studied product.This review will examine both preclinical
and clinical evidence that supports
or refutes the therapeutic utility of medicinal cannabis for the treatment of pathological pain,
neurodegeneration,
substance use disorders,
as well as anxiety - related disorders.We will predominately focus on purified THC
and CBD,
as well as other compounds isolated
from
cannabis for the aforementioned reasons but will also include discussion over those studies
where
whole plant cannabis has been used.In this review we also consider the current challenges associated with the advancement of medicinal cannabis
and its derived potential therapeutics into clinical applications.
OPEN ACCESS -
Current Neuropharmacology -
Revisão -
2021
In the last few years research into Cannabis
and its constituent phytocannabinoids has burgeoned,
particularly in the potential application of novel ... (Ver mais)
In the last few years research into Cannabis
and its constituent phytocannabinoids has burgeoned,
particularly in the potential application of novel cannabis phytochemicals for the treatment of diverse illnesses related to neurodegeneration
and dementia,
including Alzheimer ’ s (AD),
Parkinson ’ s (PD)
and Huntington ’ s disease (HD).To date,
these neurological diseases have mostly relied on symptomatological management.However,
with an aging population globally,
the search for more efficient
and disease - modifying treatments that could delay
or mitigate disease progression is imperative.In this context,
this review aims to present state of the art in the research with cannabinoids
and novel cannabinoid - based drug candidates that have been emerged as novel promising alternatives for drug development
and innovation in the therapeutics of a number of diseases,
especially those related to CNS - disturbance
and impairment.
OPEN ACCESS -
Biomolecules -
Artigo Original -
2020
Schizophrenia (SCZ) is a neurodevelopmental disorder with a high genetic component,
but the presence of environmental stressors can be important ... (Ver mais)
Schizophrenia (SCZ) is a neurodevelopmental disorder with a high genetic component,
but the presence of environmental stressors can be important for its onset
and progression.Cannabis use can be a major risk factor for developing SCZ.However,
despite the available data on the neurobiological underpinnings of SCZ,
there is an important lack of studies in human neuronal tissue
and living cells addressing the effects of cannabis in SCZ patients.In this study,
we analysed the most relevant bio - macromolecular constituents in olfactory neuroepithelium (ON) cells of healthy controls non - cannabis users,
healthy cannabis users,
SCZ patients non - cannabis users,
and SCZ patients cannabis users using Synchrotron Radiation - Fourier Transform Infrared (SR - FTIR) spectrometry
and microscopy.Our results revealed that SCZ patients non - cannabis users,
and healthy cannabis users exhibit similar alterations in the macromolecular profile of ON cells,
including disruption in lipid composition,
increased lipid membrane renewal rate
and lipid peroxidation,
altered proteins containing more β - sheet structures,
and showed an increase in DNA
and histone methylation.Notably,
these alterations were not observed in SCZ patients who use cannabis regularly.These data suggest a differential effect of cannabis in healthy controls
and in SCZ patients in terms of the macromolecular constituents of ON cells.
OPEN ACCESS -
Canadian Psychiatric Association -
Revisão -
2020
In 2016,
the global number of individuals living with dementia was 43.8 million,
representing a 117 % increase
from
1990 — mainly due to incre ... (Ver mais)
In 2016,
the global number of individuals living with dementia was 43.8 million,
representing a 117 % increase
from
1990 — mainly due to increases in aging
and population growth.Up to 90 % of individuals with dementia experience neuropsychiatric symptoms (NPS).However,
the limitations of current treatments for NPS have drivent he search for safer pharmacotherapies — including cannabinoids.To assess the efficacy
and acceptability of cannabinoids for the treatment of NPS in individuals with dementia.Systematic review
and meta - analysis of clinical trials.Of 6,
902 papers,
9 were eligible (
n = 205,
44 % female,
78 ± 7 years,
85 % Alzheimer disease
).Trials were in North America
and Europe
and explored tetrahydrocannabinol (n = 3),
dronabinol (n = 5),
or nabilone (n = 1).Titles / abstracts were independently screened by one reviewer
and reviewed by a second.Full - text screening was by two reviewers with discrepancies resolved via a third reviewer.We extracted data on the standardized mean difference (SMD) for several NPS instruments,
trial completion,
and adverse events.Data were pooled using random - effects models.Cannabinoids led to significant improvements across NPS instruments,
including the Cohen Mansfield Agitation Inventory (
SMD = − 0.80;
95 % confidence interval [CI],
− 1.45 to − 0.16
),
the Neuropsychiatric Inventory (
SMD = − 0.61;
CI,
− 1.07 to − 0.15
),
and nocturnal actigraphy (
SMD = − 1.05;
CI,
− 1.56 to − 0.54h
).Cannabinoids were well - tolerated,
with an overall trial completion rate of 93 % (193 / 205)
and no serious treatment - related adverse events.Treatment efficacy was associated with baseline dementia severity
and dose,
but not dementia subtype,
age,
or sex.The overall study quality was rated as low.There is preliminary evidence for the efficacy
and tolerability of cannabinoids as treatments for NPS.Population - based studies are needed to characterize their real - world effectiveness
and acceptability.
OPEN ACCESS -
Neurology Neuroimmunology & Neuroinflammation -
Artigo Original -
2020
To determine whether cannabis may reduce HIV - related persistent inflammation,
we evaluated the relationship of cannabis use in people with HIV (PWH ... (Ver mais)
To determine whether cannabis may reduce HIV - related persistent inflammation,
we evaluated the relationship of cannabis use in people with HIV (PWH) to inflammatory cytokines in CSF
and blood plasma.We measured a panel of proinflammatory cytokines (
interleukin [IL] -16,
C - reactive protein [CRP],
IL -6,
interferon gamma - induced protein [IP] -10,
soluble CD14,
and soluble tumor necrosis factor receptor type II [sTNFRII]
) in CSF
and blood plasma in PWH
and HIV − individuals who did
or did not use cannabis at various levels of exposure.Participants in this observational cohort were recruited
from
community sources
and underwent lumbar puncture
and phlebotomy.Cannabis use parameters were characterized by self - report based on a semistructured timeline follow - back interview.Cytokines were measured using commercially available immunoassays.Data were analyzed using factor analysis.Participants were 35 PWH
and 21 HIV − individuals,
mean (SD) age 45.4 (14.5) years,
41 cannabis ever users,
and 15 never users.PWH
and HIV − were not different in recency,
cumulative months,
grams,
or density of cannabis use.A factor analysis using CSF biomarkers yielded a factor loading on CRP,
IL -16,
and sTNFRII that was significantly associated with recency of cannabis use (
more recent use associated with lower factor 1
values
,
reflecting less inflammation;
r = 0.331 [95% CI 0.0175, 0.586]
).In particular,
more recent cannabis use was related to lower IL -16 levels (r = 0.549 [0.282, 0.737]).Plasma biomarkers yielded a factor loading on sTNFRII
and IP -10 that was associated with more recent cannabis use (
more recent use related to less inflammation;
r = 0.374 [0.0660, 0.617]
).Recent cannabis use was associated with lower levels of inflammatory biomarkers,
both in CSF
and blood,
but in different patterns.These results are consistent with compartmentalization of immune effects of cannabis.The principal active components of cannabis are highly lipid soluble
and sequestered in brain tissue;
thus,
our findings are consistent with specific anti - neuroinflammatory effects that may benefit HIV neurologic dysfunction.
OPEN ACCESS -
Frontiers in Psychiatry -
Revisão -
2021
" Medicinal cannabis ” is defined as the use of cannabis - based products for the treatment of an illness.Investigations of cannabis compounds in psyc ... (Ver mais)
" Medicinal cannabis ” is defined as the use of cannabis - based products for the treatment of an illness.Investigations of cannabis compounds in psychiatric
and neurological illnesses primarily focus on the major cannabinoids,
cannabidiol (CBD)
and Δ9 - tetrahydrocannabinol (Δ9 - THC),
which are hypothesised to benefit multiple illnesses manifesting cognitive impairment,
neurodegeneration
and neuro - inflammation,
as well as chronic pain,
epilepsy
and post - traumatic stress disorder,
respectively.The cannabis plant contains > 500 compounds,
including terpenes responsible for the flavour
and fragrance profiles of plants.Recently,
research has begun providing evidence on the potential use of certain plant - derived terpenes in modern medicine,
demonstrating anti - oxidant,
anti - inflammatory,
and neuroprotective effects of these compounds.This review examined the effects of two key terpenes,
pinene
and linalool,
on parameters relevant to neurological
and psychiatric disorders,
highlighting gaps in the literature
and recommendations for future research into terpene therapeutics.Overall,
evidence is mostly limited to preclinical studies
and well - designed clinical trials are lacking.Nevertheless,
existing data suggests that pinene
and linalool are relevant candidates for further investigation as novel medicines for illnesses,
including stroke,
ischemia,
inflammatory
and neuropathic pain (including migraine),
cognitive impairment (
relevant to Alzheimers disease
and ageing
),
insomnia,
anxiety,
and depression.Linalool
and pinene influence multiple neurotransmitter,
inflammatory
and neurotrophic signals as well as behaviour,
demonstrating psycho - activity (albeit non - intoxicating).Optimising the phytochemical profile of cannabis chemovars to yield therapeutic levels of beneficial terpenes
and cannabinoids,
such as linalool,
pinene
and CBD,
could present a unique opportunity to discover novel medicines to treat psychiatric
and neurological illnesses;
however,
further research is needed.
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2020
Inflammatory bowel diseases (IBD) are characterized by a chronic
and recurrent gastrointestinal condition,
including mainly ulcerative colitis (UC) ... (Ver mais)
Inflammatory bowel diseases (IBD) are characterized by a chronic
and recurrent gastrointestinal condition,
including mainly ulcerative colitis (UC)
and Crohn ’ s disease (CD).Cannabis sativa (CS) is widely used for medicinal,
recreational,
and religious purposes.The most studied compound of CS is tetrahydrocannabinol (THC)
and cannabidiol (CBD).Besides many relevant therapeutic roles such as anti - inflammatory
and antioxidant properties,
there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems.Because of these reasons,
the aim of this review is to investigate the effects of CS on the treatment of UC
and CD.The literature search was performed in PubMed / Medline,
PMC,
EMBASE,
and Cochrane databases.The use of CS leads to the improvement of UC
and CD scores
and quality of life.The medical use of CS is on the rise.Although the literature shows relevant antioxidant
and anti - inflammatory effects that could improve UC
and CD scores,
it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety
and part of the plant that is used,
route of administration
and doses.Therefore,
we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization
and a relevant number of patients are performed.
OPEN ACCESS -
Frontiers in Aging Neuroscience -
Revisão -
2022
Several lines of evidence suggest that older adults (aged 65 +) sharply increased their cannabis use over the last decade,
highlighting a need to und ... (Ver mais)
Several lines of evidence suggest that older adults (aged 65 +) sharply increased their cannabis use over the last decade,
highlighting a need to understand the effects of cannabis in this age group.Pre - clinical models suggest that cannabinoids affect the brain
and cognition in an age - dependent fashion,
having
generally beneficial effects on older animals
and deleterious effects on younger ones.However,
there is little research on how cannabis affects the brains of older adults
or how older adults differ
from
younger adults who use cannabis.Resting state functional connectivity (rsFC) measures provide sensitive metrics of age - related cognitive decline.Here we compared rsFC in older adults who are either regular users of cannabis
or non - users.We found stronger connectivity between sources in the hippocampus
and parahippocampal cortex,
and targets in the anterior lobes of the cerebellum in older adult cannabis users relative to non - users.A similar pattern of strengthened connectivity between hippocampal
and cerebellar structures was also present in 25 – 35 year old non - users in comparison to 60 – 88 year old non - users.These findings suggest that future studies should examine both the potential risks of cannabinoids,
as well as a potential benefits,
on cognition
and brain health for older adults.
OPEN ACCESS -
BioMed Research International -
Revisão -
2018
In the last decades,
a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L.,
such as Δ9 - tetrahydrocannabinol (Δ ... (Ver mais)
In the last decades,
a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L.,
such as Δ9 - tetrahydrocannabinol (Δ9 - THC)
and cannabidiol (CBD),
and their effects on inflammation
and cancer - related pain.The National Cancer Institute (NCI) currently recognizes medicinal C.sativa as an effective treatment for providing relief in a number of symptoms associated with cancer,
including pain,
loss of appetite,
nausea
and vomiting,
and anxiety.Several studies have described CBD as a multitarget molecule,
acting as an adaptogen,
and as a modulator,
in different ways,
depending on the type
and location of disequilibrium both in the brain
and in the body,
mainly interacting with specific receptor proteins CB1
and CB2.CBD is present in both medicinal
and fibre - type C.sativa plants,
but,
unlike Δ9 - THC,
it is completely nonpsychoactive.Fibre - type C.sativa (hemp) differs
from
medicinal C.sativa,
since it contains only few levels of Δ9 - THC
and high levels of CBD
and related nonpsychoactive compounds.In recent years,
a number of preclinical researches have been focused on the role of CBD as an anticancer molecule,
suggesting CBD (
and CBD - like molecules present in the hemp extract
) as a possible candidate for future clinical trials.CBD has been found to possess antioxidant activity in many studies,
thus suggesting a possible role in the prevention of both neurodegenerative
and cardiovascular diseases.In animal models,
CBD has been shown to inhibit the progression of several cancer types.Moreover,
it has been found that coadministration of CBD
and Δ9 - THC,
followed by radiation therapy,
causes an increase of autophagy
and apoptosis in cancer cells.In addition,
CBD is able to inhibit cell proliferation
and to increase apoptosis in different types of cancer models.These activities seem to involve also alternative pathways,
such as the interactions with TRPV
and GRP55 receptor complexes.Moreover,
the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells
and to downregulate the proto - oncogene c - fos
and the cyclooxygenase -2 (COX -2) highlights the possibility that CBDA might act on a common pathway of inflammation
and cancer mechanisms,
which might be responsible for its anticancer activity.In the light of all these findings,
in this review we explore the effects
and the molecular mechanisms of CBD on inflammation
and cancer processes,
highlighting also the role of minor cannabinoids
and noncannabinoids constituents of Δ9 - THC deprived hemp.
OPEN ACCESS -
Pharmaceutics. -
Artigo Original -
2022
The purpose of this analytical study was to develop an advanced formulation of medical Cannabis oil (MCO) comparing the chemical profile of different ... (Ver mais)
The purpose of this analytical study was to develop an advanced formulation of medical Cannabis oil (MCO) comparing the chemical profile of different extracts obtained with two existing methods (
SIFAP
and CALVI
)
and one original upgraded (CERFIT) method.Preparation methods were applied with varying solvent,
temperature,
and duration of the decarboxylation
and extraction steps.HPLC - MS / MS TSQ
and GC / FID - HS analyses were performed to investigate cannabinoid
and terpene contents in the three oil extracts.Cannabinoids profile remained comparable between the formulations.CERFIT extracts exhibited a superior quantity of total terpene hydrocarbon forms (
e.g.,
limonene
and α - pinene
) with no degradation occurrence (i.e., oxidized terpenes not quantifiable).Thus,
this new method optimized the phytochemical profile of the MCO presenting a value opportunity to obtain a standardized high - level therapeutic product.
Cannabinoid - based medicines (CBMs) are being used widely in the elderly.However,
their safety
and tolerability in older adults remains unclear.We ... (Ver mais)
Cannabinoid - based medicines (CBMs) are being used widely in the elderly.However,
their safety
and tolerability in older adults remains unclear.We aimed to conduct a systematic review
and meta - analysis of safety
and tolerability of CBMs in adults of age ≥ 50 years.A systematic search was performed using MEDLINE,
PubMed,
EMBASE,
CINAHL PsychInfo,
Cochrane Library,
and ClinicalTrials.gov (1 January 1990 to 3 October 2020).Randomised clinical trials (RCTs) of CBMs in those with mean age of ≥ 50 years for all indications,
evaluating the safety / tolerability of CBMs
where
adverse events have been quantified,
were included.Study quality was assessed using the GRADE (
Grading of Recommendations Assessment,
Development,
and Evaluation
) criteria
and Preferred Reporting Items for Systematic Reviews
and Meta - analyses (PRISMA) guidelines were followed.Two reviewers conducted all review stages independently.
Where
possible,
data were pooled using random - effects meta - analysis.Effect sizes were calculated as incident rate ratio (IRR) for outcome data such as adverse events (AEs),
serious AEs (SAEs),
and death
and risk ratio (RR) for withdrawal
from
study
and reported separately for studies using tetrahydrocannabinol (THC),
THC :cannabidiol (CBD) combination,
and CBD.A total of 46 RCTs were identified as suitable for inclusion of which 31 (67 %) were conducted in the United Kingdom
and Europe.There were 6,
216 patients (
mean age 58.6 ± 7.5 years;
51 % male
) included in the analysis,
with 3,
469 receiving CBMs.Compared with controls,
delta -9 - tetrahydrocannabinol (THC) - containing CBMs significantly increased the incidence of all - cause
and treatment - related AEs: THC alone (IRR: 1.42 [95% CI, 1.12 to 1.78])
and (IRR: 1.60 [95% CI, 1.26 to 2.04]);
THC :CBD combination (IRR: 1.58 [95% CI,1.26 to 1.98])
and (IRR: 1.70 [95% CI,1.24 to 2.33]),
respectively.IRRs of SAEs
and deaths were not significantly greater under CBMs containing THC with
or without CBD.THC :CBD combination (RR: 1.40 [95% CI, 1.08 to 1.80]) but not THC alone (RR: 1.18 [95% CI, 0.89 to 1.57]) significantly increased risk of AE - related withdrawals.CBD alone did not increase the incidence of all - cause AEs (IRR: 1.02 [95% CI, 0.90 to 1.16])
or other outcomes as per qualitative synthesis.AE - related withdrawals were significantly associated with THC dose in THC only [QM (df = 1) = 4.696, p = 0.03]
and THC :CBD combination treatment (
[QM (df = 1) = 4.554, p = 0.033].THC - containing CBMs significantly increased incidence of dry mouth,
dizziness / light - headedness,
and somnolence / drowsiness.Study limitations include inability to fully exclude data
from
those < 50 years of age in our primary analyses as well as limitations related to weaknesses in the included trials particularly incomplete reporting of outcomes
and heterogeneity in included studies.This pooled analysis,
using data
from
RCTs with mean participant age ≥ 50 years,
suggests that although THC - containing CBMs are associated with side effects,
CBMs in general are safe
and acceptable in older adults.However,
THC :CBD combinations may be less acceptable in the dose ranges used
and their tolerability may be different in adults over 65
or 75 years of age.
OPEN ACCESS -
European Archives of Psychiatry
and Clinical Neuroscience -
Revisão -
2019
We conducted a review of systematic reviews (SRs)
and randomized - controlled trials (RCTs) to analyze efficacy
and safety of cannabis - based medic ... (Ver mais)
We conducted a review of systematic reviews (SRs)
and randomized - controlled trials (RCTs) to analyze efficacy
and safety of cannabis - based medication in patients with mental disorders.Five data bases were systematically searched (2006 — August 2018);
4 SRs (of 11 RCTs)
and 14 RCTs (1629 participants) were included.Diagnoses were: dementia,
cannabis
and opioid dependence,
psychoses / schizophrenia,
general social anxiety,
posttraumatic stress disorder,
anorexia nervosa,
attention - deficit hyperactivity disorder,
and Tourette `s disorder. Outcome variables were too heterogeneous to conduct a meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists. THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.
OPEN ACCESS -
Current Addiction Reports -
Revisão -
2020
Older adults currently represent the fastest growing demographic of cannabis users, yet few studies have investigated the effects of cannabis use on co ... (Ver mais)
Older adults currently represent the fastest growing demographic of cannabis users, yet few studies have investigated the effects of cannabis use on cognitive functioning in aging. We conducted a systematic review of the recent literature examining cognitive outcomes associated with cannabis use in older adults, with and without neurocognitive disorders, to clarify the potential neuroprotective benefits and risks of cognitive decline in this population. We identified 26 studies examining cognitive outcomes associated with medical and recreational use of cannabis in healthy aging, dementia, Parkinson’s disease, multiple sclerosis, HIV, and pain populations. Although variability in the cannabis products used, outcomes assessed, and study quality limits the conclusions that can be made, modest reductions in cognitive performance were generally detected with higher doses and heavier lifetime use.This review highlights the need for additional high-quality research using standardized, validated assessments of cannabis exposure and cognitive outcomes. Reliable measures and longitudinal data are necessary to better characterize the effects of cannabis use on cognitive aging, as well as differential effects of recreational and medical cannabis.
OPEN ACCESS -
JAMA Neurology -
Artigo Original -
2018
Synaptic loss is well established as the major structural correlate of cognitive impairment in Alzheimer disease (AD). The ability to measure synaptic ... (Ver mais)
Synaptic loss is well established as the major structural correlate of cognitive impairment in Alzheimer disease (AD). The ability to measure synaptic density in vivo could accelerate the development of disease-modifying treatments for AD. Synaptic vesicle glycoprotein 2A is an essential vesicle membrane protein expressed in virtually all synapses and could serve as a suitable target for synaptic density. To compare hippocampal synaptic vesicle glycoprotein 2A (SV2A) binding in participants with AD and cognitively normal participants using positron emission tomographic (PET) imaging.This cross-sectional study recruited 10 participants with AD and 11 participants who were cognitively normal between November 2015 and June 2017. We hypothesized a reduction in hippocampal SV2A binding in AD, based on the early degeneration of entorhinal cortical cell projections to the hippocampus (via the perforant path) and hippocampal SV2A reductions that had been observed in postmortem studies. Participants underwent high-resolution PET scanning with ((R)-1-((3-(11C-methyl-11C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one), a compound more commonly known as 11C-UCB-J, for SV2A. They also underwent high-resolution PET scanning with carbon 11–labeled Pittsburgh Compound B (11C-PiB) for β-amyloid, magnetic resonance imaging, and cognitive and neurologic evaluation.Outcomes were 11C-UCB-J–specific binding (binding potential [BPND]) via PET imaging in brain regions of interest in participants with AD and participants who were cognitively normal.Ten participants with AD (5 male and 5 female; mean [SD] age, 72.7 [6.3] years; 10 [100%] β-amyloid positive) were compared with 11 participants who were cognitively normal (5 male and 6 female; mean [SD] age, 72.9 [8.7] years; 11 [100%] β-amyloid negative). Participants with AD spanned the disease stages from amnestic mild cognitive impairment (n = 5) to mild dementia (n = 5). Participants with AD had significant reduction in hippocampal SV2A specific binding (41%) compared with cognitively normal participants, as assessed by 11C-UCB-J–PET BPND (cognitively normal participants: mean [SD] BPND, 1.47 [0.37]; participants with AD: 0.87 [0.50]; P = .005). These reductions remained significant after correction for atrophy (ie, partial volume correction; participants who were cognitively normal: mean [SD], 2.71 [0.46]; participants with AD: 2.15 [0.55]; P = .02). Hippocampal SV2A-specific binding BPND was correlated with a composite episodic memory score in the overall sample (R = 0.56; P = .01).To our knowledge, this is the first study to investigate synaptic density in vivo in AD using 11C-UCB-J–PET imaging. This approach may provide a direct measure of synaptic density, and it therefore holds promise as an in vivo biomarker for AD and as an outcome measure for trials of disease-modifying therapies, particularly those targeted at the preservation and restoration of synapses.
OPEN ACCESS -
Frontiers in Pharmacology -
Artigo Original -
2020
Reduced brain glucose consumption arising from impaired glucose uptake and utilization has been linked to the pathogenesis and complications of neurode ... (Ver mais)
Reduced brain glucose consumption arising from impaired glucose uptake and utilization has been linked to the pathogenesis and complications of neurodegenerative diseases. The ability of Cannabis sativa L. tetrahydrocannabinol (THC)-rich extracts to stimulate brain glucose uptake and utilization as well as its modulatory effect on gluconeogenesis, antioxidative, purinergic and cholinergic activities were investigated in isolated rats’ brains. C. sativa leaves were sequentially extracted to yield the hexane and dichloromethane extracts. The extracts were incubated at 37°C with freshly harvested brains in the presence of glucose for 2 h. The control consisted of incubation without the extracts, while brains without the extracts and glucose served as the normal control. Metformin was used as the standard drug. C. sativa extracts caused a significant (p < 0.05) increase in brain glucose uptake, with concomitant elevation of glutathione level, superoxide dismutase, catalase, and ecto-nucleoside triphosphate diphosphohydrolase activities compared to the controls. Incubation with C. sativa extracts also led to depletion in malondialdehyde and nitric oxide levels, acetylcholinesterase, butyrylcholinesterase, glucose 6-phosphatase and fructose-1,6-biphosphatase activities. GC-MS analysis of the extracts revealed the presence of THC. In silico analysis predicted THC to be permeable across the blood-brain-barrier. THC was also predicted to have an oral LD50 and toxicity class values of 482 mg/kg and 4 respectively. These results indicate that C. sativa improves glucose consumption with concomitant suppression of oxidative stress and cholinergic dysfunction, and modulation of purinergic and gluconeogenic activities in brain tissues
OPEN ACCESS -
Frontiers in Psychiatry -
Artigo Original -
2022
Emotional behavior, memory, and learning have been associated with alterations in the immune system in neuropsychiatric and neurodegenerative diseases. ... (Ver mais)
Emotional behavior, memory, and learning have been associated with alterations in the immune system in neuropsychiatric and neurodegenerative diseases. In recent years, several studies pointed out the involvement of the cannabinoid receptor 2 (CB2r) in the immune system and the regulation of inflammation. This receptor is widely distributed in different tissues and organs with higher expression in spleen and immune system cells. However, CB2r has also been detected in several brain areas and different brain cell types, such as neurons and glia. These findings suggest that CB2r may closely relate the immune system and the brain circuits regulating inflammation, mood, and cognitive functions. Therefore, we review the studies that may help elucidate the molecular bases of CB2r in regulating inflammation in different brain cells and its role in the pathophysiology of psychiatric and neurodegenerative disorders.
