humulene and Seizures

The active principles of Cannabis sativa are potential treatments for several diseases, such as pain, seizures and anorexia. With the increase in the use of cannabis for medicinal purposes, a more careful assessment of the possible impacts on embryonic development becomes necessary. Surveys indicate that approximately 3.9% of pregnant women use cannabis in a recreational and/or medicinal manner. However, although the literature has already described the presence of endocannabinoid system components since the early stages of CNS development, many of their physiological effects during this stage have not yet been established. Moreover, it is still uncertain how the endocannabinoid system can be altered in terms of cell proliferation and cell fate, neural migration, neural differentiation, synaptogenesis and particularly cell death. In relation to cell death in the CNS, knowledge about the effects of cannabinoids is scarce. Thus, the present work aims to review the role of the endocannabinoid system in different aspects of CNS development and discuss possible side effects or even opportunities for treating some conditions in the development of this tissue.

Topics: Cannabinoids; Cannabis; Cell Proliferation; Endocannabinoids; Female; Humans; Pregnancy; Seizures

Cannabidiol (CBD) is one of the main phytocannabinoids found in Cannabis sativa. In contrast to Δ9-tetrahydrocannabinol, it has a low affinity for cannabinoid receptors CB1 and CB2, thereby it does not induce significant psychoactive effects. However, CBD may interact with other receptors, including peroxisome proliferator-activated receptor gamma (PPARγ). CBD is a PPARγ agonist and changes its expression. There is considerable evidence that CBD's effects are mediated by its interaction with PPARγ. So, we reviewed studies related to the interaction of CBD and PPARγ.. In this comprehensive literature review, the term 'cannabidiol' was used in combination with the following keywords including 'PPARγ', 'Alzheimer's disease', 'Parkinson's disease', 'seizure', 'multiple sclerosis', 'immune system', 'cardiovascular system', 'cancer', and 'adipogenesis'. PubMed, Web of Science, and Google Scholar were searched until December 20, 2022. A total of 78 articles were used for the reviewing process.. CBD, via activation of PPARγ, promotes significant pharmacological effects. The present review shows that the effects of CBD on Alzheimer's disease and memory, Parkinson's disease and movement disorders, multiple sclerosis, anxiety and depression, cardiovascular system, immune system, cancer, and adipogenesis are mediated, at least in part, via PPARγ.. CBD not only activates PPARγ but also affects its expression in the body. It was suggested that the late effects of CBD are mediated via PPARγ activation. We suggested that CBD's chemical structure is a good backbone for developing new dual agonists. Combining it with other chemicals enhances their biological effectiveness while reducing their dosage. The present study indicated that PPARγ is a key target for CBD, and its activation by CBD should be considered in all future studies.

Topics: Cannabidiol; Cannabis; Humans; PPAR gamma; Sclerosis; Seizures

The endocannabinoid system (ECS) is an integral neuromodulatory system involved in neuronal development, synaptic plasticity, and homeostasis regarding immunity, as well as brain and other physiological functions such as anxiety, pain, metabolic regulation, and bone growth. Cannabis is a plant that contains exogenous cannabinoids, which have the potential for profound interplay within the ECS as enzymatic inhibitors or receptor-mediated interactions. Activation of cannabinoid receptors leads to various intracellular signaling processes that are involved in cellular functions, but those interactions are diverse due to different affinities of each cannabinoid with relevant receptors. Among the exogenous cannabinoids, cannabidiol (CBD) has drawn attention due to its potential anticancer, antiangiogenic, anti-inflammatory, and antiseizure properties using in vitro and in vivo models. Although scientific evidence is limited in dogs, there appears to be cautious optimism regarding the utilization of CBD in conjunction with other therapeutics for a range of disorders. This review will primarily focus on current scientific research on the efficacy of CBD on seizure, anxiety, osteoarthritis, and atopic dermatitis, following a brief discussion of endo- and exogenous cannabinoids, ECS, their molecular mechanism, and potential side effects in veterinary medicine. Cannabinoid pharmacology and pharmacokinetics will be addressed in the companion Currents in One Health by Schwark and Wakshlag, AJVR, May 2023.

Topics: Animals; Cannabidiol; Cannabinoids; Cannabis; Dog Diseases; Dogs; Humans; Seizures

Cannabis use in the United States is growing at an unprecedented pace. Most states in the United States have legalized medical cannabis use, and many have legalized nonmedical cannabis use. In this setting, health care professionals will increasingly see more patients who have questions about cannabis use, its utility for medical conditions, and the risks of its use. This narrative review provides an overview of the background, pharmacology, therapeutic use, and potential complications of cannabis.

Topics: Adult; Cachexia; Cannabis; Endocannabinoids; Female; Health Personnel; Humans; Legislation, Drug; Male; Medical Marijuana; Nausea; Neurobiology; Opioid-Related Disorders; Seizures; Severity of Illness Index; Somatoform Disorders; Spasm; Stress Disorders, Post-Traumatic; United States

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' effect on seizure activity is an emerging topic that remains without consensus and merits further investigation. We therefore performed a scoping review to identify the available evidence and knowledge gaps within the existing literature on cannabis product exposures as a potential cause of seizures in humans.. A scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews guidelines. The PubMed and Scopus databases were searched over a 20-year period from the date of the database query (12/21/2020). Inclusion criteria were (1) English language original research articles, (2) inclusion of human subjects, and (3) either investigation of seizures as a part of recreational cannabinoid use OR of exogenous cannabinoids as a cause of seizures.. A total of 3104 unique articles were screened, of which 68 underwent full-text review, and 13 met inclusion/exclusion criteria. Ten of 11 studies evaluating acute cannabis exposures reported a higher seizure incidence than would be expected based on the prevalence of epilepsy in the general and pediatric populations (range 0.7-1.2% and 0.3-0.5% respectively). The remaining two studies demonstrated increased seizure frequency and/or seizure-related hospitalization in recreational cannabis users and those with cannabis use disorder.. This scoping review demonstrates that a body of literature describing seizures in the setting of cannabis exposure exists, but it has several limitations. Ten identified studies showed a higher than expected incidence of seizures in populations exposed to cannabis products. Based on the Bradford Hill criteria, delta-9 tetrahydrocannabinol (THC) may be the causative xenobiotic for this phenomenon.

