humulene and Epilepsy

Marijuana, also known as cannabis, is the second most widely used illegal psychoactive substance smoked worldwide after tobacco, mainly due to the psychoactive effects induced by D-9-tetrahydrocannabinol (9-THC). Cannabidiol (CBD) is extracted from cannabis and may be used as an anti-inflammatory agent. Some patents on cannabidiol are discussed in this review. The cannabinoid is a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC); and is available in several administration modes, most known as CBD oil.. This study aims to provide an enhanced review of cannabidiol properties used in treating inflammation. This review also emphasises the current safety profile of cannabidiol.. Cannabis is also called Marijuana. It is the second most commonly used illegal psychoactive substance in the universe after tobacco. D-9-tetrahydrocannabinol (9-THC) present in cannabis produces psychoactive effects. Cannabidiol (CBD) extracted from cannabis is used for antiinflammatory purposes. Cannabis smoking causes various types of cancer, such as lung, tongue, and jaw. The current review took literature from Google Scholar, PubMed, and Google Patents. Many clinical investigations are included in this review.. After analysing the literature on cannabis, it has been suggested that although cannabis is banned in some countries, it may be included in the treatment and mitigation of some diseases and symptoms like pain management, epilepsy, cancer, and anxiety disorder. Mild side effects were frequently observed in cannabis medications, which included infertility in females, liver damage, etc. Conclusion: Cannabis contains chemical compounds such as the cannabinoids delta-9- tetrahydrocannabinol (THC), a psychoactive substance, and non-psychoactive cannabidiol (CBD). Cannabidiol has been confirmed as an efficient treatment of epilepsy in several clinical trials, with one pure CBD product named Epidiolex. It is also used in treating anxiety and acne, as a pain reliever, and has anti-inflammatory properties.

Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Epilepsy; Female; Humans

Cannabidiol (CBD), a nonpsychotropic phytocannabinoid that was once largely disregarded, is currently the subject of significant medicinal study. CBD is found in Cannabis sativa, and has a myriad of neuropharmacological impacts on the central nervous system, including the capacity to reduce neuroinflammation, protein misfolding and oxidative stress. On the other hand, it is well established that CBD generates its biological effects without exerting a large amount of intrinsic activity upon cannabinoid receptors. Because of this, CBD does not produce undesirable psychotropic effects that are typical of marijuana derivatives. Nonetheless, CBD displays the exceptional potential to become a supplementary medicine in various neurological diseases. Currently, many clinical trials are being conducted to investigate this possibility. This review focuses on the therapeutic effects of CBD in managing neurological disorders like Alzheimer's disease, Parkinson's disease and epilepsy. Overall, this review aims to build a stronger understanding of CBD and provide guidance for future fundamental scientific and clinical investigations, opening a new therapeutic window for neuroprotection. Please cite this article as: Tambe SM, Mali S, Amin PD, Oliveira M. Neuroprotective potential of Cannabidiol: Molecular mechanisms and clinical implications. J Integr Med. 2023; 21(3): 236-244.

Topics: Cannabidiol; Cannabinoids; Cannabis; Epilepsy; Humans; Neuroprotection; Neuroprotective Agents

Topics: Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Dronabinol; Epilepsy; Humans; Pain

There is international interest for consensus advice for prescribers working in the field of drug resistant epilepsy intending to trial potential therapies that are nonregistered or off-label. Cannabinoids are one such therapy. In 2017, the New South Wales State Government (Australia) set up a cannabinoid prescribing guidance service for a wide variety of indications, based on known pharmacology together with the relevant new literature as it became available. Increasing interest in cannabis medicines use outside this State over the following 5 years together with a paucity of registration-standard clinical trials, lack of information around dosing issues, drug interactions and biological plausibility meant there remained a large unmet need for such advice. To address the unmet need in epilepsy, and until medicines were registered or regulator quality data were available, it was agreed to bring together a working group comprising paediatric and adult epilepsy specialists, clinical pharmacists., clinical pharmacologists and cannabis researchers from across Australia to develop interim consensus advice for prescribers. Although interim, this consensus advice addresses much of the current practice gap by providing an informed overview of the different cannabis medicines currently available for use in the treatment of epilepsy in paediatric and adult settings, with information on dose, drug interactions, toxicity, type of seizure and frequency of symptom relief. As such it supplements the limited evidence currently available from clinical trials with experience from front-line practice. It is expected that this consensus advice will be updated as new evidence emerges and will provide guidance for a subsequent Guideline.

Topics: Adult; Analgesics; Australia; Cannabinoids; Cannabis; Child; Epilepsy; Hallucinogens; Humans; Seizures

Cannabis is used in the treatment of several human conditions; however, its use is still less explored in veterinary medicine. This systematic review aims to summarize the evidence of efficacy and safety of the use of cannabis for the treatment of animal disease. A literature search was performed for studies published until 16 March 2021 in five databases. Randomized clinical trials (RCTs) that reported the efficacy or safety of cannabis in the treatment of animal disease were included. The RoB 2 Tool was used to assess the risk of bias. A total of 2427 records were identified, of which six studies fully met the eligibility criteria. RCTs were conducted in dogs with osteoarthritis (

Topics: Animals; Cannabidiol; Cannabis; Dog Diseases; Dogs; Epilepsy; Humans; Osteoarthritis; Randomized Controlled Trials as Topic

In February 2020 parliament passed the Cannabis Regulation Bill (2020) which regulates the cultivation and production of industrial hemp and medical cannabis. The country will only fully benefit from this development if the medical and scientific community can take the lead in enabling the country to exploit the plant's potential to help address some of our economic and public health challenges. This special communication provides some basic information on cannabis and discusses its history and medical uses. Cannabidiol (CBD) has emerged as one of the most important cannabis-derived phytochemicals and has formed the basis for the growth of the medical cannabis industry. The scientific data on the mechanisms of the effects of CBD on the human neuroendocrine-immune network is reviewed and the first effective cannabis-based FDA-approved treatment for epilepsy discussed. Some clinical research that is being done on the antipsychotic and neuroprotective properties of CBD is also reviewed. A case is made for the potential of CBD as a neuroprotective adjunctive therapy for the prevention of neuropsychological sequelae associated with complicated malaria. The safety profile of CBD is reviewed and finally, the potential importance of the re-medicalization of cannabis-based therapies for the broader field of phytomedicine is pointed out.

Topics: Cannabidiol; Cannabis; Epilepsy; Humans; Malawi; Medical Marijuana

The use of Cannabis for medicinal purposes has been documented since ancient times, where one of its principal cannabinoids extracted from

Topics: Anticonvulsants; Cannabidiol; Cannabinoids; Cannabis; Epilepsy; Humans

Epilepsy is a chronic neurological disease characterized by recurrent epileptic seizures. Studies have shown the complexity of epileptogenesis and ictogenesis, in which immunological processes and epigenetic and structural changes in neuronal tissues have been identified as triggering epilepsy. Cannabidiol (CBD) is a major active component of the Cannabis plant and the source of CBD-enriched products for the treatment of epilepsy and associated diseases. In this review, we provide an up-to-date discussion on cellular and molecular mechanisms triggered during epilepsy crises, and the phytochemical characteristics of CBD that make it an attractive candidate for controlling rare syndromes, with excellent therapeutic properties. We also discuss possible CBD anticonvulsant mechanisms and molecular targets in neurodegenerative disorders and epilepsy. Based on these arguments, we conclude that CBD presents a biotecnological potential in the anticonvulsant process, including decreasing dependence on health care in hospitals, and could make the patient's life more stable, with regard to neurological conditions.

Topics: Anticonvulsants; Cannabidiol; Cannabis; Epilepsy; Humans; Seizures

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.

Topics: Australia; Cannabis; Child; Epilepsy; Humans; Legislation, Drug; Medical Marijuana; United Kingdom

This review focuses on the possible roles of phytocannabinoids, synthetic cannabinoids, endocannabinoids, and "transient receptor potential cation channel, subfamily V, member 1" (TRPV1) channel blockers in epilepsy treatment. The phytocannabinoids are compounds produced by the herb Cannabis sativa, from which Δ

Topics: Animals; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Epilepsy; Humans

Topics: Animals; Cannabinoids; Cannabis; COVID-19 Drug Treatment; Drug Discovery; Drug Synergism; Endocannabinoids; Epilepsy; Humans; Inflammatory Bowel Diseases; Parkinson Disease; Phytochemicals; Receptors, Cannabinoid; Schizophrenia; Terpenes; Tourette Syndrome

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 (Δ

Topics: Adolescent; Anticonvulsants; Cannabidiol; Cannabis; Epilepsy; Humans; Seizures

Epilepsy is a chronic disease characterized by recurrent unprovoked seizures. Up to 30% of children with epilepsy will be refractory to standard anticonvulsant therapy, and those with epileptic encephalopathy can be particularly challenging to treat. The endocannabinoid system can modulate the physiologic processes underlying epileptogenesis. The anticonvulsant properties of several cannabinoids, namely Δ-tetrahydrocannabinol and cannabidiol (CBD), have been demonstrated in both in vitro and in vivo studies. Cannabis-based therapies have been used for millennia to treat a variety of diseases including epilepsy. Several studies have shown that CBD, both in isolation as a pharmaceutical-grade preparation or as part of a CBD-enriched cannabis herbal extract, is beneficial in decreasing seizure frequency in children with treatment-resistant epilepsy. Overall, cannabis herbal extracts appear to provide greater efficacy in decreasing seizure frequency, but the studies assessing cannabis herbal extract are either retrospective or small-scale observational studies. The two large randomized controlled studies assessing the efficacy of pharmaceutical-grade CBD in children with Dravet and Lennox-Gastaut syndromes showed similar efficacy to other anticonvulsants. Lack of data regarding appropriate dosing and pediatric pharmacokinetics continues to make authorization of cannabis-based therapies to children with treatment-resistant epilepsy challenging.

