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  • Epilepsy
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Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis Updated

Abstract This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products. The systematic search took place in February/2017 and updated in December/2017 using the keywords “epilepsy” or “Dravet” or “Lennox-Gastaut” or “CDKL5” combined with “Cannabis,” “cannabinoid,” “cannabidiol,” or “CBD” resulting in 199 papers. The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4...
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Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models

Summary Objective Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD) in a battery of acute seizure models. Additionally, we defined the disease-modifying potential of chronic oral administration of CBD on associated comorbidities in the reduced intensity status epilepticus–spontaneous recurrent seizures (RISE-SRS) model of temporal lobe epilepsy (TLE). Methods We evaluated the acute antiseizure effect of CBD in the maximal electroshock seizure, 6-Hz psychomotor seizure, and pentylenetetrazol acute seizure tests, as well as the corneal kindling model of chronic seizures in mice following intraperitoneal administration. Median effective or behavioral toxic dose was...
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Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study

Abstract Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10–12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified. Results: All seven participants tolerated the...
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Synthetic, non-intoxicating 8,9-dihydrocannabidiol for the mitigation of seizures

Abstract There can be a fine line between therapeutic intervention and substance abuse, and this point is clearly exemplified in herbal cannabis and its products. Therapies involving cannabis have been the treatment of last resort for some cases of refractory epilepsy, and this has been among the strongest medical justifications for legalization of marijuana. In order to circumvent the narcotic effects of Δ9-tetrahydrocannabinol (THC), many studies have concentrated on its less intoxicating isomer cannabidiol (CBD). However, CBD, like all natural cannabinoids, is a controlled substance in most countries, and its conversion into THC can be easily performed using common chemicals. We describe here the...
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Medical Cannabis in Children

Abstract The use of medical cannabis in children is rapidly growing. While robust evidence currently exists only for pure cannabidiol (CBD) to treat specific types of refractory epilepsy, in most cases, artisanal strains of CBD-rich medical cannabis are being used to treat children with various types of refractory epilepsy or irritability associated with autism spectrum disorder (ASD). Other common pediatric disorders that are being considered for cannabis treatment are Tourette syndrome and spasticity. As recreational cannabis use during youth is associated with serious adverse events and medical cannabis use is believed to have a relatively high placebo effect, decisions to use medical cannabis during...
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The level of evidence of medical marijuana use for treating disabilities: a scoping review

Please use this link to access this publication. Abstract Purpose: Twenty-nine states have bypassed federal regulations by legalizing marijuana (MJ) either medicinally, recreationally or both. The FDA states that there is no empirical evidence that MJ is effective to treat these disorders. With over a billion individuals living with a disability across the globe, it is crucial to fully research the efficaciousness and safety of medical MJ to treat this population. The purpose to present the results of a scoping review of studies focused on the levels of evidence currently available on medical MJ’s efficacy in treatment across a large range of disabilities. Methods: Databases were...
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Cannabidiol in the Treatment of Epilepsy: A Focused Review of Evidence and Gaps

Abstract Approximately one third of epilepsy patients do not become seizure free with antiseizure medications. This treatment gap motivates research for new therapeutic options, such as cannabidiol (CBD). CBD differs from other cannabis derivatives because of its consistent efficacy and lack of a psychoactive effect. CBD can be recommended as adjunctive therapy in patients with Dravet and Lennox-Gastaut syndromes. The most common adverse effects (AEs) are drowsiness, reduced appetite, diarrhea, and vomiting. Transaminase elevation is the most common AE that leads to CBD discontinuation. Coadministration with valproate may increase the risk of hepatotoxicity. The combination of CBD and clobazam may increase both the effectiveness...
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Development of cannabidiol as a treatment for severe childhood epilepsies

Abstract In recent years, there has been a growing appreciation by regulatory authorities that cannabis-based medicines can play a useful role in disease therapy. Although often conflagrated by proponents of recreational use, the legislative rescheduling of cannabis-derived compounds, such as cannabidiol (CBD), has been associated with the steady increase in the pursuit of use of medicinal cannabis. One key driver in this interest has been the scientific demonstration of efficacy and safety of CBD in randomised, placebo-controlled clinical trials in children and young adults with difficult-to-treat epilepsies, which has encouraged increasing numbers of human trials of CBD for other indications and in other populations....
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Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects

Abstract Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fat-containing meals). It is mainly...
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Is cannabidiol a drug acting on unconventional targets to control drug-resistant epilepsy?

Abstract Cannabis has been considered as a therapeutic strategy to control intractable epilepsy. Several cannabis components, especially cannabidiol (CBD), induce antiseizure effects. However, additional information is necessary to identify the types of epilepsies that can be controlled by these components and the mechanisms involved in these effects. This review presents a summary of the discussion carried out during the 2nd Latin American Workshop on Neurobiology of Epilepsy entitled “Cannabinoid and epilepsy: myths and realities.” This event was carried out during the 10th Latin American Epilepsy Congress in San José de Costa Rica (September 28, 2018). The review focuses to discuss the use of CBD...
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