Topics: Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Child; Hallucinogens; Humans; Seizures

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

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

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

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

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

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

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

Topics: Amphetamines; Animals; Brain; Brain Damage, Chronic; Cannabis; Catecholamines; DOM 2,5-Dimethoxy-4-Methylamphetamine; Dose-Response Relationship, Drug; Dronabinol; Hallucinogens; Haplorhini; Humans; Injections, Intravenous; Lysergic Acid Diethylamide; Mescaline; N,N-Dimethyltryptamine; Narcolepsy; Psilocybin; Rats; Seizures; Serotonin Antagonists; Substance-Related Disorders

The safety and efficacy of a formulation high in cannabidiol (CBD) and low in ∆. An open-label, prospective cohort, single-center in adult patients with DRFE, were receiving stable doses of antiepileptic drugs (AEDs). A cannabis based-magistral formulation (CBMF) (100 mg/ml CBD and THC <1.9 mg/ml) was administrated 0.1 ml sublingually every 12 hours, up-titrated weekly. The primary outcome was to establish a reduction in seizures frequency >50% at 12 weeks. Adverse-drug reactions monitoring was done. p-value <0.05 was statistically significant.. Between August 2020 and July 2022, 44 (38.6%) patients completed >3 months of follow-up. The median daily dose of CBD was 200 mg, that of THC was 4 mg, and that of CBD per kilogram of weight was 3.7 mg. The median number of seizures per month before CBD treatment was 11, and after CBD treatment was 2.5 (p<0.001). A reduction in seizures >50% at 12 week was achieved in 79.5% of the patients. The median percentage change in seizure frequency per month was 84.1% at 12 weeks. Five patients reported any adverse-drug reactions.. The CBMF is a highly effective and safety therapy to treat adult patients with DRFE. The reduction in seizures frequency is maintained over time.

Topics: Adjuvants, Immunologic; Adult; Anticonvulsants; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Child; Drug Resistant Epilepsy; Epilepsies, Partial; Humans; Prospective Studies; Seizures

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

Delta-8-tetrahydrocannabinol (THC) is a known isomer of delta-9-THC, both found naturally in the Cannabis sativa plant and thought to have similar potency. Delta-8-THC products are widely accessible in retail shops which may lead to a rise in pediatric exposures with substantial clinical effects.. This is a case series of four pediatric patients that were seen between June and September 2021. The patients presented with varied clinical symptoms including confusion, somnolence, seizure-like activity, hypotension, and tachycardia after exposure to delta-8-THC products obtained in retail shops. Basic urine drug screen immunoassays revealed positive results for cannabinoids in all patients. Subsequent confirmatory drug analysis of residual biological samples of blood and/or urine was sent to the University of California San Francisco Clinical Toxicology and Environment Biomonitoring Laboratory with the assistance of the Drug Enforcement Administration's Toxicology Testing Program (DEA TOX). Confirmatory testing revealed 11-nor-9-carboxy-delta-8-THC, the metabolite of delta-8-THC. Delta-9-THC and its metabolites were not detected on confirmatory testing in any of the cases.. Clinical effects of delta-8-THC in children include but are not limited to altered mental status, seizure-like activity, and vital sign abnormalities. Delta-8-THC exposure may lead to a positive urine drug screen for cannabinoids, but confirmatory testing is needed to differentiate from delta-9-THC.

Topics: Cannabinoids; Cannabis; Child; Dronabinol; Humans; Seizures

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

Cannabis has demonstrated anticonvulsant properties, and about thirty percent of epileptic patients do not have satisfactory seizure management with standard treatment and could potentially benefit from cannabis-based intervention. Here, we report the use of cannabinoids to treat pentylenetetrazol (PTZ)-induced convulsions in a zebrafish model, their effect on gene expression, and a simple assay for assessing their uptake in zebrafish tissues. Using an optimized behavioral assay, we show that cannabidiol (CBD) and cannabichromene (CBC) and cannabinol (CBN) are effective at reducing seizures at low doses, with little evidence of sedation, and our novel HPLC assay indicates that CBC is effective with the lowest accumulation in larval tissues. All cannabinoids tested were effective at higher concentrations. Pharmacological manipulation of potential receptors demonstrates that Gpr55 partially mediates the anticonvulsant effects of CBD. Treatment of zebrafish larvae with endocannabinoids, such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA), altered larvae movement, and the expression of genes that regulate their metabolism was affected by phytocannabinoid treatment, highlighting the possibility that changes to endocannabinoid levels may represent one facet of the anticonvulsant effect of phytocannabinoids.