OPEN ACCESS -
Pharmaceuticals (Basel). -
Artigo Original -
2020
In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were invest ... (Ver mais)
In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells. The oxidative stress was induced by hydrogen peroxide, as reactive oxygen species (ROS). Alzheimer’s disease (AD)-like pathological conditions were mimicked in vitro by treating the differentiated neuronal cells with amyloid-β1–42 (Aβ1–42) in the presence of Cu(II). We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the ratio of the THC and CBD. However, our results did not suggest any antagonist effect of the CBD on the antioxidant activity of THC. The effect of cannabis extracts on the cell viability of differentiated human neuronal SY-SH5Y cells was also investigated, which emphasized the differences between the bioactivity of cannabis extracts due to their composition. Our preliminary results demonstrated that cannabis extracts and phytocannabinoids have a promising potential as antioxidants, which can be further investigated to develop novel pharmaceuticals targeting oxidative stress therapy.
OPEN ACCESS -
Biomolecules. -
Artigo Original -
2020
The study documented here was aimed to find the molecular interactions of some of the cannabinoid constituents of cannabis with acetylcholinesterase (A ... (Ver mais)
The study documented here was aimed to find the molecular interactions of some of the cannabinoid constituents of cannabis with acetylcholinesterase (AChE). Molecular docking and LogP determination were performed to predict the AChE inhibitory effect and lipophilicity. AChE enzyme activity was measured in the blood of cannabis addicted human subjects. Further, genetic predisposition to cannabis addiction was investigated by association analysis of cannabinoid receptor 1 (CNR1) single nucleotide polymorphism (SNP) rs806368 and ACHE rs17228602 using restriction fragment length polymorphism (RFLP) method. All the understudied cannabis constituents showed promising binding affinities with AChE and are lipophilic in nature. The AChE activity was observed to be indifferent in cannabis addicted and non-addicted healthy controls. There was no significant association with CNR1 SNP rs806368 and ACHE rs17228602. The study concludes that in silico prediction for individual biomolecules of cannabis is different from in vivo physiological action in human subjects when all are present together. However, for a deeper mechanistic insight into these interactions and association, multi-population studies are suggested. Further studies to explore the inhibitory potential of different cannabis constituents for intended AChE inhibitor-based drug are warranted.
OPEN ACCESS -
International Psychogeriatrics -
Revisão -
2016
The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzhei ... (Ver mais)
The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzheimer’s disease (AD). Few effective pharmacological or non-pharmacological options are available. Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing. This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to methodological issues such as the choice of outcomes. The aim of this review was to highlight key methodological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD.We searched PubMed/Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD, between January 2008 and December 2013.We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing. Of the ongoing RCTs, only one is in Phase III. Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo. Each of the completed RCTs used a different definition of “clinically significant A/A”. There was considerable heterogeneity in study desin. The primary endpoints were largely proxy-based but a variety of scales were used. The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous. Placebo response was notable in all trials.This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key methodological issues such as definition of A/A, choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design.
OPEN ACCESS -
Frontiers in Pharmacology -
Revisão -
2019
Alzheimer disease (AD) is characterized as a chronic neurodegenerative disease associated with aging. The clinical manifestations of AD include latent ... (Ver mais)
Alzheimer disease (AD) is characterized as a chronic neurodegenerative disease associated with aging. The clinical manifestations of AD include latent episodes of memory and cognitive impairment, psychiatric symptoms and behavioral disorders, as well as limited activities in daily life. In developed countries, AD is now acknowledged as the third leading cause of death, following cardiovascular disease and cancer. The pathogenesis and mechanism of AD remain unclear, although some theories have been proposed to explain AD, such as the theory of β-amyloid, the theory of the abnormal metabolism of tau protein, the theory of free radical damage, the theory of the inflammatory response, the theory of cholinergic damage, etc. Effective methods to predict, prevent or reverse AD are unavailable, and thus the development of new, efficient therapeutic drugs has become a current research hot spot worldwide. The isolation and extraction of active components from natural drugs have great potential in treating AD. These drugs possess the advantages of multiple targets in multiple pathways, fewer side effects and a long duration of curative effects. This article summaries the latest research progress regarding the mechanisms of natural drugs in the treatment of AD, providing a review of the literature and a theoretical basis for improving the clinical treatment of AD.
OPEN ACCESS -
Journal of Cannabis Research -
Revisão -
2022
We undertook this systematic review to determine the efficacy and safety of cannabis-based medicine as a treatment for behavioral, psychological, and m ... (Ver mais)
We undertook this systematic review to determine the efficacy and safety of cannabis-based medicine as a treatment for behavioral, psychological, and motor symptoms associated with neurocognitive disorders.We conducted a PRISMA-guided systematic review to identify studies using cannabis-based medicine to treat behavioral, psychological, and motor symptoms among individuals with Alzheimers disease (AD) dementia, Parkinson’s disease (PD), and Huntington’s disease (HD). We considered English-language articles providing original data on three or more participants, regardless of design.We identified 25 studies spanning 1991 to 2021 comprised of 14 controlled trials, 5 pilot studies, 5 observational studies, and 1 case series. In most cases, the cannabinoids tested were dronabinol, whole cannabis, and cannabidiol, and the diagnoses included AD (n = 11), PD (n = 11), and HD (n = 3). Primary outcomes were motor symptoms (e.g., dyskinesia), sleep disturbance, cognition, balance, body weight, and the occurrence of treatment-emergent adverse events.A narrative summary of the findings from the limited number of studies in the area highlights an apparent association between cannabidiol-based products and relief from motor symptoms in HD and PD and an apparent association between synthetic cannabinoids and relief from behavioral and psychological symptoms of dementia across AD, PD, and HD. These preliminary conclusions could guide using plant-based versus synthetic cannabinoids as safe, alternative treatments for managing neuropsychiatric symptoms in neurocognitive vulnerable patient populations.
OPEN ACCESS -
Psychopharmacology (Berl) -
Artigo Original -
2015
Data on safety, pharmacodynamics, and pharmacokinetics of tetrahydrocannabinol (THC) are lacking in dementia patients.In this randomized, double-blind, ... (Ver mais)
Data on safety, pharmacodynamics, and pharmacokinetics of tetrahydrocannabinol (THC) are lacking in dementia patients.In this randomized, double-blind, placebo-controlled, crossover trial, we evaluated the safety, pharmacodynamics, and pharmacokinetics of THC in ten patients with dementia (mean age 77.3 ± 5.6). For 12 weeks, participants randomly received oral THC (weeks 1–6, 0.75 mg; weeks 7–12, 1.5 mg) or placebo twice daily for 3 days, separated by a 4-day washout period.Only 6 of the 98 reported adverse events were related to THC. Visual analog scale (VAS) feeling high, VAS external perception, body sway-eyes-open, and diastolic blood pressure were not significantly different with THC. After the 0.75-mg dose, VAS internal perception (0.025 units; 95 % CI 0.010–0.040) and heart rate (2 beats/min; 95 % CI 0.4–3.8) increased significantly. Body sway-eyes-closed increased only after 1.5 mg (0.59°/s; 95 % CI 0.13–1.06). Systolic blood pressure changed significantly after both doses of THC (0.75 mg, −7 mmHg, 95 % CI −11.4, −3.0; 1.5 mg, 5 mmHg, 95 % CI 1.0–9.2). The median T max was 1–2 h, with THC pharmacokinetics increasing linearly with increasing dose, with wide interindividual variability (CV% up to 140 %). The mean C max (ng/mL) after the first dose (0–6 h) was 0.41 (0.18–0.90) for the 0.75-mg dose and 1.01 (0.53–1.92) for the 1.5-mg dose. After the second dose (6–24 h), the C max was 0.50 (0.27–0.92) and 0.98 (0.46–2.06), respectively.THC was rapidly absorbed and had dose-linear pharmacokinetics with considerable interindividual variation. Pharmacodynamic effects, including adverse events, were minor. Further studies are warranted to evaluate the pharmacodynamics and efficacy of higher THC doses in older persons with dementia.
eurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functio ... (Ver mais)
eurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functional and mental impairment due to loss of neurons. Recent evidence highlights the link between neurodegenerative and inflammatory diseases of the CNS. These are typically associated with several neurological disorders. These diseases have fundamental differences regarding their underlying physiology and clinical manifestations, although there are aspects that overlap. The endocannabinoid system (ECS) is comprised of receptors (type-1 (CB1R) and type-2 (CB2R) cannabinoid-receptors, as well as transient receptor potential vanilloid 1 (TRPV1)), endogenous ligands and enzymes that synthesize and degrade endocannabinoids (ECBs). Recent studies revealed the involvement of the ECS in different pathological aspects of these neurodegenerative disorders. The present review will explore the roles of cannabinoid receptors (CBRs) and pharmacological agents that modulate CBRs or ECS activity with reference to Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and multiple sclerosis (MS).
OPEN ACCESS -
Current Neuropharmacology -
Revisão -
2018
Chronic pain is a significant clinical problem and a very complex pathophysiological phenomenon. There is growing evidence that targeting the endocanna ... (Ver mais)
Chronic pain is a significant clinical problem and a very complex pathophysiological phenomenon. There is growing evidence that targeting the endocannabinoid system may be a useful approach to pain alleviation. Classically, the system includes G protein-coupled receptors of the CB1 and CB2 subtypes and their endogenous ligands. More recently, several subtypes of the large superfamily of cation TRP channels have been coined as “ionotropic cannabinoid receptors”, thus highlighting their role in cannabinoid signalling. Thus, the aim of this review was to explore the intimate connection between several “painful” TRP channels, endocannabinoids and nociceptive signalling.Research literature on this topic was critically reviewed allowing us not only summarize the existing evidence in this area of research, but also propose several possible cellular mechanisms linking nociceptive and cannabinoid signaling with TRP channels.We begin with an overview of physiology of the endocannabinoid system and its major components, namely CB1 and CB2 G protein-coupled receptors, their two most studied endogenous ligands, anandamide and 2-AG, and several enzymes involved in endocannabinoid biosynthesis and degradation. The role of different endocannabinoids in the regulation of synaptic transmission is then discussed in detail. The connection between the endocannabinoid system and several TRP channels, especially TRPV1-4, TRPA1 and TRPM8, is then explored, while highlighting the role of these same channels in pain signalling.There is increasing evidence implicating several TRP subtypes not only as an integral part of the endocannabinoid system, but also as promising molecular targets for pain alleviation with the use of endo- and phytocannabinoids, especially when the function of these channels is upregulated under inflammatory conditions.
OPEN ACCESS -
Canadian Medical Association Journal -
Relato de Caso -
2015
Now educational opportunities are emerging. The College of Family Physicians of Canada (CFPC) has approved seven programs on dried cannabis; the two ... (Ver mais)
Now educational opportunities are emerging. The College of Family Physicians of Canada (CFPC) has approved seven programs on dried cannabis; the two online ones were funded by Tilray, a licensed producer. Another cannabis producer, Tweed Marijuana Inc., launched its education program this spring. Physicians seeking an education free of industry influence can look to the Advancing Practice online certificate program approved by the Canadian Council on Continuing Education in Pharmacy. In addition, doctors can attend seminars or dinner lectures led by researchers or fellow doctors. Dr. David Hepburn, a family physician in Victoria, BC, is one of the latter. Over the next few weeks, he will travel to five provinces to educate other doctors on medical cannabis. “One of the things I ask physicians, in a room of about 100 doctors, is ‘How many of you have cannabis in your blood system right now?’ You might get one or two brave souls who put a hand up, but I say the fact is you all do because you’re all making your own cannabinoids.”
OPEN ACCESS -
Portuguese Journal of Gastroenterology -
Relato de Caso -
2021
Cannabinoid hyperemesis syndrome (CHS) is characterized by episodic bursts of nausea, vomiting and abdominal pain, affecting chronic cannabis users. ... (Ver mais)
Cannabinoid hyperemesis syndrome (CHS) is characterized by episodic bursts of nausea, vomiting and abdominal pain, affecting chronic cannabis users. The clinical picture mimics an acute abdomen, usually leading to multiple assessments in the emergency department. Several complementary diagnostic examinations are performed with non-specific results, making differential diagnosis puzzling. We present a case of a 42-year-old man, who has been admitted multiple times to the emergency department in the last 3 months for abdominal pain, nausea and vomiting, without triggering factors and improving only with hot water baths. He was evaluated by different specialties, the various complementary diagnostic tests performed showed no significant results, and no definitive diagnosis was obtained. Treatment resulted only in a partial and transient resolution of symptoms. A more detailed medical history revealed cannabis use for more than 5 years, with a recent increase in the amount consumed. After psychoeducation, explaining the risks associated with consumption and its relationship with the clinical symptoms, which resulted in complete suspension of cannabis, there have been no new symptomatic episodes since then. We present an illustrative case of a poorly reported clinical entity despite having a probable significant prevalence, raising awareness in order that clinicians identify and properly manage these cases.
OPEN ACCESS -
Advances in Experimental Medicine and Biology -
Revisão -
2020
Cannabis and cannabinoid-based extracts have long been utilized for their perceived therapeutic value, and support for the legalization of cannabis f ... (Ver mais)
Cannabis and cannabinoid-based extracts have long been utilized for their perceived therapeutic value, and support for the legalization of cannabis for medicinal purposes continues to increase worldwide. Since the discovery of Δ9-tetrahydrocannabinol (THC) as the primary psychoactive component of cannabis over 50 years ago, substantial effort has been directed toward detection of endogenous mediators of cannabinoid activity. The discovery of anandamide and 2-arachidonoylglycerol as two endogenous lipid mediators of cannabinoid-like effects (endocannabinoids) has inspired exponential growth in our understanding of this essential pathway, as well as the pathological conditions that result from dysregulated endocannabinoid signaling. This review examines current knowledge of the endocannabinoid system including metabolic enzymes involved in biosynthesis and degradation and their receptors, and evaluates potential druggable targets for therapeutic intervention.
OPEN ACCESS -
Oncotarget. -
Artigo Original -
2017
Breast cancer is the second leading cause of cancer deaths among women. Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabino ... (Ver mais)
Breast cancer is the second leading cause of cancer deaths among women. Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabinoid system. Although CNR2 is highly expressed in the breast cancer tissues as well as breast cancer cell lines, its functional role in breast tumorigenesis is not well understood. We observed that estrogen receptor-α negative (ERα-) breast cancer cells highly express epidermal growth factor receptor (EGFR) as well as insulin-like growth factor-I receptor (IGF-IR). We also observed IGF-IR upregulation in ERα+ breast cancer cells. In addition, we found that higher CNR2 expression correlates with better recurrence free survival in ERα- and ERα+ breast cancer patients. Therefore, we analyzed the role of CNR2 specific agonist (JWH-015) on EGF and/or IGF-I-induced tumorigenic events in ERα- and ERα+ breast cancers. Our studies showed that CNR2 activation inhibited EGF and IGF-I-induced migration and invasion of ERα+ and ERα- breast cancer cells. At the molecular level, JWH-015 inhibited EGFR and IGF-IR activation and their downstream targets STAT3, AKT, ERK, NF-kB and matrix metalloproteinases (MMPs). In vivo studies showed that JWH-015 significantly reduced breast cancer growth in ERα+ and ERα- breast cancer mouse models. Furthermore, we found that the tumors derived from JWH-015-treated mice showed reduced activation of EGFR and IGF-IR and their downstream targets. In conclusion, we show that CNR2 activation suppresses breast cancer through novel mechanisms by inhibiting EGF/EGFR and IGF-I/IGF-IR signaling axes.
OPEN ACCESS -
International Review of Neurobiology -
Artigo Original -
2019
The purpose of this chapter is to provide an introduction to the mechanisms for the regulation of endocannabinoid signaling through CB1 cannabinoid r ... (Ver mais)
The purpose of this chapter is to provide an introduction to the mechanisms for the regulation of endocannabinoid signaling through CB1 cannabinoid receptors in the central nervous system. The processes involved in the synthesis and degradation of the two most well studied endocannabinoids, 2-arachidonoylglycerol and N-arachidonylethanolamine are outlined along with information regarding the regulation of the proteins involved. Signaling mechanisms and pharmacology of the CB1 cannabinoid receptor are outlined, as is the paradigm of endocannabinoid/CB1 receptor regulation of neurotransmitter release. The reader is encouraged to appreciate the importance of the endocannabinoid/CB1 receptor signaling system in the regulation of synaptic activity in the brain.
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2022
Over the last 25 years, the human endocannabinoid system (ECS) has come into the limelight as an imperative neuro-modulatory system. It is mainly com ... (Ver mais)
Over the last 25 years, the human endocannabinoid system (ECS) has come into the limelight as an imperative neuro-modulatory system. It is mainly comprised of endogenous cannabinoid (endocannabinoid), cannabinoid receptors and the associated enzymes accountable for its synthesis and deterioration. The ECS plays a proven role in the management of several neurological, cardiovascular, immunological, and other relevant chronic conditions. Endocannabinoid or endogenous cannabinoid are endogenous lipid molecules which connect with cannabinoid receptors and impose a fashionable impact on the behavior and physiological processes of the individual. Arachidonoyl ethanolamide or Anandamide and 2-arachidonoyl glycerol or 2-AG were the endocannabinoid molecules that were first characterized and discovered. The presence of lipid membranes in the precursor molecules is the characteristic feature of endocannabinoids. The endocannabinoids are released upon rapid enzymatic reactions into the extracellular space via activation through G-protein coupled receptors, which is contradictory to other neurotransmitter that are synthesized beforehand, and stock up into the synaptic vesicles. The current review highlights the functioning, synthesis, and degradation of endocannabinoid, and explains its functioning in biological systems.
OPEN ACCESS -
Cellular and Molecular Life Sciences -
Revisão -
2021
The crucial role of the hypothalamus in the pathogenesis of obesity is widely recognized, while the precise molecular and cellular mechanisms involve ... (Ver mais)
The crucial role of the hypothalamus in the pathogenesis of obesity is widely recognized, while the precise molecular and cellular mechanisms involved are the focus of intense research. A disrupted endocannabinoid system, which critically modulates feeding and metabolic functions, through central and peripheral mechanisms, is a landmark indicator of obesity, as corroborated by investigations centered on the cannabinoid receptor CB1, considered to offer promise in terms of pharmacologically targeted treatment for obesity. In recent years, novel insights have been obtained, not only into relation to the mode of action of CB receptors, but also CB ligands, non-CB receptors, and metabolizing enzymes considered to be part of the endocannabinoid system (particularly the hypothalamus). The outcome has been a substantial expansion in knowledge of this complex signaling system and in drug development. Here we review recent literature, providing further evidence on the role of hypothalamic endocannabinoids in regulating energy balance and the implication for the pathophysiology of obesity. We discuss how these lipids are dynamically regulated in obesity onset, by diet and metabolic hormones in specific hypothalamic neurons, the impact of gender, and the role of endocannabinoid metabolizing enzymes as promising targets for tackling obesity and related diseases.
OPEN ACCESS -
International Journal of Molecular Sciences -
Artigo Original -
2020
Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain a ... (Ver mais)
Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in the brain. Alternative approaches have been developed to overcome this problem by selectively targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoids that may be locally synthesized on demand at sites where their actions are pertinent. Many preclinical studies have reported that these strategies are effective for treating neuropathic pain and produce no or minimal side effects. Recently, we observed that inhibition of degradation of a major endocannabinoid, 2-arachydonoylglycerol, can attenuate NOP following trigeminal nerve injury in mice. This review will discuss the above-mentioned alternative approaches that show potential for treating neuropathic pain including NOP.
OPEN ACCESS -
Neuropsychopharmacology -
Revisão -
2018
The goal of this review is to summarize studies in which concentrations of circulating endocannabinoids in humans have been examined in relationship ... (Ver mais)
The goal of this review is to summarize studies in which concentrations of circulating endocannabinoids in humans have been examined in relationship to physiological measurements and pathological status. The roles of endocannabinoids in the regulation of energy intake and storage have been well studied and the data obtained consistently support the hypothesis that endocannabinoid signaling is associated with increased consumption and storage of energy. Physical exercise mobilizes endocannabinoids, which could contribute to refilling of energy stores and also to the analgesic and mood-elevating effects of exercise. Circulating concentrations of 2-arachidonoylglycerol are very significantly circadian and dysregulated when sleep is disrupted. Other conditions under which circulating endocannabinoids are altered include inflammation and pain. A second important role for endocannabinoid signaling is to restore homeostasis following stress. Circulating endocannabinoids are stress-responsive and there is evidence that their concentrations are altered in disorders associated with excessive stress, including post-traumatic stress disorder. Although determination of circulating endocannabinoids can provide important information about the state of endocannabinoid signaling and thus allow for hypotheses to be defined and tested, the large number of physiological factors that contribute to their circulating concentrations makes it difficult to use them in isolation as a biomarker for a specific disorder.
Cardiometabolic syndrome encompasses intertwined risk factors such as hypertension, dyslipidemia, elevated triglycerides, abdominal obesity, and othe ... (Ver mais)
Cardiometabolic syndrome encompasses intertwined risk factors such as hypertension, dyslipidemia, elevated triglycerides, abdominal obesity, and other maladaptive metabolic and inflammatory aberrations. As the molecular mechanisms linking cardiovascular disease and metabolic disorders are investigated, endocannabinoids have emerged as molecules of interest. The endocannabinoid system (ECS) of biologically active lipids has been implicated in several conditions, including chronic liver disease, osteoporosis, and more recently in cardiovascular diseases. The gut microbiome is a major regulator of inflammatory and metabolic signaling in the host, and if disrupted, has the potential to drive metabolic and cardiovascular diseases. Extensive studies have unraveled the impact of the gut microbiome on host physiology, with recent reports showing that gut microbes exquisitely control the ECS, with significant influences on host metabolic and cardiac health. In this review, we outline how modulation of the gut microbiome affects host metabolism and cardiovascular health via the ECS, and how these findings could be exploited as novel therapeutic targets for various metabolic and cardiac diseases.
OPEN ACCESS -
Infection and Immunity -
Artigo Original -
2018
Helminths have coevolved with their hosts, resulting in the development of specialized host immune mechanisms and parasite-specific regulatory produc ... (Ver mais)
Helminths have coevolved with their hosts, resulting in the development of specialized host immune mechanisms and parasite-specific regulatory products. Identification of new pathways that regulate helminth infection could provide a better understanding of host-helminth interaction and may identify new therapeutic targets for helminth infection. Here we identify the endocannabinoid system as a new mechanism that influences host immunity to helminths. Endocannabinoids are lipid-derived signaling molecules that control important physiologic processes, such as feeding behavior and metabolism. Following murine infection with Nippostrongylus brasiliensis, an intestinal nematode with a life cycle similar to that of hookworms, we observed increased levels of endocannabinoids (2-arachidonoylglycerol [2-AG] or anandamide [AEA]) and the endocannabinoid-like molecule oleoylethanolamine (OEA) in infected lung and intestine. To investigate endocannabinoid function in helminth infection, we employed pharmacological inhibitors of cannabinoid subtype receptors 1 and 2 (CB1R and CB2R). Compared to findings for vehicle-treated mice, inhibition of CB1R but not CB2R resulted in increased N. brasiliensis worm burden and egg output, associated with significantly decreased expression of the T helper type 2 cytokine interleukin 5 (IL-5) in intestinal tissue and splenocyte cultures. Strikingly, bioinformatic analysis of genomic and transcriptome sequencing (RNA-seq) data sets identified putative genes encoding endocannabinoid biosynthetic and degradative enzymes in many parasitic nematodes. To test the novel hypothesis that helminth parasites produce their own endocannabinoids, we measured endocannabinoid levels in N. brasiliensis by mass spectrometry and quantitative PCR and found that N. brasiliensis parasites produced endocannabinoids, especially at the infectious larval stage. To our knowledge, this is the first report of helminth- and host-derived endocannabinoids that promote host immune responses and reduce parasite burden.
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2021
Endocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to t ... (Ver mais)
Endocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to the primary cannabinoid receptors CB1/2, mediate multiple mechanisms of intercellular communication within the body. Endocannabinoid signaling is implicated in brain development, memory formation, learning, mood, anxiety, depression, feeding behavior, analgesia, and drug addiction. It is now recognized that the endocannabinoid system mediates not only neuronal communications but also governs the crosstalk between neurons, glia, and immune cells, and thus represents an important player within the neuroimmune interface. Generation of primary endocannabinoids is accompanied by the production of their congeners, the N-acylethanolamines (NAEs), which together with N-acylneurotransmitters, lipoamino acids and primary fatty acid amides comprise expanded endocannabinoid/endovanilloid signaling systems. Most of these compounds do not bind CB1/2, but signal via several other pathways involving the transient receptor potential cation channel subfamily V member 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)-α and non-cannabinoid G-protein coupled receptors (GPRs) to mediate anti-inflammatory, immunomodulatory and neuroprotective activities. In vivo generation of the cannabinoid compounds is triggered by physiological and pathological stimuli and, specifically in the brain, mediates fine regulation of synaptic strength, neuroprotection, and resolution of neuroinflammation. Here, we review the role of the endocannabinoid system in intrinsic neuroprotective mechanisms and its therapeutic potential for the treatment of neuroinflammation and associated synaptopathy.
OPEN ACCESS -
Progress in neuropharmacology and biological psychiatry -
Revisão -
2020
Despite widespread evidence of endocannabinoid system involvement in the pathophysiology of psychiatric disorders, our understanding remains rudiment ... (Ver mais)
Despite widespread evidence of endocannabinoid system involvement in the pathophysiology of psychiatric disorders, our understanding remains rudimentary. Here we review studies of the endocannabinoid system in humans with psychotic and mood disorders. Postmortem, peripheral, cerebrospinal fluid and in vivo imaging studies provide evidence for the role of the endocannabinoid system in both psychotic and mood disorders. Psychotic disorders and major depressive disorder exhibit alterations of brain cannabinoid CB1 receptors and peripheral blood endocannabinoids. Further, these changes may be sensitive to treatment status, disease state, and symptom severity. Evidence from psychotic disorder extend to endocannabinoid metabolizing enzymes in the brain and periphery, whereas these lines of evidence remain poorly developed in mood disorders. A lack of studies examining this system in bipolar disorder represents a notable gap in the literature. Despite a growing body of productive work in this field of research, there is a clear need for investigation beyond the CB1 receptor in order to more fully elucidate the role of the endocannabinoid system in psychotic and mood disorders.
