Current Aspects of the Endocannabinoid System and Targeted THC and CBD Phytocannabinoids as Potential Therapeutics for Parkinson’s and Alzheimer’s Diseases: a Review
OPEN ACESS - Molecular Neurobiology (2020) 57:4878–4890 - Revisão - 2020
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.
Cannabis, cannabinoids, and health
OPEN ACCESS - 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.
The Cannabis Terpenes
OPEN ACCESS - Molecules - Revisão - 2020
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.
Cannabis Addiction and the Brain: a Review
OPEN ACCESS - 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.
Cannabis Use, Lung Cancer, and Related Issues
OPEN ACCESS - 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 and cannabis use disorder
OPEN ACCESS - Nature Reviews Disease Primers - Revisão - 2021
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.
Cannabis, from plant to pill
OPEN ACCESS - 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.
Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis
OPEN ACCESS - 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
Terpenes in Cannabis sativa – From plant genome to humans
OPEN ACCESS - Plant Science - Revisão - 2019
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
Therapeutic potential of Cannabis sativa
OPEN ACCESS - 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.
Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects
OPEN ACCESS - 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.
The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial
OPEN ACCESS - 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.
Safety of Medical Cannabis in Neuropathic Chronic Pain Management
OPEN ACCESS - Molecules - Revisão - 2021
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.
Changing landscape of cannabis: novel products, formulations, and methods of administration
OPEN ACCESS - 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.
Cannabis and pain: a scoping review
OPEN ACCESS - 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.
Applications of Cannabis Sativa L. in Food and Its Therapeutic Potential: From a Prohibited Drug to a Nutritional Supplement
OPEN ACCESS - Molecules - Revisão - 2021
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.
Cannabis/Cannabinoids for Treating COVID-19 Associated Neuropsychiatric Complications
OPEN ACCESS - 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.
General and oral health implications of cannabis use
OPEN ACCESS - 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.
Low-dose vaporized cannabis significantly improves neuropathic pain
OPEN ACCESS - 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
The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease
OPEN ACCESS - 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.
Recent advances in Cannabis sativa genomics research
OPEN ACCESS - New Phytologist - Revisão - 2021
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.
It Is Our Turn to Get Cannabis High: Put Cannabinoids in Food and Health Baskets
OPEN ACCESS - Molecules - Revisão - 2020
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
The Current State of Pharmacological Treatments for Cannabis Use Disorder and Withdrawal
OPEN ACCESS - 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
Cannabis, the Endocannabinoid System and Immunity-the Journey from the Bedside to the Bench and Back
OPEN ACCESS - 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.
Medical cannabis education among healthcare trainees: A scoping review
OPEN ACCESS - 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.
Cannabis related side effects in otolaryngology: a scoping review
OPEN ACCESS - 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
Different Effects of Cannabis Abuse on Adolescent and Adult Brain
OPEN ACCESS - Pharmacology - Revisão - 2020
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.
Adverse Effects of Recreational and Medical Cannabis
OPEN ACCESS - 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.
Traditional uses of Cannabis: An analysis of the CANNUSE database
OPEN ACCESS - 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.
Inflammatory Bowel Disease and Cannabis: A Practical Approach for Clinicians
OPEN ACCESS - 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.
Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community
OPEN ACCESS - 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.
Evaluation of Patient Reported Safety and Efficacy of Cannabis From a Survey of Medical Cannabis Patients in Canada
OPEN ACCESS - 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.
Cannabinoids and Epilepsy
OPEN ACCESS - Neurotherapeutics - Revisão - 2015
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.
Children as voices and images for medicinal cannabis law reform
OPEN ACCESS - 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.
Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment
OPEN ACCESS - 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.
Species‐specific susceptibility to cannabis‐induced convulsions
OPEN ACCESS - 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.
Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives
OPEN ACCESS - 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.
Family attitudes about and experiences with medical cannabis in children with cancer or epilepsy: an exploratory qualitative study
OPEN ACCESS - CMAJ Open - Artigo Original - 2021
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.
Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances
OPEN ACCESS - 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.
Daily Cannabis Use is Associated with Lower CNS Inflammation in People with HIV
OPEN ACCESS - 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.
Full-Spectrum Cannabis Extract Microdepots Support Controlled Release of Multiple Phytocannabinoids for Extended Therapeutic Effect
OPEN ACCESS - 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.
Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews
OPEN ACCESS - 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.
Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials
OPEN ACCESS - Molecules - Revisão - 2019
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.
Cannabis Contaminants Limit Pharmacological Use of Cannabidiol
OPEN ACCESS - 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.
Cannabis Exposure is Associated with a Lower Likelihood of Neurocognitive Impairment in People Living with HIV
OPEN ACCESS - 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.
Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders
OPEN ACCESS - Epilepsia. - Revisão - 2016
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.
Bioactive Chemical Composition of Cannabis Extracts and Cannabinoid Receptors
OPEN ACCESS - Molecules - Revisão - 2020
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 and Athletic Performance
OPEN ACCESS - Sports Med - Revisão - 2021
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.
Cannabis for pediatric epilepsy: protocol for a living systematic review
OPEN ACCESS - Systematic Reviews - Revisão - 2018
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.
Human Laboratory Models of Cannabis Use: Applications for Clinical and Translational Psychiatry Research
OPEN ACCESS - 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.
Cannabinoids and Terpenes: How Production of Photo-Protectants Can Be Manipulated to Enhance Cannabis sativa L. Phytochemistry
OPEN ACCESS - 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.