Topics: Anticonvulsants; Cannabinoids; Cannabis; Child; Epilepsy; Epilepsy, Generalized; Humans; Medical Marijuana; Retrospective Studies; Seizures

Marijuana is the dried leaves, stems, and flowers of a 1- to 5-m weed originating from Central Asia. The most common varieties are Cannabis sativa and Cannabis indica. It is usually inhaled as smoke but can also be used as a vapor, taken by mouth as a spray, ingested in tea or as butter in baked goods, or in capsule form and used as an oil. Cannabis has been widely used to treat many medical conditions such as multiple sclerosis symptoms, mood disorders, pain, sleep disorders, and seizures among others. Preclinical and clinical studies have been done over the past decade, among them there are few randomized placebo-controlled trials. In the last few years, Cannabis has been proposed as a potential therapy for patients with drug-resistant epilepsy. This review analyzes the best information about the use of cannabis in adult patients, reviewing aspects of efficacy and safety.

Topics: Adult; Cannabis; Epilepsy; Humans; Medical Marijuana; Seizures

Cannabis has been used for millennia in religious ceremonies, for recreation and for its medicinal qualities. There are multiple accounts detailing the specific ailments cannabis has been used to treat, many of which have included epilepsy. Racial discrimination and political stigmatization led to prohibition, which limited both patients' and researchers' access to the drug through the 20th century. Recently, academic interest has been renewed in cannabis, especially regarding the modulation of cortical excitability via the human endocannabinoid system. Modern research has produced several promising studies regarding the treatment of epileptic encephalopathies. Legalization of marijuana in Canada has potentially allowed for further trials, but it is by no means an end to the controversy surrounding the treatment of epilepsy with cannabinoids.

Topics: Cannabinoids; Cannabis; Epilepsy; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; History, Medieval; Humans; Medical Marijuana

Herein, 11 general types of natural cannabinoids from Cannabis sativa as well as 50 (-)-CBD analogues with therapeutic potential were described. The underlying molecular mechanisms of CBD as a therapeutic candidate for epilepsy and neurodegenerative diseases were comprehensively clarified. CBD indirectly acts as an endogenous cannabinoid receptor agonist to exert its neuroprotective effects. CBD also promotes neuroprotection through different signal transduction pathways mediated indirectly by cannabinoid receptors. Furthermore, CBD prevents the glycogen synthase kinase 3β (GSK-3β) hyperphosphorylation caused by Aβ and may be developed as a new therapeutic candidate for Alzheimer's disease.

Topics: Alzheimer Disease; Animals; Biological Products; Cannabidiol; Cannabis; Epilepsy; Humans; Neuroprotective Agents

Cannabidiol (CBD), which is nonintoxicating pharmacologically relevant constituents of Cannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology. Currently, as lot of clinical trials are underway, CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.

Topics: Anticonvulsants; Cannabidiol; Cannabis; Epilepsy; Humans; Lennox Gastaut Syndrome

The compounds present in cannabis have been in use for both recreational and medicinal purposes for many centuries. Changes in the legislation in South Africa have led to an increase in the number of people interested in using these compounds for self-medication. Many of them may approach their general practitioner as the first source of information about possible therapeutic effects. It is important that medical professionals are able to give patients the correct information. Cannabidiol (CBD) is one of the main compounds in cannabis plants, and there is evidence that it can successfully treat certain patients with epilepsy. This review looks at the most recent evidence on the use of CBD in the treatment of epilepsy and explores the mechanisms behind these beneficial effects.

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabis; Epilepsy; Humans; South Africa

In the United States, access to marijuana and its related products has been outlawed since passing the Controlled Substance Act (CSA) in 1970. Under this act, marijuana is classified as Schedule I substance and is considered to have a high potential for dependency and abuse as well as unaccepted medical use. From that time, multiple states have taken measures to legalize and decriminalize the use of marijuana. In June 2018, Epidiolex® (cannabidiol, CBD) was the first cannabis-derived drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of severe forms of epilepsy, Lennox-Gastaut syndrome, or Dravet syndrome. In December 2018, Farm Bill was significant progress in cannabis-related law by which hemp was removed from the definition of marijuana in the CSA. This paper provides an up-to-date overview of the legal status of cannabis-related aspects, including medical marijuana, home cultivation, patient registration, and hemp-derived CBD from the medical perspective in the United States.

Topics: Cannabidiol; Cannabis; Epilepsy; Humans; Lennox Gastaut Syndrome; Medical Marijuana; United States

Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from

Topics: Anti-Anxiety Agents; Anticonvulsants; Antipsychotic Agents; Cannabidiol; Cannabis; Clinical Trials as Topic; Epilepsy; Humans; Seizures

Interest in cannabis and its related cannabinoids THC and CBD for use as anti-convulsant therapy has been progressively increasing. While the destigmatization of cannabis and cannabis related research have progressed in the last few decades, there are still many questions that remain unanswered. This review seeks to summarize the progress made in cannabis research in the past four decades and to identify possible directions for future research that are critical for the development of cannabinoid-based therapy in epilepsy.

Topics: Animals; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Epilepsy; Hippocampus; Humans

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5-55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.. CRD42017055412.

Topics: Cannabinoids; Cannabis; Epilepsy; Humans; Medical Marijuana

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.. PROSPERO CRD42018084755.

Topics: Anticonvulsants; Cannabidiol; Cannabis; Child; Epilepsy; Humans; Quality of Life; Seizures

For millennia, there has been interest in the use of cannabis for the treatment of epilepsy. However, it is only recently that appropriately powered controlled studies have been completed. In this review, we present an update on the research investigating the use of cannabidiol (CBD), a non-psychoactive component of cannabis, in the treatment of epilepsy.. While the anticonvulsant mechanism of action of CBD has not been entirely elucidated, we discuss the most recent data available including its low affinity for the endocannabinoid receptors and possible indirect modulation of these receptors via blocking the breakdown of anandamide. Additional targets include activation of the transient receptor potential of vanilloid type-1 (TRPV1), antagonist action at GPR55, targeting of abnormal sodium channels, blocking of T-type calcium channels, modulation of adenosine receptors, modulation of voltage-dependent anion selective channel protein (VDAC1), and modulation of tumor necrosis factor alpha release. We also discuss the most recent studies on various artisanal CBD products conducted in patients with epilepsy in the USA and internationally. While a high percentage of patients in these studies reported improvement in seizures, these studies were either retrospective or conducted via survey. Dosage/preparation of CBD was either unknown or not controlled in the majority of these studies. Finally, we present data from both open-label expanded access programs (EAPs) and randomized placebo-controlled trials (RCTs) of a highly purified oral preparation of CBD, which was recently approved by the FDA in the treatment of epilepsy. In the EAPs, there was a significant improvement in seizure frequency seen in a large number of patients with various types of treatment-refractory epilepsy. The RCTs have shown significant seizure reduction compared to placebo in patients with Dravet syndrome and Lennox-Gastaut syndrome. Finally, we describe the available data on adverse effects and drug-drug interactions with highly purified CBD. While this product is overall well tolerated, the most common side effects are diarrhea and sedation, with sedation being much more common in patients taking concomitant clobazam. There was also an increased incidence of aspartate aminotransferase and alanine aminotransferase elevations while taking CBD, with many of the patients with these abnormalities also taking concomitant valproate. CBD has a clear interaction with clobazam, significantly increasing the levels of its active metabolite N-desmethylclobazam in several studies; this is felt to be due to CBD's inhibition of CYP2C19. EAP data demonstrate other possible interactions with rufinamide, zonisamide, topiramate, and eslicarbazepine. Additionally, there is one case report demonstrating need for warfarin dose adjustment with concomitant CBD. U

Topics: Anticonvulsants; Cannabidiol; Cannabis; Drug Resistant Epilepsy; Endocannabinoids; Epilepsies, Myoclonic; Epilepsy; Epileptic Syndromes; Humans; Lennox Gastaut Syndrome; Medical Marijuana; Randomized Controlled Trials as Topic; Retrospective Studies; Seizures; Spasms, Infantile; Treatment Outcome; TRPV Cation Channels

Topics: Animals; Anxiety; Brazil; Cannabidiol; Cannabis; Clinical Trials as Topic; Epilepsy; Humans; Neuroprotective Agents; Parkinson Disease; Psychotic Disorders; Translational Research, Biomedical

Click here to listen to the Podcast The one-third of people who do not gain seizure control through current treatment options need a revolution in epilepsy therapeutics. The general population appears to be showing a fundamental and rapid shift in its opinion regarding cannabis and cannabis-related drugs. It is quite possible that cannabidiol, licensed in the USA for treating rare genetic epilepsies, may open the door for the widespread legalisation of recreational cannabis. It is important that neurologists understand the difference between artisanal cannabidiol products available legally on the high street and the cannabidiol medications that have strong trial evidence. In the UK in 2018 there are multiple high-profile reports of the response of children taking cannabis-derived medication, meaning that neurologists are commonly asked questions about these treatments in clinic. We address what an adult neurologist needs to know now, ahead of the likely licensing of Epidiolex in the UK in 2019.