OPEN ACCESS -
Nature Communications -
Artigo Original -
2020
Endocannabinoids retrogradely regulate synaptic transmission and their abundance is controlled by the fine balance between endocannabinoid synthesis ... (Ver mais)
Endocannabinoids retrogradely regulate synaptic transmission and their abundance is controlled by the fine balance between endocannabinoid synthesis and degradation. While the common assumption is that “on-demand” release determines endocannabinoid signaling, their rapid degradation is expected to control the temporal profile of endocannabinoid action and may impact neuronal signaling. Here we show that memory formation through fear conditioning selectively accelerates the degradation of endocannabinoids in the cerebellum. Learning induced a lasting increase in GABA release and this was responsible for driving the change in endocannabinoid degradation. Conversely, Gq-DREADD activation of cerebellar Purkinje cells enhanced endocannabinoid signaling and impaired memory consolidation. Our findings identify a previously unappreciated reciprocal interaction between GABA and the endocannabinoid system in which GABA signaling accelerates endocannabinoid degradation, and triggers a form of learning-induced metaplasticity.
OPEN ACCESS -
ACS Chemical Neuroscience -
Revisão -
2012
Redundancy of metabolic pathways and molecular targets is a typical feature of all lipid mediators, and endocannabinoids, which were originally defin ... (Ver mais)
Redundancy of metabolic pathways and molecular targets is a typical feature of all lipid mediators, and endocannabinoids, which were originally defined as endogenous agonists at cannabinoid CB1 and CB2 receptors, are no exception. In particular, the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol, are inactivated through alternative biochemical routes, including hydrolysis and oxidation, and more than one enzyme might be used even for the same type of inactivating reaction. These enzymes also recognize as substrates other concurrent lipid mediators, whereas, in turn, endocannabinoids might interact with noncannabinoid receptors with subcellular distribution and ultimate biological actions either similar to or completely different from those of cannabinoid receptors. Even splicing variants of endocannabinoid hydrolyzing enzymes, such as FAAH-1, might play distinct roles in endocannabinoid inactivation. Finally, the products of endocannabinoid catabolism may have their own targets, with biological roles different from those of cannabinoid receptors. These peculiarities of endocannabinoid signaling have complicated the use of inhibitors of its inactivation mechanisms as a safer and more efficacious alternative to the direct targeting of cannabinoid receptors for the treatment of several pathological conditions, including pain. However, new strategies, including the rediscovery of “dirty drugs”, and the use of certain natural products (including non-THC cannabis constituents), are emerging that might allow us to make a virtue of necessity and exploit endocannabinoid redundancy to develop new analgesics.
OPEN ACCESS -
Journal of Lipid Research -
Artigo Original -
2016
The endocannabinoids and their main receptor, cannabinoid type-1 (CB1), suppress intracellular cyclic AMP levels and have emerged as key players in t ... (Ver mais)
The endocannabinoids and their main receptor, cannabinoid type-1 (CB1), suppress intracellular cyclic AMP levels and have emerged as key players in the control of energy metabolism. CB1 agonists and blockers have been reported to influence the thermogenic function of white and brown adipose tissue (WAT and BAT), affecting body weight through the inhibition and stimulation of energy expenditure, respectively. The purpose of the current study was to investigate the regulation of the endocannabinoid system in WAT and BAT following exposure to either cold or specific agonism of β3-adrenoceptors using CL316,243 (CL), conditions known to cause BAT activation and WAT browning. To address this question, we performed quantitative PCR-based mRNA profiling of genes important for endocannabinoid synthesis, degradation, and signaling, and determined endocannabinoid levels by LC-MS in WAT and BAT of control, cold-exposed, and CL-treated wild-type mice as well as primary brown adipocytes. Treatment with CL and exposure to cold caused an upregulation of endocannabinoid levels and biosynthetic enzymes in WAT. Acute β3-adrenoceptor activation increased endocannabinoids and a subset of genes of biosynthesis in BAT and primary brown adipocytes. We suggest that the cold-mediated increase in endocannabinoid tone is part of autocrine negative feed-back mechanisms controlling β3-adrenoceptor-induced BAT activation and WAT browning.
Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) and subsequent oxidative tissue damage, which is a criti ... (Ver mais)
Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) and subsequent oxidative tissue damage, which is a critical event in the course of neurodegenerative diseases. It is still not fully elucidated, however, whether oxidative stress is the primary trigger or a consequence in the process of neurodegeneration. Increasing evidence suggests that oxidative stress is involved in the propagation of neuronal injury and consequent inflammatory response, which in concert promote development of pathological alterations characteristic of most common neurodegenerative diseases.Accumulating recent evidence also suggests that there is an important interplay between the lipid endocannabinoid system [ECS; comprising the main cannabinoid 1 and 2 receptors (CB1 and CB2), endocannabinoids, and their synthetic and metabolizing enzymes] and various key inflammatory and redox-dependent processes.Targeting the ECS to modulate redox state-dependent cell death and to decrease consequent or preceding inflammatory response holds therapeutic potential in a multitude of oxidative stress-related acute or chronic neurodegenerative disorders from stroke and traumatic brain injury to Alzheimers and Parkinsons diseases and multiple sclerosis, just to name a few, which will be discussed in this overview. Antioxid. Redox Signal. 29, 75–108.
OPEN ACCESS -
Current Neuropharmacology -
Revisão -
2021
According to the World Health Organization (WHO), 47 million people display mental health disorders Worldwide. In addition, epidemiological studies h ... (Ver mais)
According to the World Health Organization (WHO), 47 million people display mental health disorders Worldwide. In addition, epidemiological studies have shown that the extension of life expectancy and the increase in aged population will significantly impact the prevalence of several mental impairments. Although there are strategies for preventing and alleviating mental illnesses, such as pharmacological and psychological approaches, limited results have been observed. Thus, the search for new therapeutics for managing psychiatric disorders has explored multiple roads. In recent years, it has been demonstrated that physical activity and exercise promote health benefits. On the other hand, among the neurobiological systems that participate in the genesis and development of mental disruptions, the endocannabinoid system has been suggested as an active player. Supporting this hypothesis, data suggest that the elements comprising the endocannabinoid system, such as the CB1/CB2 cannabinoid receptors, endogenous ligands (N-arachidonoylethanolamine [anandamide, AEA] and 2-arachidonoylglycerol [2-AG]), transporters and the enzymes involved in the biosynthesis and degradation of the AEA and 2-AG, modulate mental diseases. In this review, we discuss that the endocannabinoid system might be considered as a modulator for the positive outcomes of exercise in the management of mental disorders. Clinically, this promising field might be exploited by targeting the elements of the endocannabinoid system aimed to increase the exercise benefits applied to patients with mental illnesses.
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2022
The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The end ... (Ver mais)
The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The endocannabinoid system (ECS) components have gained high interest as potential new targets for treating psychiatry diseases because of their neuromodulator role, which is essential to understanding the regulation of many brain functions. This article reviewed the molecular alterations in ECS occurring in different psychiatric conditions. The methods used to identify alterations in the ECS were also described. We used a translational approach. The animal models reproducing some behavioral and/or neurochemical aspects of psychiatric disorders and the molecular alterations in clinical studies in post-mortem brain tissue or peripheral tissues were analyzed. This article reviewed the most relevant ECS changes in prevalent psychiatric diseases such as mood disorders, schizophrenia, autism, attentional deficit, eating disorders (ED), and addiction. The review concludes that clinical research studies are urgently needed for two different purposes: (1) To identify alterations of the ECS components potentially useful as new biomarkers relating to a specific disease or condition, and (2) to design new therapeutic targets based on the specific alterations found to improve the pharmacological treatment in psychiatry.
Endocannabinoids are lipid mediators able to bind to and activate cannabinoid receptors, the primary molecular targets responsible for the pharmacolo ... (Ver mais)
Endocannabinoids are lipid mediators able to bind to and activate cannabinoid receptors, the primary molecular targets responsible for the pharmacological effects of the Δ9-tetrahydrocannabinol. These bioactive lipids belong mainly to two classes of compounds: N-acylethanolamines and acylesters, being N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, their main representatives. During the last twenty years, an ever growing number of fatty acid derivatives (endocannabinoids and endocannabinoid-like compounds) have been discovered and their activities biological is the subject of intense investigations. Here, the most recent advances, from a therapeutic point of view, on endocannabinoids, related compounds, and their metabolic routes will be reviewed.
In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cel ... (Ver mais)
In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.
Palmitoylethanolamide (PEA) is an endogenous anti-inflammatory lipid mediator and a widely used nutraceutical. In this study, we designed, realized, ... (Ver mais)
Palmitoylethanolamide (PEA) is an endogenous anti-inflammatory lipid mediator and a widely used nutraceutical. In this study, we designed, realized, and tested a drug-carrier conjugate between PEA (the active drug) and glucuronic acid (the carrier). The conjugate, named GLUPEA, was characterized for its capability of increasing PEA levels and exerting anti-inflammatory activity both in vitro and in vivo. GLUPEA treatment, compared to the same concentration of PEA, resulted in higher cellular amounts of PEA and the endocannabinoid 2-arachidonoyl glycerol (2-AG), and increased 2-AG-induced transient receptor potential vanilloid type 1 (TRPV1) channel desensitization to capsaicin. GLUPEA inhibited pro-inflammatory monocyte chemoattractant protein 2 (MCP-2) release from stimulated keratinocytes, and it was almost as efficacious as ultra-micronized PEA at reducing colitis in dinitrobenzene sulfonic acid (DNBS)-injected mice when using the same dose. GLUPEAisanovel pro-drug able to efficiently mimic the anti-inflammatory and endocannabinoid enhancing actions of PEA.
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2020
Leukocytes are part of the tumor microenvironment (TME) and are critical determinants of tumor progression. Because of the immunoregulatory propertie ... (Ver mais)
Leukocytes are part of the tumor microenvironment (TME) and are critical determinants of tumor progression. Because of the immunoregulatory properties of cannabinoids, the endocannabinoid system(ECS)mayhaveanimportantroleinshapingtheTME.MembersoftheECS,anentitythatconsists of cannabinoid receptors, endocannabinoids and their synthesizing/degrading enzymes, have been associated with both tumor growth and rejection. Immune cells express cannabinoid receptors and produce endocannabinoids, thereby forming an “immune endocannabinoid system”. Although in vitro effects of exogenous cannabinoids on immune cells are well described, the role of the ECS in the TME, and hence in tumor development and immunotherapy, is still elusive. This review/opinion discusses the possibility that the “immune endocannabinoid system” can fundamentally influence tumor progression. The widespread influence of cannabinoids on immune cell functions makes the members of the ECS an interesting target that could support immunotherapy.
Polypharmacology breaks up the classical paradigm of “one-drug, one target, one disease” electing multitarget compounds as potential therapeutic tool ... (Ver mais)
This review posits that fatty acid amide hydrolase (FAAH) inhibition has therapeutic potential against neuropathological states including traumatic b ... (Ver mais)
This review posits that fatty acid amide hydrolase (FAAH) inhibition has therapeutic potential against neuropathological states including traumatic brain injury, Alzheimers, Huntingtons, and Parkinsons diseases, and stroke.This proposition is supported by data from numerous in vitro and in vivo experiments establishing metabolic and pharmacological contexts for the neuroprotective role of the endogenous cannabinoid (“endocannbinoid”) system and selective FAAH inhibitors.The systems biology of endocannabinoid signaling involves two main cannabinoid receptors, the principal endocannabinoid lipid mediators N-arachidonoylethanolamine (“anandamide”) (AEA) and 2-arachidonoyl glycerol (2-AG), related metabolites, and the proteins involved in endocannabinoid biosynthesis, biotransformation, and transit. The endocannabinoid system is capable of activating distinct signaling pathways on-demand in response to pathogenic events or stimuli, thereby enhancing cell survival and promoting tissue repair. Accumulating data suggest that endocannabinoid system modulation at discrete targets is a promising pharmacotherapeutic strategy for treating various medical conditions. In particular, neuronal injury activates cannabinoid signaling in the central nervous system as an intrinsic neuroprotective response. Indirect potentiation of this salutary response through pharmacological inhibition of FAAH, an endocannabinoid-deactivating enzyme, and consequent activation of signaling pathways downstream from cannabinoid receptors, have been shown to promote neuronal maintenance and function.This therapeutic modality has the potential to offer site- and event-specific therapeutic relief in those tissues where endocannabinoids are being produced as part of a physiological protective mechanism. In contrast, direct application of cannabinoid receptor agonists to the central nervous system may activate CB receptors indiscriminately and invite unwanted psychotrophic effects.
The use of cannabinoids to treat fibrotic skin diseases is an emergent issue. Therefore, we aimed to evaluate systemic and skin endocannabinoid respo ... (Ver mais)
The use of cannabinoids to treat fibrotic skin diseases is an emergent issue. Therefore, we aimed to evaluate systemic and skin endocannabinoid responses in the wound‑healing process in humans. A prospective study was performed in 50 patients who underwent body‑contouring surgery. Anandamide (N‑arachidonoylethanolamine, AEA), 2‑arachidonoylglycerol (2‑AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were quantified using LC–MS/MS. Ten (20%) patients developed hypertrophic (HT) scars. No significant changes were observed between the normal (N) scar and HT scar groups in terms of plasma and skin endocannabinoids. Nevertheless, a positive correlation between plasma and skin AEA concentrations was found in the N group (r = 0.38, p = 0.015), which was absent in the HT group. Moreover, the AEA concentration was significantly lower in HT scar tissue than in normal scar tissue (0.77 ± 0.12 ng/g vs 1.15 ± 0.15 ng/g, p < 0.001). Interestingly, in all patients, the surgical intervention produced a time‑dependent effect with a U shape for AEA, PEA and OEA plasma concentrations. In contrast, 2‑AG plasma concentrations increased 5 days after surgery and were reduced and stabilized 3 months later. These results suggest crosstalk between systemic and local skin endocannabinoid systems during human wound healing. AEA appears to be the most likely candidate for this link, which is deficient in patients with HT scars.
The endocannabinoid system (ECS) is an endogenous signaling system formed by specific receptors (cannabinoid type 1 and type 2 (CB1 and CB2)), their ... (Ver mais)
The endocannabinoid system (ECS) is an endogenous signaling system formed by specific receptors (cannabinoid type 1 and type 2 (CB1 and CB2)), their endogenous ligands (endocannabinoids), and enzymes involved in their synthesis and degradation. The ECS, centrally and peripherally, is involved in various physiological processes, including regulation of energy balance, promotion of metabolic process, food intake, weight gain, promotion of fat accumulation in adipocytes, and regulation of body homeostasis; thus, its overactivity may be related to obesity. In this review, we try to explain the role of the ECS and the impact of genetic factors on endocannabinoid system modulation in the pathogenesis of obesity, which is a global and civilizational problem affecting the entire world population regardless of age. We also emphasize that the search for potential new targets for health assessment, treatment, and the development of possible therapies in obesity is of great importance.
OPEN ACCESS -
The Journal of Neuroscience -
Revisão -
2012
The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoidsins ... (Ver mais)
The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoidsinsocialplaybehavior,ahighlyrewardingformofsocialinteractioninadolescentrats.Here,wetestedthehypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampusof4-to5-week-oldmaleWistarrats.Furthermore,socialplayincreasedphosphorylationofCB1cannabinoidreceptorsin the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented theassociatedelevationinanandamidelevelsintheamygdala,butnottheNAc.InfusionofURB597intothebasolateralamygdala(BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A preventedtheplay-enhancingeffectsofsystemicadministrationofURB597.InfusionofURB597intotheNAcalsoincreasedsocialplay,but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716AdidnotaffectsocialplayafterinfusionintothecoreandshellsubregionsoftheNAc,whileitreducedsocialplaywheninfused into theBLA.ThesedatashowthatincreasedanandamidesignalingintheamygdalaandNAcaugmentssocialplay,andidentifytheBLA as aprominentsite of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats.
We sought to replicate prior findings that low endogenous opioid (EO) function predicts greater morphine analgesia, and extended these findings by ex ... (Ver mais)
We sought to replicate prior findings that low endogenous opioid (EO) function predicts greater morphine analgesia, and extended these findings by examining whether circulating endocannabinoids and related lipids moderate EO-related predictive effects. Individuals with chronic low back pain (n=46) provided blood samples for endocannabinoid analyses, then underwent separate identical laboratory sessions under three drug conditions: saline placebo, i.v. naloxone (opioid antagonist; 12mg total), and i.v. morphine (0.09 mg/kg total). During each session, participants rated low back pain intensity, evoked heat pain intensity, and non-pain subjective effects four times in sequence following incremental drug dosing. Mean morphine effects (morphine-placebo difference) and opioid blockade effects (naloxone-placebo difference; to index EO function) for each primary outcome (low back pain intensity, evoked heat pain intensity, non-pain subjective effects) were derived by averaging across the four incremental doses. The association between EO function and morphine-induced back pain relief was significantly moderated by endocannabinoids [2-Arachidonoylglycerol (2-AG) and Narachidonoylethanolamide (AEA)]. Lower EO function predicted greater morphine analgesia only for those with relatively lower endocannabinoids. Endocannabinoids also significantly moderated EO effects on morphine-related changes in VAS evoked pain intensity (2-AG), drug liking (AEA and 2-AG), and desire to take again (AEA and 2-AG). Absent significant interactions, lower EO function predicted significantly greater morphine analgesia (as in past work) and euphoria. Results indicate that EO effects on analgesic and subjective responses to opioid medications are greatest
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2019
Epilepsy is a neurological disorder that affects approximately 50 million people worldwide. There is currently no definitive epilepsy cure. However, ... (Ver mais)
Epilepsy is a neurological disorder that affects approximately 50 million people worldwide. There is currently no definitive epilepsy cure. However, in recent years, medicinal cannabis has been successfully trialed as an effective treatment for managing epileptic symptoms, but whose mechanisms of action are largely unknown. Lately, there has been a focus on neuroinflammation as an important factor in the pathology of many epileptic disorders. In this literature review, we consider the links that have been identified between epilepsy, neuroinflammation, the endocannabinoid system (ECS), and how cannabinoids may be potent alternatives to more conventional pharmacological therapies. WereviewtheresearchthatdemonstrateshowtheECScancontributetoneuroinflammation, and could therefore be modulated by cannabinoids to potentially reduce the incidence and severity of seizures. In particular, the cannabinoid cannabidiol has been reported to have anti-convulsant and anti-inflammatory properties, and it shows promise for epilepsy treatment. There are a multitude of signaling pathways that involve endocannabinoids, eicosanoids, and associated receptors by which cannabinoids could potentially exert their therapeutic effects. Further research is needed to better characterize these pathways, and consequently improve the application and regulation of medicinal cannabis.
OPEN ACCESS -
British Journal of Pharmacology -
Artigo Original -
2022
Endocannabinoids are implicated in appetite and body weight regulation. In rodents, anandamide stimulates eating by actions at central CB1 receptors, ... (Ver mais)
Endocannabinoids are implicated in appetite and body weight regulation. In rodents, anandamide stimulates eating by actions at central CB1 receptors, and hypothalamic endocannabinoids may be under the negative control of leptin. However, changes to brain endocannabinoid levels in direct relation to feeding or changing nutritional status have not been investigated. 2 Wemeasured anandamide and 2-arachidonoyl glycerol (2-AG) levels in feeding-associated brain regions of rats, during fasting, feeding of a palatable food, or after satiation. Endocannabinoid levels were compared to those in rats fed ad libitum, at a point in their daily cycle when motivation to eat was absent. Fasting increased levels of anandamide and 2-AG in the limbic forebrain and, to a lesser extent, of 2-AG in the hypothalamus. By contrast, hypothalamic 2-AG declined as animals ate. No changes were detected in satiated rats. Endocannabinoid levels in the cerebellum, a control region not directly involved in the control of food intake, were una€ected by any manipulation. 3 As 2-AG was most sensitive to variation during feeding, and to leptin regulation in a previous study, we examined the behavioural e€ects of 2-AG when injected into the nucleus accumbens shell, a limbic forebrain area strongly linked to eating motivation. 2-AG potently, and dose-dependently, stimulated feeding. This e€ect was attenuated by the CB1 receptor antagonist SR141716. 4 These ®ndings provide the ®rst direct evidence of altered brain levels of endocannabinoids, and of 2-AG in particular, during fasting and feeding. The nature of these e€ects supports a role for endocannabinoids in the control of appetitive motivation.
OPEN ACCESS -
Progress in Neuropsychopharmacology & Biological Psychiatry -
Revisão -
2021
Posttraumatic stress disorder (PTSD) is a persistent, trauma induced psychiatric condition characterized by lifelong complex cognitive, emotional and ... (Ver mais)
Posttraumatic stress disorder (PTSD) is a persistent, trauma induced psychiatric condition characterized by lifelong complex cognitive, emotional and behavioral phenotype. Although many individuals that experience trauma are able to gradually diminish their emotional responding to trauma-related stimuli over time, known as extinction learning, individuals suffering from PTSD are impaired in this capacity. An inability to decline this initially normal and adaptive fear response, can be confronted with exposure-based therapies, often in combination with pharmacological treatments. Due to the complexity of PTSD, currently available pharmacotherapeutics are inadequate in treating the deficient extinction observed in many PTSD patients. To develop novel therapeutics, researchers have exploited the conserved nature of fear and stress-associated behavioral responses and neurocircuits across species in an attempt to translate knowledge gained from preclinical studies into the clinic. There is growing evidence on the endocannabinoid modulation of fear and stress due to their ‘on demand’ synthesis and degradation. Involvement of the endocannabinoids in fear extinction makes the endocannabinoid system very attractive for finding effective therapeutics for trauma and stress related disorders. In this review, a brief introduction on neuroanatomy and circuitry of fear extinction will be provided as a model to study PTSD. Then, the endocannabinoid system will be discussed as an important component of extinction modulation. In this regard, anandamide degrading enzyme, fatty acid amide hydrolase (FAAH) will be exemplified as a target identified and validated strongly from preclinical to clinical translational studies of enhancing extinction.
OPEN ACCESS -
Trends in Molecular Medicine' s -
Revisão -
2020
The endocannabinoid signaling system (ECSS) is altered by exposure to stress
and both mediates
and modulates the effects of stress ... (Ver mais)
The endocannabinoid signaling system (ECSS) is altered by exposure to stress
and both mediates
and modulates the effects of stress on the brain.Considerable preclinical data support critical roles for the endocannabinoids
and their target,
the CB1 cannabinoid receptor,
in the adaptation of the brain to repeated stress exposure.Chronic stress exposure increases vulnerability to mental illness,
so the ECSS has attracted attention as a potential therapeutic target for the prevention
and treatment of stress - related psychopathology.We discuss human genetic studies indicating that the ECSS contributes to risk for mental illness in those exposed to severe stress
and trauma earlier in life,
and we explore the potential difficulties in pharmacologic manipulation of the ECSS.
OPEN ACCESS -
Proceedings of the National Academy of Sciences -
Artigo Original -
2013
Acute or chronic alterations in energy status alter the balance between excitatory and inhibitory synaptic transmission and associated synaptic plast ... (Ver mais)
Acute or chronic alterations in energy status alter the balance between excitatory and inhibitory synaptic transmission and associated synaptic plasticity to allow for the adaptation of energy metabolism to new homeostatic requirements. The impact of such changesonendocannabinoidandcannabinoidreceptortype1(CB1)mediated modulation of synaptic transmission and strength is not known, despite the fact that this signaling system is an important target for the development of new drugs against obesity. We investigated whether CB1-expressing excitatory vs. inhibitory inputs to orexin-A–containing neurons in the lateral hypothalamus are altered in obesity and how this modifies endocannabinoid control of these neurons. In lean mice, these inputs are mostly excitatory. By confocal and ultrastructural microscopic analyses, we observed that in leptin-knockout(ob/ob) obese mice,andinmicewithdiet-induced obesity, orexinergic neurons receive predominantly inhibitory CB1expressing inputs and overexpress the biosynthetic enzyme for the endocannabinoid2-arachidonoylglycerol,whichretrogradelyinhibits synaptic transmission at CB1-expressing axon terminals. Patchclamp recordings also showed increased CB1-sensitive inhibitory innervation of orexinergic neurons in ob/obmice. These alterations are reversed by leptin administration, partly through activation of the mammalian target of rapamycin pathway in neuropeptideY-ergic neurons of the arcuate nucleus, and are accompanied by CB1-mediated enhancement of orexinergic innervation of target brain areas. We propose that enhanced inhibitory control of orexin-A neurons, and their CB1-mediated disinhibition, are a consequenceofleptin signaling impairment in the arcuatenucleus. We also provide initial evidence of the participation of this phenomenon in hyperphagia and hormonal dysregulation in obesity.
OPEN ACCESS -
Brazilian Journal of Medical and Biological Research -
Artigo Original -
2021
Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the ... (Ver mais)
Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80mg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 mg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 mg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 mg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 mg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 mg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 mg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.