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinol; Cannabis; Endocannabinoids; Gene Expression; Humans; Seizures; Zebrafish

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

Topics: Benzoates; Cannabidiol; Cannabis; Humans; Seizures

In Algeria, hashish is by far the most common illicit drug. This study explores Algerian hashish over a two-year period (2019-2020). A total of 2583 hashish samples from 1707 seizures for a total quantity of 108 tons were analyzed using a validated high-performance liquid chromatography-diode array detection method (HPLC-DAD). The yearly arithmetic mean tetrahydrocannabinol (THC) concentration shows relative stability-18.67% in 2019 and 19.03% in 2020 with an overall mean THC content of 18.87% and standard deviation of 10.99%. High-potency hashish (THC content > 20%) is by far the most predominant type, representing almost 50% of the total Algerian hashish seizures (mean and median around 29%). The overall mean of cannabidiol (CBD) was 2.45%, and 12% of the total studied seizures were of very low CBD concentration (CBD content<1%). Three distinct hashish chemotypes were identified: Chemotype I described the traditional Moroccan hashish with THC content ranging from 0% to 16%, Chemotype II hashish included most of the seizures and characterized by THC content ranging from 16% to 30%, and Chemotype III was characterized by hashish potency higher than 30% and very low CBD content. The identified chemotypes I, II, and III were characterized in a ternary plot, and the relative contents (THC:CBD:CBN) were about 67%:29%:4%, 88%:9%:3%, and 96%:2%:2%, respectively.

Topics: Algeria; Cannabidiol; Cannabis; Dronabinol; Seizures

To investigate if clinical features associated with acute cannabis intoxication in patients presenting to Emergency Departments for medical assistance differ according to patient age and sex.. We analysed presentations in the Euro-DEN Plus dataset from 2014 to 2019 in which cannabis was the only drug involved (except for alcohol), and age, sex and alcohol co-ingestion had been recorded. Age was considered as categorical (five groups; <20, 20-29, 30-39, 40-49 and ≥50 years), and sex as binary variable (male/female). We evaluated 12 key clinical features recorded during emergency department (ED) care. Risks of presenting with each of these clinical features according to patient age and sex were calculated by logistic regression models, and adjusted for sex, age and alcohol co-ingestion.. 4,268 of 43,633 Euro-DEN presentations (9.8%) fulfilled the inclusion criteria (median age: 26 years (IQR = 20-34), 70% male, 52% co-ingested alcohol). The frequency of clinical features was: anxiety 28%, vomiting 24%, agitation 23%, palpitations 14%, reduced consciousness 13%, acute psychosis 9%, hallucinations 9%, chest pain 7%, headache 6%, hypotension 4%, hypertension 3% and seizures 2%. Patients younger than 20 years more frequently had vomiting (34.7% of cases), reduced consciousness (21.5%), and headache (10.8%); and less frequently acute psychosis (5.5%). Patients older than 49 years more often had hypotension (6.5%) and less frequently vomiting (20%), anxiety (14%), agitation (14%) and reduced consciousness (10%). Males more frequently presented with hypertension (3.7 vs. 1.5%; OR = 2.311, 95%CI = 1.299-3.816), psychosis (10.4 vs 6.3%; 1.948, 1.432-2.430), chest pain (8.1 vs 4.5%; 1.838, 1.390-2.430) and seizures (2.5 vs 1.4%; 1.805, 1.065-3.060), and less frequently with vomiting (21.8 vs 28.2%; 0.793, 0.677-0.930), anxiety (25.4 vs 32.3%; 0.655, 0.561-0.766) and hypotension (2.9 vs 5.8%; 0.485, 0.350-0.671).. The prevalence of some clinical features typically associated with acute cannabis intoxication differed according to age and sex. The causes for these differences should be further investigated in order to better understand the pathophysiology of cannabis-related acute toxicity, and they may be relevant particularly for developing prevention campaigns and for treatment in specific sex and/or age groups.

Topics: Adult; Cannabis; Chest Pain; Emergency Service, Hospital; Ethanol; Female; Headache; Humans; Hypertension; Hypnotics and Sedatives; Hypotension; Male; Middle Aged; Psychotropic Drugs; Seizures; Vomiting

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

We present five cases of pediatric drug-resistant epilepsy (DRE) that failed management using high cannabidiol (CBD) doses, but had significant reduction in seizure frequency with reintroduction or increasing doses of tetrahydrocannabinol (THC). There is growing evidence supporting the use of whole-plant CBD-rich extracts (containing THC and other cannabinoids) in the treatment of pediatric DRE. Based on our experiences and reports in the literature, we propose that, in patients who fail management with an initial trial of high-dose CBD-focused therapy, there may be a role for add-on THC-focused formulations.

Topics: Cannabidiol; Cannabis; Child; Dronabinol; Drug Resistant Epilepsy; Humans; Plant Extracts; Seizures

Due to the popularity of recreational cannabis use, contamination of this drug with diverse classes of chemicals, including pesticides, mycotoxins, and synthetic cannabinoids, has been identified as major threat for public health. For the detection of these compounds in seized cannabis, a screening workflow involving non-targeted liquid chromatography-tandem mass spectrometry (LCMS/MS) was developed. A Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method was used for the extraction of small bioorganic molecules from ground dried material. Instrumental analysis involved chromatographic separation of compounds and subsequent mass spectrometric detection. Collection of MS and MS/MS information was accomplished by data-dependent acquisition. Compound identification was primarily based on matching acquired MS/MS-spectra to several thousands of reference spectra stored in multiple libraries. Additionally, for selected cannabinoid and pesticide standards, a retention time library was developed. Performance of the workflow was evaluated for 182 pesticides. All tested pesticides were detectable at 5000 μg/kg, 94 % at 500 μg/kg, and 50 % at 50 μg/kg. The workflow was applied to the screening of seized cannabis samples. 41 out of 93 analysed samples (44 %) were tested positive for one or more contaminants impairing quality and/or safety of the material. The detected contaminants included a synthetic cannabinoid (5F-MDMB-PINACA), fifteen pesticide residues (boscalid, carbendazim, chlorantraniliprole, chlorpyrifos, chlorotoluron, cyprodinil, diflubenzuron, ethiofencarb sulfoxide, hexythiazox, iprodione, metalaxyl, pyrimethanil, terbutryn, thiophanate methyl, and trifloxystrobin), and a mycotoxin (sterigmatocystin).