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabis; Epilepsy; Humans

Cannabis has been associated with the treatment of epilepsy throughout history, and if ancient Assyrian sources referring to "hand of ghost" are considered credible, this relationship may span four millennia. A tradition of usage continued in Arabic medicine and Ayurvedic practice in India, which led, in turn, to early experiments in Europe and North America with "Indian hemp." Lack of standardization, bioavailability issues, and ultimately prohibition were all factors in cannabis-based medicines failing to maintain mainstream usage in seizure treatment, but investigation was resumed in the 1970s with interesting signals noted in both laboratory and clinical settings. Early case studies showed promise, but lacked sufficient rigor. Resumption of research coupled with mass experimentation by families of epilepsy patients has led to intense interest in cannabis-based medicines for its treatment once more, with greatest focus on cannabidiol, but additional investigation of tetrahydrocannabinol, tetrahydrocannabinolic acid, and other phytocannabinoids. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Epilepsy; Europe; History, Ancient; Humans; India; Medical Marijuana; North America; Seizures

The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use. This article summarizes the available scientific data of pharmacology from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including ∆9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), ∆9-tetrahydrocannabivarin (∆9-THCV), cannabidivarin (CBDV), and ∆9-tetrahydrocannabinolic acid (Δ9-THCA). It has long been known that ∆9-THC has partial agonist activity at the endocannabinoid receptors CB1 and CB2, though it also binds to other targets which may modulate neuronal excitability and neuroinflammation. The actions of Δ9-THCV and Δ9-THCA are less well understood. In contrast to ∆9-THC, CBD has low affinity for CB1 and CB2 receptors and other targets have been investigated to explain its anticonvulsant properties including TRPV1, voltage gated potassium and sodium channels, and GPR55, among others. We describe the absorption, distribution, metabolism, and excretion of each of the above mentioned compounds. Cannabinoids as a whole are very lipophilic, resulting in decreased bioavailability, which presents challenges in optimal drug delivery. Finally, we discuss the limited drug-drug interaction data available on THC and CBD. As cannabinoids and cannabis-based products are studied for efficacy as anticonvulsants, more investigation is needed regarding the specific targets of action, optimal drug delivery, and potential drug-drug interactions. This article is part of a Special Issue titled Cannabinoids and Epilepsy.

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Epilepsy; Humans; Receptor, Cannabinoid, CB1; Treatment Outcome

There has been a dramatic surge in the interest of utilizing cannabis for epilepsy treatment in the US. Yet, access to cannabis for research and therapy is mired in conflicting regulatory policies and shifting public opinion. Understanding the current state of affairs in the medical cannabis debate requires an examination of the history of medical cannabis use. From ancient Chinese pharmacopeias to the current Phase III trials of pharmaceutical grade cannabidiol, this review covers the time span of cannabis use for epilepsy therapy so as to better assess the issues surrounding the modern medical opinion of cannabis use. This article is part of a Special Issue titled Cannabinoids and Epilepsy.

Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Epilepsy; History, Ancient; Humans; Medical Marijuana

Recent interest for the use of cannabis-derived products as therapeutic agents in the treatment of epilepsies has necessitated a reevaluation of their effects on brain and behavior. Overall, prolonged cannabis use is thought to result in functional and structural brain alterations. These effects may be dependent on a number of factors: e.g., which phytocannabinoid is used (e.g., cannabidiol (CBD) vs. tetrahyrocannabinol (THC)), the frequency of use (occasional vs. heavy), and at what age (prenatal, childhood, adulthood) the use began. However, due to the fact that there are over seven hundred constituents that make up the Cannabis sativa plant, it is difficult to determine which compound or combination of compounds is responsible for specific effects when studying recreational users. Therefore, this review focuses only on the functional MRI studies investigating the effects of specific pharmacological preparations of cannabis compounds, specifically THC, tetrahydrocannabivarin (THCV), and CBD, on brain function in healthy individuals and persons with epilepsy with references to non-epilepsy studies only to underline the gaps in research that need to be filled before cannabis-derived products are considered for a wide use in the treatment of epilepsy. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

Topics: Brain; Cannabidiol; Cannabinoids; Cannabis; Comprehension; Dronabinol; Drug Combinations; Epilepsy; Humans; Marijuana Smoking; Medical Marijuana; Neuroimaging

In the United States, federal and state laws regarding the medical use of cannabis and cannabinoids are in conflict and have led to confusion among patients, caregivers, and healthcare providers. Currently, cannabis is legal for medical purposes in 50% of the states, and another seventeen states allow products that are high in cannabidiol (CBD) and low in THC (tetrahydrocannabinol) for medical use. Many of these artisanal products are sold in dispensaries or over the internet. However, none of these products has been approved by the Food and Drug Administration (FDA). Understanding how federal laws apply to clinical research and practice can be challenging, and the complexity of these laws has resulted in particular confusion regarding the legal status of CBD. This paper provides an up-to-date overview (as of August 2016) of the legal aspects of cannabis and cannabidiol, including cultivation, manufacture, distribution, and use for medical purposes. This article is part of a Special Issue title, Cannabinoids and Epilepsy.

Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Epilepsy; Federal Government; Humans; Marijuana Use; Medical Marijuana; State Government; United States

As studies continue to reveal favorable findings for the use of cannabidiol in the management of childhood epilepsy syndromes and other disorders, best practices for the large-scale production of Cannabis are needed for timely product development and research purposes. The processes of two institutions with extensive experience in producing large-scale cannabidiol chemotype Cannabis crops-GW Pharmaceuticals and the University of Mississippi-are described, including breeding, indoor and outdoor growing, harvesting, and extraction methods. Such practices have yielded desirable outcomes in Cannabis breeding and production: GW Pharmaceuticals has a collection of chemotypes dominant in any one of eight cannabinoids, two of which-cannabidiol and cannabidivarin-are supporting epilepsy clinical trial research, whereas in addition to a germplasm bank of high-THC, high-CBD, and intermediate type cannabis varieties, the team at University of Mississippi has established an in vitro propagation protocol for cannabis with no detectable variations in morphologic, physiologic, biochemical, and genetic profiles as compared to the mother plants. Improvements in phytocannabinoid yields and growing efficiency are expected as research continues at these institutions. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

Topics: Agriculture; Cannabis; Epilepsy; Humans; Medical Marijuana; Pharmacognosy; Phytotherapy; Plant Extracts

Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options.

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabis; Epilepsy; Humans; Medical Marijuana

Several antiepileptic drugs (AEDs), about 25, are currently clinically available for the treatment of patients with epilepsy. Despite this armamentarium and the many recently introduced AEDs, no major advances have been achieved considering the number of drug resistant patients, while many benefits have been indeed obtained for other clinical outcomes (e.g. better tolerability, less interactions). Cannabinoids have long been studied for their potential therapeutical use and more recently phytocannabinoids have been considered a valuable tool for the treatment of several neurological disorders including epilepsy. Among this wide class, the most studied is cannabidiol (CBD) considering its lack of psychotropic effects and its anticonvulsant properties.. Analyse the currently available literature on CBD also in light of other data on phytocannabinoids, reviewing data spanning from the mechanism of action, pharmacokinetic to clinical evidences.. Several preclinical studies have tried to understand the mechanism of action of CBD, which still remains largely not understood. CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures; beneficial effects were reported also in animal models of epileptogenesis and chronic models of epilepsy, although not substantial. In contrast, data coming from some studies raise questions on the effects of other cannabinoids and above all marijuana.. There is indeed sufficient supporting data for clinical development and important antiepileptic effects and the currently ongoing clinical studies will permit the real usefulness of CBD and possibly other cannabinoids. Undoubtedly, several issues also need to be addressed in the next future (e.g. better pharmacokinetic profiling). Finally, shading light on the mechanism of action and the study of other cannabinoids might represent an advantage for future developments.

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabis; Epilepsy; Humans

The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures. However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done. Proper dosage and means of administration remain unknown. Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy. This is a review of this topic from a Canadian perspective.