OPEN ACCESS -
Philosophical Transactions of the Royal Society: Biological Sciences -
Revisão -
2019
Cannabinoid-based therapies have long been used to treat pain, but there remain questions about their actual mechanisms and efficacy. From an evoluti ... (Ver mais)
Cannabinoid-based therapies have long been used to treat pain, but there remain questions about their actual mechanisms and efficacy. From an evolutionary perspective, the cannabinoid system would appear to be highly conservedgiventhatthemostprevalentendogenouscannabinoid(endocannabinoid) transmitters, 2-arachidonyl glycerol and anandamide, have been found throughout the animal kingdom,at least inthe speciesthat have been analysed to date. This review will first examine recent findings regarding the potential conservation across invertebrates and chordates of the enzymes responsible for endocannabinoid synthesis and degradation and the receptors that these transmitters act on. Next, comparisons of how endocannabinoids modulate nociception will be examined for commonalities between vertebrates and invertebrates, with a focus on the medicinal leech Hirudo verbana. Evidence is presented that there are distinct, evolutionarily conserved anti-nociceptive and pro-nociceptive effects. The combined studies across various animal phyla demonstrate the utility of using comparative approaches to understand conserved mechanisms for modulating nociception. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
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American Journal of Physiology-Gastrointestinal and Liver Physiology -
Revisão -
2008
Recent studies have implicated dysregulation of the endocannabinoid system in various liver diseases and their complications (e.g., hepatitis, fibros ... (Ver mais)
Recent studies have implicated dysregulation of the endocannabinoid system in various liver diseases and their complications (e.g., hepatitis, fibrosis, cirrhosis, cirrhotic cardiomyopathy, and ischemiareper-fusion), and demonstrated that its modulation by either cannabinoid 2 (CB2) receptor agonists or CB1 antagonists may be of significant therapeutic benefits. This review is aimed to focus on the triggers and sources of endocannabinoids during liver inflammation and on the novel role of CB2 receptors in the interplay between the activated endothelium and various inflammatory cells (leukocytes, lymphocytes, etc.), which play pivotal role in the early development and progression of inflammatory and other liver diseases.
The endocannabinoid system is involved in a wide range of processes including the control of energy acquisition and expenditure. Endocannabinoids and ... (Ver mais)
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Molecular Autism -
Artigo Original -
2019
The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in se ... (Ver mais)
The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet.Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age=13.1±4.1, range 6–21; 79% boys) and 93 age- and gender-matched neurotypical children (age =11.8±4.3, range 5.5–21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2)Children with ASD had lower levels (pmol/mL, mean±SEM) of AEA (0.722±0.045 vs. 1.252±0.072, P< 0.0001, effect size 0.91), OEA (17.3 ± 0.80 vs. 27.8 ± 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 ± 0.32 vs. 7.15 ± 0.37, P <0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons.We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid “tone” in the brain, as found in animal models of ASD.
The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in ... (Ver mais)
The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in liver, intestine and in the case of humans also in kidney. While the rat FABP1 is well studied, the extent these findings translate to human FABP1 is not clear—especially in view of recent studies showing that endocannabinoids and cannabinoids represent novel rat FABP1 ligands and FABP1 gene ablation impacts the hepatic endocannabinoid system, known to be involved in non-alcoholic fatty liver (NAFLD) development. Although not detectable in brain, FABP1 ablation nevertheless also impacts brain endocannabinoids. Despite overall tertiary structure similarity, human FABP1 differs significantly from rat FABP1 in secondary structure, much larger ligand binding cavity, and affinities/ specificities for some ligands. Moreover, while both mouse and human FABP1 mediate ligand induction of peroxisome proliferator activated receptor-α, (PPARα), they differ markedly in pattern of genes induced. This is critically important because a highly prevalent human SNP (2638% minor allele frequency and 8.3±1.9% homozygous) results in a FABP1 T94A substitution that further accentuates these species differences. The human FABP1 T94A variant is associated with altered body mass index (BMI), clinical dyslipidemias (elevated plasma triglycerides and LDL cholesterol), atherothrombotic cerebral infarction, and non-alcoholic fatty liver disease (NAFLD). Resolving human FABP1 and the T94A variant’s impact on the endocannabinoid and cannabinoid system is an exciting challenge due to the importance of this system on hepatic lipid accumulation as well as behavior, pain, inflammation, and satiety.
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2020
The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and ... (Ver mais)
The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and biosynthetic and hydrolysing machineries. The impairment of the ES has been associated to several pathological conditions like behavioural, neurological, or metabolic disorders and infertility, suggesting that the modulation of this system may be critical for the maintenance of health status and disease treatment. Lifestyle and environmental factors canexertlong-termeffectsongeneexpressionwithoutanychangeinthenucleotidesequenceof DNA,affecting health maintenance and influencing both disease load and resistance. This potentially reversible “epigenetic” modulation of gene expression occurs through the chemical modification of DNAandhistone protein tails or the specific production of regulatory non-coding RNA (ncRNA). Recent findings demonstrate the epigenetic modulation of the ES in biological tissues; in the same way, endocannabinoids, phytocannabinoids, and cannabinoid receptor agonists and antagonists induce widespread or gene-specific epigenetic changes with the possibility of trans-generational epigenetic inheritance in the offspring explained by the transmission of deregulated epigenetic marks in the gametes. Therefore, this review provides an update on the epigenetics of the ES, with particular attention on the emerging role in reproduction and fertility.
OPEN ACCESS -
Trends in Pharmacological Sciences -
Revisão -
2009
The newly discovered endocannabinoid system (ECS; comprising the endogenous lipid mediators endocannabinoids present in virtually all tissues, their ... (Ver mais)
The newly discovered endocannabinoid system (ECS; comprising the endogenous lipid mediators endocannabinoids present in virtually all tissues, their G-protein-coupled cannabinoid receptors, biosynthetic pathways and metabolizing enzymes) has been implicated in multiple regulatory functions both in health and disease. Recent studies have intriguingly suggested the existence of a functional ECS in the skin and implicated it in various biological processes (e.g. proliferation, growth, differentiation, apoptosis and cytokine, mediator or hormone production of various cell types of the skin and appendages, such as the hair follicle and sebaceous gland). It seems that the main physiological function of the cutaneous ECS is to constitutively control the proper and well-balanced proliferation, differentiation and survival, as well as immune competence and/or tolerance, of skin cells. The disruption of this delicate balance might facilitate the development of multiple pathological conditions and diseases of the skin (e.g. acne, seborrhea, allergic dermatitis, itch and pain, psoriasis, hair growth disorders, systemic sclerosis and cancer).
OPEN ACCESS -
Neurobiology of Disease -
Revisão -
2013
Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosi ... (Ver mais)
Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial progress in understanding the molecular mechanisms of the endocannabinoid system for synaptic communications in the central nervous system. Furthermore, the impact of endocannabinoid signaling on diverse cellular processes during brain development has emerged. Thus, although schizophrenia has etiological complexities, including genetic heterogeneities and multiple environmental factors, it now becomes crucial to explore molecular pathways of convergence of genetic risk factors and endocannabinoid signaling, which may provide us with clues to find novel targets for therapeutic intervention. In this review, epidemiological, clinical, and pathological evidences on the role of the endocannabinoid system in the pathophysiologies of schizophrenia will be presented. We will also make a brief overview of the recent progress in understanding molecular mechanisms of the endocannabinoid system for brain development and function, with particular focus on cannabinoid receptor type 1 (CB1R)mediated cascade, the most well-characterized cannabinoid receptor. Lastly, we will discuss the potential of the endocannabinoid system in finding novel therapeutic targets for prevention and treatment of schizophrenia.
OPEN ACCESS -
Alcoholism: Clinical and Experimental Research -
Revisão -
2020
Endocannabinoids are lipid mediators that interact with the same cannabinoid receptors that recognize Δ9-tetrahydrocannabinol (THC), the psychoactive ... (Ver mais)
Endocannabinoids are lipid mediators that interact with the same cannabinoid receptors that recognize Δ9-tetrahydrocannabinol (THC), the psychoactive constituent of marijuana, to induce similar effects in the brain and periphery. Alcohol and THC are both addictive substances whose acute use elicits rewarding effects that can lead to chronic and compulsive use via engaging similar signaling pathways in the brain. In the liver, both alcohol and endocannabinoids activate lipogenic gene expression leading to fatty liver disease. This review focuses on evidence accumulated over the last two decades to indicate that both the addictive neural effects of ethanol and its organ toxic effects in the liver and elsewhere are mediated, to a large extent, by endocannabinoids signaling via cannabinoid-1 receptors (CB1R). The therapeutic potential of CB1R blockade, globally or in peripheral tissues only is also discussed.
OPEN ACCESS -
Pain Research and Management -
Revisão -
2018
ere is a scarcity of drugs to either prevent or properly manage chemotherapy-induced neuropathic pain (CINP). Cannabis or cannabinoids have been repo ... (Ver mais)
ere is a scarcity of drugs to either prevent or properly manage chemotherapy-induced neuropathic pain (CINP). Cannabis or cannabinoids have been reported to improve pain measures in patients with neuropathic pain. For this review, a search was done in PubMed for papers that examined the expression of and/or evaluated the use of cannabinoids or drugs that prevent or treat established CINP in a CB receptor-dependent manner in animal models. Twenty-eight articles that fulfilled the inclusion and exclusion criteria established were analysed. Studies suggest there is a specific deficiency of endocannabinoids in the periphery during CINP.Inhibitors of FAAHandMGL,enzymesthatdegradetheendocannabinoids,CBreceptoragonists,desipramine,and coadministered indomethacin plus minocycline were found to either prevent the development and/or attenuate established CINP in a CBreceptor-dependent manner. e studies analysed suggest that targeting the endocannabinoid system for prevention and treatment of CINP is a plausible therapeutic option. Almost 90% of the studies on animal models of CINP analysed utilised male rodents. Taking into consideration clinical and experimental findings that show gender differences in the mechanisms involved in pain including CINP and in response to analgesics, it is imperative that future studies on CINP utilise more female models.
OPEN ACCESS -
British Journal of Pharmacology -
Artigo Original -
2009
Endocannabinoids in tissues controlling energy homeostasis are altered in obesity, thus contributing to metabolic disorders. Here we evaluate endocan ... (Ver mais)
Endocannabinoids in tissues controlling energy homeostasis are altered in obesity, thus contributing to metabolic disorders. Here we evaluate endocannabinoid dysregulation in the small intestine of mice with diet-induced obesity (DIO) and in peripheral tissues of Zucker and lean rats following food deprivation and re-feeding.Intestinal transit, evaluated using rhodamine-B-labelled dextran, and small intestinal endocannabinoid levels, measured by liquid chromatography mass spectrometry, were measured in mice fed normal or high-fat diets (HFDs). Endocannabinoid levels were measured also in various tissues of lean and Zucker rats fed ad libitum or following overnight food deprivation with and without subsequent re-feeding.After 8 weeks of HFD, baseline intestinal transit was increased in DIO mice and enhanced by cannabinoid CB1 receptor antagonism less efficaciously than in lean mice. Small intestinal anandamide and 2-arachidonoylglycerol levels were reduced and increased respectively. In Zucker rats, endocannabinoids levels were higher in the pancreas, liver and duodenum, and lower in the subcutaneous adipose tissue. Food deprivation increased endocannabinoid levels in the duodenum and liver of both rat strains, in the pancreas of lean rats and in adipose tissues of Zucker rats.Reduced anandamide levels might account for increased intestinal motility in DIO mice. Regulation of endocannabinoid levels in rat peripheral tissues, induced by food deprivation and re-feeding, might participate in food intake and energy processing and was altered in Zucker rats. These data, together with previous observations, provide further evidence for dysregulation of peripheral endocannabinoids in obesity.
OPEN ACCESS -
Nature Reviews Neuroscience -
Revisão -
2015
The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiol ... (Ver mais)
The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment. eCB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism’s long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders. An understanding of the underlying neural cell populations and cellular processes enables the development of therapeutic strategies to mitigate behavioural maladaptation.
OPEN ACCESS -
International Journal of Molecular Sciences -
Revisão -
2021
The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immu ... (Ver mais)
The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ9-tetrahydroca ... (Ver mais)
The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ9-tetrahydrocannabinol (but not for most other plant cannabinoids or phytocannabinoids)—cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R); their two most studied endogenous ligands, the “endocannabinoids” N-arachidonoylethanolamine anandamide) and 2-arachidonoylglycerol (2-AG); and the enzymes responsible for endocannabinoid metabolism. However, anandamide and 2-AG, and also the phytocannabinoids, have more molecular targets than just CB1RandCB2R. Furthermore, the endocannabinoids, like most other lipid mediators, have more than just one set of biosynthetic and degrading pathways and enzymes, which they often share with “endocannabinoid-like” mediators that may or may not interact with the same proteins as Δ9-tetrahydrocannabinol and other phytocannabinoids. In some cases, these degrading pathways and enzymes lead to molecules that are not inactive and instead interact with other receptors. Finally, some of the metabolic enzymes may also participate in the chemical modification of molecules that have very little to do with endocannabinoid and cannabinoid targets. Here, we review the whole world of ligands, receptors, and enzymes, a true “endocannabinoidome”, discovered after the cloning of CB1RandCB2R and the identification of anandamide and 2-AG, and its interactions with phytocannabinoids.
OPEN ACCESS -
Human Reproduction -
Artigo Original -
2021
This study included an in vivo cohort assessment of cannabis exposure and its effects on the follicle and in vitro assays conducted to validate the i ... (Ver mais)
This study included an in vivo cohort assessment of cannabis exposure and its effects on the follicle and in vitro assays conducted to validate the in vivo findings and to explore possible mechanisms of action.Overall, 17 patients (6.4%) were positive for cannabis consumption. Furthermore, the prevalence of cannabis positivity in the FF increased from 4% of the tested samples that were collected prior to national legalisation in October 2018 to 12% of those collected following legalisation. Of note, 59% of patients who tested positive for PCs (10 of 17) reported previous or ongoing exposure to cannabis upon their initial intake. Endocannabinoid levels were not affected by the presence of PCs. CB2R was more prevalent than CB1R in GCs and its expression increased following acute and chronic in vitro exposure to PCs. The expression of DNMT3b and global methylation decreased following exposure, suggesting that cannabis may affect the epigenome in the follicular niche. The acute changes were sustained throughout chronic treatment.To our knowledge, this is the first study measuring PCs in FF by LC-MS/MS. We show that consuming cannabis alters the ECS in the developing follicle, and directly affects DNMT expression and global DNA methylation levels. Cannabis legalisation and use is increasing worldwide, therefore further understanding its role in female fertility and folliculogenesis is critical.
OPEN ACCESS -
Proceedings of the National Academy of Sciences -
Artigo Original -
2017
Clinical studies suggest that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) provide beneficial anti-inflammatory effects, in part through the ... (Ver mais)
Clinical studies suggest that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) provide beneficial anti-inflammatory effects, in part through their conversion to bioactive metabolites. Here we report ontheendogenousproductionofapreviouslyunknownclassofω-3 PUFA–derived lipid metabolites that originate from the crosstalk between endocannabinoid and cytochrome P450 (CYP) epoxygenase metabolic pathways. The ω-3 endocannabinoid epoxides are derived from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to form epoxyeicosatetraenoic acid-ethanolamide (EEQ-EA) and epoxydocosapentaenoic acid-ethanolamide (EDP-EA), respectively. Both EEQ-EAs and EDP-EAs are endogenously present in rat brain and peripheral organs as determined via targeted lipidomics methods. These metabolites were directly produced by direct epoxygenation of the ω-3 endocannabinoids, docosahexanoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA) by activated BV-2 microglial cells, and by human CYP2J2. Neuroinflammation studies revealed that the terminal epoxides 17,18EEQ-EA and 19,20-EDP-EA dose-dependently abated proinflammatory IL-6 cytokines while increasing anti-inflammatory IL-10 cytokines, in part through cannabinoid receptor-2 activation. Furthermore the ω-3 endocannabinoid epoxides 17,18-EEQ-EA and 19,20-EDP-EA exerted antiangiogenic effects in human microvascular endothelial cells (HMVEC) and vasodilatory actions on bovine coronary arteries and reciprocally regulated platelet aggregation in washed human platelets. Taken together, the ω-3 endocannabinoid epoxides’ physiological effects are mediated through both endocannabinoid and epoxyeicosanoid signaling pathways. In summary, the ω-3 endocannabinoid epoxides are found at concentrations comparable to those of other endocannabinoids and are expected to play critical roles during inflammation in vivo; thus their identification may aid in the development of therapeutics for neuroinflammatory and cerebrovascular diseases.
OPEN ACCESS -
Nature Reviews Neuroscience -
Artigo Original -
2015
Brain endocannabinoid signaling influences the motivation for natural rewards (such as palatable food, sexual activity and social interaction) and mo ... (Ver mais)
Brain endocannabinoid signaling influences the motivation for natural rewards (such as palatable food, sexual activity and social interaction) and modulates the rewarding effects of addictive drugs. Pathological forms of natural and drug-induced reward are associated with dysregulated endocannabinoid signaling that may derive from pre-existing genetic factors or from prolonged drug exposure. Impaired endocannabinoid signaling contributes to dysregulated synaptic plasticity, increased stress responsivity, negative emotional states, and craving that propel addiction. Understanding the contributions of endocannabinoid disruptions to behavioral and physiological traits provides insight into the endocannabinoid influence on addiction vulnerability.
OPEN ACCESS -
British Journal of Pharmacology -
Revisão -
2008
Food, drugs and brain stimulation can serve as strong rewarding stimuli and are all believed to activate common brain circuits that evolved in mammal ... (Ver mais)
Food, drugs and brain stimulation can serve as strong rewarding stimuli and are all believed to activate common brain circuits that evolved in mammals to favour fitness and survival. For decades, endogenous dopaminergic and opioid systems have been considered the most important systems in mediating brain reward processes. Recent evidence suggests that the endogenous cannabinoid (endocannabinoid) system also has an important role in signalling of rewarding events. First, CB1 receptors are found in brain areas involved in reward processes, such as the dopaminergic mesolimbic system. Second, activation of CB1 receptors by plant-derived, synthetic or endogenous CB1 receptor agonists stimulates dopaminergic neurotransmission, produces rewarding effects and increases rewarding effects of abused drugs and food. Third, pharmacological or genetic blockade of CB1 receptors prevents activation of dopaminergic neurotransmission by several addictive drugs and reduces rewarding effects of food and these drugs. Fourth, brain levels of the endocannabinoids anandamide and 2arachidonoylglycerol are altered by activation of reward processes. However, the intrinsic activity of the endocannabinoid system does not appear to play a facilitatory role in brain stimulation reward and some evidence suggests it may even oppose it. The influence of the endocannabinoid system on brain reward processes may depend on the degree of activation of the different brain areas involved and might represent a mechanism for fine-tuning dopaminergic activity. Although involvement of the various components of the endocannabinoid system may differ depending on the type of rewarding event investigated, this system appears to play a major role in modulating reward processes.
Non-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the class ... (Ver mais)
Non-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone exert weak anti-inflammatory activity, their antinociceptive effects appearing to be mostly due to mechanisms other than peripheral cyclooxygenase inhibition. In this review, we classify classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone as “non-opioid analgesics” and discuss the mechanisms mediating participation of the endocannabinoid system in their antinociceptive effects. Non-opioid analgesics and their metabolites may activate cannabinoid receptors, as well as elevate endocannabinoid levels through different mechanisms: reduction of endocannabinoid degradation via fatty acid amide hydrolase and/or cyclooxygenase-2 inhibition, mobilization of arachidonic acid for the biosynthesis of endocannabinoids due to cyclooxygenase inhibition, inhibition of endocannabinoid cellular uptake directly or through the inhibition of nitric oxide synthase production, and induction of endocannabinoid release
OPEN ACCESS -
Proceedings of the National Academy of Sciences -
Revisão -
2014
Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to chan ... (Ver mais)
Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to changes in the expression of genes involved in its metabolism, the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in vitro from murine C2C12 myoblasts and during mouse muscle growth in vivo. The endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide, prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1 antagonists, which, per se, instead stimulate differentiation. Importantly, 2-AG also inhibits differentiation of primary human satellite cells. Muscle fascicles from CB1 knockout embryos contain more muscle fibers, and postnatal mice show muscle fibers of an increased diameter relative to wild-type littermates. Inhibition of Kv7.4 channel activity, which plays a permissive role in myogenesis and depends on phosphatidylinositol 4,5-bisphosphate (PIP2), underlies the effects of 2-AG. We find that CB1 stimulation reduces both total and Kv7.4-bound PIP2 levels in C2C12 cells and inhibits Kv7.4 currents in transfected CHO cells. We suggest that 2-AG is an endogenous repressor of myoblast differentiation via CB1-mediated inhibition of Kv7.4 channels.
Theworldwideprevalenceofneurologicalandneurodegenerativedisorders,suchasdepression orAlzheimer’sdisease,hasspreadextensivelythroughoutthelastdecades,becominganenormoushealth issue. Numerous data indicate a distinct correlation between the altered endocannabinoid signaling and different aspects of brain physiology, such as memory or neurogenesis. Moreover, the endocannabinoid system is widely regarded as a crucial factor in the development of neuropathologies. Thus, targeting those disorders via synthetic cannabinoids, as well as phytocannabinoids, becomes a widespread research issue. Over the last decade, the endocannabinoid system has been extensively studied for its correlation with physical activity. Recent data showed that physical activity correlates with elevated endocannabinoid serum concentrations and increased cannabinoid receptor type 1 (CB1R) expression in the brain, which results in positive neurological effects including antidepressant effect, ameliorated memory, neuroplasticity development, and reduced neuroinflammation. However, none of the prior reviews presented a comprehensive correlation between physical activity, the endocannabinoid system, and neuropathologies. Thus, our review provides a current state of knowledge of the endocannabinoid system, its action in physical activity, as well as neuropathologies and a possible correlation between all those fields. We believe that this might contribute to finding a new preventive and therapeutic approach to both neurological and neurodegenerative disorders
OPEN ACCESS -
Biochemistry -
Artigo Original -
2016
Endocannabinoids (EC) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecu ... (Ver mais)
Endocannabinoids (EC) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, 5, 7) serve this function in brain, relatively little is known about how such hydrophobic EC and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1, L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA—suggesting that FABP1 may also bind ARA-derived ECs (AEA, 2-AG). Indeed, FABP1 bound EC with high affinity as shown by displacement of FABP1-bound fluorescent ligands and by quenching of FABP1 intrinsic tyrosine fluorescence. FABP1 also had high affinity for most non-ARA containing ECs, FABP1 inhibitors, EC uptake/ hydrolysis inhibitors, phytocannabinoids, and less so synthetic cannabinoid receptor (CBR) agonists and antagonists. Physiological impact was examined with liver from wild-type (WT) versus FABP1 gene ablated (LKO) male mice. As shown by LC/MS, FABP1 gene ablation significantly increased hepatic levels of AEA, 2-AG, and 2-OG. These increases were not due to increased protein levels of EC synthetic enzymes (NAPEPLD, DAGL) or decreased level of EC degradative enzyme (FAAH), but correlated with complete loss of FABP1, decreased SCP2 (8-fold less prevalent than FABP1, but also binds ECs), and decreased degradative enzymes (NAAA, MAGL). These data indicated that FABP1 is not only the most prominent endocannabinoid and cannabinoid binding protein, but also impacts hepatic endocannabinoid levels.
OPEN ACCESS -
Human Reproduction Update -
Revisão -
2020
The endocannabinoid system (ECS) consists of the cannabinoid receptors CB1 and CB2, the main endocannabinoids anandamide (AEA)and2-arachidonoylglycer ... (Ver mais)
The endocannabinoid system (ECS) consists of the cannabinoid receptors CB1 and CB2, the main endocannabinoids anandamide (AEA)and2-arachidonoylglycerol (2-AG) and their metabolic enzymes N-acylphosphatidylethanolamine-specific phospholipase D, fatty acid amide hydrolase, diacylglycerol lipase and monoacylglycerol lipase. This system is involved in the modulation of essential physiological processes. Its role in the reproductive system has become significantly important in recent years, given its major role in events such as gametogenesis, decidualisation, implantation and placentation. In this paper, we review the literature and summarize the role of the ECS elements in reproduction and their potential as early markers for diagnosis of reproductive disorders or as pharmacological targets for treatment. Original research and review papers published from 1964 to June 2019 were selected in terms of relevance, reliability and quality by searching PubMed, MEDLINE and Web of Science, using the following search terms: endocannabinoid system and endometriosis; endocannabinoid system and ectopic pregnancy; endocannabinoid system and miscarriage; endocannabinoid system and pre-eclampsia;endocannabinoidsystemandendometrial cancer; endocannabinoid system and reproduction; endocannabinoid,endometrium; placenta;N-acylethanolamines;anandamide;2-arachidonoylglycerol;and cannabinoids.
OPEN ACCESS -
Frontiers in Neural Circuits -
Revisão -
2022
Research on endocannabinoid signaling has greatly advanced our understanding of how the excitability of neural circuits is controlled in health and d ... (Ver mais)
Research on endocannabinoid signaling has greatly advanced our understanding of how the excitability of neural circuits is controlled in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses excitability by inhibiting glutamate release, while that at inhibitory synapses promotes excitability by inhibiting GABA release, although there are some exceptions in genetically epileptic animal models. In the epileptic brain, the physiological distributions of endocannabinoid signaling molecules are disrupted during epileptogenesis, contributing to the occurrence of spontaneous seizures. However, it is still unknown how endocannabinoid signaling changes during seizures and how the redistribution of endocannabinoid signaling molecules proceeds during epileptogenesis. Recent development of cannabinoid sensors has enabled us to investigate endocannabinoid signaling in much greater spatial and temporal details than before. Application of cannabinoid sensors to epilepsy research has elucidated activity-dependent changes in endocannabinoid signaling during seizures. Furthermore, recent endocannabinoid research has paved the way for the clinical use of cannabidiol for the treatment of refractory epilepsy, such as Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Cannabidiol significantly reduces seizures and is considered to have comparable tolerability to conventional antiepileptic drugs. In this article, we introduce recent advances in research on the roles of endocannabinoid signaling in epileptic seizures and discuss future directions.
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Nature Reviews Neuroscience -
Artigo Original -
2015
Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including c ... (Ver mais)
Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including chronic inflammation and neurodegenerative diseases. These disorders have common molecular mechanisms that can be targeted therapeutically. In the wake of the approval of the first cannabinoid-based drug for the symptomatic treatment of multiple sclerosis, we examine how endocannabinoid (eCB) signalling controls — and is affected by — normal ageing and neuroinflammatory and neurodegenerative disorders. We propose a conceptual framework linking eCB signalling to the control of the cellular and molecular hallmarks of these processes, and categorize the key components of endocannabinoid signalling that may serve as targets for novel therapeutics.
Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress and neu ... (Ver mais)
Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress and neuronal depletion. The broadspectrum neuroprotective activity of the Mediterranean diet is widely documented, but it is not yet known whether its nutritional and caloric balance can induce a modulation of the endocannabinoid system. In recent decades, many studies have shown how endocannabinoid tone enhancement may be a promising new therapeutic strategy to counteract the main hallmarks of neurodegeneration. Fromaphylogenetic point of view, the humanco-evolution betweentheendocannabinoid systemand dietary habits could play a key role in the pro-homeostatic activity of the Mediterranean lifestyle: this adaptive balance among our ancestors has been compromised by the modern Western diet, resulting in a “clinical endocannabinoid deficiency syndrome”. This review aims to evaluate the evidence accumulated in the literature on the neuroprotective, immunomodulatory and antioxidant properties of the Mediterranean diet related to the modulation of the endocannabinoid system, suggesting new prospects for research and clinical interventions against neurodegenerative diseases in light of a nutraceutical paradigm
The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the p ... (Ver mais)
The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the physiopathological mechanisms leading to obesity and type 2 diabetes. New knowledge on the role of this system in humans has been acquired by measuring blood endocannabinoids. Here we explored endocannabinoids and related N-acylethanolamines in saliva and verified their changes in relation to body weight status and in response to a meal or to body weight loss.
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Journal of Cachexia, Sarcopenia and Muscle -
Artigo Original -
2022
Activation of the endocannabinoid system (ECS) is associated with the development of obesity and insulin resistance, and with perturbed skeletal musc ... (Ver mais)
Activation of the endocannabinoid system (ECS) is associated with the development of obesity and insulin resistance, and with perturbed skeletal muscle development. Age‐related sarcopenia is a progressive and generalized skeletal muscle disorder involving an accelerated loss of muscle mass and function, with changes in skeletal muscle protein homeostasis due to lipid accumulation and anabolic resistance. Hence, both obesity and sarcopenia share a common set of pathophysiological alterations leading to skeletal muscle impairment. The aim of this study was to characterize how sarcopenia impacts the ECS and f these modifications were related to the loss of muscle mass and function associated with aging in rats
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International Journal of Molecular Sciences -
Artigo Original -
2021
The activity of specific populations of neurons in different brain areas makes decisions regarding proper synaptic transmission, the ability to make ... (Ver mais)
Endocannabinoids are among the most intensively studied lipid mediators of cardiovascular functions. In the present study the effects of decreased an ... (Ver mais)
Endocannabinoids are among the most intensively studied lipid mediators of cardiovascular functions. In the present study the effects of decreased and increased activity of the endocannabinoid system (achieved by cannabinoid-1 (CB1) receptor blockade and inhibition of cannabinoid reuptake, respectively) on the systemic and cerebral circulation were analyzed under steady-state physiological conditions and during hypoxia and hypercapnia (H/H).n anesthetized spontaneously ventilating rats the CB1-receptor antagonist/inverse agonist AM-251 (10 mg/kg, i.v.) failed to influence blood pressure (BP), cerebrocortical blood flow (CoBF, measured by laser-Doppler flowmetry) or arterial blood gas levels. In contrast, the putative cannabinoid reuptake inhibitor AM-404 (10 mg/kg, i.v.) induced triphasic responses, some of which could be blocked by AM-251. Hypertension during phase I was resistant to AM-251, whereas the concomitant CoBF-increase was attenuated. In contrast, hypotension during phase III was sensitive to AM-251, whereas the concomitant CoBF-decrease was not. Therefore, CoBF autoregulation appeared to shift towards higher BP levels after CB1-blockade. During phase II H/H developed due to respiratory depression, which could be inhibited by AM-251. Interestingly, however, the concomitant rise in CoBF remained unchanged after AM-251, indicating that CB1-blockade potentially enhanced the reactivity of the CoBF to H/H. In accordance with this hypothesis, AM-251 induced a significant enhancement of the CoBF responses during controlled stepwise H/H.Under resting physiological conditions CB1-receptor mediated mechanisms appear to have limited influence on systemic or cerebral circulation. Enhancement of endocannabinoid levels, however, induces transient CB1-independent hypertension and sustained CB1-mediated hypotension. Furthermore, enhanced endocannabinoid activity results in respiratory depression in a CB1-dependent manner. Finally, our data indicate for the first time the involvement of the endocannabinoid system and CB1-receptors in the regulation of the cerebral circulation during H/H and also raise the possibility of their contribution to the autoregulation of CoBF.
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American College of Neuropsychopharmacology -
Artigo Original -
2018
Negative emotional states that are associated with excessive alcohol intake, particularly anxiety-like states, have been linked to opponent processes ... (Ver mais)
Negative emotional states that are associated with excessive alcohol intake, particularly anxiety-like states, have been linked to opponent processes in the central nucleus of the amygdala (CeA), affecting stress-related transmitters and monoamines. This study extends these observations to include endocannabinoid signaling in alcohol-dependent animals. Rats and mice were exposed to chronic intermittent alcohol with vapor inhalation or liquid diet to induce dependence. In vivo microdialysis was used to estimate interstitial concentrations of endocannabinoids [N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG)] and amino acids (glutamate and GABA) in rat CeA. Additionally, we evaluated the inhibition of endocannabinoids clearance enzymes [monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase] on anxiety-like behavior and alcohol consumption in alcohol-dependent rats and mice. Results revealed that alcohol dependence produced decreases in baseline 2-AG dialysate levels and increases in baseline levels of glutamate and GABA. Acute alcohol abstinence induced an enhancement of these dependenceinduced effects and the levels of 2-AG and GABA were restored upon alcohol re-exposure. Additional studies showed that the increased CeA 2-AG levels induced by restraint stress and alcohol self-administration were blunted in alcohol-dependent rats. Pharmacological studies in rats and mice showed that anxiety-like behavior and alcohol consumption were increased in alcoholdependent animals, and these behavioral effects were attenuated mainly by MAGL inhibitors [MJN110 (10 and 20mg/kg) in rats and JZL184 (1 and 3mg/kg) in mice]. The present results suggest a key role for endocannabinoid signaling in motivational neuroadaptations during alcohol dependence, in which a deficiency in CeA 2-AG signaling in alcohol-dependent animals is linked to stress and excessive alcohol consumption.
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Cannabis and Cannabinoid Research -
Artigo Original -
2019
A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medi ... (Ver mais)
A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy. A published Markov model comparing conventional therapies for painful diabetic neuropathy was modified to include arms for augmenting first-line, second-line (if first-line failed), or third-line (if first- and second-line failed) therapies with smoked cannabis. Microsimulation of 1,000,000 patients compared the cost (2017 U.S. dollars) and effectiveness (quality-adjusted life years [QALYs]) of usual care with and without adjunctive cannabis using a composite of third-party and out-of-pocket costs. Model efficacy inputs for cannabis were adapted from clinical trial data. Adverse event rates were derived from a prospective study of cannabis for chronic noncancer pain and applied to probability inputs for conventional therapies. Cannabis cost was derived from retail market pricing. Parameter uncertainty was addressed with one-way and probabilistic sensitivity analysis. Adding cannabis to first-line therapy was incrementally less effective and costlier than adding cannabis to second-line and third-line therapies. Third-line adjunctive cannabis was subject to extended dominance, that is, the second-line strategy was more effective with a more favorable incremental cost-effectiveness ratio of $48,594 per QALY gained, and therefore, third-line adjunctive cannabis was not as cost-effective. At a modest willingness-to-pay threshold of $100,000/QALY gained, second-line adjunctive cannabis was the strategy most likely to be cost-effective. As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain.
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International Journal of Molecular Sciences -
Artigo Original -
2021
As many jurisdictions consider relaxing cannabis legislation and usage is increasing in North America and other parts of the world, there is a need t ... (Ver mais)
As many jurisdictions consider relaxing cannabis legislation and usage is increasing in North America and other parts of the world, there is a need to explore the possible genetic differences underlying the subjective effects of cannabis. This pilot study investigated specific genetic variations within the cannabinoid receptor 1 (CNR1) gene for association with the subjective effects of smoked cannabis. Data were obtained from a double-blinded, placebo-controlled clinical trial studying the impact of cannabis intoxication on driving performance. Participants randomized to the active cannabis group who consented to secondary genetic analysis (n = 52) were genotyped at the CNR1 rs1049353 and rs2023239 polymorphic areas. Maximum value and area under the curve (AUC) analyses were performed on subjective measures data. Analysis of subjective effects by genotype uncovered a global trend towards greater subjective effects for rs1049353 T-allele- and rs2023239 C-allele-carrying subjects. However, significant differences attributed to allelic identity were only documented for a subset of subjective effects. Our findings suggest that rs1049353 and rs2023239 minor allele carriers experience augmented subjective effects during acute cannabis intoxication.
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Drug and alcohol dependence -
Revisão -
2020
here is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding ... (Ver mais)
here is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding optimal outcomes may have hindered development and approval of new pharmacotherapies. The goal of this paper is to summarize an evaluation of assessment measures and clinical endpoints for CUD clinical trials, and propose a research agenda and priorities to improve CUD clinical outcome assessments. The primary recommendation is that sustained abstinence from cannabis should not be considered the primary outcome for all CUD clinical trials as it has multiple limitations. However, there are multiple challenges to the development of a reliable and valid indicator of cannabis reduction, including the lack of a standard unit of measure for the various forms of cannabis and products and the limitations of currently available biological and self-report assessments. Development of a core toolkit of assessments is needed to both allow flexibility for study design, while facilitating interpretation of outcomes across trials. Four primary agenda items for future research are identified to expedite development of improved clinical outcome assessments for this toolkit: (1) determine whether minimally invasive biologic assays could identify an acute level of cannabis use associated with psychomotor impairment or other cannabis-related harms; (2) create an indicator of quantity of cannabis use that is consistent across product types; (3) examine the presence of cannabis-specific functional outcomes; and (4) identify an optimal duration to assess changes in CUD diagnostic criteria
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The American journal of drug and alcohol abuse -
Revisão -
2019
Pain is the most frequent indication for which medical cannabis treatment is sought. The clinical potential of cannabis and cannabis-derived products ... (Ver mais)
Pain is the most frequent indication for which medical cannabis treatment is sought. The clinical potential of cannabis and cannabis-derived products (CDPs) relies on their efficacy to treat an indication and potential adverse effects that impact outcomes, including abuse liability and neurocognitive effects. To ascertain the extent to which these effects impact therapeutic utility, studies investigating cannabis and CDPs for pain were reviewed for analgesic efficacy and assessments of abuse liability and neurocognitive effects. A comprehensive review of placebo-controlled studies investigating cannabis and CDP analgesia was performed. Methods and findings related to adverse effects, abuse liability, and neurocognitive effects were extracted. Thirty-eight studies were reviewed; 29 assessed cannabis and CDPs for chronic pain, 1 for acute pain, and 8 used experimental pain tests. Most studies ascertained adverse effects through self-report (N = 27). Fewer studies specifically probed abuse liability (N = 7) and cognitive and psychomotor effects (N = 12). Many studies related to chronic and experimental pain (N = 18 and N = 5 respectively) found cannabis and CDPs to reduce pain. Overall, adverse effects were mild to moderate, and dose-related. Studies investigating the impact of cannabis and CDPs of abuse liability and neurocognitive endpoints were mostly limited to inhaled administration and confirmed dose-related effects. Few studies investigating cannabis and CDP analgesia assess abuse liability and cognitive endpoints, adverse effects that impact long-term clinical utility of these drugs. Future studies should include these measures to optimize research and clinical care related to cannabis-based therapeutics.
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Psychopharmacology -
Artigo Original -
2021
Topiramate is an anticonvulsant currently under study for treating substance use disorders. Topiramate is thought to reduce substance use by attenuat ... (Ver mais)
Topiramate is an anticonvulsant currently under study for treating substance use disorders. Topiramate is thought to reduce substance use by attenuating craving and the rewarding effects of acute substance use through its concurrent GABAergic agonism and glutamatergic antagonism. Importantly, topiramate also impacts mood states central to many models of substance use. Despite this, little previous research has examined whether topiramate attenuates the respective associations of affect and craving with substance use. We conducted a secondary analysis of 63 youths that exhibited heavy cannabis use, aged 15–24 years, who were randomized in a double-blinded 6-week clinical trial comparing the effects of topiramate (up to 200 mg/day) and placebo on cannabis use. Ecological momentary assessment data were leveraged to model the role positive affect, negative affect, and craving on use over the 6-week period and whether topiramate attenuated associations between these feeling states and cannabis use. Findings showed that craving was positively associated with use at the within-person level, while positive affect was negatively associated with use at the between-person level. Topiramate appears to attenuate the negative association of between-person positive affect (i.e., average) and cannabis use. Specifically, those in the placebo condition exhibited this inverse association between average positive affect and use while those in topiramate condition did not. No other significant affect or affect × medication condition interactions were observed. These findings implicate craving and low positive affect as important risk factors for cannabis use in youth in treatment. Topiramate may attenuate this association for positive affect.
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Drug and alcohol dependence -
Revisão -
2019
Cannabis use disorder (CUD) is prevalent and demand for treatment is increasing, yet few individuals engage in formal treatment and the efficacy of e ... (Ver mais)
Cannabis use disorder (CUD) is prevalent and demand for treatment is increasing, yet few individuals engage in formal treatment and the efficacy of established interventions for CUD is modest. Existing clinical trials evaluating psychosocial and pharmacological treatments for CUD have incorporated a wide variety of measures for assessing cannabis use outcomes, including abstinence, self-reported frequency and quantity used, withdrawal, use/dependence severity, and other psychosocial outcomes. The heterogeneity of measures and outcomes has limited quantitative analyses of the comparative effectiveness of existing interventions. The purpose of this systematic review is to: 1) identify and characterize approaches for measuring cannabis use in existing CUD intervention trials, including abstinence, frequency and quantity of use, and 2) summarize measures used to assess treatment efficacy in other outcome domains (e.g., cannabis use severity, psychosocial functioning, cannabis withdrawal), and provide a platform for future research to evaluate which outcome measures are most likely to reflect treatment efficacy and clinically significant improvement in other outcome domains.
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Drug and alcohol dependence -
Revisão -
2019
Despite the high prevalence of blunt smoking among cannabis users, very few studies examine the clinical profile of blunt smokers relative to those u ... (Ver mais)
Despite the high prevalence of blunt smoking among cannabis users, very few studies examine the clinical profile of blunt smokers relative to those using more common methods of cannabis use, such as joints. The current study uses baseline data from the ACCENT (Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment) study, a multi-site randomized pharmacotherapy clinical trial within the National Drug Abuse Treatment Clinical Trials Network, to predict the association between blunt and joint use frequency and cannabis use characteristics (e.g., grams of cannabis used) and consequences (e.g., withdrawal) among past-month cannabis users (N = 377) who were screened for study participation. After controlling for race, age, gender, other forms of cannabis use (including joint use) and nicotine dependence, multivariable linear regression models indicated that the number of days of blunt use in the past month was a significant predictor of the average amount of cannabis per using day (t = 3.04, p < .01), the estimated average cost of cannabis (t = 2.28, p < .05) and Cannabis Withdrawal Scale scores (t = 1.94, p < .05). Frequency of joint use did not significantly predict any of the cannabis use characteristics or consequences. Blunt smokers may present to treatment with greater amounts of cannabis smoked and more intense withdrawal symptoms, which may adversely impact their likelihood of successful abstinence. Cannabis-dependent blunt smokers may be more likely to benefit from treatment that targets physiological and mood-related withdrawal symptoms.
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American Journal of Public Health -
Revisão -
2017
Cannabis use is common in North America, especially among young people, and is associated with a risk of various acute and chronic adverse health out ... (Ver mais)
Cannabis use is common in North America, especially among young people, and is associated with a risk of various acute and chronic adverse health outcomes. Cannabis control regimes are evolving, for example toward a national legalization policy in Canada, with the aim to improve public health, and thus require evidence-based interventions. As cannabis-related health outcomes may be influenced by behaviors that are modifiable by the user, evidence-based Lower-Risk Cannabis Use Guidelines (LRCUG)—akin to similar guidelines in other health fields—offer a valuable, targeted prevention tool to improve public health outcomes. To systematically review, update, and quality-grade evidence on behavioral factors determining adverse health outcomes from cannabis that may be modifiable by the user, and translate this evidence into revised LRCUG as a public health intervention tool based on an expert consensus process.. We used pertinent medical search terms and structured search strategies, to search MEDLINE, EMBASE, PsycINFO, Cochrane Library databases, and reference lists primarily for systematic reviews and meta-analyses, and additional evidence on modifiable risk factors for adverse health outcomes from cannabis use. For most recommendations, there was at least “substantial” (i.e., good-quality) evidence. We developed 10 major recommendations for lower-risk use: (1) the most effective way to avoid cannabis use–related health risks is abstinence, (2) avoid early age initiation of cannabis use (i.e., definitively before the age of 16 years), (3) choose low-potency tetrahydrocannabinol (THC) or balanced THC-to-cannabidiol (CBD)–ratio cannabis products, (4) abstain from using synthetic cannabinoids, (5) avoid combusted cannabis inhalation and give preference to nonsmoking use methods, (6) avoid deep or other risky inhalation practices, (7) avoid high-frequency (e.g., daily or near-daily) cannabis use, (8) abstain from cannabis-impaired driving, (9) populations at higher risk for cannabis use–related health problems should avoid use altogether, and (10) avoid combining previously mentioned risk behaviors (e.g., early initiation and high-frequency use).Evidence indicates that a substantial extent of the risk of adverse health outcomes from cannabis use may be reduced by informed behavioral choices among users. The evidence-based LRCUG serve as a population-level education and intervention tool to inform such user choices toward improved public health outcomes. However, the LRCUG ought to be systematically communicated and supported by key regulation measures (e.g., cannabis product labeling, content regulation) to be effective. All of these measures are concretely possible under emerging legalization regimes, and should be actively implemented by regulatory authorities. The population-level impact of the LRCUG toward reducing cannabis use–related health risks should be evaluated.
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Journal of Cannabis Research -
Revisão -
2022
The wide heterogeneity of available cannabis products makes it difficult for physicians to appropriately guide patients. In the current study, our ob ... (Ver mais)
The wide heterogeneity of available cannabis products makes it difficult for physicians to appropriately guide patients. In the current study, our objective was to characterize naturalistic cannabis use routines and explore associations between routines and reported benefits from consuming cannabis. We performed a mixed methods analysis of n=1087 cross-sectional survey responses from adults with self-reported chronic pain using cannabis for symptom management in the USA and Canada. First, we qualitatively analyzed responses to an open-ended question that assessed typical cannabis use routines, including administration routes, cannabinoid content, and timing. We then sub-grouped responses into categories based on inhalation (smoking, vaporizing) vs. non-inhalation (e.g., edibles). Finally, we investigated subgroups perceptions of how cannabis affected pain, overall health, and use of medications (e.g., substituting for opioids, benzodiazepines). Substitutions were treated as a count of medication classes, while responses for both pain and health were analyzed continuously, with − 2 indicating health declining a lot or pain increasing a lot and 2 indicating that health improved a lot or pain decreased a lot.Routines varied widely in terms of administration routes, cannabinoid content, and use timing. Overall, 18.8%, 36.2%, and 45% used non-inhalation, inhalation, and non-inhalation + inhalation routes, respectively. Those who used inhalation routes were younger (mean age 46.5 [inhalation] and 49.2 [non-inhalation + inhalation] vs. 56.3 [inhalation], F=36.1, p<0.001), while a higher proportion of those who used non-inhalation routes were female (72.5% non-inhalation vs. 48.3% inhalation and 65.3% non-inhalation + inhalation, X2=59.6, p<0.001). THC-rich products were typically used at night, while CBD-rich products were more often used during the day. While all participants reported similarly decreased pain, participants using non-inhalation + inhalation administration routes reported larger improvements in health than the non-inhalation (mean difference = 0.32, 95% CI: 0.07–0.37, p<0.001) and inhalation subgroups (mean difference = 0.22, 95% CI: 0.07–0.37, p=0.001). Similarly, the non-inhalation + inhalation group had significantly more medication substitutions than those using non-inhalation (mean difference = 0.62, 95% CI: 0.33–0.90, p<0.001) and inhalation administration routes (mean difference = 0.45, 95% CI: 0.22–0.69, p<0.001), respectively.Subgrouping medical cannabis patients based on administration route profile may provide useful categories for future studies examining the risks and benefits of medical cannabis
Whilst access to cannabis-based medicinal products (CBMPs) has increased globally subject to relaxation of scheduling laws globally, one of the main ... (Ver mais)
Whilst access to cannabis-based medicinal products (CBMPs) has increased globally subject to relaxation of scheduling laws globally, one of the main barriers to appropriate patient access remains a paucity of high-quality evidence surrounding their clinical effects. Whilst randomised controlled trials (RCTs) remain the gold-standard for clinical evaluation, there are notable barriers to their implementation. Development of CBMPs requires novel approaches of evidence collection to address these challenges. Real world evidence (RWE) presents a solution to not only both provide immediate impact on clinical care, but also inform well-conducted RCTs. RWE is defined as evidence derived from health data sourced from non-interventional studies, registries, electronic health records and insurance data. Currently it is used mostly to monitor post-approval safety requirements allowing for long-term pharmacovigilance. However, RWE has the potential to be used in conjunction or as an extension to RCTs to both broaden and streamline the process of evidence generation.Novel approaches of data collection and analysis will be integral to improving clinical evidence on CBMPs. RWE can be used in conjunction or as an extension to RCTs to increase the speed of evidence generation, as well as reduce costs. Currently, there is an abundance of potential data however, whilst a number of platforms now exist to capture real world data it is important the right tools and analysis are utilised to unlock potential insights from these.
OPEN ACCESS -
Psychopharmacology -
Artigo Original -
2020
Depression is common among individuals with cannabis use disorder (CUD), particularly individuals who present to CUD treatment. Treatments that consi ... (Ver mais)
Depression is common among individuals with cannabis use disorder (CUD), particularly individuals who present to CUD treatment. Treatments that consider this comorbidity are essential. The goal of this secondary analysis was to examine whether N-Acetylcysteine (NAC) reduced depressive symptoms among adults (age 18–50) with CUD (N=302) and whether the effect of NAC on cannabis cessation varied as a result of baseline levels of depression. Bidirectional associations between cannabis use amount and depression were also examined.Data for this secondary analysis were from a National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) multi-site clinical trial for CUD. Adults with CUD (N=302) were randomized to receive 2400 mg of NAC daily or matched placebo for 12 weeks. All participants received abstinence-based contingency management. Cannabis quantity was measured by self-report, and weekly urinary cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) confirmed abstinence. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale. Depressive symptoms did not differ between the NAC and placebo groups during treatment. There was no significant interaction between treatment and baseline depression predicting cannabis abstinence during treatment. Higher baseline depression was associated with decreased abstinence throughout treatment and a significant gender interaction suggested that this may be particularly true for females. Cross-lagged panel models suggested that depressive symptoms preceded increased cannabis use amounts (in grams) during the subsequent month. The reverse pathway was not significant (i.e, greater cannabis use preceding depressive symptoms).Results from this study suggest that depression may be a risk factor for poor CUD treatment outcome and therefore should be addressed in the context of treatment. However, results do not support the use of NAC to concurrently treat co-occurring depressive symptoms and CUD in adults.
Some patients diagnosed with cancer use medical cannabis to self-manage undesirable symptoms, including nausea and pain. To improve patient safety an ... (Ver mais)
Some patients diagnosed with cancer use medical cannabis to self-manage undesirable symptoms, including nausea and pain. To improve patient safety and oncological care quality, the routes of administration for use of medical cannabis, patients’ reasons, and prescribed indications must be better understood. Based on the Joanna Briggs Institute guidelines, a scoping review was conducted to map the current evidence regarding the use of medical cannabis in oncological settings based on the experiences of patients diagnosed with cancer and their healthcare providers. A search strategy was developed with a scientific librarian which included five databases (CINAHL, Web of Science, Medline, Embase, and PsycINFO) and two grey literature sources (Google Scholar and ProQuest). The inclusion criteria were: 1) population: adults aged 18 and over diagnosed with cancer; 2) phenomena of interest: reasons for cannabis use and/or the prescribed indications for medical cannabis; 3) context: oncological setting. French- or English-language primary empirical studies, knowledge syntheses, and grey literature published between 2000 and 2021 were included. Data were extracted by two independent reviewers and subjected to a thematic analysis. A narrative description approach was used to synthesize and present the findings. We identified 5,283 publications, of which 163 met the eligibility criteria. Two main reasons for medical cannabis use emerged from the thematic analysis: limiting the impacts of cancer and its side effects; and staying connected to others. Our results also indicated that medical cannabis is mostly used for three approved indications: to manage refractory nausea and vomiting, to complement pain management, and to improve appetite and food intake. We highlighted 11 routes of administration for medical cannabis, with oils and oral solutions the most frequently reported.Future studies should consider the multiple routes of administration for medical cannabis, such as inhalation and edibles. Our review highlights that learning opportunities would support the development of healthcare providers’ knowledge and skills in assessing the needs and preferences of patients diagnosed with cancer who use medical cannabis.