Topics: Cannabis; Chromatography, Liquid; Pesticide Residues; Seizures; Tandem Mass Spectrometry

CDKL5 Deficiency Disorder (CDD) is a severe treatment-resistant form of early-onset epilepsy. Current treatment options are often ineffective and associated with adverse effects, forcing families to seek alternative therapies for their children including products derived from cannabis. Reportsof miraculous cures and a public preferencefor 'natural' therapies have resulted in considerable public interest, and so this study aimed to characterize the use of cannabis in these individuals, as well as compare caregiver perceptions of efficacy and safety to objective evidence of seizure control and number of antiepileptic drugs used.. Families from the International CDKL5 Disorder Database were invited to complete questionnaires which included data relating to their child's current and past treatments, including use of any cannabis-derived preparations. Perceived effects on seizure control, as well as additional benefits and adverse effects were reported. Seizure frequency and number of antiepileptic drugs were compared between those actively using cannabis products and those who were not. Longitudinal analysis was performed on a subset of the study population to compare these same variables at pre-treatment and post-treatment time points.. Three hundred and twelve caregivers answered questions regarding their child's use of antiepileptic medications. Of these, 82 (26%) described use of cannabis preparations either at present, or in the past, with the most common being cannabidiol. Of 70 caregivers that described their perceived effect on seizure control, more than two thirds reported an improvement in seizure control, either temporary (16%) or lasting (54%). Additional benefits included improvements in attention, cognition, and sleep. The majority of responses (78%) described adverse effects as 'none', though some reported an increase in sedation and gastrointestinal upset. There was no reduction in the median seizure frequency nor the number of different antiepileptic drugs, for those who were actively using cannabis products compared to those who were not. Similarly, individuals who were not using cannabis products at an initial time point had no differences in seizure frequency nor number of antiepileptic drugs at a second timepoint when they had started using this treatment.. Although this is an observational study, limited by potential participation bias and the unreliable nature of unblinded self-assessment, it suggests that caregivers perceive cannabis products, especially cannabidiol, to have a tolerable adverse effect profile and adequate efficacy. Despite this, cannabis was not associated with a reduction in seizure frequency nor number of antiepileptic drugs when compared to non-users or when compared to pre-treatment. Randomized controlled trials are urgently needed to more reliably assess this treatment's safety and efficacy.

Topics: Cannabis; Child; Drug Resistant Epilepsy; Epileptic Syndromes; Humans; Protein Serine-Threonine Kinases; Seizures; Spasms, Infantile

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

Electronic nicotine delivery systems (ENDS) use poses significant and avoidable health risks to young people. Until recently, seizures were most often associated with cases of liquid nicotine ingestion.. We examined 122 voluntary reports of seizures (n = 114) and neurological symptoms (syncope, n = 7; and tremor, n = 1) in 123 ENDS users (one report contained information on two users) received by the Food and Drug Administration between December 1, 2010, and June 30, 2019.. The median age (interquartile range) of users was 20 years (17-27); 67% of reports were in youth and young adults aged 14-24 years. Fifty-one (41%) reported other underlying medical conditions, including previous history of anxiety (n = 11), attention deficit hyperactivity disorder (n = 7), seizure (n = 6), and depression (n = 5). Of the 79 reports with available information, 67 (85%) reported seizure occurred within 24 hours of last use; 49 (62%) reported seizure within 30 minutes. The potential impact of concomitant use of marijuana or cannabidiol oil could not be evaluated from the eight reports that mentioned concomitant use.. Findings suggest an association between ENDS use and seizures. Additional information will help to clarify the relationship between ENDS use and seizures and to understand how product attributes such as nicotine content, formulation, quantity, and other ingredients or contaminants may contribute to seizures. It is important that health care providers ask about ENDS use when evaluating neurological symptoms and that users, parents, school personnel, and health care providers report adverse experiences involving tobacco products to Food and Drug Administration via the Safety Reporting Portal (www.safetyreporting.hhs.gov).

Topics: Adolescent; Adult; Cannabis; Electronic Nicotine Delivery Systems; Humans; Nicotine; Seizures; Tobacco Products; Vaping; Young Adult

The therapeutic effect of the

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabis; Delayed-Action Preparations; Drug Liberation; Mice; Pentylenetetrazole; Plant Extracts; Seizures

Current antiepileptic drugs (AEDs) are undesirable for many reasons including the inability to reduce seizures in certain types of epilepsy, such as Dravet syndrome (DS) where in one-third of patients does not respond to current AEDs, and severe adverse effects that are frequently experienced by patients. Epidiolex, a cannabidiol (CBD)-based drug, was recently approved for treatment of DS. While Epidiolex shows great promise in reducing seizures in patients with DS, it is used in conjunction with other AEDs and can cause liver toxicity. To investigate whether other cannabis-derived compounds could also reduce seizures, the antiepileptic effects of CBD, Δ9-tetrahydrocannabinol (THC), cannabidivarin (CBDV), cannabinol (CBN), and linalool (LN) were compared in both a chemically-induced (pentylenetetrazole, PTZ) and a DS (scn1Lab