Topics: Anticonvulsants; Canada; Cannabinoids; Cannabis; Epilepsy; Humans; Medical Marijuana; Phytotherapy

Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia. Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts. This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD). Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians' and patients' opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.

Topics: Animals; Anticonvulsants; Cannabinoids; Cannabis; Epilepsy; Humans; Medical Marijuana

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Epilepsy; Humans; Medical Marijuana

Phytocannabinoids isolated from the cannabis plant have broad potential in medicine that has been well recognized for many centuries. It is presumed that these lipid soluble signaling molecules exert their effects in both the central and peripheral nervous system in large part through direct interaction with metabotropic cannabinoid receptors. These same receptors are also targeted by a variety of endogenous cannabinoids including 2-arachidonoyl glycerol and anandamide. Significant effort over the last decade has produced an enormous advance in our understanding of both the cellular and the synaptic physiology of endogenous lipid signaling systems. This increase in knowledge has left us better prepared to carefully evaluate the potential for both natural and synthetic cannabinoids in the treatment of a variety of neurological disorders. In the case of epilepsy, long standing interest in therapeutic approaches that target endogenous cannabinoid signaling systems are, for the most part, not well justified by available clinical data from human epileptics. Nevertheless, basic science experiments have clearly indicated a key role for endogenous cannabinoid signaling systems in moment to moment regulation of neuronal excitability. Further it has become clear that these systems can both alter and be altered by epileptiform activity in a wide range of in vitro and in vivo models of epilepsy. Collectively these observations suggest clear potential for effective therapeutic modulation of endogenous cannabinoid signaling systems in the treatment of human epilepsy, and in fact, further highlight key obstacles that would need to be addressed to reach that goal.

Topics: Animals; Cannabinoids; Cannabis; Cerebral Cortex; Epilepsy; Humans; Signal Transduction

Cannabis has been known as a medicine for several thousand years across many cultures. It reached a position of prominence within Western medicine in the nineteenth century but became mired in disrepute and legal controls early in the twentieth century. Despite unremitting world-wide suppression, recreational cannabis exploded into popular culture in the 1960s and has remained easily obtainable on the black market in most countries ever since. This ready availability has allowed many thousands of patients to rediscover the apparent power of the drug to alleviate symptoms of some of the most cruel and refractory diseases known to humankind. Pioneering clinical research in the last quarter of the twentieth century has given some support to these anecdotal reports, but the methodological challenges to human research involving a pariah drug are formidable. Studies have tended to be small, imperfectly controlled, and have often incorporated unsatisfactory synthetic cannabinoid analogues or smoked herbal material of uncertain composition and irregular bioavailability. As a result, the scientific evaluation of medicinal cannabis in humans is still in its infancy. New possibilities in human research have been opened up by the discovery of the endocannabinoid system, a rapidly expanding knowledge of cannabinoid pharmacology, and a more sympathetic political environment in several countries. More and more scientists and clinicians are becoming interested in exploring the potential of cannabis-based medicines. Future targets will extend beyond symptom relief into disease modification, and already cannabinoids seem to offer particular promise in the treatment of certain inflammatory and neurodegenerative conditions. This chapter will begin with an outline of the development and current status of legal controls pertaining to cannabis, following which the existing human research will be reviewed. Some key safety issues will then be considered, and the chapter will conclude with some suggestions as to future directions for human research.

Topics: Appetite; Cannabinoids; Cannabis; Cognition; Epilepsy; Glaucoma; Humans; Marijuana Abuse; Multiple Sclerosis; Nausea; Neoplasms; Neuroprotective Agents; Pain; Phytotherapy; Spinal Cord Injuries; Vomiting

Neurons intensively exchange information among each other using both inhibitory and excitatory neurotransmitters. However, if the balance of excitation and inhibition is perturbed, the intensity of excitatory transmission may exceed a certain threshold and epileptic seizures can occur. As the occurrence of epilepsy in the human population is about 1%, the search for therapeutic targets to alleviate seizures is warranted. Extracts of Cannabis sativa have a long history in the treatment of various neurological diseases, including epilepsy. However, cannabinoids have been reported to exert both pro- and anti-convulsive activities. The recent progress in understanding the endogenous cannabinoid system has allowed new insights into these opposing effects of cannabinoids. When excessive neuronal activity occurs, endocannabinoids are generated on demand and activate cannabinoid type 1 (CB1) receptors. Using mice lacking CB1 receptors in principal forebrain neurons in a model of epileptiform seizures, it was shown that CB1 receptors expressed on excitatory glutamatergic neurons mediate the anti-convulsive activity of endocannabinoids. Systemic activation of CB1 receptors by exogenous cannabinoids, however, are anti- or pro-convulsive, depending on the seizure model used. The pro-convulsive activity of exogenous cannabinoids might be explained by the notion that CB1 receptors expressed on inhibitory GABAergic neurons are also activated, leading to a decreased release of GABA, and to a concomitant increase in seizure susceptibility. The concept that the endogenous cannabinoid system is activated on demand suggests that a promising strategy to alleviate seizure frequency is the enhancement of endocannabinoid levels by inhibiting the cellular uptake and the degradation of these endogenous compounds.

Topics: Animals; Cannabinoid Receptor Modulators; Cannabis; Endocannabinoids; Epilepsy; Humans; Models, Animal; Neurons

Topics: Anorexia; Cachexia; Cannabinoids; Cannabis; Epilepsy; Hiccup; Humans; Migraine Disorders; Muscle Spasticity; Nausea; Pain; Palliative Care; Randomized Controlled Trials as Topic; Seizures; Vomiting

Review commissioned in 1996 by the Department of Health (DOH).. Assess therapeutic profile of cannabis and cannabinoids.. Medline search, references supplied by DOH and others, and personal communications.. Cannabis and some cannabinoids are effective anti-emetics and analgesics and reduce intra-ocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

Topics: Analgesics, Non-Narcotic; Appetite; Cannabinoids; Cannabis; Epilepsy; Government Agencies; Humans; Legislation, Drug; Male; Multiple Sclerosis; Nausea; Phytotherapy; United Kingdom

Topics: Animals; Asthma; Cannabis; Dronabinol; Epilepsy; Glaucoma; Humans; Nausea; Neoplasms; Pain

Recent work aimed at the introduction of natural and synthetic cannabinoids as drugs is reviewed. Delta1-Tetrahydrocannabinol (delta1-THC) is mainly investigated as a potential drug against glaucoma and asthma, and as an antiemetic agent in cancer chemotherapy. Cannabidiol is being tried in the clinic against epilepsy and as a hypnotic. Numerous synthetic cannabinoids are currently being investigated as analgetics and as sedative-relaxants.

Topics: Analgesics; Anti-Inflammatory Agents; Antiemetics; Asthma; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Epilepsy; Glaucoma; History, Ancient; History, Medieval; History, Modern 1601-; Humans; Hypertension; Medicine, Arabic; Medicine, East Asian Traditional; Phytotherapy; Sleep Initiation and Maintenance Disorders; Structure-Activity Relationship

Topics: Airway Resistance; Alcoholism; Animals; Asthma; Cannabinoids; Cannabis; Depression; Dose-Response Relationship, Drug; Epilepsy; Glaucoma; Humans; Intraocular Pressure; Neoplasms, Experimental; Pain; Preanesthetic Medication; Seizures; Sleep

Violence is a symptom of an underlying mental state such as a psychosis, a characterological problem, or brain dysfunction. Thus drugs used to treat aggression in man exert effects by their specific pharmacological actions (e.g., antipsychotic, anticonvulsant). Most literature to date has dealt with animals and human models of aggression and lacks conceptual clarity. Aggression differs from depression, a coherent clinical entity, in its etiological diversity and its paroxysmal or impulsive basis, and this may account for the relationship seen in literature linking violence to epilepsy; yet literature on anticonvulsants is equivocal with regard to beneficial effects on aggression. Lithium has been shown to have positive effects, although its mode of action is unclear. A variety of antipsychotic agents and minor tranquilizers have been mentioned. Central nervous system stimulants have been found useful to treat hyperkinetic syndromes in both children and adults where aggression is a symptom. Hormonal agents are discussed. Drug treatment of aggression should not obscure the need for verbal therapies, and social and environmental factors should always be regarded.