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Alcohol and Alcoholism -
Artigo Original -
2020
Alcohol and cannabis are frequently co-used, as 20–50% of those who drink alcohol report co-using cannabis. This study is based on the argument that ... (Ver mais)
Alcohol and cannabis are frequently co-used, as 20–50% of those who drink alcohol report co-using cannabis. This study is based on the argument that alcohol researchers should enroll cannabis users in human laboratory studies of alcohol use disorder (AUD) to strengthen generalizability. This study examines how heavy drinking cannabis users differ from non-cannabis using heavy drinkers. In a community sample of non-treatment-seeking heavy drinkers (n = 551, 35% female), cannabis users were identified through: (a) self-reported cannabis use in the past 6 months and (b) positive urine toxicology test for tetrahydrocannabinol (THC). Cannabis users, identified as described previously, were compared with non-cannabis users on demographic and clinical characteristics.Those who endorsed cannabis use in the past 6 months reported more binge drinking days. Participants who tested positive for THC had higher Alcohol Use Disorder Identification Test scores and more binge drinking days. Younger age and being a tobacco smoker were associated with an increased likelihood of cannabis use in the past 6 months, whereas male gender and being a tobacco use were associated with a greater likelihood of testing positive for THC. Individuals with cannabis use disorder (CUD) endorsed more depression and anxiety and had higher AUD symptom counts than cannabis users without CUD. The inclusion of cannabis users in AUD samples allows for increased clinical severity. Excluding cannabis users from AUD studies may limit representativeness and expend unnecessary study resources. Lastly, tobacco use may explain a large portion of the effects of cannabis use on sample characteristics.
The current lack of pharmacological treatments for cannabis use disorder (CUD) warrants novel approaches and further investigation of promising pharm ... (Ver mais)
The current lack of pharmacological treatments for cannabis use disorder (CUD) warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that nabiximols (27 mg/ml Δ9-tetrahydrocannabinol (THC)/ 25 mg/ml cannabidiol (CBD), Sativex®) can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants. Subjects participated in a double blind randomized clinical trial, with as-needed nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time. Medication was well tolerated and no serious adverse events (SAEs) were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS). There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with nabiximols or placebo treatments (F1,40 = 0.585, NS). Cannabis use was reduced in the nabiximols (70.5%) and placebo groups (42.6%). Nabiximols reduced cannabis craving but no significant differences between the nabiximols and placebo groups were observed on withdrawal scores. Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of nabiximols for cannabis dependence.
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Drug and alcohol dependence -
Artigo Original -
2018
Quantifying cannabis use is complex due to a lack of a standardized packaging system that contains specified amounts of constituents. A laboratory pr ... (Ver mais)
Quantifying cannabis use is complex due to a lack of a standardized packaging system that contains specified amounts of constituents. A laboratory procedure has been developed for estimating physical quantity of cannabis use by utilizing a surrogate substance to represent cannabis, and weighing the amount of the surrogate to determine typical use in grams. This secondary analysis utilized data from a multi-site, randomized, controlled pharmacological trial for adult cannabis use disorder (N=300), sponsored by the National Drug Abuse Treatment Clinical Trials Network, to test the incremental validity of this procedure. In conjunction with the Timeline Followback, this physical scale-based procedure was used to determine whether average grams per cannabis administration predicted urine cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) and problems due to use, after accounting for self-reported number of days used (in the past 30 days) and number of administrations per day in a 12-week clinical trial for cannabis use disorder.Likelihood ratio tests suggest that model fit was significantly improved when grams per administration and relevant interactions were included in the model predicting urine cannabinoid level (X2=98.3; p<0.05) and in the model predicting problems due to cannabis use (X2=6.4; p<0.05), relative to a model that contained only simpler measures of quantity and frequency.This study provides support for the use of a scale-based method for quantifying cannabis use in grams. This methodology may be useful when precise quantification is necessary (e.g., measuring reduction in use in a clinical trial).
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Drug and alcohol dependence -
Artigo Original -
2017
Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased p ... (Ver mais)
Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment Episodes Data Set – Admissions. Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users.These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings.
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Regional anesthesia and pain medicine -
Artigo Original -
2021
Despite increases in cannabis use generally and for pain management, data regarding cannabis use in patients undergoing surgery are lacking. This stu ... (Ver mais)
Despite increases in cannabis use generally and for pain management, data regarding cannabis use in patients undergoing surgery are lacking. This study examined the prevalence of cannabis use among patients undergoing elective surgery and explored differences in clinical characteristics and surgical outcomes between cannabis users and non-cannabis users. This prospective study included 1,335 adults undergoing elective surgery. Participants completed self-report questionnaires preoperative and at 3- and 6-months post-surgery to assess clinical characteristics and surgical outcomes. Overall, 5.9% (N=79) of patients reported cannabis use (53.2% medical, 19.0% recreational, and 25.3% medical and recreational). On the day of surgery, cannabis users reported worse pain, more centralized pain symptoms, greater functional impairment, higher fatigue, greater sleep disturbances, and more symptoms of anxiety and depression versus non-cannabis users (all ps < 0.01). Additionally, a larger proportion of cannabis users reported opioid (27.9%) and benzodiazepine use (19.0%) compared to non-cannabis users (17.5% and 9.2% respectively). At 3 and 6 months, cannabis users continued to report worse clinical symptoms; however, both groups showed improvement across most domains (ps ≤ 0.05). At 6-months, the groups did not differ on surgical outcomes, including surgical site pain (p = 0.93) or treatment efficacy (p = 0.88). Cannabis use is relatively low in this surgical population, yet cannabis users have higher clinical pain, poorer scores on quality of life indicators, and higher opioid use before and after surgery. Cannabis users reported similar surgical outcomes, suggesting that cannabis use did not impede recovery.
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Biomedicines -
Artigo Original -
2021
Cannabis sativa (Cannabis) is one of the world’s most well-known, yet maligned plant species. However, significant recent research is starting to unv ... (Ver mais)
Cannabis sativa (Cannabis) is one of the world’s most well-known, yet maligned plant species. However, significant recent research is starting to unveil the potential of Cannabis to produce secondary compounds that may offer a suite of medical benefits, elevating this unique plant species from its illicit narcotic status into a genuine biopharmaceutical. This review summarises the lengthy history of Cannabis and details the molecular pathways that underpin the production of key secondary metabolites that may confer medical efficacy. We also provide an up-to-date summary of the molecular targets and potential of the relatively unknown minor compounds offered by the Cannabis plant. Furthermore, we detail the recent advances in plant science, as well as synthetic biology, and the pharmacology surrounding Cannabis. Given the relative infancy of Cannabis research, we go on to highlight the parallels to previous research conducted in another medically relevant and versatile plant, Papaver somniferum (opium poppy), as an indicator of the possible future direction of Cannabis plant biology. Overall, this review highlights the future directions of cannabis research outside of the medical biology aspects of its well-characterised constituents and explores additional avenues for the potential improvement of the medical potential of the Cannabis plant.
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International Journal of Environmental Research and Public Health -
Revisão -
2022
Depression and anxiety disorders are two of the most common and growing mental health concerns in adolescents. Consequently, antidepressant medicatio ... (Ver mais)
Depression and anxiety disorders are two of the most common and growing mental health concerns in adolescents. Consequently, antidepressant medication (AD) use has increased widely during the last decades. Several classes of antidepressants are used mainly to treat depression, anxiety, and obsessive-compulsive disorders by targeting relevant brain neurochemical pathways. Almost all randomized clinical trials of antidepressants examined patients with no concomitant medications or drugs. This does not address the expected course of therapy and outcome in cannabis users. Cannabis is the most commonly used illicit substance globally. Substantial changes in its regulation are recently taking place. Many countries and US states are becoming more permissive towards its medical and recreational use. The psychological and physiological effects of cannabis (mainly of its major components, tetrahydrocannabinol (THC) and cannabidiol (CBD)) have been extensively characterized. Cannabis use can be a risk factor for depressive and anxiety symptoms, but some constituents or mixtures may have antidepressant and/or anxiolytic potential. The aim of this literature review is to explore whether simultaneous use of AD and cannabis in adolescence can affect AD treatment outcomes. Based on the current literature, it is reasonable to assume that antidepressants are less effective for adolescents with depression/anxiety who frequently use cannabis. The mechanisms of action of antidepressants and cannabis point to several similarities and conjunctions that merit future investigation regarding the potential effectiveness of antidepressants among adolescents who consume cannabis regularly.
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Scientific Reports -
Artigo Original -
2019
It is well established that cannabis use promotes appetite. However, how cannabis interacts with the brain’s appetite center, the hypothalamus, to st ... (Ver mais)
It is well established that cannabis use promotes appetite. However, how cannabis interacts with the brain’s appetite center, the hypothalamus, to stimulate feeding behavior is unknown. A growing body of evidence indicates that the hypothalamic transcriptome programs energy balance. Here, we tested the hypothesis that cannabis targets alternative polyadenylation (APA) sites within hypothalamic transcripts to regulate transcriptomic function. To do this, we used a novel cannabis vapor exposure model to characterize feeding in adult male Long Evans rats and aligned this behavioral response with APA events using a Whole Transcriptome Termini Sequencing (WTTS-Seq) approach as well as functional RNA abundance measurements with real-time quantitative polymerase chain reactions. We found that vapor cannabis exposure promoted food intake in free-feeding and behaviorally sated rats, validating the appetite stimulating properties of cannabis. Our WTTS-Seq analysis mapped 59 unique cannabis-induced hypothalamic APAs that occurred primarily within exons on transcripts that regulate synaptic function, excitatory synaptic transmission, and dopamine signaling. Importantly, APA insertions regulated RNA abundance of Slc6a3, the dopamine transporter, suggesting a novel genetic link for cannabis regulation of brain monoamine function. Collectively, these novel data indicate that a single cannabis exposure rapidly targets a key RNA processing mechanism linked to brain transcriptome function.
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Harvard review of psychiatry -
Revisão -
2021
Systematically review the scientific literature to characterize the effects of cannabis use on brain structure, function, and neurodevelopmental outc ... (Ver mais)
Systematically review the scientific literature to characterize the effects of cannabis use on brain structure, function, and neurodevelopmental outcomes in adolescents and young adults with ADHD. Systematic review following PRISMA guidelines utilizing PubMed, Embase, PsycINFO, and Cochrane CENTRAL trials register from inception until 1 January 2020. Articles that examined the impact of cannabis use on youth with ADHD were included. Eleven studies were identified that compared outcomes for individuals with ADHD who used cannabis or synthetic cannabinoids against those with ADHD who did not. Seven of these studies used neuroimaging techniques, including fMRI, structural MRI, and SPECT. Differential regions of activation were identified, including the right hippocampus and cerebellar vermis, and bilateral temporal lobes. Morphological differences were identified in the right precentral and postcentral gyri, left nucleus accumbens, right superior frontal and postcentral gyri. No study identified any additive or ADHD × cannabis use interaction on neuropsychological tasks of executive function. Two studies found adverse differential impacts of early-onset cannabis use in this population. A dearth of evidence is available on the impact of cannabis use on the developing brain and functioning for individuals with ADHD, despite the elevated risk for substance use in this population. The limited, potentially underpowered evidence does not support the hypothesis that cannabis use has a deleterious impact on neuropsychological tasks in transitional age youth with ADHD. Larger and longer-term studies are needed, however, to better inform clinicians and patients as to the impacts of cannabis use in youth with ADHD.
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Frontiers in Pharmacology -
Revisão -
2016
This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirement ... (Ver mais)
This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety, and public health issues remain.
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Saudi Journal of Biological Sciences -
Revisão -
2021
Cannabis sativa, widely known as ‘Marijuana’ poses a dilemma for being a blend of both good and bad medicinal effects. The historical use of Cannabis ... (Ver mais)
Cannabis sativa, widely known as ‘Marijuana’ poses a dilemma for being a blend of both good and bad medicinal effects. The historical use of Cannabis for both medicinal and recreational purposes suggests it to be a friendly plant. However, whether the misuse of Cannabis and the cannabinoids derived from it can hamper normal body physiology is a focus of ongoing research. On the one hand, there is enough evidence to suggest that misuse of marijuana can cause deleterious effects on various organs like the lungs, immune system, cardiovascular system, etc. and also influence fertility and cause teratogenic effects. However, on the other hand, marijuana has been found to offer a magical cure for anorexia, chronic pain, muscle spasticity, nausea, and disturbed sleep. Indeed, most recently, the United Nations has given its verdict in favour of Cannabis declaring it as a non-dangerous narcotic. This review provides insights into the various health effects of Cannabis and its specialized metabolites and indicates how wise steps can be taken to promote good use and prevent misuse of the metabolites derived from this plant.
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Integrative Cancer Therapies -
Revisão -
2022
As medical cannabis becomes legal in more states, cancer patients are increasingly interested in the potential utility of the ancient botanical in th ... (Ver mais)
As medical cannabis becomes legal in more states, cancer patients are increasingly interested in the potential utility of the ancient botanical in their treatment regimen. Although eager to discuss cannabis use with their oncologist, patients often find that their provider reports that they do not have adequate information to be helpful. Oncologists, so dependent on evidence-based data to guide their treatment plans, are dismayed by the lack of published literature on the benefits of medical cannabis. This results largely from the significant barriers that have existed to effectively thwart the ability to conduct trials investigating the potential therapeutic efficacy of the plant. This is a narrative review aimed at clinicians, summarizing cannabis phytochemistry, trials in the areas of nausea and vomiting, appetite, pain and anticancer activity, including assessment of case reports of antitumor use, with reflective assessments of the quality and quantity of evidence. Despite preclinical evidence and social media claims, the utility of cannabis, cannabinoids or cannabis-based medicines in the treatment of cancer remains to be convincingly demonstrated. With an acceptable safety profile, cannabis and its congeners may be useful in managing symptoms related to cancer or its treatment. Further clinical trials should be conducted to evaluate whether the preclinical antitumor effects translate into benefit for cancer patients. Oncologists should familiarize themselves with the available database to be able to better advise their patients on the potential uses of this complementary botanical therapy.
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Translational Psychiatry -
Artigo Original -
2021
Cannabis is known to produce acute, transient psychotic-like experiences. However, it is unclear whether cannabis disproportionately increases the ri ... (Ver mais)
Cannabis is known to produce acute, transient psychotic-like experiences. However, it is unclear whether cannabis disproportionately increases the risk of specific types of psychotic experiences and whether genetic predisposition influences the relationship between cannabis use and psychotic experiences. In this cross-sectional study of 109,308 UK Biobank participants, we examined how schizophrenia polygenic risk modulates the association between self-reported cannabis use and four types of self-reported psychotic experiences (auditory hallucinations, visual hallucinations, persecutory delusions, and delusions of reference). Cohort-wide, we found a strong, dose-dependent relationship between cannabis use and all four types of psychotic experiences, especially persecutory delusions. Cannabis users’ psychotic experiences tended to be earlier-onset and cause greater distress than non-users’, but were not more likely to lead to help-seeking. Participants with high schizophrenia polygenic risk scores showed stronger associations between cannabis use and auditory hallucinations, visual hallucinations, and delusions of reference, as well as psychotic experiences overall. For instance, cannabis ever-use was associated with 67% greater adjusted odds of delusions of reference among individuals in the top fifth of polygenic risk, but only 7% greater adjusted odds among the bottom fifth. Our results suggest that cannabis use is a predictive risk factor for psychotic experiences, including early-onset and distressing experiences. Individuals genetically predisposed to schizophrenia may be especially vulnerable to psychotic experiences as a result of using cannabis, supporting a long-postulated hypothesis. This study exemplifies the utility of population-scale biobanks for elucidating gene-by-environment interactions relating substance use to neuropsychiatric outcomes and points to the translational potential of using polygenic risk scores to inform personalized harm reduction interventions.
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Translational Behavior Medicine -
Artigo Original -
2021
Cannabis-using youth are a large epidemiologic subgroup whose age and smoking-related risks underscore the importance of examining the impact of the ... (Ver mais)
Cannabis-using youth are a large epidemiologic subgroup whose age and smoking-related risks underscore the importance of examining the impact of the COVID-19 pandemic in this population. Within a clinical trial (n = 36 received an intervention prior to data collection reported herein), we surveyed cannabis-using emerging adults (ages 18–25) about perceived COVID-19 impacts. Participants (n = 141) reporting weekly cannabis use (M = 18.6 use days in the past 30) were enrolled and completed online surveys as part of either their baseline or 3 month assessment. COVID-19-related measures included symptoms, substance use, mood, etc. Participants were 57% female (mean age = 21, standard deviation = 2.2), with 21% Hispanic/Latinx, 70% White, 20% Black/African American, and 10% of other races. Most participants (86%) reported quarantine/self-isolation (M = 59 days). Several had COVID-19 symptoms (16%), but none reported testing COVID-19 positive. Many respondents felt their cannabis use (35%–50%, across consumption methods) and negative emotions (e.g., loneliness, stress, and depression; 69.5%, 69.5%, and 61.8%, respectively) increased. They reported decreased in-person socialization (90.8%) and job losses (23.4%). Reports of increased cannabis smoking were associated with increased negative emotions. On an open-response item, employment/finances and social isolation were frequently named negative impacts (33.3% and 29.4%, respectively). Although cannabis-using emerging adults’ reports of increases in cannabis use, coupled with mental health symptoms and social isolation, are concerning, the full impact of the pandemic on their health and well-being remains unknown. Future studies examining the relationship between social isolation, mental health, and cannabis use among young people are needed.
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Nicotine & Tobacco Research -
Artigo Original -
2020
The co-use of cannabis and alcohol among tobacco-using youth is common. Alcohol co-use is associated with worse tobacco cessation outcomes, but resul ... (Ver mais)
The co-use of cannabis and alcohol among tobacco-using youth is common. Alcohol co-use is associated with worse tobacco cessation outcomes, but results are mixed regarding the impact of cannabis on tobacco outcomes and if co-use leads to increased use of non-treated substances. This secondary analysis from a youth smoking cessation trial aimed to (1) evaluate the impact of cannabis or alcohol co-use on smoking cessation, (2) examine changes in co-use during the trial, and (3) explore secondary effects of varenicline on co-use. The parent study was a 12-week, randomized clinical trial of varenicline for smoking cessation among youth (ages 14–21, N = 157; Mage = 19, 40% female; 76% White). Daily cigarette, cannabis, and alcohol use data were collected via daily diaries during treatment and Timeline Follow-back for 14 weeks post-treatment. Baseline cannabis co-users (68%) had double the odds of continued cigarette smoking throughout the trial compared with noncannabis users, which was pronounced in males and frequent cannabis users. Continued smoking during treatment was associated with higher probability of concurrent cannabis use. Baseline alcohol co-users (80%) did not have worse smoking outcomes compared with nonalcohol users, but continued smoking was associated with higher probability of concurrent drinking. Varenicline did not affect co-use.Inconsistent with prior literature, results showed that alcohol co-users did not differ in smoking cessation, whereas cannabis co-users had poorer cessation outcomes. Youth tobacco treatment would benefit from added focus on substance co-use, particularly cannabis, but may need to be tailored appropriately to promote cessation.
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Frontiers in Pharmacology -
Artigo Original -
2022
Cannabis has long been regarded as a recreational substance in the Western world. The recent marketing authorization of some medicinal products of in ... (Ver mais)
Cannabis has long been regarded as a recreational substance in the Western world. The recent marketing authorization of some medicinal products of industrial origin and the introduction onto the market of inflorescences for medical use mean that medical doctors can now prescribe Cannabis-based medicines in those countries which allow it. Nevertheless, there is still considerable controversy on this topic in the scientific community. In particular, this controversy concerns: the plant species to be used; the pathologies that can be treated and consequently the efficacy and safety of use; the routes of administration; the methods of preparation; the type and dosage of cannabinoids to be used; and, the active molecules of interest. As such, although medical Cannabis has been historically used, the results of currently completed and internationally published studies are inconclusive and often discordant. In light of these considerations, the aim of this work is to analyse the current legislation in countries that allow the use of medical Cannabis, in relation to the impact that this legislation has had on clinical trials. First of all, a literature search has been performed (PubMed and SciFinder) on clinical trials which involved the administration of Cannabis for medical use over the last 3 years. Of the numerous studies extrapolated from the literature, only about 43 reported data on clinical trials on medical Cannabis, with these mainly being performed in Australia, Brazil, Canada, Denmark, Germany, Israel, Netherlands, Switzerland, the United Kingdom and the United States of America. Once the reference countries were identified, an evaluation of the legislation in relation to Cannabis for medical use in each was carried out via the consultation of the pertinent scientific literature, but also of official government documentation and that of local regulatory authorities. This analysis provided us with an overview of the different legislation in these countries and, consequently, allowed us to analyse, with greater awareness, the results of the clinical trials published in the last 3 years in order to obtain general interest indications in the prosecution of scientific research in this area.
Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharm ... (Ver mais)
Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials.
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Drug and alcohol dependence -
Artigo Original -
2021
Time from first cannabis use to cannabis dependence (latency) may be an important prognostic indicator of cannabis-related problems and treatment out ... (Ver mais)
Time from first cannabis use to cannabis dependence (latency) may be an important prognostic indicator of cannabis-related problems and treatment outcomes. Gender differences in latency have been found; however, research in this general area is limited. As cannabis use increases and perceived risk declines, a better understanding of how these factors interact in predicting treatment outcomes is critical. A secondary data analysis of a randomized, double-blind, placebo-controlled pharmacotherapy trial for cannabis dependence (N=302) examined the associations between age of cannabis use onset, time to cannabis dependence (latency), and gender on cannabis use during the trial. Mediation analysis tested whether the association between age of onset and cannabis use during the trial was mediated by latency to cannabis dependence differentially for men and women. Age of use initiation was inversely correlated with latency to dependence prior to treatment [HR(95% CI)=1.18 (1.06, 1.30); p=.002] and cannabis use during treatment (β=−1.27; SE=0.37; p<.001). There was a significant mediation effect between age of onset, latency, and cannabis use that varied by gender. Earlier age of onset predicted longer latency, and subsequently, greater cannabis use during the trial in men (21.4% mediated; p<.05), but not women. Other substance use, race, and past psychiatric diagnosis did not predict latency either independently or in interaction models. Findings support existing evidence that early cannabis use onset is associated with worse outcomes and add new knowledge on the differential associations between age of onset, latency to cannabis dependence, and treatment outcomes for men and women.
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Human Reproduction -
Artigo Original -
2021
Is cannabis use assessed via urinary metabolites and self-report during preconception associated with fecundability, live birth and pregnancy loss? P ... (Ver mais)
Is cannabis use assessed via urinary metabolites and self-report during preconception associated with fecundability, live birth and pregnancy loss? Preconception cannabis use was associated with reduced fecundability among women with a history of pregnancy loss attempting pregnancy despite an increased frequency of intercourse. Women aged 18–40 years with a history of pregnancy loss (n = 1228) were recruited from four clinical centers. Women self-reported preconception cannabis use at baseline and urinary tetrahydrocannabinol metabolites were measured throughout preconception and early pregnancy (up to four times during the study: at baseline, after 6 months of follow-up or at the beginning of the conception cycle, and weeks 4 and 8 of pregnancy). Time to hCG-detected pregnancy, and incidence of live birth and pregnancy loss were prospectively assessed. Fecundability odds ratios (FOR) and 95% CI were estimated using discrete time Cox proportional hazards models, and risk ratios (RRs) and 95% CI using log-binomial regression adjusting for age, race, BMI, education level, baseline urine cotinine, alcohol use and antidepressant use. Preconception cannabis use was 5% (62/1228), based on combined urinary metabolite measurements and self-report, and 1.3% (11/789) used cannabis during the first 8 weeks of gestation based on urinary metabolites only. Women with preconception cannabis use had reduced fecundability (FOR 0.59; 95% CI 0.38, 0.92). Preconception cannabis use was also associated with increased frequency of intercourse per cycle (9.4 ± 7 versus 7.5 ± 7 days; P = 0.02) and higher LH (percentage change 64%, 95% CI 3, 161) and higher LH:FSH ratio (percentage change 39%, 95% CI 7, 81). There were also suggestive, though imprecise, associations with anovulation (RR 1.92, 95% CI 0.88, 4.18), and live birth (42% (19/45) cannabis users versus 55% (578/1043) nonusers; RR 0.80, 95% CI 0.57, 1.12). No associations were observed between preconception cannabis use and pregnancy loss (RR 0.81, 95% CI 0.46, 1.42). Similar results were observed after additional adjustment for parity, income, employment status and stress. We were unable to estimate associations between cannabis use during early pregnancy and pregnancy loss due to limited sample size.
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Journal of Primary Care & Community Health -
Revisão -
2022
The use of cannabis products to help with sleep and various other medical conditions by the public has increased significantly in recent years. Withd ... (Ver mais)
The use of cannabis products to help with sleep and various other medical conditions by the public has increased significantly in recent years. Withdrawal from cannabinoids can lead to sleep disturbance. Here, we describe a patient who developed significant insomnia leading to worsening anxiety, mood, and suicidal ideation in the setting of medical cannabis withdrawal, prompting presentation to the Emergency Department and inpatient admission. There is a limited evidence base for the use of cannabis products for sleep. We provide a comprehensive review evaluating the literature on the use of cannabis products on sleep, including an overview of cannabis and related psychoactive compounds, the current state of the law as it pertains to the prescribing and use of these substances, and potential side effects and drug interactions. We specifically discuss the impact of cannabis products on normal sleep and circadian sleep-wake rhythms, insomnia, excessive daytime sleepiness, sleep apnea, parasomnias, and restless legs syndrome. We also describe the effects of cannabis withdrawal on sleep and how this increases relapse to cannabis use. Most of the studies are observational but the few published randomized controlled trials are reviewed. Our comprehensive review of the effects of cannabis products on normal sleep and sleep disorders, relevant to primary care providers and other clinicians evaluating and treating patients who use these types of products, shows that cannabis products have minimal to no effects on sleep disorders and may have deleterious effects in some individuals. Further research examining the differential impact of the various types of cannabinoids that are currently available on each of these sleep disorders is required.