Topics: Acyclic Monoterpenes; Animals; Animals, Genetically Modified; Anticonvulsants; Cannabidiol; Cannabinoids; Cannabinol; Cannabis; Dose-Response Relationship, Drug; Dronabinol; NAV1.1 Voltage-Gated Sodium Channel; Pentylenetetrazole; Seizures; Zebrafish; Zebrafish Proteins

Cannabis extract effects on in vivo neurological and behavioural responses, and on bioanalyte levels, were measured in rats and dogs. Extract effects on seizure activity were measured using electroencephalography telemetry in rats. eCB signalling was also investigated using radioligand binding in cannabis extract-treated rats and treatment-naïve rat, mouse, chicken, dog and human tissue.. Prolonged exposure to cannabis extracts caused spontaneous, generalized seizures, subserved by epileptiform discharges in rats, but not dogs, and produced higher THC, but lower 11-hydroxy-THC (11-OH-THC) and CBD, plasma concentrations in rats versus dogs. In the same rats, prolonged exposure to cannabis also impaired cannabinoid type 1 receptor (CB. Sustained cannabis extract treatment caused differential seizure, behavioural and bioanalyte levels between rats and dogs. Supporting radioligand binding data suggest species differences in eCB signalling. Interspecies variations may have important implications for predicting cannabis-induced convulsions from animal models.

Topics: Animals; Behavior, Animal; Cannabinoids; Cannabis; Dogs; Dose-Response Relationship, Drug; Female; Male; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Seizures; Signal Transduction; Species Specificity

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

AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects.. The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ. For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. Furthermore, this study outlines the potential detrimental effects of SCBs on human health.

Topics: Adamantane; Aggression; Animals; Behavior, Animal; Binding, Competitive; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Cannabis; Catalepsy; Dopamine; Dronabinol; Humans; In Vitro Techniques; Indazoles; Indoles; Male; Mice; Motor Activity; Naphthalenes; Nucleus Accumbens; Pain Threshold; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Reflex, Abnormal; Seizures

Oral cannabis extracts (OCEs) have been used in the treatment of epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort of pediatric patients with epilepsy who were given OCE and followed in a single tertiary epilepsy center.. A retrospective chart review of children and adolescents who were given OCE for treatment of their epilepsy was performed.. Seventy-five patients were identified of which 57% reported any improvement in seizure control and 33% reported a >50% reduction in seizures (responders). If the family had moved to CO for OCE treatment, the responder rate was 47% vs. 22% for children who already were in CO. The responder rate varied based on epilepsy syndrome: Dravet 23%, Doose 0%, and Lennox-Gastaut syndrome (LGS) 88.9%. The background EEG of the 8 responders where EEG data were available was not improved. Additional benefits reported included: improved behavior/alertness (33%), improved language (10%), and improved motor skills (10%). Adverse events (AEs) occurred in 44% of patients including increased seizures (13%) and somnolence/fatigue (12%). Rare adverse events included developmental regression, abnormal movements, status epilepticus requiring intubation, and death.. Our retrospective study of OCE use in pediatric patients with epilepsy demonstrates that some families reported patient improvement with treatment; however, we also found a variety of challenges and possible confounding factors in studying OCE retrospectively in an open-labeled fashion. We strongly support the need for controlled, blinded studies to evaluate the efficacy and safety of OCE for treatment of pediatric epilepsies using accurate seizure counts, formal neurocognitive assessments, as well as EEG as a biomarker. This study provides Class III evidence that OCE is well tolerated by children and adolescents with epilepsy.

Topics: Adolescent; Anticonvulsants; Cannabis; Child; Child, Preschool; Drug Resistant Epilepsy; Epilepsies, Myoclonic; Female; Humans; Infant; Lennox Gastaut Syndrome; Male; Parents; Plant Extracts; Retrospective Studies; Seizures; Treatment Outcome

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: Adolescent; Appetite; Biomedical Research; Cannabis; Child; Colorado; Confounding Factors, Epidemiologic; Dronabinol; Humans; Marijuana Abuse; Marijuana Smoking; Medical Marijuana; Multiple Sclerosis; Netherlands; New Zealand; Prevalence; Schizophrenia; Seizures; Sweden; Young Adult

Topics: Acquired Immunodeficiency Syndrome; Biomedical Research; California; Canada; Cannabinoids; Cannabis; Clinical Trials as Topic; Crohn Disease; Drug and Narcotic Control; Female; Humans; Inflammation; Leadership; Male; Medical Marijuana; Multiple Sclerosis; Pain; Policy Making; Research Personnel; Seizures; Stress Disorders, Post-Traumatic

Topics: Allosteric Site; Analgesics; Animals; Cannabidiol; Cannabinoids; Cannabis; Child; Clinical Trials as Topic; Congresses as Topic; Dronabinol; Drug Combinations; Drug Discovery; Endocannabinoids; Humans; Mice; Plant Extracts; Receptors, Cannabinoid; Seizures; Terpenes

Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors.. The anticonvulsant profiles of two CBDV BDSs (50-422 mg·kg(-1) ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays.. CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg(-1) ) and audiogenic seizure models (≥87 mg·kg(-1) ), and suppressed pilocarpine-induced convulsions (≥100 mg·kg(-1) ). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ(9) -tetrahydrocannabinol and Δ(9) -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV.. CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.