Topics: Adolescent; Adult; Aggression; Alcoholic Intoxication; Animals; Anti-Anxiety Agents; Anticonvulsants; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Butyrophenones; Cannabis; Chlordiazepoxide; Disease Models, Animal; Epilepsy; Gonadal Steroid Hormones; Humans; Hyperkinesis; Impulsive Behavior; Lithium; Male; Methadone; Paranoid Disorders; Phenothiazines; Phenytoin; Psychopharmacology; Psychosurgery; Schizophrenia; Thiothixene; Violence

This study sought to identify differences in cannabis use and perceptions about cannabis in mitigating seizure-related symptoms in patients with epilepsy, and to evaluate differences in these patterns between drug-resistant versus pharmacoresponsive epilepsy. A collection of self-report surveys completed by patients with epilepsy (n = 76) were used to retrospectively compare differences in those with drug-resistant versus pharmacoresponsive epilepsy regarding 1) proportion who used cannabis, 2) frequency of use, 3) method of use, and 4) reason for use. A Cochran-Armitage test for trend indicated that of patients who used cannabis, a higher proportion of patients in the drug-resistant group used more frequently than in the pharmacoresponsive group. Almost half (48%) of those in the drug-resistant group reported daily use compared to approximately a third (36%) of those in the pharmacoresponsive group. Additionally, no patient in either group reported that cannabis was harmful in relation to seizure-related symptoms. Results from this study highlight the need for epilepsy providers to formally assess patients' perceptions and use of non-prescribed cannabis to inform clinical care decisions, particularly in the drug-resistant epilepsy population.

Topics: Anticonvulsants; Cannabinoid Receptor Agonists; Cannabis; Drug Resistant Epilepsy; Epilepsy; Hallucinogens; Humans; Retrospective Studies; Seizures; Tertiary Care Centers

Marijuana-based therapies (MBTs) have been shown to reduce seizure frequency in patients with severe and drug-resistant epilepsy (DRE). Pharmaceutical-grade CBD (Epidiolex. Thirty patients were identified as taking more than 1 type of MBT. Our findings suggest that seizure frequencies do not change significantly from baseline to after the first MBT and to after the second MBT (p = .4). However, we did find that patients with greater baseline seizure frequency were significantly more likely to respond to treatment after the second MBT (p = .03). To our second endpoint of side effect profile, we found that patients who experienced side effects after a second MBT had significantly greater seizure frequency compared to those who did not (p = .04).. We found no significant seizure frequency reduction from baseline to after a second MBT in patients who tried at least 2 different formulations of MBT. This suggests a low probability of seizure frequency reduction with a second MBT therapy in patients with epilepsy who tried at least two different MBTs. While these findings need to be replicated in a larger sample, they suggest that clinicians should not delay care by trying alternative MBT formulations after a patient has already tried one. Instead, it may be more prudent to attempt an alternative class of therapy.

Topics: Anticonvulsants; Cannabidiol; Cannabis; Child, Preschool; Drug Resistant Epilepsy; Epilepsy; Humans; Lennox Gastaut Syndrome; Retrospective Studies; Seizures

Topics: Cannabis; Epilepsy; Humans

Topics: Anticonvulsants; Cannabinoids; Cannabis; Drug Resistant Epilepsy; Epilepsy; Humans

Previous studies have reported inconsistent results regarding the potential relationships between addictive behaviors and the risk of epilepsy.. To assess whether genetically predicted addictive behaviors are causally associated with the risk of epilepsy outcomes.. The causation between five addictive behaviors (including cigarettes per day, alcoholic drinks per week, tea intake, coffee intake, and lifetime cannabis use) and epilepsy was evaluated by using a two-sample Mendelian Randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR Egger, weighted median, simulation extrapolation corrected MR-Egger, and Mendelian Randomization Pleiotropy Residual Sum and Outlier (MR-PRESSO)) were performed to complement IVW. In addition, the robustness of the MR analysis results was assessed by leave-one-out analysis.. The IVW analysis method indicated an approximately 20% increased risk of epilepsy per standard deviation increase in lifetime cannabis use (odds ratio [OR], 1.20; 95% confidence interval [CI]), 1.02-1.42, P = 0.028). However, there is no causal association between the other four addictive behaviors and the risk of epilepsy (cigarettes per day: OR, 1.04; 95% CI, 0.92-1.18, P = 0.53; alcoholic drinks per week: OR, 1.31; 95% CI, 0.93-1.84, P = 0.13; tea intake: OR, 1.15; 95% CI, 0.84-1.56, P = 0.39; coffee intake: OR, 0.86; 95% CI, 0.59-1.23, P = 0.41). The other MR analysis methods and further leave-one-out sensitivity analysis suggested the results were robust.. This MR study indicated a potential genetically predicted causal association between lifetime cannabis use and higher risk of epilepsy. As for the other four addictive behaviors, no evidence of a causal relationship with the risk of epilepsy was found in this study.

Topics: Behavior, Addictive; Cannabinoid Receptor Agonists; Cannabis; Coffee; Epilepsy; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Tea

Pediatric epilepsy is a debilitating disease cluster that is much less researched than adult epilepsy. With approximately 30% of patients with pediatric epilepsy experiencing refractory seizures, novel treatment modalities are sometimes necessary to provide benefit. The use of marijuana, and more specifically cannabidiol, in people with seizures is much more broadly researched in adults compared with pediatric patients, although several recent review articles have been published. This article seeks to provide a pathophysiological basis for cannabidiol in epilepsy, discuss commercially available products and nonpharmaceutical marijuana, and review recent evidence in pediatric epilepsy.

Topics: Anticonvulsants; Cannabidiol; Cannabis; Child; Epilepsy; Humans; Seizures

Despite recent approval of pharmaceutical-grade cannabis products for the treatment of childhood epilepsy, some families continue to use artisanal cannabis products as a way to manage seizures in their children. However, such products are typically of unknown composition and quality, and may therefore pose an unpredictable health risk to the child. In the present analysis, 78 samples of cannabis products collected (as part of a previous study) from families of children with epilepsy (average age 8.8 ± 4.6 years) were analyzed for heavy metals (arsenic, cadmium, lead, and mercury), residual solvents (panel of 19 solvents) and pesticides (panel of 57 pesticides). Due to small sample volumes obtained, only a subset of samples was used in each analysis. Results showed that no cannabis sample exceeded the toxicity limits for heavy metals (n = 51 samples tested). Of the 58 cannabis samples tested for residual solvents, 17 (29%) contained concentrations of ethanol or isopropanol above the generally accepted limit of 5000 parts per million. With the volumes consumed, it was thought unlikely that children were consuming hazardous amounts of residual solvents, although this could not be ruled out in every case. Most samples (n = 31 samples tested) yielded inconclusive results for the pesticides, although one sample contained concentrations of bifenthrin that were 4.9 times higher than the acceptable limit. Overall, these results highlight the need for improved access to quality-assured cannabis products and the education of doctors, patients, and artisanal manufacturers around the contaminant exposure risk in unregulated cannabis products.

Topics: Adolescent; Australia; Cannabis; Child; Child, Preschool; Epilepsy; Humans; Metals, Heavy; Pesticides

The current study sought: (i) to explore whether health profession students possess formal medical cannabis (MC) education, feel prepared to answer questions about MC, and perceive it as an effective therapy for epilepsy; (ii) to assess students' attitudes and beliefs about MC use; and (iii) to explore the associations between students' background characteristics, MC-related attitudes and beliefs regarding its effectiveness for epilepsy. A sample of 310 students (141 from medicine and 169 from social work) voluntarily participated in the anonymous online survey. The vast majority (92.5%) indicated they had no formal education about MC, and only 11.2 % reported being prepared to answer clients' MC-related questions. Participants reported favorable beliefs about MC benefits, the need for training, and recreational marijuana use legalization. Less supportive attitudes were reported regarding MC risks. Prior cannabis use (e.g., self-use, friends, or family) and individuals from a secular background were associated with more positive beliefs about MC benefits and its legalization for recreational purposes. Prior recreational cannabis use [OR=1.541] and having friends who recreationally use the substance [OR=1.891] were associated with the belief that MC is an effective therapy for epilepsy. These findings indicate an urgent need for students' MC education to provide future physicians and social workers with MC-related capacities. Development of curricula and training programs in Israel are encouraged.