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Journal of Otolaryngology – Head & Neck Surgery -
Revisão -
2021
Cannabis has been rapidly legalized in North America; however, limited evidence exists around its side effects. Health Canada defines side effect as ... (Ver mais)
Cannabis has been rapidly legalized in North America; however, limited evidence exists around its side effects. Health Canada defines side effect as a harmful and unintended response to a health product. Given drug safety concerns, this study’s purpose was to review the unintended side effects of cannabis in otolaryngology. The Preferred Reporting Items For Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR) protocol was used to conduct a scoping review of the MEDLINE, EMBASE, CINAHL, and CENTRAL databases. (PROSPERO: CRD42020153022). English studies in adults were included from inception to the end of 2019. In-vitro, animal, and studies with n < 5 were excluded. Primary outcome was defined as unintended side effects (defined as any Otolaryngology symptom or diagnosis) following cannabis use. Oxford Centre for Evidence-Based Medicine: Levels of Evidence and risk of bias using the Risk of Bias in randomized trials (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tools were assessed.. Two authors independently reviewed all studies; the senior author settled any discrepancies. Five hundred and twenty-one studies were screened; 48 studies were analysed. Subspecialties comprised: Head and Neck (32), Otology (8), Rhinology (5), Airway (5), Laryngology (1). Cannabis use was associated with unintended tinnitus, vertigo, hearing loss, infection, malignancy, sinusitis, allergic rhinitis, thyroid dysfunction, and dyspnea. About half (54.1%) of studies showed increased side effects, or no change in symptoms following cannabis use. Oxford Levels of Evidence was 2–4 with substantial heterogeneity. Risk of bias assessment with RoB2 was low to high and ROBINS-1 was moderate to critical. This was the first comprehensive scoping review of unintended side effects of cannabis in Otolaryngology. The current literature is limited and lacks high-quality research Future randomized studies are needed to focus on therapeutic effects of cannabis in otolaryngology. Substantial work remains to guide clinicians to suggest safe, evidence-based choices for cannabis use.
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Drug and alcohol dependence -
Artigo Original -
2016
Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to hu ... (Ver mais)
Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans. This retrospective analysis compared the analgesic, subjective and physiological effects of active cannabis (3.56 - 5.60% THC) and inactive cannabis (0.00% THC) in male (N = 21) and female (N = 21) cannabis smokers under double-blind, placebo-controlled conditions. Pain response was measured using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4°C); times to report pain (pain sensitivity) and withdraw the hand (pain tolerance) were recorded. Subjective drug ratings were also measured. Among men, active cannabis significantly decreased pain sensitivity relative to inactive cannabis (p < 0.01). In women, active cannabis failed to decrease pain sensitivity relative to inactive. Active cannabis increased pain tolerance in both men women immediately after smoking (p < 0.001); a trend was observed for differences between men and women (p < 0.10). Active cannabis also increased subjective ratings of cannabis associated with abuse liability (‘Take again,’ ‘Liking,’ ‘Good drug effect’), drug strength, and ‘High’ relative to inactive in both men and women (p < 0.01). These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women. These sex-dependent differences are independent of cannabis-elicited subjective effects associated with abuse-liability, which were consistent between men and women. As such, sex-dependent differences in cannabiss analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief.
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Frontiers in endocrinology -
Artigo Original -
2021
Inflammatory bowel diseases (IBDs) are chronic, idiopathic, inflammatory, gastrointestinal disorders. The endocannabinoid system may have a role in t ... (Ver mais)
Inflammatory bowel diseases (IBDs) are chronic, idiopathic, inflammatory, gastrointestinal disorders. The endocannabinoid system may have a role in the pathogenesis of IBD. We aimed to assess whether cannabis treatment influences endocannabinoids (eCBs) level and clinical symptoms of IBD patients. Blood samples and biopsies were taken from IBD patients treated by either cannabis or placebo for 8 weeks. Immunohistochemistry for N-acyl-phosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH) expression was done on colon biopsies, and sample levels of anandamide (AEA), eCB2-arachidonylglycerol (2-AG), arachidonic acid (AA), palmitoylethanolamine (PEA), and oleoylethanolamine (OEA) were measured in patient’s sera before and after cannabis treatment. Caco-2 cells were cultured with extracts of cannabis with/without tetrahydrocannabinol (THC) and their proteins extracted, and Western blotting for NAPE-PLD and FAAH expression was done.Thirteen patients with Crohn’s disease (CD) and nine patients with ulcerative colitis (UC) were treated with cannabis. Seventeen patients with CD and 10 with UC served as placebo groups. In all CD patients, the levels of eCBs remained unaltered during the treatment period. In UC patients treated with placebo, but not in those treated with cannabis, the levels of PEA, AEA, and AA decreased significantly. The percent reduction in bowel movements was negatively correlated with changes observed in the circulating AEA and OEA, whereas improvement in quality of life was positively correlated with the levels of 2-AG. In the biopsies from UC patients, FAAH levels increased over the study period. In Caco-2 cells, both cannabis extracts increased NAPE-PLD levels but reduced FAAH expression levels.Our study supports the notion that cannabis use affects eCB “tone” in UC patients and may have beneficial effects on disease symptoms in UC patients.
Persistent inflammation occurs in people with HIV (PWH) and has many downstream adverse effects including myocardial infarction, neurocognitive impai ... (Ver mais)
Persistent inflammation occurs in people with HIV (PWH) and has many downstream adverse effects including myocardial infarction, neurocognitive impairment and death. Because the proportion of people with HIV who use cannabis is high and cannabis may be anti-inflammatory, it is important to characterize the impact of cannabis use on inflammation specifically in PWH. We performed a selective, non-exhaustive review of the literature on the effects of cannabis on inflammation in PWH. Research in this area suggests that cannabinoids are anti-inflammatory in the setting of HIV. Anti-inflammatory actions are mediated in many cases through effects on the endocannabinoid system (ECS) in the gut, and through stabilization of gut–blood barrier integrity. Cannabidiol may be particularly important as an anti-inflammatory cannabinoid. Cannabis may provide a beneficial intervention to reduce morbidity related to inflammation in PWH.
As cannabis-derived products have become more available, veterinarians are seeing more cases of toxicosis. In addition, animal owners are having an i ... (Ver mais)
As cannabis-derived products have become more available, veterinarians are seeing more cases of toxicosis. In addition, animal owners are having an increasing interest in using these products for their pets. This review looks at the situation in Europe and North America, the different types of cannabis and cannabis-derived products with historical examples of use in animals, and the cannabis industry. The existing regulatory framework for use in humans and animals as medicines and/or supplements was examined. Finally, a review of the clinical indications for which medicinal cannabis is authorised, a discussion of toxicosis, and recommendations and warnings around medical cannabis use are presented.
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International Journal of Environmental Research and Public Health -
Revisão -
2020
There is evidence that sex- and gender-related factors are involved in cannabis patterns of use, health effects and biological mechanisms. Women and ... (Ver mais)
There is evidence that sex- and gender-related factors are involved in cannabis patterns of use, health effects and biological mechanisms. Women and men report different cannabis use disorder (CUD) symptoms, with women reporting worse withdrawal symptoms than men. The objective of this systematic review was to examine the effectiveness of cannabis pharmacological interventions for women and men and the uptake of sex- and gender-based analysis in the included studies. Two reviewers performed the full-paper screening, and data was extracted by one researcher. The search yielded 6098 unique records—of which, 68 were full-paper screened. Four articles met the eligibility criteria for inclusion. From the randomized clinical studies of pharmacological interventions, few studies report sex-disaggregated outcomes for women and men. Despite emergent evidence showing the influence of sex and gender factors in cannabis research, sex-disaggregated outcomes in pharmacological interventions is lacking. Sex- and gender-based analysis is incipient in the included articles. Future research should explore more comprehensive inclusion of sex- and gender-related aspects in pharmacological treatments for CUD
To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain. Opioid dose reduction, pai ... (Ver mais)
To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain. Opioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events. We included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome. enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) −3.4 milligram morphine equivalent (MME); 95% CI (CI) −12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD −0.18 cm; 95% CI −0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD −0.22 cm; 95% CI −0.4 to −0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD −1%; 95% CI −4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD −22.5 MME; 95% CI −43.06 to −1.97). Opioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.
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Clinical pharmacology and therapeutics -
Revisão -
2022
There has been growing interest in developing therapeutic agents and other consumer products derived from cannabis and its components. To date, the U ... (Ver mais)
There has been growing interest in developing therapeutic agents and other consumer products derived from cannabis and its components. To date, the US Food and Drug Administration (FDA) has not approved cannabis as a safe and effective drug for any indication. With the progressive state legalization of cannabis for medical use, healthcare providers and consumers must understand what is known about the safety and efficacy linked to cannabis. Cannabis (Cannabis sativa) contains more than 500 chemicals, including more than 100 cannabinoids. The most well-known cannabinoids are nonpsychoactive cannabidiol (CBD) and psychoactive Δ-9-tetrahydrocannabinol (THC) (The terms “cannabis” and “marijuana” are often used interchangeably, but they are not the same. “Cannabis” refers to all products derived from the plant Cannabis sativa, whereas “marijuana” refers to parts of or products from the plant Cannabis sativa that contain > 0.3% THC (from https://www.nccih.nih.gov/health/cannabis-marijuana-and-cannabinoids-what-you-need-to-know).). As cannabis remains federally illegal in the United States and elsewhere, a comprehensive understanding of the safety and efficacy of cannabis remains lacking due largely to the many legal and regulatory approvals needed to conduct research studies with cannabis (Figure 1). This perspective provides an overview and update on both scientific and regulatory approaches and challenges to study pharmacokinetic (PK) cannabis-drug interactions and the pharmacodynamics (PDs) of cannabis, with the goal of fostering research in the community to develop appropriate cannabis and cannabis-derived products that are safe and effective to meet unmet medical needs.
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Neuropsychopharmacology -
Revisão -
2018
There have been extensive policy shifts in the legality of recreational and therapeutic use of cannabis in the United States, as well as a steady inc ... (Ver mais)
There have been extensive policy shifts in the legality of recreational and therapeutic use of cannabis in the United States, as well as a steady increase in the number of people using the drug on a regular basis. Given these rapid societal changes, defining what is known scientifically about the consequences of cannabis use on mental health takes on added public health significance. The purpose of this circumspectives piece is to discuss evidence of cannabis effects on two psychiatric conditions: post-traumatic stress disorder and psychotic disorders. Dr Haney and Dr Evins will discuss two viewpoints regarding the benefit and harm of cannabis use for these conditions, while outlining what remains unproven and requires further testing to move the field forward. Attitudes toward cannabis in the United States have undergone a substantive shift, with, for the first time in history, a majority of Americans favoring cannabis legalization. Nationwide, marked public opinion and policy changes are occurring in what is largely a scientific vacuum, with well-controlled, scientific evidence contributing little to the debate on legalization of cannabis for medical or recreational use. Even among scientists, debates on cannabis can be polarized and high in emotional content, making it difficult to distinguish evidence from hyperbole. In adolescents, increased social acceptance and decreases in the perception of cannabis risks are associated with increased use (Hall and Weier, 2015; Scheurmeyer et al, 2014). Already 2.6 million more people in the United States report near-daily cannabis use in 2013 compared with 2008 (Substance Abuse and Mental Health Services Administration (SAMHSA), 2014). And cannabis legalization creates a powerful profit motive to create and maintain cannabis users, with the burgeoning marijuana industry following a similar business strategy as the tobacco industry (Richter and Levy, 2014), which will likely further increase cannabis use. In light of these major policy changes, defining what is known about the potential consequences of cannabis use has considerable public health significance and is the purpose of this circumspectives piece. We will discuss the influence of cannabis use on post-traumatic stress disorder (PTSD) and psychotic disorders. Each author will present data supporting one perspective regarding the link between cannabis use and the course of these disorders, and they will then present their shared perspectives on critical studies needed to move the field forward. An important caveat: clearly, cannabis is a pharmacologically complex plant with constituents that have the potential for producing both positive and negative effects. We will take opposing positions to accommodate the circumspectives framework, but emphasize that there is considerable overlap and nuance in our viewpoints.
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Pain Medicine: The Official Journal of the American Academy of Pain Medicine -
Artigo Original -
2020
To determine the benefit of a tetrahydrocannabinol (THC)-rich cannabis oil on symptoms and quality of life of fibromyalgia patients. A double-blind, ... (Ver mais)
To determine the benefit of a tetrahydrocannabinol (THC)-rich cannabis oil on symptoms and quality of life of fibromyalgia patients. A double-blind, randomized, placebo-controlled clinical trial was conducted for eight weeks to determine the benefit of a THC-rich cannabis oil (24.44 mg/mL of THC and 0.51 mg/mL of cannabidiol [CBD]) on symptoms and quality of life of 17 women with fibromyalgia, residents of a neighborhood with a low socioeconomic profile and a high incidence of violence in the city of Florianopolis, Brazil. The initial dose was one drop (∼1.22 mg of THC and 0.02 mg of CBD) a day with subsequent increases according to symptoms. The Fibromyalgia Impact Questionnaire (FIQ) was applied at pre- and postintervention moments and in five visits over eight weeks.
There were no significant differences on baseline FIQ score between groups. However, after the intervention, the cannabis group presented a significant decrease in FIQ score in comparison with the placebo group (P = 0.005) and in comparison with cannabis group baseline score. (P < 0.001). Analyzing isolated items on the FIQ, the cannabis group presented significant improvement on the “feel good,” “pain,” “do work,” and “fatigue” scores. The placebo group presented significant improvement on the “depression” score after intervention. There were no intolerable adverse effects. Phytocannabinoids can be a low-cost and well-tolerated therapy to reduce symptoms and increase the quality of life of patients with fibromyalgia. Future studies are still needed to assess long-term benefits, and studies with different varieties of cannabinoids associated with a washout period must be done to enhance our knowledge of cannabis action in this health condition.
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Psychopharmacology -
Artigo Original -
2016
Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empiri ... (Ver mais)
Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007).Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.
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IBRO Neuroscience Reports -
Revisão -
2021
Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a ... (Ver mais)
Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or therapeutic modalities that can alleviate HIV-NP. Smoked cannabis has been reported to improve pain measures in patients with neuropathic pain. Cannabis, phytocannabinoids, and the endocannabinoids such N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), produce some of their effects via cannabinoid receptors (CBRs). Endocannabinoids are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase. We searched PubMed, Google Scholar, clinicaltrials.gov and clinicaltrialsregister.eu using various key words and their combinations for published papers that studied HIV-NP and cannabis, cannabinoids, or endocannabinoids up to 27th December 2020. All original research articles that evaluated the efficacy of molecules that modulate the endocannabinoid system (ECS) for the prevention and/or treatment of pain in HIV-NP animal models and patients with HIV-NP were included. The PubMed search produced a total of 117 articles, whereas the Google Scholar search produced a total of 9467 articles. Amongst the 13 articles that fulfilled the inclusion criteria 11 articles were found in both searches whereas 2 articles were found in Google Scholar only. The clinicaltrials.gov and clinicaltrialsregister.eu searches produced five registered trials of which three were completed and with results. Ten preclinical studies found that the endocannabinoids (2-AG and AEA), synthetic mixed CB1R/CB2R agonist WIN 55,212-2, a CB2R-selective phytocannabinoid β-caryophyllene, synthetic CB2R-selective agonists (AM1710, JWH015, JWH133 and Gp1a, but not HU308); FAAH inhibitors (palmitoylallylamide, URB597 and PF-3845) and a drug combination of indomethacin plus minocycline, which produces its effects in a CBR-dependent manner, either prevented the development of and/or attenuated established HIV-NP. Two clinical trials demonstrated greater efficacy of smoked cannabis over placebo in alleviating HIV-NP, whereas another clinical trial demonstrated that cannabidivarin, a cannabinoid that does not activate CBRs, did not reduce HIV-NP. The available preclinical results suggest that targeting the ECS for prevention and treatment of HIV-NP is a plausible therapeutic option. Clinical evidence shows that smoked cannabis alleviates HIV-NP. Further research is needed to find out if non-psychoactive drugs that target the ECS and are delivered by other routes than smoking could be useful as treatment options for HIV-NP.
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Biological psychiatry. Cognitive neuroscience and neuroimaging -
Artigo Original -
2021
Efficacy of inhaled cannabis for treating pain is controversial. Effective treatment for chemotherapy-induced neuropathy represents an unmet medical ... (Ver mais)
Efficacy of inhaled cannabis for treating pain is controversial. Effective treatment for chemotherapy-induced neuropathy represents an unmet medical need. We hypothesized that cannabis reduces neuropathic pain by reducing functional coupling in the raphe nuclei. We assessed the impact of inhalation of vaporized cannabis plant (containing 10.3% Δ9-tetrahydrocannabinol/0.05% cannabidiol) or placebo cannabis on brain resting-state blood oxygen level–dependent functional connectivity and pain behavior induced by paclitaxel in rats. Rats received paclitaxel to produce chemotherapy-induced peripheral neuropathy or its vehicle. Behavioral and imaging experiments were performed after neuropathy was established and stable. Images were registered to, and analyzed using, a 3D magnetic resonance imaging rat atlas providing site-specific data on more than 168 different brain areas. Prior to vaporization, paclitaxel produced cold allodynia. Inhaled vaporized cannabis increased cold withdrawal latencies relative to prevaporization or placebo cannabis, consistent with Δ9-tetrahydrocannabinol-induced antinociception. In paclitaxel-treated rats, the midbrain serotonergic system, comprising the dorsal and median raphe, showed hyperconnectivity to cortical, brainstem, and hippocampal areas, consistent with nociceptive processing. Inhalation of vaporized cannabis uncoupled paclitaxel-induced hyperconnectivity patterns. No such changes in connectivity or cold responsiveness were observed following placebo cannabis vaporization. Inhaled vaporized cannabis plant uncoupled brain resting-state connectivity in the raphe nuclei, normalizing paclitaxel-induced hyperconnectivity to levels observed in vehicle-treated rats. Inhaled vaporized cannabis produced antinociception in both paclitaxel- and vehicle-treated rats. Our study elucidates neural circuitry implicated in the therapeutic effects of Δ9-tetrahydrocannabinol and supports a role for functional imaging studies in animals in guiding indications for future clinical trials.
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The Journal of Headache and Pain -
Artigo Original -
2018
Medicinal cannabis registries typically report pain as the most common reason for use. It would be clinically useful to identify patterns of cannabis ... (Ver mais)
Medicinal cannabis registries typically report pain as the most common reason for use. It would be clinically useful to identify patterns of cannabis treatment in migraine and headache, as compared to arthritis and chronic pain, and to analyze preferred cannabis strains, biochemical profiles, and prescription medication substitutions with cannabis. Via electronic survey in medicinal cannabis patients with headache, arthritis, and chronic pain, demographics and patterns of cannabis use including methods, frequency, quantity, preferred strains, cannabinoid and terpene profiles, and prescription substitutions were recorded. Cannabis use for migraine among headache patients was assessed via the ID Migraine™ questionnaire, a validated screen used to predict the probability of migraine.n = 861) overall; chronic pain 29.4% (n = 598;), arthritis 9.3% (n = 188), and headache 3.7% (n = 75;). Across all 21 illnesses, headache was a symptom treated with cannabis in 24.9% (n = 505). These patients were given the ID Migraine™ questionnaire, with 68% (n = 343) giving 3 “Yes” responses, 20% (n = 102) giving 2 “Yes” responses (97% and 93% probability of migraine, respectively). Therefore, 88% (n = 445) of headache patients were treating probable migraine with cannabis. Hybrid strains were most preferred across all pain subtypes, with “OG Shark” the most preferred strain in the ID Migraine™ and headache groups. Many pain patients substituted prescription medications with cannabis (41.2–59.5%), most commonly opiates/opioids (40.5–72.8%). Prescription substitution in headache patients included opiates/opioids (43.4%), anti-depressant/anti-anxiety (39%), NSAIDs (21%), triptans (8.1%), anti-convulsants (7.7%), muscle relaxers (7%), ergots (0.4%).Chronic pain was the most common reason for cannabis use, consistent with most registries. The majority of headache patients treating with cannabis were positive for migraine. Hybrid strains were preferred in ID Migraine™, headache, and most pain groups, with “OG Shark”, a high THC (Δ9-tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes β-caryophyllene and β-myrcene, most preferred in the headache and ID Migraine™ groups. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of β-caryophyllene and β-myrcene. Opiates/opioids were most commonly substituted with cannabis. Prospective studies are needed, but results may provide early insight into optimizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and patterns of use in the treatment of headache, migraine, and chronic pain syndromes.
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Journal of Cannabis Research -
Artigo Original -
2020
Social media and academic literature suggest that more people are using cannabis to treat their own or their dog’s chronic pain. This study identifie ... (Ver mais)
Social media and academic literature suggest that more people are using cannabis to treat their own or their dog’s chronic pain. This study identifies the reasons people use cannabis products to treat their own pain or their dog’s pain and explores whether these products have fulfilled their expectations. An anonymous, online survey was used to collect quantitative and qualitative self-report data on respondents’ perceptions, motivations and expectations about their or their dog’s chronic pain and cannabis use. The analyses are based on U.S. adults who reported using cannabis products to treat their own (N = 313) or their dog’s (N = 204) chronic pain. Quantitative responses from the two groups were compared using Chi-Square tests and qualitative data were analyzed using a thematic analysis.Human patients and dog owners reported similar motivations for using cannabis products to treat chronic pain, with the more popular reasons being that cannabis products are natural, are preferred over conventional medication, are believed to be the best treatment or good treatment option for pain. Similar proportions of human patients and dog owners reported that the use of cannabis products fulfilled their expectations (86% vs. 82% respectively, χ2 (1, 200) = .59, p = .32). The qualitative data revealed that their expectations were met by reducing pain, increasing relaxation, and improving sleep, coping, functionality and overall well being. Additionally, the qualitative data suggests that cannabis products offer a return to normalcy and a restored sense of self to human and dog patients.The results suggest that people choose cannabis products because they are natural and a possible solution to managing chronic pain when conventional medicines have not been effective. Most people report that their expectations regarding pain management are fulfilled by these products. More accurate assessments are vital, however, for understanding both the objective biomedical and subjective socioemotional benefits of cannabis products for effective pain management for human and dog patients. In addition, objective factual information regarding cannabis products for effective pain management in humans and dogs is needed. It is recommended that both physicians and veterinarians work towards feeling more comfortable proactively broaching the subject of cannabis use with additional training and education.
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Journal of Analytical Toxicology -
Artigo Original -
2022
The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the ... (Ver mais)
The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g., 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n = 18). A subset of participants (n = 6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50 and 100 ng/mL) for Δ9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC–MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Δ8- or Δ9-THC in any route or formulation in which pure CBD was administered. Following acute administration of vaporized CBD-dominant cannabis, 3 of 18 participants provided a total of six urine samples in which Δ9-THCCOOH concentrations ≥15 ng/mL. All six specimens screened positive at a 20 ng/mL IA cutoff, and two of six screened positive at a 50 ng/mL cutoff. These data show that absorption/elimination of CBD is impacted by drug formulation, route of administration and gastric contents. Although pure CBD is unlikely to impact drug testing, it is possible that hemp products containing low amounts of Δ9-THC may produce a cannabis-positive urine drug test.
We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and ... (Ver mais)
We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.
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Journal of Clinical Sleep Medicine -
Artigo Original -
2015
Sleep disturbance is a hallmark feature of cannabis withdrawal. In this study we explored the effects of lithium treatment supplemented with nitrazep ... (Ver mais)
Sleep disturbance is a hallmark feature of cannabis withdrawal. In this study we explored the effects of lithium treatment supplemented with nitrazepam on objective and subjective measures of sleep quality during inpatient cannabis withdrawal. Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo, twice daily in a double-blind RCT. Restricted nitrazepam (10 mg) was available on demand (in response to poor sleep) on any 3 of the 7 nights. Dependent outcome measures for analysis included repeated daily objective actigraphy and subjective sleep measures throughout the 8 day detox, subjective cannabis withdrawal ratings, and detoxification completion rates. Based on actigraphy, lithium resulted in less fragmented sleep compared to placebo (p = 0.04), but no other objective measures were improved by lithium. Of the subjective measures, only nightmares were suppressed by lithium (p = 0.04). Lithium did not have a significant impact on the use of nitrazepam. Sleep bout length (p < 0.0001), sleep efficiency (p < 0.0001), and sleep fragmentation (p = 0.05) were improved on nights in which nitrazepam was used. In contrast, only night sweats improved with nitrazepam from the subjective measures (p = 0.04). A Cox regression with daily repeated measures of sleep efficiency averaged across all people in the study a predictor suggests that a one-unit increase in sleep efficiency (the ratio of total sleep time to the total time in bed expressed as a percentage) resulted in a 14.6% increase in retention in treatment (p = 0.008, Exp(B) = 0.854, 95% CI = 0.759–0.960). None of the other sleep measures, nor use of lithium or nitrazepam were significantly associated with retention in treatment. Lithium seems to have only limited efficacy on sleep disturbance in cannabis withdrawal. However the nitrazepam improved several actigraphy measures of sleep disturbance, warranting further investigation. Discord between objective and subjective sleep indices suggest caution in evaluating treatment interventions with self-report sleep data only.
With the legalization of cannabis in Canada, there is an increase trend in use. Cannabis has been known to have several health implications, one of w ... (Ver mais)
With the legalization of cannabis in Canada, there is an increase trend in use. Cannabis has been known to have several health implications, one of which is the development of cannabis use disorder (CUD). CUD is more common in males than females, as well as in certain ethnic groups such as Native Americans. Additionally, both environmental and genetic risk factors have been found for cannabis use. The objective of this systematic review will be to summarize the genetic variants associated with cannabis use which have reached borderline genome-wide significance. This systematic review will incorporate articles that have performed a genome-wide association study (GWAS) investigating cannabis use. MEDLINE, Web of Science, EMBASE, GWAS Catalog, GWAS Central, and NIH Database of Genotype and Phenotype will be searched using a comprehensive search strategy. The quality of genetic association studies (Q-Genie) tool will be utilized to assess the quality of the included studies. All screening and data extraction will occur independently by two authors. If feasible, a random-effects meta-analysis will be conducted on pooled odds ratios of single nucleotide polymorphisms reaching borderline genome-wide significance. This systematic review will synthesize available GWAS on cannabis use. Results from this review will inform and direct further investigation of genetic variants associated with cannabis use.