Topics: Animals; Anticonvulsants; Brain; Cannabidiol; Cannabinoids; Cannabis; Disease Models, Animal; Dose-Response Relationship, Drug; Hand Strength; Male; Mice; Mice, Inbred DBA; Motor Activity; Noise; Pentylenetetrazole; Phytotherapy; Pilocarpine; Plant Extracts; Plants, Medicinal; Protein Binding; Rats; Rats, Inbred WKY; Receptor, Cannabinoid, CB1; Seizures

Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models.. The effect of CBDV (1-100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-aminopyridine (4-AP) application or Mg(2+) -free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50-200 mg·kg(-1) ) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile of CBDV was investigated using static beam and grip strength assays.. CBDV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg(2+) -free conditions. CBDV had significant anticonvulsant effects on the mES (≥100 mg·kg(-1) ), audiogenic (≥50 mg·kg(-1) ) and PTZ-induced seizures (≥100 mg·kg(-1) ). CBDV (200 mg·kg(-1) ) alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at this dose. CBDV had no effect on motor function.. These results indicate that CBDV is an effective anticonvulsant in a broad range of seizure models. Also it did not significantly affect normal motor function and, therefore, merits further investigation as a novel anti-epileptic in chronic epilepsy models.. This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8.

Topics: Animals; Anticonvulsants; Cannabinoids; Cannabis; Disease Models, Animal; Female; Hippocampus; In Vitro Techniques; Male; Mice; Mice, Inbred DBA; Mice, Inbred ICR; Motor Activity; Pentylenetetrazole; Phytotherapy; Pilocarpine; Rats; Rats, Inbred WKY; Seizures

While animal models of epilepsy suggest that exogenous cannabinoids may have anticonvulsant properties, scant evidence exists for these compounds' efficacy in humans. Here, we report on two patients whose focal epilepsy was nearly controlled through regular outpatient marijuana use. Both stopped marijuana upon admission to our epilepsy monitoring unit (EMU) and developed a dramatic increase in seizure frequency documented by video-EEG telemetry. These seizures occurred in the absence of other provocative procedures, including changes to anticonvulsant medications. We review these cases and discuss mechanisms for the potentially anticonvulsant properties of cannabis, based on a review of the literature.

Topics: Adult; Brain; Cannabis; Electroencephalography; Epilepsies, Partial; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Phytotherapy; Seizures; Substance Withdrawal Syndrome; Tomography, Emission-Computed, Single-Photon

This report describes clinical signs and plasma biochemical changes associated with significant cannabis consumption in three Green iguanas (Iguana iguana) which resulted in seizures, cardiovascular and digestive tract aberrations, elevated hepatic enzymes and bile acid concentrations for a number of weeks post recovery. One case required extensive antiseizuring therapy to recover. All Green iguanas eventually made a full recovery.

Topics: Animals; Anticonvulsants; Cannabis; Diazepam; Female; Iguanas; Male; Seizures; Treatment Outcome

Topics: Cannabis; Child, Preschool; Humans; Plant Poisoning; Seizures

Topics: Ataxia; Cannabis; Child, Preschool; Diagnosis, Differential; Female; Humans; Plant Poisoning; Seizures; Tremor

Topics: Administration, Oral; Age Factors; Cannabis; Diagnosis, Differential; Humans; Hypothermia; Infant; Male; Poisoning; Reflex, Abnormal; Seizures

Topics: Cannabis; Drug and Narcotic Control; Government Agencies; Humans; Nausea; Needs Assessment; Patient Advocacy; Phytotherapy; Risk; Seizures; Spasm; State Government; Substance-Related Disorders; Treatment Outcome; United States

Topics: Anticonvulsants; Cannabinoids; Cannabis; Case-Control Studies; Female; Humans; Male; New York City; Risk Factors; Seizures

Prisoners deserve to be taken seriously and treated with respect by the physician, as does any person seeking medical care. Treatment should include an adequate history and physical examination as well as indicated laboratory tests. Anxiety is a ubiquitous problem in prison life and can adversely affect any medical condition. The diagnosis of malingering is and should be one of exclusion, and the physician should keep in mind that a seemingly healthy prisoner might have several other reasons for seeking medical help. The physician needs to be confident of the diagnosis before returning the person to the cell block, as prisoners do not have freedom of access to medical care. New standards, programs, literature, journals, and conferences have drawn attention to the jail as a place where the physician can intervene in a positive way to decrease the recycling of crime and illness. It is not enough to be able to practice good medicine in a jail. Such practice must recognize the special needs of prisoners and the special problems inherent in the jail environment.

Topics: Adult; Alcoholism; Cannabis; Diazepam; Ethics, Medical; Female; Health Services; Heroin; Humans; Male; Mental Disorders; Physician-Patient Relations; Prisoners; Prisons; Seizures; Substance-Related Disorders; Tuberculosis; United States

In a genetically unique colony of tetrahydrocannabinol-seizure susceptible (THC-SS) rabbits, nonfatal convulsions are elicited by delta 9THC, the major psychoactive ingredient of marijuana. The major characteristics of cannabinoid-produced psychoactivity (the "high") in humans, e.g., dose-effect relationships, specificity of response to only psychoactive cannabinoids, tolerance development, EEG correlates, and delta 9THC-cannabidiol interactive effects, are also characteristics of cannabinoid-induced behavioral convulsions in the rabbits. Because of these and other theoretical and practical considerations, it is hypothesized that the THC-SS rabbit represents a novel laboratory animal model of marijuana-induced psychoactivity in humans.