Topics: Cannabis; Epilepsy; Health Knowledge, Attitudes, Practice; Humans; Medical Marijuana; Social Work; Students, Medical; Surveys and Questionnaires

It is known from medical practise that patients and physicians can have positive experiences with little-researched and unapproved interventions. Under certain circumstances, effects even go beyond the placebo effect.. Based on casuistics of chronic pain patients, the question of whether self-medication in the context of a good doctor-patient relationship can optimize the efficacy of cannabinoids and reduce dose and undesirable side effects is investigated. Using medicinal cannabis as an example, a new view on self-medication and medical support is proposed.. The casuistics show that daily requirements (average of approximately 75 mg) for Δ. If the patient has "discovered" cannabis as medicine for himself and can draw on positive experiences, something very powerful can emerge. In addition to the specific effects demonstrated by studies, there are non-specific effects or contextual factors at work that tend to be neglected in evidence-based medicine. These non-specific effects include, above all, those factors through which a patient gives a (subjective) meaning to a specific intervention. A new view on self-medication and medical support in chronic diseases is needed.. Hintergrund: Erfahrungsmedizinisch bekannt ist, dass Patienten und Ärzte positive Erfahrungen mit nur wenig erforschten und nicht zugelassenen Interventionen machen können. Dabei gehen Wirkungen unter bestimmten Umständen über den Placeboeffekt hinaus.. Ausgehend von Kasuistiken chronischer Schmerzpatienten wird der Frage nachgegangen, ob durch Selbstmedikation im Kontext einer vertrauensvollen Arzt-Patienten-Beziehung die Wirksamkeit von Cannabinoiden optimiert werden kann und sich Dosis sowie unerwünschte Nebenwirkungen reduzieren lassen. Am Beispiel von Medizinalcannabis wird eine neue Sicht auf Selbstmedikation und ärztliche Begleitung vorgeschlagen.Ergebnisse: Die Erfahrungen aus den Kasuistiken zeigen, dass sich der tägliche Bedarf (durchschnittlich ca. 75 mg) an Tetrahydrocannabinol(THC)-Dosen reduzieren lässt. Eine unbegleitete und risikoreiche Selbstmedikation kann in eine effektive Therapie mit deutlich weniger Medizinalcannabis transformiert werden. Die Vorgehensweise besteht darin, die bis dato stattgefundene Selbstmedikation nachzuvollziehen und den Patienten dort abzuholen, wo er selber für sich etwas "entdeckt" hat. Erklären lässt sich die spezifische Wirkweise von Cannabis bei chronischen Erkrankungen über die Mechanismen im Endocannabinoidsystem. Cannabinoide entlasten Patienten im Kontext von Stress, Angst und Depression, die bei chronischen Erkrankungen immer beteiligt sind. In ihrem körperlichen sowie psychischen Empfinden werden Patienten gestärkt und schließlich in die Selbstwirksamkeit geführt.Schlussfolgerungen: Hat der Patient "Cannabis als Medizin" selbst für sich "entdeckt" und kann auf positive Erfahrungen zurückgreifen, so kann etwas sehr Wirkmächtiges entstehen. Neben den spezifischen Effekten, die durch Studien nachgewiesen werden, wirken unspezifische Effekte bzw. Kontextfaktoren, die in der evidenzbasierten Medizin eher vernachlässigt werden. Zu diesen unspezifischen Effekten gehören vor allem solche Faktoren, durch die ein Patient einem Wirkmittel eine (subjektive) Bedeutung gibt. Eine neue Sicht auf Selbstmedikation und ärztliche Begleitung bei chronischen Erkrankungen ist erforderlich.Schlüsselwörter: Cannabinoide, Selbstmedikation, Endocannabinoidsystem, Placeboanalgesie, ValeboEingereicht am 12.8.2021 - Revision akzeptiert am 17.1.2022.

Topics: Analgesics; Cannabinoids; Cannabis; Chronic Disease; Epilepsy; Humans; Male; Medical Marijuana; Physician-Patient Relations

Several retrospective studies on pediatric epilepsy reported positive effects of cannabidiol-enriched artisanal cannabis oil and pure cannabidiol oil on seizure reduction.. This is a retrospective study of children and adolescents with refractory epilepsy caused by various etiologies who were treated with artisanal cannabis oil during January 2014 to June 2019, with at least one year follow-up.. Of 114 patients, 84 (73.3%) reported some improvement in seizure frequency at some point during treatment. Fifty-one (59%) of the 86 patients who continued treatment for at least one year showed >50% improvement in seizure frequency. Seizure etiology, seizure type, and patients' age and sex were not found to be associated with the response to cannabidiol-enriched cannabis oil. Side effects were minor, and positive effects beyond seizure reduction were noted.. Artisanal cannabidiol-enriched cannabis may be an effective and safe long-term treatment for refractory epilepsy.

Topics: Adolescent; Anticonvulsants; Cannabidiol; Cannabis; Child; Drug Resistant Epilepsy; Epilepsy; Humans; Retrospective Studies; Seizures

Taking into consideration the latest reported beneficial anticolvusant effects of cannabidiol (CBD) and cannabiodiolic acid (CBDA) for clinical applications and the advantages of lipid nano-systems as carriers for targeted brain delivery, the aim of this study was set in direction of in vitro physico-chemical and biopharmaceutical characterization and in vivo evaluation of nanoliposomes and nanostructured lipid carriers loaded with Cannabis sativa extract intended for safe and efficient transport via blood-brain barrier and treatment of epilepsy. These nanoliposomes and nanostructured lipid formulations were characterized with z-average diameter <200 nm, following unimodal particle size distribution, negative values for Z-potential, high drug encapsulation efficiency and prolonged release during 24h (38.84-60.91 %). Prepared formulations showed statistically significant higher antioxidant capacity compared to the extract. The results from in vivo studies of the anticonvulsant activity demonstrated that all formulations significantly elevated the latencies for myoclonic, clonic and tonic seizures and, therefore, could be used in preventing different types of seizures. A distinction in the potential of the nano-systems was noted, which was probably anticipated by the type and the characteristics of the prepared formulations.

Topics: Cannabis; Epilepsy; Lipids; Particle Size; Plant Extracts; Seizures

Topics: Anticonvulsants; Cannabidiol; Cannabis; Child; Epilepsy; Humans

Cannabis has been used to treat epilepsy for millennia, with such use validated by regulatory approval of cannabidiol (CBD) for Dravet syndrome. Unregulated artisanal cannabis-based products used to treat children with intractable epilepsies often contain relatively low doses of CBD but are enriched in other phytocannabinoids. This raises the possibility that other cannabis constituents might have anticonvulsant properties.. We used the Scn1a. The initial screen identified three phytocannabinoids with novel anticonvulsant properties: CBGA, cannabidivarinic acid (CBDVA) and cannabigerovarinic acid (CBGVA). CBGA was most potent and potentiated the anticonvulsant effects of clobazam against hyperthermia-induced and spontaneous seizures, and was anticonvulsant in the MES threshold test. However, CBGA was proconvulsant in the 6-Hz threshold test and a high dose increased spontaneous seizure frequency in Scn1a. These results suggest that CBGA, CBDVA and CBGVA may contribute to the effects of cannabis-based products in childhood epilepsy. Although these phytocannabinoids have anticonvulsant potential and could be lead compounds for drug development programmes, several liabilities would need to be overcome before CBD is superseded by another in this class.

Topics: Animals; Anticonvulsants; Benzoates; Cannabidiol; Cannabis; Epilepsies, Myoclonic; Epilepsy; Mice; NAV1.1 Voltage-Gated Sodium Channel; Receptors, Cannabinoid; Seizures

In psychiatry, routine EEGs are often abnormal and not very specific, raising questions about the clinical relevance and consequences of potential anomalies. One such question is whether the administration of anticonvulsants would be useful if epileptic discharges are detected in patients without any clinical correlates. With regard to this question, we present a case study in which abnormal EEG patterns were observed in a patient with chronic migraine and cannabis addiction. The patient was a 34-year-old woman with a 14-year history of cannabis abuse who, during withdrawal, showed epileptic spikes, without any corresponding clinical symptoms, and migraine attacks of increasing intensity and frequency. This case study is in line with the new

Topics: Adult; Anticonvulsants; Brain; Cannabis; Electroencephalography; Epilepsy; Female; Humans; Migraine Disorders; Substance Withdrawal Syndrome

Despite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study was to determine the disposition of oral cannabidiol cannabis extracts and drug interactions in children with pediatric epilepsy.. We conducted a prospective observational study evaluating the disposition of oral cannabidiol in children (< 18 years of age) receiving cannabidiol extracts for epilepsy. Subjects underwent serial blood draws after oral cannabidiol administration. Cannabidiol and metabolites, along with anticonvulsant concentrations were determined.. Twenty-nine patients had sufficient pharmacokinetic data and were included in the analysis. Mean age was 9.7 years (standard deviation 4.3) and 17 patients (59%) were male. Median peak plasma cannabidiol concentrations was 13.1 ng/mL (interquartile range 6.8-39.3 ng mL); median time to peak of 2.0 h (interquartile range 2.0-4.0 h). Mean acute elimination half-life of oral cannabidiol was 6.2 h (standard deviation 1.8 h). There was an observed half-life of degradation of 533 days noted for cannabidiol concentrations when stored for 0.6-3.1 years. There was some impact on cannabidiol pharmacokinetic parameters when cannabidiol was co-administered with zonisamide (elimination rate constant and V1) and levetiracetam (elimination rate constant).. In pediatric patients using oral cannabidiol-rich cannabis extract for epilepsy, the time to peak concentration of plasma cannabidiol and average acute elimination half-life were shorter than those reported for adults. Co-administration of zonisamide and levetiracetam had some impact on cannabidiol pharmacokinetic parameters. There was an observed degradation of plasma cannabidiol in long-term storage.. ClinicalTrials.gov Identifer no. NCT02447198.