The Use of Cannabis for Headache Disorders
OPEN ACCESS - 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.
Medical Cannabis for Older Patients—Treatment Protocol and Initial Results
OPEN ACCESS - 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.
Acute and Severe Acute Pancreatitis and the Effect of Cannabis in States Before and After Legalization Compared to States Without Legalized Cannabis
OPEN ACCESS - Pancreas. - Revisão - 2022
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.
Medical Cannabis in Pediatric Oncology: Friend or Foe?
OPEN ACCESS - 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.
Cannabis against chronic musculoskeletal pain: a scoping review on users and their perceptions
OPEN ACCESS - 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.
Is cannabidiol a drug acting on unconventional targets to control drug‐resistant epilepsy?
OPEN ACCESS - Epilepsia Open - Revisão - 2020
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.
The antimicrobial effect behind Cannabis sativa
OPEN ACCESS - 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.
A narrative review of the ethnomedicinal usage of Cannabis sativa Linnaeus as traditional phytomedicine by folk medicine practitioners of Bangladesh
OPEN ACCESS - 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.
THERAPEUTIC POTENTIAL AND SAFETY CONSIDERATIONS FOR THE CLINICAL USE OF SYNTHETIC CANNABINOIDS
OPEN ACCESS - 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.
Cannabis and the Developing Adolescent Brain
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.
Cannabidiol Treatment for Refractory Epilepsies in Pediatrics
OPEN ACCESS - 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.
Cannabis and cannabidiol use among autistic and non-autistic adults in the UK: a propensity score-matched analysis
OPEN ACCESS - BMJ Open - Revisão - 2021
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.
Secondary Metabolites Profiled in Cannabis Inflorescences, Leaves, Stem Barks, and Roots for Medicinal Purposes
OPEN ACCESS - Scientific Reports - Revisão - 2020
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.
Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy
OPEN ACCESS - 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.
Pain in the neurodegenerating brain: insights into pharmacotherapy for Alzheimer disease and Parkinson disease
OPEN ACCESS - Pain. - Revisão - 2021
Cannabis, a Miracle Drug with Polyvalent Therapeutic Utility: Preclinical and Clinical-Based Evidence
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.
Interaction of Cannabis Use and Aging: From Molecule to Mind
OPEN ACCESS - 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.
Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain
OPEN ACCESS - Drugs - Revisão - 2021
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.
Metabolomic Fingerprint of Behavioral Changes in Response to Full-Spectrum Cannabis Extracts
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.
From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases
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.
Relationship Between Cannabis Use and Erectile Dysfunction: A Systematic Review and Meta-Analysis
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.
Potential and Limits of Cannabinoids in Alzheimer ’ s Disease Therapy
OPEN ACCESS - Biology (Basel). - Revisão - 2021
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.
Can We Treat Neuroinflammation in Alzheimer ’ s Disease ?
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.
What Do We Know About Medical Cannabis in Neurological Disorders and What Are the Next Steps ?
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.
Methamphetamine and Cannabis: A Tale of Two Drugs and their Effects on HIV, Brain, and Behavior
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.
Medicinal Cannabis and Central Nervous System Disorders
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.
Phytocannabinoids: General Aspects and Pharmacological Potential in Neurodegenerative Diseases
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.
Effects of Cannabis Use on the Protein and Lipid Profile of Olfactory Neuroepithelium Cells from Schizophrenia Patients Studied by Synchrotron - Based FTIR Spectroscopy
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.
Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta - Analysis
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.
Recent cannabis use in HIV is associated with reduced inflammatory markers in CSF and blood
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.
A Review of the Potential Use of Pinene and Linalool as Terpene - Based Medicines for Brain Health: Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis
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.
Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse
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.
Cannabis Use and Resting State Functional Connectivity in the Aging Brain
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.
Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer
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.
An Optimized Terpene Profile for a New Medical Cannabis Oil
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.
Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta - analysis
OPEN ACCESS - PLoS Med - Revisão - 2021
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.
How effective and safe is medical cannabis as a treatment of mental disorders ? A systematic review
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.
A Systematic Review of the Neurocognitive Effects of Cannabis Use in Older Adults
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.
Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging
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.
Tetrahydrocannabinol-Rich Extracts From Cannabis Sativa L. Improve Glucose Consumption and Modulate Metabolic Complications Linked to Neurodegenerative Diseases in Isolated Rat Brains
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
Immunomodulatory Role of CB2 Receptors in Emotional and Cognitive Disorders
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.
Attenuation of Oxidative Stress by Cannabinoids and Cannabis Extracts in Differentiated Neuronal Cells
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.
Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602
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.
Medication Development for Agitation and Aggression in Alzheimer Disease: Review and Discussion of Recent Randomized Clinical Trial Design
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.
Therapeutic Effects of Natural Drugs on Alzheimer’s Disease
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.
Cannabinoids in the management of behavioral, psychological, and motor symptoms of neurocognitive disorders: a mixed studies systematic review
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.
Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia
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.
Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty
OPEN ACCESS - Biology (Basel) - Revisão - 2022
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).
TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids and Nociceptive Signalling
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.
Filling the cannabis knowledge gap
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.”
Cannabinoid Hyperemesis Syndrome: A Case Report of an Underdiagnosed Condition
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.
Druggable Targets in Endocannabinoid Signaling
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.
Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer
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.
The Endocannabinoid Signaling System in the CNS: A Primer
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.
Exploration of Multiverse Activities of Endocannabinoids in Biological Systems
OPEN ACCESS - International Journal of Molecular Sciences -