Topics: Animals; Behavior, Animal; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Tolerance; Electroencephalography; Humans; Models, Biological; Rabbits; Seizures

Topics: Adolescent; Brain; Cannabis; Child; Dronabinol; Humans; Lung; Seizures

Topics: Animals; Behavior, Animal; Cannabis; Dogs; Drug Synergism; Electroencephalography; Penicillin G; Seizures; Time Factors

Various basic esters of nitrogen (2) and carbocyclic (3 and 4) analogs of cannabinoids were synthesized using dicyclohexylcarbodiimide in methylene chloride. The compounds in the three series werw studied in selected pharmacological tests in mice, rats, dogs, and cats. It was shown that making the basic ester from the phenol retains biological activity and can lead to a greater selectivity of action, particularly the antinociceptive activity. The most interesting esters were 5, 6, 10, and 14 in the nitrogen analogs series and 19 and 20 in the carbocyclic series. Compound 5 was more potent than codeine in the writhing, hot-plate, and tail-flick tests and is at present undergoing clinical testing. Compound 20 was very potent in the mouse audiogenic seizure test and is of interest as an anticovulsant agent.

Topics: Acoustic Stimulation; Aggression; Analgesics; Animals; Ataxia; Behavior, Animal; Cannabis; Cats; Dihydroxyphenylalanine; Dogs; Dronabinol; Esters; Haplorhini; Humans; Hypnotics and Sedatives; Lethal Dose 50; Male; Mice; Motor Activity; Phytotherapy; Rats; Reaction Time; Seizures; Sleep; Structure-Activity Relationship

Various CNS-active cannabinoids in which the alicyclic ring was thiopheno, cyclopenteno, or cyclohexeno with the alkyl substituent in various positions (structural types 1-6) were synthesized by procedures described previously. These compounds were compared in selected pharmacological tests in mice, rats, dogs, and cats. The results suggested that methyl substitution in the close proximity of the phenolic hydroxyl group strongly influenced the activity of some cannabinoids, particularly of those which had a planar five-membered alicyclic ring rather than a six-membered ring.

Topics: Acoustic Stimulation; Aggression; Analgesics; Animals; Ataxia; Cannabis; Cats; Cyclohexanes; Cyclopentanes; Dihydroxyphenylalanine; Dogs; Humans; Hypnotics and Sedatives; Mice; Motor Activity; Phytotherapy; Rats; Reaction Time; Seizures; Structure-Activity Relationship; Thiophenes

Delta9-tetrahydrocannabinol (THC) was compared with diphenylhydantoin (DPH), phenobarbital (PB) and chlordiazepoxide (CDP) using several standard laboratory procedures to determine anticonvulsant activity in mice, i.e., the maximal electroshock test (MES), and seizures induced by pentylenetetrazol, strychnine and nicotine. In the MES test, THC was the least potent and DPH the most potent blocker of hind limb tonic extensor convulsions whereas THC was the most potent and DPH the least potent in increasing the latency to this response and in preventing mortality. Seizures and mortality induced by pentylenetetrazol or by strychnine were enhanced by THC and DPH and were blocked by PB and CDP. In the test with nicotine, none of the four anticonvulsant agents prevented seizures; DPH was the only one which failed to increase latency; THC and DPH were less potent than PB and CDP in preventing mortality. THC most closely resembled DPH in the tests with chemical convulsant agents, but a sedative action of THC, resembling that of PB and CDP, was indicated by low ED5 0 for increased latency and for prevention of mortality in the MES test.

Topics: Animals; Anticonvulsants; Cannabis; Chlordiazepoxide; Dronabinol; Electroshock; Male; Mice; Nicotine; Pentylenetetrazole; Pharmaceutical Vehicles; Phenobarbital; Phenytoin; Seizures; Strychnine; Time Factors

Topics: Animals; Cannabis; Drug Synergism; Electroshock; Male; Mice; Phenobarbital; Seizures

Intraperitoneal injections of delta 8-tetrahydrocannabinol (THC) and delta 9-THC failed to affect myoclonic response to photic stimulation in Senegalese baboons (Papio papio). However, both isomers of THC exerted dose-related antiepileptic effects upon established kindled convulsions provoked by electrical stimulation of amygdala in the same species. Delta 9-THC was more potent than delta 8-THC, in terms of both antiepileptic effects and general toxicity. The antiepileptic effects of the THC isomers appear to be due mainly to the suppression of propagation of the induced afterdischarge to distant cerebral structures, although high doses also seem to suppress afterdischarge at the site of stimulation.

Topics: Amygdala; Animals; Anticonvulsants; Behavior, Animal; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Electroencephalography; Female; Haplorhini; Isomerism; Light; Male; Papio; Phytotherapy; Seizures; Time Factors

Topics: Animals; Anticonvulsants; Cannabis; Dronabinol; Electroshock; Male; Mice; Pentylenetetrazole; Phenobarbital; Phenytoin; Plant Extracts; Seizures; Uridine

Topics: Administration, Oral; Aggression; Animals; Behavior, Animal; Brain; Cannabis; Dronabinol; Female; Humans; Male; Organ Size; Rats; Seizures; Time Factors

Topics: Acetylcholinesterase; Administration, Oral; Aggression; Animals; Behavior, Animal; Brain; Brain Chemistry; Cannabis; Catatonia; Depression, Chemical; Dronabinol; Female; Humans; Hyperkinesis; Male; Nerve Tissue Proteins; Rats; RNA; Seizures; Stimulation, Chemical; Time Factors

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabis; Dronabinol; Female; Gerbillinae; Male; Motor Activity; Seizures