Topics: Anticonvulsants; Cannabidiol; Cannabis; Child; Epilepsy; Female; Humans; Male; Plant Extracts

Topics: Cannabis; Epilepsy; Hallucinogens; Humans; Medical Marijuana; Muscle Spasticity; Myalgia

Patients with epilepsy are at increased risk for mental health and substance abuse disorders. Given ongoing contemporary societal controversies about medicinal and recreational cannabis use, we aimed to ascertain recent nationwide prevalence, trends, and psychiatric diagnoses associated with cannabis use disorders (CUD) among epilepsy patients.. We interrogated the National Inpatient Sample database comprising a total of 398,936 adults (aged 18 years and above) with epilepsy between the years 2006 and 2014, identified using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 780.39 and 345.X. A subset of these patients with a secondary discharge diagnosis of CUD (ICD-9-CM: 304.30, 304.31, 304.32, 305.20, 305.21, and 305.22), excluding those in remission, were selected. Logistic regression model adjusting for gender, race, age, primary payer, bed size, household income, region, teaching hospital, admission day, length of stay (LOS), Charleson Comorbidity Index (CCI) and, year category was used to ascertain the independent associations of demographic features and mental health comorbidities with CUD. Finally, we generated CUD trend estimates overall and by psychiatric diagnoses.. Of all hospitalized patients with epilepsy, 3.19 % had CUD. After adjusting for confounders, CUD was higher in males, Blacks, those aged 18-44 years, those with lower incomes, and those hospitalized during more recent years. CUD was more likely to be present in epilepsy patients with depression, bipolar disorder, and tobacco use disorder (TUD). In contrast, alcohol use disorder (AUD) was associated with lower odds of CUD. Overall, CUD prevalence more than doubled among epilepsy patients (2.18 % in 2006 to 4.41 % in 2014). Among patients with PTSD, CUD prevalence increased over fivefold, and it nearly tripled in those with tobacco use disorder.. Documented CUD has doubled among hospitalized patients with epilepsy in the United States over the last decade and is especially more prevalent in specific demographic and mental health disorder groups. Increased awareness and potential screening for CUD in high-risk epilepsy patients may be warranted, given the risk for potential complications.

Topics: Adolescent; Adult; Aged; Cannabis; Comorbidity; Epilepsy; Female; Hospitalization; Humans; Male; Middle Aged; Prevalence; Substance-Related Disorders; Tobacco Use Disorder; United States

A special component of cannabis, cannabidiol (CBD), is currently in the focus of epilepsy treatment and research. In this context, we investigated patients' expectations and preferences pertaining to plant-derived versus synthetic formulation of cannabidiol, as well as their willingness to get this treatment.. One hundred and four of 153 patients with different forms of epilepsy (54 % female, mean age 40 ± 16 yrs.) responded to the survey. The survey consisted of 8 questions addressing expectations of and concerns towards CBD treatment, preferences of plant-derived versus synthetic CBD, estimated monthly costs, and willingness to buy CBD at one's own expense.. The majority (73 %) of the responding epilepsy patients wished to receive plant-derived CBD; 5 % preferred synthetic CBD. Reasons for this choice were botanic origin, lack of chemistry, and the assumption of fewer and less dangerous side effects. Eighty-two percent of the patients estimated the monthly costs of CBD treatment to be below €500. Using the willingness-to-pay approach to assess the commitment of patients, 68 % could imagine buying the drug themselves. Fifty-three percent of these would be willing to pay up to €100, 40 % €100 to €200, and another 7 % €200 to €500 per month.. There is an overwhelming preference towards plant-derived cannabidiol in epilepsy patients, driven by the idea of organic substances being safer and better tolerated than synthetic. The willingness-to-pay approach reflects the high burden and pressure of uncontrolled epilepsy and the expectation of relief. Non-realistic ideas of pricing as well as what patients would be willing and able to pay confirm this perception.

Topics: Adolescent; Anticonvulsants; Cannabidiol; Cannabis; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Male

The purpose of this study was to evaluate whether the topic of using cannabis as a treatment option for epilepsy is relevant among adult patients with the disorder and assess the possible determinant attitudes for having a history of cannabis consumption or being inclined to try it for medical purposes.. Willing adult (≥18 years) patients with diagnosed epilepsy participated in a cross-sectional survey study at a tertiary epilepsy center. The questions were related to cannabis use and opinions towards the safety and efficacy profile of cannabis for treating epilepsy.. From 250 respondents, 41 (16.4%) reported prior use of cannabis or its preparations (15 [36.6%] for self-treatment). There were 81 (32.4%) participants further interested in cannabis use for treating epilepsy. In a binary regression model (Nagelkerke R. Among adult patients with epilepsy, we report no particularly high rate of cannabis use or interest in applying cannabis for medical purposes. In order to clarify the scientific and legal status of the preparations, treating neurologists should consult prior users and patients interested in the possibility of trying cannabis as an epilepsy remedy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Cannabidiol; Cannabis; Cross-Sectional Studies; Epilepsy; Female; Humans; Lithuania; Male; Marijuana Smoking; Medical Marijuana; Middle Aged; Surveys and Questionnaires; Tertiary Care Centers; Young Adult

Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures. Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population. Although randomized controlled trials of CBD are ongoing and promising, data regarding artisanal formulations of CBD are minimal and largely anecdotal. Here, we report a retrospective study to define the efficacy of artisanal CBD preparations in children with epilepsy. Given the known interaction between CBD and clobazam, we also conducted a subgroup comparison to determine if clobazam use was related to any beneficial effects of CBD. Additionally, we compared response rates with CBD and with clobazam alone within an overlapping patient cohort. A pediatric cohort with epilepsy of 108 patients was identified through a medical record search for patients using CBD oil. The addition of CBD resulted in 39% of patients having a >50% reduction in seizures, with 10% becoming seizure-free. The responder rate for clobazam was similar. No patients achieved CBD monotherapy, although the weaning of other antiepileptic drugs (AEDs) became possible in 22% of patients. A comparable proportion had AED additions during CBD therapy. With concomitant use of clobazam, 44% of patients had a 50% reduction in seizures upon addition of CBD compared with 33% in the population not taking clobazam; this difference was not statistically significant. The most common reported side effect of CBD was sedation in less than 4% of patients, all of whom were also taking clobazam. Increased alertness and improved verbal interactions were reported in 14% of patients in the CBD group and 8% of patients in the CBD and clobazam group. Benefits were more marked in the CBD alone group, in contrast to the CBD and clobazam group, but this difference was not statistically significant. In summary, these findings support efficacy of artisanal CBD preparations in seizure reduction with few significant side effects. The response to CBD was independent of concurrent clobazam use, although clobazam may contribute to the sedation seen with concurrent CBD use.

Topics: Adolescent; Anticonvulsants; Attention; Cannabidiol; Cannabis; Child; Child, Preschool; Clobazam; Drug Resistant Epilepsy; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Hospitals; Humans; Longitudinal Studies; Male; Retrospective Studies; Seizures; Treatment Outcome; United States; United States Food and Drug Administration

Topics: Alcoholism; Animals; Biomedical Research; Brazil; Cannabidiol; Cannabis; Dronabinol; Epilepsy; Freedom; Humans; Medical Marijuana; Police; Psychopharmacology; Research Personnel

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 Δ

Topics: Adolescent; Australia; Cannabinoids; Cannabis; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Routes; Epilepsy; Female; Humans; Infant; Male; Plant Extracts; Terpenes

Topics: Anticonvulsants; Cannabidiol; Cannabis; Drug Approval; Epilepsy; Europe; Humans; Legislation, Drug; Medical Marijuana; United States; United States Food and Drug Administration

Topics: Adult; Alcoholism; Aortic Coarctation; Cannabis; Cocaine-Related Disorders; Epilepsy; Female; Fetal Alcohol Spectrum Disorders; Gestational Age; Humans; Hydrops Fetalis; Hypoplastic Left Heart Syndrome; Infant, Newborn; Male; Oxazolidinones; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care; Prognosis; Substance-Related Disorders; Tobacco Use; Ultrasonography, Prenatal

Topics: Anticonvulsants; Cannabidiol; Cannabis; Child; Clinical Trials as Topic; Epilepsy; Health Services Accessibility; Humans; Legislation, Drug; Medical Marijuana; Neurologists; Parents; State Medicine; United Kingdom

Epilepsy Action Australia conducted an Australian nationwide online survey seeking opinions on and experiences with the use of cannabis-based products for the treatment of epilepsy. The survey was promoted via the Epilepsy Action Australia's main website, on their Facebook page, and by word of mouth. The survey consisted of 39 questions assessing demographics, clinical factors, including diagnosis and seizure types, and experiences with and opinions towards cannabis use in epilepsy. A total of 976 responses met the inclusion criteria. Results show that 15% of adults with epilepsy and 13% of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after commencing cannabis products. The main reasons for medicinal cannabis use were to manage treatment-resistant epilepsy and to obtain a more favorable side-effect profile compared to standard antiepileptic drugs. The number of past antiepileptic drugs tried was a significant predictor of medicinal cannabis use in both adults and children with epilepsy. Fifty-six percent of adults with epilepsy and 62% of parents/guardians of children with epilepsy expressed willingness to participate in clinical trials of cannabinoids. This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

Topics: Adolescent; Adult; Aged; Anticonvulsants; Australia; Cannabinoids; Cannabis; Child; Child, Preschool; Drug Resistant Epilepsy; Epilepsy; Female; Forecasting; Humans; Infant; Male; Marijuana Smoking; Medical Marijuana; Middle Aged; Surveys and Questionnaires; Young Adult

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation. Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and:pain and diarrhea in Crohn's disease. Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse. Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing. Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.