Cannabis, as a natural medicinal remedy, has long been used for palliative treatment to alleviate the side effects caused by diseases. Cannabis-based ... (Ver mais)
Cannabis, as a natural medicinal remedy, has long been used for palliative treatment to alleviate the side effects caused by diseases. Cannabis-based products isolated from plant extracts exhibit potent immunoregulatory properties, reducing chronic inflammatory processes and providing much needed pain relief. They are a proven effective solution for treatment-based side effects, easing the resulting symptoms of the disease. However, we discuss the fact that cannabis use may promote the progression of a range of malignancies, interfere with anti-cancer immunotherapy, or increase susceptibility to viral infections and transmission. Most cannabis preparations or isolated active components cause an overall potent immunosuppressive impact among users, posing a considerable hazard to patients with suppressed or compromised immune systems. In this review, current knowledge and perceptions of cannabis or cannabinoids and their impact on various immune-system components will be discussed as the “two sides of the same coin” or “double-edged sword”, referring to something that can have both favorable and unfavorable consequences. We propose that much is still unknown about adverse reactions to its use, and its integration with medical treatment should be conducted cautiously with consideration of the individual patient, effector cells, microenvironment, and the immune system.
OPEN ACCESS -
The Cochrane Database of Systematic Reviews -
Revisão -
2019
To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing ... (Ver mais)
To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use. We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science.Randomised controlled trials (RCTs) and quasi‐RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent. There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N‐acetylcysteine is weak, but these medications are also worth further investigation.
OPEN ACCESS -
The Permanente Journal -
Revisão -
2021
Amidst a rapidly changing legal landscape, cannabis use in the United States has become increasingly common in the past several years. There is stron ... (Ver mais)
Amidst a rapidly changing legal landscape, cannabis use in the United States has become increasingly common in the past several years. There is strong evidence to suggest that chronic and early cannabis use increases the risk of developing a psychotic disorder, and there is at least moderate evidence that suggests ongoing cannabis use among individuals with a psychotic disorder worsens clinical outcomes (eg, decreased psychiatric medication adherence, more frequent psychiatric hospitalizations). In this Review Article, we provide a focused, clinically oriented overview of the epidemiology and characteristics of cannabis use among individuals with first-episode psychosis; evaluation of cannabis use; and treatment modalities, focusing on behavioral interventions suitable for outpatient primary care settings. We discuss the limited data supporting pharmacologic interventions for cannabis use disorder, specifically among individuals with first-episode psychosis, and the unique potential of cannabidiol to serve as a harm-reduction strategy for individuals who are not able or willing to achieve abstinence for cannabis.
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Internet Interventions -
Artigo Original -
2021
Given the widespread use of cannabis, and the concomitant risks associated with the drug, there is a need to increase the availability of interventio ... (Ver mais)
Given the widespread use of cannabis, and the concomitant risks associated with the drug, there is a need to increase the availability of interventions designed to reduce risky cannabis use. One promising intervention in the addictions employs personalized normative feedback to motivate change. A two-arm randomized controlled trial (RCT) was conducted in which participants who used cannabis in a risky fashion were randomly assigned to one of two groups – those who received an online personalized feedback report in addition to educational materials about risky cannabis use and those who just received the online educational materials. Follow-up assessment occurred at three- and six-months post-randomization. Outcome variables included: number of days cannabis was used in the past 30, risky cannabis use (ASSIST score of four or more), and participant estimates of the proportion of cannabis users among those of the same age and gender. A total of 744 participants with risky cannabis use were recruited for the trial using online advertisements. There were no significant differences between intervention and educational materials only groups at three- and six-month follow-ups for the outcome variables, number of days used cannabis in the last 30 (p = 0.927) and proportion of participants engaging in risky cannabis use (p = 0.557). At three and six month follow-ups, participants who received the feedback intervention were more likely than those in the educational materials group to estimate that a larger proportion of people their age and gender did not use cannabis in the last year (p = 0.028).While there was some evidence that the personalized feedback intervention modified normative perceptions about cannabis use, there did not appear to be support for the prediction that the intervention reduced cannabis consumption.
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Movement Disorders Clinical Practice -
Artigo Original -
2022
Despite limited evidence,
people with Parkinsons disease (PD) use cannabis for therapeutic purposes.Given barriers to performing randomized ... (Ver mais)
Despite limited evidence,
people with Parkinsons disease (PD) use cannabis for therapeutic purposes.Given barriers to performing randomized trials,
exploring real ‐ world experiences with cannabis in PD is valuable.Investigate the frequency
and magnitude of symptomatic effects reported with cannabis use in PD.An anonymous,
15 ‐ question,
web ‐ based survey was deployed on Fox Insight.Cannabis product types were defined (
by relative tetrahydrocannabinol [THC]
and cannabidiol [CBD] content
)
and respondents were asked to reference product labels.Questions focused on use patterns
and subjective effects on 36 predefined symptoms (
rated − 2 ‐ markedly worse to + 2 ‐ markedly better
).1,
881 people with PD responded (
58.5 % men;
mean age 66.5;
50.5 % < 3 years of PD
).73.0 % of respondents reported medicinal use,
though 30.8 % did not inform their doctor.86.7 % knew their type of cannabis product: 54.6 % took higher CBD,
30.2 % higher THC,
and 15.2 % took similar amounts of THC
and CBD products.Most common use was oral administration,
once daily,
for less than six months.Frequent improvements were reported for pain,
anxiety,
agitation,
and sleep (
> 50 % of respondents,
mean magnitude 1.28 – 1.51
).Dry mouth,
dizziness,
and cognitive changes were common adverse effects (20.9 % – 30.8 %, mean − 1.13 to − 1.21).Higher THC users reported more frequent improvements in depression,
anxiety,
and tremor,
and more frequent worsening in dry mouth
and bradykinesia than other product types.Respondents with PD reported using more CBD products,
via oral administration,
with mild subjective benefits primarily for sleep,
pain,
and mood.Higher THC products may be higher risk / higher reward for PD ‐ related symptoms.
OPEN ACCESS -
Cannabis
and Cannabinoid Research -
Revisão -
2018
The opioid epidemic has become an immense problem in North America,
and despite decades of research on the most effective means to treat op ... (Ver mais)
The opioid epidemic has become an immense problem in North America,
and despite decades of research on the most effective means to treat opioid use disorder (OUD),
overdose deaths are at an all - time high,
and relapse remains pervasive.Although there are a number of FDA - approved opioid replacement therapies
and maintenance medications to help ease the severity of opioid withdrawal symptoms
and aid in relapse prevention,
these medications are not risk free nor are they successful for all patients.Furthermore,
there are legal
and logistical bottlenecks to obtaining traditional opioid replacement therapies such as methadone
or buprenorphine,
and the demand for these services far outweighs the supply
and access.To fill the gap between efficacious OUD treatments
and the widespread prevalence of misuse,
relapse,
and overdose,
the development of novel,
alternative,
or adjunct OUD treatment therapies is highly warranted.In this article,
we review emerging evidence that suggests that cannabis may play a role in ameliorating the impact of OUD.Herein,
we highlight knowledge gaps
and discuss cannabis potential to prevent opioid misuse (as an analgesic alternative),
alleviate opioid withdrawal symptoms,
and decrease the likelihood of relapse.The compelling nature of these data
and the relative safety profile of cannabis warrant further exploration of cannabis as an adjunct
or alternative treatment for OUD.
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Journal of the National Cancer Institute -
Revisão -
2021
The use of cannabis is not unfamiliar to many cancer patients,
as there is a long history of its use for cancer pain
and /
or pain,
nausea,
and ... (Ver mais)
The use of cannabis is not unfamiliar to many cancer patients,
as there is a long history of its use for cancer pain
and /
or pain,
nausea,
and cachexia induced by cancer treatment.To date,
the US Food
and Drug Administration has approved 2 cannabis - based pharmacotherapies for the treatment of cancer chemotherapy - associated adverse effects: dronabinol
and nabilone.Over the proceeding decades,
both research investigating
and societal attitudes toward the potential utility of cannabinoids for a range of indications have progressed dramatically.The following monograph highlights recent preclinical research focusing on promising cannabinoid - based approaches for the treatment of the 2 most common adverse effects of cancer chemotherapy: chemotherapy - induced peripheral neuropathy
and chemotherapy - induced nausea
and vomiting.Both plant - derived
and synthetic approaches are discussed,
as is the potential relative safety
and effectiveness of these approaches in relation to current treatment options,
including opioid analgesics.
OPEN ACCESS -
Clinical Journal of Sport Medicine -
Revisão -
2018
Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical
and nonmedical access.Cannabis has potentia ... (Ver mais)
Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical
and nonmedical access.Cannabis has potential impact on the health of athletes as well as on performance in both training
and in competition.The aim of this general review is to identify
and highlight the challenges in interpreting information with respect to elite athletic performance,
and to point to important research areas that need to be addressed.A nonsystematic literature review was conducted using Medline
and PubMed for articles related to cannabis / marijuana use
and sports / athletic performance;
abstracts were reviewed by lead author
and key themes identified
and explored.Cannabis may be primarily inhaled
or ingested orally for a range of medical
and nonmedical reasons;
evidence for efficacy is limited but promising for chronic pain management.Although evidence for serious harms
from
cannabis use on health of athletes is limited,
one should be cognizant of the potential for abuse
and mental health issues.Although the prevalence of cannabis use among elite athletes is not well - known,
use is associated with certain high - risk sports.There is no evidence for cannabis use as a performance - enhancing drug.Medical
and nonmedical cannabis use among athletes reflects changing societal
and cultural norms
and experiences.Although cannabis use is more prevalent in some athletes engaged in high - risk sports,
there is no direct evidence of performance - enhancing effects in athletes.The potential beneficial effects of cannabis as part of a pain management protocol,
including reducing concussion - related symptoms,
deserve further attention.
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British Journal of Clinical Pharmacology -
Revisão -
2018
During the past decade we have been witnessing a rise in medical cannabis use,
yet the evidence for the safety
and efficacy of the various cannabi ... (Ver mais)
During the past decade we have been witnessing a rise in medical cannabis use,
yet the evidence for the safety
and efficacy of the various cannabinoid compounds is scarce.The State of Israel has always been at the forefront of clinical
and translational research in support of Evidence Based Medicine.With respect to cannabis Israel has created a medical
and regulatory environment that enables clinical studies with cannabis which may lead to improved Evidence Based use of these compounds.This opinion paper discusses selected studies into the safety
and effects of cannabis derived products.
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Journal of Primary Care & Community Health -
Revisão -
2019
Medical cannabis use is common in the United States
and increasingly more socially acceptable.As more patients seek out
and acquire medical cannab ... (Ver mais)
Medical cannabis use is common in the United States
and increasingly more socially acceptable.As more patients seek out
and acquire medical cannabis,
primary care physicians will be faced with a growing number of patients seeking information on the indications,
efficacy,
and safety of medical cannabis.We present a case
of a patient with several chronic health conditions who asks her primary care provider whether she should try medical cannabis.We provide a review of the pharmacology of medical cannabis,
the state of evidence regarding the efficacy of medical cannabis,
variations in the types of medical cannabis,
and safety monitoring considerations for the primary care physician.
OPEN ACCESS -
EBioMedicine -
Artigo Original -
2021
Little is known about chronic cannabis smoking - associated oral microbiome
and its effects on central nervous system (CNS) functions.In the curren ... (Ver mais)
Little is known about chronic cannabis smoking - associated oral microbiome
and its effects on central nervous system (CNS) functions.In the current study,
we have analyzed the saliva microbiome in individuals who chronically smoked cannabis with cannabis use disorder (n = 16)
and in non - smoking controls (n = 27).The saliva microbiome was analyzed using microbial 16S rRNA sequencing.To investigate the function of cannabis use - associated oral microbiome,
mice were orally inoculated with live Actinomyces meyeri,
Actinomyces odontolyticus,
or Neisseria elongata twice per week for six months,
which mimicked human conditions.We found that cannabis smoking in humans was associated with oral microbial dysbiosis.The most increased oral bacteria were Streptococcus
and Actinomyces genus
and the most decreased bacteria were Neisseria genus in chronic cannabis smokers compared to those in non - smokers.Among the distinct species bacteria in cannabis smokers,
the enrichment of Actinomyces meyeri was inversely associated with the age of first cannabis smoking.Strikingly,
oral exposure of Actinomyces meyeri,
an oral pathobiont,
but not the other two control bacteria,
decreased global activity,
increased macrophage infiltration,
and increased β - amyloid 42 protein production in the mouse brains.This is the first study to reveal that long - term oral cannabis exposure is associated oral enrichment of Actinomyces meyeri
and its contributions to CNS abnormalities.
Cancer patients have been at the forefront of policy discussions leading to legalization of medical Cannabis (marijuana). Unfortunately, Cannabis use ... (Ver mais)
Cancer patients have been at the forefront of policy discussions leading to legalization of medical Cannabis (marijuana). Unfortunately, Cannabis use among those with cancer is poorly understood. A diverse group of patients seeking certification for medical Cannabis in the state of Michigan were surveyed at the time of their presentation to medical dispensaries. The survey assessed demographics, employment/disability, pain, physical functioning, mental health, mode of Cannabis use, and frequency/amount of Cannabis use. Chi-square and t-tests were performed to compare those who did and did not endorse cancer diagnosis. Analysis of data from 1485 adults pursuing medical Cannabis certification, including 72 (4.8%) reporting a cancer diagnosis, indicated that those with cancer were older [mean age 53.4 years (SD = 10.5) vs. 44.7 years (SD = 13.0); p<0.001] than those without cancer. They also differed regarding employment status (p<0.001; working: 20.8% vs. 46.2%; disabled: 44.4% vs. 26.5% for those with vs. those without cancer, respectively). Those with cancer used less Cannabis (p = 0.033 for quantity used) and used Cannabis less often (p = 0.032 for frequency of use); they less frequently endorsed smoking Cannabis (80% vs 91%; p = 0.015). There was a non-significant trend to increased edible use in those with cancer (57% vs. 44%; p = 0.052). Patients with cancer who are seeking medical Cannabis are different from those seeking medical Cannabis without cancer, and they report using Cannabis differently. Further research to characterize the patterns and consequences of Cannabis use in cancer patients is needed.
OPEN ACCESS -
The Lancet. Public health -
Revisão -
2018
There has been growing interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain (CNCP). Cannabis and cannabinoids have attra ... (Ver mais)
There has been growing interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain (CNCP). Cannabis and cannabinoids have attracted attention because of their greater safety compared with opioids, and the possibility that their use can reduce opioid dose requirements via an opioid-sparing effect. Both factors have been proposed to contribute to fewer opioid-related deaths. We used The Pain and Opioids IN Treatment (POINT) study, a national cohort of 1,514 people living with CNCP prescribed opioids, to examine relationships between cannabis use, opioid use and pain outcomes over four years. Cannabis use was common, and by four-year follow-up, 24.3% had used cannabis for pain. Interest in using cannabis for pain doubled from 33% (baseline) to 60% (four years). We found that patients who had used cannabis had greater pain severity and interference, lower pain self-efficacy, and greater GAD severity than patients who had not used cannabis. We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. CNCP prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. Those who used cannabis had greater pain and lower self-efficacy in managing pain and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect.
his manuscript illustrates the findings from individual interviews conducted with Canadian cancer survivors to explore their reasons to use cannabis ... (Ver mais)
his manuscript illustrates the findings from individual interviews conducted with Canadian cancer survivors to explore their reasons to use cannabis as a complementary therapy to manage their cancer symptoms. In Canada, we have a unique opportunity to study the impact of country‐wide recreational legalization of access to non‐medical cannabis on cancer survivors’ attitudes toward use of those substances. We used the theory of planned behaviour as the decision‐making model to understand intention and behaviour of cancer survivors regarding cannabis. The findings from our work will better inform healthcare providers how to support their patients regarding cannabis medication and to promote person‐centred and informed decision‐making.
OPEN ACCESS -
International Journal of Environmental Research and Public Health -
Revisão -
2022
The rising popularity of medical marijuana and its potential therapeutic uses has resulted in passionate discussions that have mainly focused on its ... (Ver mais)
The rising popularity of medical marijuana and its potential therapeutic uses has resulted in passionate discussions that have mainly focused on its possible benefits and applications. Although the concept itself seems promising, the multitude of presented information has noticeable ramifications—terminological chaos being one. This work aimed to synthesize and critically analyze scientific evidence on the therapeutic uses of cannabinoids in the field of psychiatry. Emphasis was placed on the anxiolytic effects of cannabis constituents and their effects on post-traumatic stress disorder, anxiety disorders, schizophrenia spectrum, and other psychotic disorders. The review was carried out from an addictological perspective. A database search of interchangeably combined keywords resulted in the identification of subject-related records. The data were then analyzed in terms of relevance, contents, methodologies, and cited papers. The results were clear in supporting one common conclusion: while most findings provide support for beneficial applications of medical marijuana in psychiatry, no certain conclusions can be drawn until larger-scaled, more methodologically rigorous, and (preferably) controlled randomized trials verify these discoveries.
OPEN ACCESS -
Frontiers in Psychyatry -
Artigo Original -
2021
Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with ... (Ver mais)
Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young adults who use these cannabis products. Preliminary research suggests that it is possible to induce dopamine homeostasis, that is, restore dopamine function with dopamine upregulation with the proposed compound and normalize behavior in chronic cannabis users with cannabis-induced hypodopaminergic anhedonia (depression) and cognitive decline. This psychological, neurobiological, anatomical, genetic, and epigenetic research also could provide evidence to use for the development of an appropriate policy regarding the decriminalization of cannabis for recreational use.
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Journal of Pharmacopuncture -
Revisão -
2020
Cannabis is a historical plant which has been used as a medicine in East Asia. These days, there are active debates about using cannabis in clinical ... (Ver mais)
Cannabis is a historical plant which has been used as a medicine in East Asia. These days, there are active debates about using cannabis in clinical field. Collecting and comparing cannabis research articles which had been published in the Opening of Japan to spot the interactions between the traditional medicine of Japan, Rangaku which was established in Edo Period and the European medicine which is transferred after Perry Expedition is academically meaningful. This study searched publications, which were listed on Open-Access databases by Dec. 11th, 2019. We collected research articles which had been published from January 3rd, 1867 to July 30th, 1912 also known as Meiji era and uploaded on Open-Access databases. Our searching databases were J-stage, CiNii (Scholarly and Academic Information Navigator), Tokyo Metropolitan Library, The National Diet Library, IRDB (Institutional Repositories DataBase) and KAKEN (Grant-in-Aid for Scientific Research Database). Searching keywords were cannabis, hemp and all their Japanese synonyms and available combinations. We selected final 15 studies which met every selection criteria in the 346,393 collected studies. Cannabis was prescribed in Meiji era of Japan to alleviate pain and cure the digestive, respiratory, urinary, and nervous system diseases such as indigestion, asthma, tuberculosis, gonorrhea and its complications, insomnia, and nervous prostration. Cannabis was medically used in Meiji era of Japan and the reporting and sharing of its clinical effect was published on the medical journals like present days. There were already Cannabis regulations in that era, but its medicinal use was more liberated than nowadays. It may be a chance to reconsider the current legal system, which strictly controls the use of Cannabis.
OPEN ACCESS -
Frontiers in Psychology -
Revisão -
2020
Research evidence suggests a dose–response relationship for the association between cannabis use and risk of psychosis. Such relationship seems to re ... (Ver mais)
Research evidence suggests a dose–response relationship for the association between cannabis use and risk of psychosis. Such relationship seems to reflect an increased risk of psychosis not only as a function of frequent cannabis use, but also of high-potency cannabis use in terms of concentration of Δ-9-tetrahydrocannabinol (Δ9-THC), its main psychoactive component. This finding would be in line with the evidence that Δ9-THC administration induces transient psychosis-like symptoms in otherwise healthy individuals. Conversely, low-potency varieties would be less harmful because of their lower amount of Δ9-THC and potential compresence of another cannabinoid, cannabidiol (CBD), which seems to mitigate Δ9-THC detrimental effects. A growing body of studies begins to suggest that CBD may have not only protective effects against the psychotomimetic effects of Δ9-THC but even therapeutic properties on its own, opening new prospects for the treatment of psychosis. Despite being more limited, evidence of the effects of cannabis on cognition seems to come to similar conclusions, with increasing Δ9-THC exposure being responsible for the cognitive impairments attributed to recreational cannabis use while CBD preventing such effects and, when administered alone, enhancing cognition. Molecular evidence indicates that Δ9-THC and CBD may interact with cannabinoid receptors with almost opposite mechanisms, with Δ9-THC being a partial agonist and CBD an inverse agonist/antagonist. With the help of imaging techniques, pharmacological studies in vivo have been able to show opposite effects of Δ9-THC and CBD also on brain function. Altogether, they may account for the intoxicating and therapeutic effects of cannabis on psychosis and cognition.
Neuropathic pain represents a broad category of pain syndromes that include a wide variety of peripheral and central disorders. The overall prevalenc ... (Ver mais)
Neuropathic pain represents a broad category of pain syndromes that include a wide variety of peripheral and central disorders. The overall prevalence of neuropathic pain in the general population is reported to be between 7 and 10%. Management of neuropathic pain presents an unmet clinical need, with less than 50% of patients achieving substantial pain relief with medications currently recommended such as pregabalin, gabapentin, duloxetine and various tricyclic antidepressants. It has been suggested that cannabis-based medicines (CbMs) and medical cannabis (MC) may be a treatment option for those with chronic neuropathic pain. CbMs/MC are available in different forms: licensed medications or medical products (plant-derived and/or synthetic products such as tetrahydrocannabinol or cannabidiol); magistral preparations of cannabis plant derivatives with defined molecular content such as dronabinol (tetrahydrocannabinol); and herbal cannabis with a defined content of tetrahydrocannabinol and/or cannabidiol, together with other active ingredients (phytocannabinoids other than cannabidiol/tetrahydrocannabinol, terpenes and flavonoids). The availability of different types of CbMs/MC varies between countries worldwide. Systematic reviews of available randomised controlled trials have stated low-quality evidence for CbMs and MC for chronic neuropathic pain. Depending on the studies included in the various quantitative syntheses, authors have reached divergent conclusions on the efficacy of CbMs/MC for chronic neuropathic pain (from not effective to a clinically meaningful benefit). Clinically relevant side effects of CbMs/MC, especially for central nervous system and psychiatric disorders, have been reported by some systematic reviews. Recommendations for the use of CbMs/MC for chronic neuropathic pain by various medical associations also differ, from negative recommendations, no recommendation possible, recommended as third-line therapy, or recommended as an alternative in selected cases failing standard therapies within a multimodal concept. After reading this paper, readers are invited to formulate their own conclusions regarding the potential benefits and harms of CbMs/MC for the treatment of chronic neuropathic pain.
OPEN ACCESS -
The Cochrane Database of Systematic Reviews -
Revisão -
2018
Crohns disease (CD) is a chronic immune ‐ mediated condition of transmural inflammation in the gastrointestinal tract,
associated with sign ... (Ver mais)
Crohns disease (CD) is a chronic immune ‐ mediated condition of transmural inflammation in the gastrointestinal tract,
associated with significant morbidity
and decreased quality of life.The endocannabinoid system provides a potential therapeutic target for cannabis
and cannabinoids
and animal models have shown benefit in decreasing inflammation.However,
there is also evidence to suggest transient adverse events such as weakness,
dizziness
and diarrhea,
and an increased risk of surgery in people with CD who use cannabis.The effects of cannabis
and cannabis oil on Crohns disease are uncertain.Thus no firm conclusions regarding the efficacy
and safety of cannabis
and cannabis oil in adults with active Crohns disease can be drawn.The effects of cannabis
or cannabis oil in quiescent Crohns disease have not been investigated.Further studies with larger numbers of participants are required to assess the potential benefits
and harms of cannabis in Crohns disease.Future studies should assess the effects of cannabis in people with active
and quiescent Crohns disease.Different doses of cannabis
and delivery modalities should be investigated.
O texto discute a possibilidade de usar o componente psicoativo da Cannabis, o Δ9-tetrahidrocanabinol (THC), como tratamento clínico para doenças in ... (Ver mais)
O texto discute a possibilidade de usar o componente psicoativo da Cannabis, o Δ9-tetrahidrocanabinol (THC), como tratamento clínico para doenças inflamatórias do intestino (DII). Ele aborda a importância do sistema endocanabinoide (ECS) na manutenção da homeostase intestinal e revisa estudos pré-clínicos que mostram o potencial dos canabinoides como alvos terapêuticos no tratamento da DII´S. O texto também menciona pesquisas clínicas e estudos observacionais em pacientes com DII´S que relatam o uso de Cannabis para aliviar sintomas como dor abdominal, diarreia e perda de apetite.
A cannabis tem sido usada desde a antiguidade para fins recreativos e medicinais. Ela contém muitos compostos químicos, principalmente fitocanabinoi ... (Ver mais)
A cannabis tem sido usada desde a antiguidade para fins recreativos e medicinais. Ela contém muitos compostos químicos, principalmente fitocanabinoides, que têm efeitos fisiológicos ao se ligarem aos receptores canabinoides CB1 e CB2. A planta tem potencial terapêutico e suas preparações têm sido utilizadas tradicionalmente para tratar dor e enjoo. As evidências científicas sobre o uso da cannabis ainda são limitadas devido a estudos com curta duração, tamanhos de amostra pequenos, falta de grupos de controle e viés em muitos estudos revisados. Portanto, são necessárias mais pesquisas com melhor qualidade metodológica para suportar o uso seguro da terapia em outras condições médicas.
RESTRICT ACCESS -
Clin. transl. oncol. (Print) ; 25(8): 2408-2418, aug. 2023 -
Artigo original -
2023
O osteossarcoma é um tumor maligno que pode se apresentar com dor nos ossos, articulações e massas locais. A incidência é maior em adolescentes, e o ... (Ver mais)
O osteossarcoma é um tumor maligno que pode se apresentar com dor nos ossos, articulações e massas locais. A incidência é maior em adolescentes, e os locais mais comuns são o fêmur distal, a tíbia proximal e a metáfise do úmero proximal. Para além do tratamento quimioterápico de primeira linha com muitos efeitos colaterais, o CBD demonstrou ser eficaz contra o osteossarcoma. No entanto, os alvos moleculares e os mecanismos de ação do CBD no osteossarcoma ainda não estão claros.