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

A pharmacological comparison between cannabidiol (CBD) and four CBD derivatives, namely CBD-aldehyde-diacetate (I), 6-oxo-CBD-diacetate (II), 6-hydroxy-CBD-tri-acetate (III), and 9-hydroxy-CBD-triacetate (IV) was carried out in mice. Protection against maximal electroshock convulsions, potentiation of pentobarbital sleeping-time and reduction of spontaneous motor activity were the effects measured. All 5 compounds were equally potent in potentiating barbiturate sleeping time at doses ranging from 6.25 to 100 mg/kg. At 12.5 and 25 mg/kg only CBD and IV were able to decrease significantly the spontaneous motor activity. CBD, II, III and IV were also active in protecting mice against electroconvulsive shock at doses of 100-200 mg/kg, although at the larger dose CBD and compound II were the most efficient. Compound I was toxic, killing about half of the animals within 24 h after injection.

Topics: Animals; Anticonvulsants; Cannabidiol; Cannabis; Cornea; Depression, Chemical; Electroshock; Male; Mice; Motor Activity; Pentobarbital; Seizures; Sleep; Time Factors

Topics: Adrenal Glands; Animals; Barbiturates; Behavior, Animal; Body Weight; Brain; Cannabis; Drinking Behavior; Drug Hypersensitivity; Extinction, Psychological; Female; Heart; Humans; Kidney; Organ Size; Pentylenetetrazole; Plant Extracts; Rats; Seizures; Substance Withdrawal Syndrome; Time Factors

Topics: Animals; Body Weight; Cannabis; Dronabinol; Drug Interactions; Drug Tolerance; Ethanol; Humans; Male; Mice; Pentylenetetrazole; Seizures; Substance Withdrawal Syndrome; Water Deprivation

Topics: Animals; Behavior, Animal; Brain; Cannabis; Dronabinol; Electroencephalography; Electrophysiology; Motor Activity; Myoclonus; Photic Stimulation; Phytotherapy; Seizures

Topics: Administration, Oral; Animals; Brain; Cannabis; Dronabinol; Electrodes; Electroencephalography; Female; Male; Rats; Seizures; Sleep; Time Factors

Topics: Anesthesia, General; Animals; Anticonvulsants; Cannabis; Cerebral Cortex; Depression, Chemical; Electric Stimulation; Electroshock; Glucose; Hippocampus; Hyponatremia; Male; Pentylenetetrazole; Phenobarbital; Phenytoin; Rats; RNA; Seizures; Time Factors; Trimethadione; Urethane

Topics: Animals; Anticonvulsants; Cannabis; Dose-Response Relationship, Drug; Electric Stimulation; Electroshock; Evoked Potentials; Hippocampus; Injections, Intraperitoneal; Neurons, Afferent; Phenobarbital; Phenytoin; Rats; Seizures; Time Factors; Trimethadione

Topics: Animals; Cannabis; Depression, Chemical; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Electroshock; Herb-Drug Interactions; Injections, Intraperitoneal; Male; Mice; Pentylenetetrazole; Phenobarbital; Phenytoin; Phytotherapy; Seizures; Stimulation, Chemical

Topics: Administration, Oral; Animals; Cannabis; Cattle; Dronabinol; Electroshock; Hindlimb; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Male; Mice; Muscle Tonus; Pharmaceutical Vehicles; Phytotherapy; Povidone; Propylene Glycols; Reaction Time; Seizures; Serum Albumin, Bovine; Time Factors

Topics: Aggression; Animals; Anticonvulsants; Barbiturates; Cannabis; Humans; Male; Mice; Pentylenetetrazole; Phytotherapy; Rats; Resorcinols; Seizures; Sound; Terpenes

Topics: Animals; Cannabis; Dronabinol; Female; Phytotherapy; Rats; Seizures; Sound

Topics: Animals; Cannabis; Electroshock; Female; Gait; Posture; Rats; Resorcinols; Seizures; Terpenes

Topics: Amygdala; Animals; Anticonvulsants; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Electric Stimulation; Electroencephalography; Male; Rats; Seizures; Synaptic Transmission

Topics: Animals; Anticonvulsants; Behavior, Animal; Cannabis; Cats; Disease Models, Animal; Dronabinol; Electric Stimulation; Electroencephalography; Female; Frontal Lobe; Hippocampus; Hypothalamus; Male; Mammillary Bodies; Phytotherapy; Seizures; Thalamic Nuclei

Topics: Animals; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Female; Male; Mice; Noise; Seizures; Time Factors

Topics: Animals; Cannabis; Electric Stimulation; Electrodes, Implanted; Hippocampus; Injections, Intraperitoneal; Phenytoin; Phytotherapy; Potassium; Primidone; Rats; Seizures

Topics: Amygdala; Animals; Behavior, Animal; Cannabis; Dronabinol; Drug Tolerance; Electric Stimulation; Electroencephalography; Limbic System; Male; Phytotherapy; Rats; Seizures

Topics: Analysis of Variance; Animals; Cannabis; Cats; Dronabinol; Electric Stimulation; Electroencephalography; Evoked Potentials; Hippocampus; Seizures

Topics: Adolescent; Adult; Age Factors; Alcoholism; Barbiturates; Black or African American; Cannabis; Cocaine; Hallucinations; Heroin Dependence; Humans; Male; Medical History Taking; Morphine Dependence; Pennsylvania; Seizures; Substance-Related Disorders; Therapeutic Community; White People

Topics: Apocynum; Cannabis; Convulsants; Hibiscus; Hostility; Isoniazid; Niacin; Nicotinic Acids; Seizures