Topics: Cannabis; Chronic Pain; Crohn Disease; Diarrhea; Drug and Narcotic Control; Epilepsy; Humans; Inappropriate Prescribing; Inflammation; Israel; Medical Marijuana; Multiple Sclerosis; Phytotherapy; Psychoses, Substance-Induced; Substance-Related Disorders

There is a great need for safe and effective therapies for treatment of infantile spasms (IS) and Lennox-Gastaut syndrome (LGS). Based on anecdotal reports and limited experience in an open-label trial, cannabidiol (CBD) has received tremendous attention as a potential treatment for pediatric epilepsy, especially Dravet syndrome. However, there is scant evidence of specific utility for treatment of IS and LGS. We sought to document the experiences of children with IS and/or LGS who have been treated with CBD-enriched cannabis preparations. We conducted a brief online survey of parents who administered CBD-enriched cannabis preparations for the treatment of their children's epilepsy. We specifically recruited parents of children with IS and LGS and focused on perceived efficacy, dosage, and tolerability. Survey respondents included 117 parents of children with epilepsy (including 53 with IS or LGS) who had administered CBD products to their children. Perceived efficacy and tolerability were similar across etiologic subgroups. Eighty-five percent of all parents reported a reduction in seizure frequency, and 14% reported complete seizure freedom. Epilepsy was characterized as highly refractory with median latency from epilepsy onset to CBD initiation of five years, during which the patient's seizures failed to improve after a median of eight antiseizure medication trials. The median duration and the median dosage of CBD exposure were 6.8 months and 4.3mg/kg/day, respectively. Reported side effects were far less common during CBD exposure, with the exception of increased appetite (30%). A high proportion of respondents reported improvement in sleep (53%), alertness (71%), and mood (63%) during CBD therapy. Although this study suggests a potential role for CBD in the treatment of refractory childhood epilepsy including IS and LGS, it does not represent compelling evidence of efficacy or safety. From a methodological standpoint, this study is extraordinarily vulnerable to participation bias and limited by lack of blinded outcome ascertainment. Appropriately controlled clinical trials are essential to establish efficacy and safety.

Topics: Adolescent; Affect; Age of Onset; Anticonvulsants; Attention; Cannabidiol; Cannabis; Child; Drug Resistant Epilepsy; Epilepsy; Female; Health Care Surveys; Humans; Infant; Lennox Gastaut Syndrome; Male; Plant Extracts; Seizures; Sleep; Spasms, Infantile; Syndrome; Young Adult

Topics: Animals; Canada; Cannabis; Dronabinol; Drug and Narcotic Control; Drug Utilization; Epilepsy; Humans; Kindling, Neurologic; Multiple Sclerosis; Phytotherapy; Plant Preparations; Public Opinion; United States

The authors sought to determine the prevalence of marijuana use in patients with epilepsy by performing a telephone survey in a tertiary care epilepsy center. Twenty-one percent of subjects had used marijuana in the past year with the majority of active users reporting beneficial effects on seizures. Twenty-four percent of all subjects believed marijuana was an effective therapy for epilepsy. Despite limited evidence of efficacy, many patients with epilepsy believe marijuana is an effective therapy for epilepsy and are actively using it.

Topics: Adult; Alberta; Anticonvulsants; Cannabis; Culture; Drug Utilization; Epilepsy; Female; Health Surveys; Hospitals, Special; Humans; Male; Marijuana Abuse; Patients; Phytotherapy; Plant Preparations

Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.

Topics: Animals; Anticonvulsants; Brain; Cannabis; Chromatography, High Pressure Liquid; Disease Models, Animal; Dronabinol; Epilepsy; Membrane Potentials; Mice; Multiple Sclerosis; Phytotherapy; Plant Preparations; Rats

Topics: Acquired Immunodeficiency Syndrome; Cannabis; Crime; Drug and Narcotic Control; Epilepsy; Evidence-Based Medicine; Humans; Marijuana Abuse; Multiple Sclerosis; Neoplasms; Ontario; Patient Advocacy

In 1998, Washington State passed a law, Initiative 692 (I-692), that gives individuals who are charged with possession of marijuana for medical purposes a possible affirmative defense. The law lets these individuals provide a note from their doctor or a copy of their medical records stating they have a condition that may benefit from the use of marijuana. I-692 does not legalize the medical use of marijuana and does not affect Federal law, which makes obtaining, possessing, and growing marijuana illegal. The Washington law limits the amount of marijuana a patient can possess to a 60-day supply and defines the conditions for which medical marijuana may be used. These conditions include HIV, cancer, multiple sclerosis, and epilepsy.

Topics: Cannabis; Epilepsy; Glaucoma; HIV Infections; Humans; Legislation, Drug; Multiple Sclerosis; Muscle Spasticity; Neoplasms; Pain, Intractable; United States

Topics: Amphetamines; Behavior; Cannabis; Drug Therapy; Epilepsy; Heroin; Humans; Illicit Drugs; Lysergic Acid Diethylamide; Mental Disorders; Nausea; Obesity; Pain; Vomiting

Topics: Asthma; Cannabinoids; Cannabis; Depression; Dronabinol; Drug Stability; Epilepsy; Glaucoma; Humans; Pain; Vomiting

Topics: Cannabis; Epilepsy; Humans; New Mexico; Substance-Related Disorders

Beta9-THC was injected daily for 6 days into gerbils from our breeding colony that exhibit spontaneous epileptiform seizures. At a dose of 20 mg/kg no effect was seen on the latency, duration or severity of the seizures induced after 1 and 6 days of treatment. Delta9-THC (50 mg/kg) completely abolished the seizures after a single injection but tolerance developed to this effect so that no protection was afforded after 6 daily doses. Severe toxic signs were evident at the higher dose level with marked depression of spontaneous motor activity. The toxic effect increased progressively with chronic treatment and half the animals failed to survive.

Topics: Animals; Cannabis; Dronabinol; Drug Tolerance; Epilepsy; Female; Gerbillinae; Male; Motor Activity; Time Factors

Acute administration of delta8-tetrahydrocannabinol (delta8-THC) or delta9-THC failed to affect partially developed or fully developed kindled amygdaloid seizures in cats. However, delta9-THC was quite effective in suppressing focal AD in the stimulated amygdala when administered very early in kindling, before the development of any clinical manifestations. This finding suggested that chronic administration of delta9-THC during kindling might block the process of seizure development, which was supported by the observation that three of four cats failed to kindle when treated with the drug. The cat that failed to be protected by delta9-THC was also insensitive to the general electroclinical effects of moderately high doses of delta9-THC. The prophylactic activity of delta9-THC is in contrast to the ineffectiveness of diphenylhydantoin, a drug whose anticonvulsant activity is often compared with that of THC.

Topics: Amygdala; Animals; Anticonvulsants; Cannabis; Cats; Dose-Response Relationship, Drug; Dronabinol; Electric Stimulation; Epilepsy; Female; Isomerism; Male; Phytotherapy; Seizures

The anticonvulsant activity of delta9-tetrahydrocannabinol (delta9-THC) has been determined against seizures induced in epileptic chickens by intermittent photic stimulation (IPS) and in epileptic and nonepileptic chickens by Metrazol. Intravenous administration of the drug reduced both the severity and incidence of seizures evoked by IPS in epileptic chickens. This anticonvulsant action was accompanied by a reduction in frequency of inter-ictal slow-wave high-voltage electroencephalographic activity and by the absence of spiking during IPS. delta9-THC did not affect the incidence of Metrazol-induced seizures in epileptic or nonepileptic chickens.

Topics: Animals; Anticonvulsants; Cannabis; Chickens; Dronabinol; Electroencephalography; Epilepsy; Female; Male; Pentylenetetrazole; Time Factors

Topics: Adolescent; Age Factors; Anxiety; Cannabis; Child; Child Development; Child Psychiatry; Diagnosis, Differential; Electroencephalography; Epilepsy; Female; Hallucinations; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Male; Meprobamate; Neurocognitive Disorders; Phenols; Prognosis; Psychoses, Substance-Induced; Psychotic Disorders; Schizophrenia

Topics: Adolescent; Adult; Affective Symptoms; Age Factors; Aged; Anxiety Disorders; Cannabis; Child; Child Behavior Disorders; Child, Preschool; Egypt; Enuresis; Epilepsy; Family Characteristics; Female; Humans; Hypochondriasis; Hysteria; Infant; Male; Mental Disorders; Middle Aged; Obsessive-Compulsive Disorder; Occupations; Personality Disorders; Schizophrenia; Sex Factors; Social Class; Stuttering; Substance-Related Disorders