Cannabinoids for epilepsy: What do we know and where do we go?

Brodie, Martin J.; Ben‐Menachem, Elinor

doi:10.1111/epi.13973

Cited by 36 publications

(27 citation statements)

References 28 publications

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“…Recently, the first plant‐derived highly purified cannabidiol (CBD) has been approved by US Food and Drug Administration (FDA) for treatment of Lennox‐Gastaut and Dravet syndromes in the United States. Its efficacy has also been shown for other epilepsy syndromes, and its use is increasing worldwide . Cannabidiol is metabolized mainly by the cytochrome P450 (CYP) system and may also be glucuronidated by several UDP‐glucuronosyltransferase (UGT) isoforms .…”

Section: Introductionmentioning

confidence: 99%

Effects of cannabidiol on brivaracetam plasma levels

et al. 2019

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The use of cannabidiol (CBD) for treatment of pharmacoresistant epilepsies is increasing. CBD is metabolized via UDP‐glucuronosyltransferase (UGT) and cytochrome 450 (CYP) enzymes, but information on interactions with common anticonvulsive drugs is incomplete. We report a case series of five patients receiving adjunctive treatment with CBD who showed increases in brivaracetam (BRV) levels by 95% to 280%. Only two patients reported mild adverse events, leading to a reduction of BRV in one patient. One possible mechanism contributing at least partially to increasing BRV level is the inhibition of CYP2C19 by cannabidiol. Further pharmacokinetic studies are required to understand other possible mechanisms of brivaracetam‐cannabidiol interaction.

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Section: Introductionmentioning

confidence: 99%

Effects of cannabidiol on brivaracetam plasma levels

et al. 2019

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“…Primetime attention by media outlets, patient advocacy groups and families concerning a mixed CBD/THC containing cannabis extract [so‐called ‘Charlotte's Web’] to treat seizures in patients with Dravet syndrome, resulted in increasing demands from advocacy groups for cannabinoids to be considered in the treatment of epilepsy . This resulted in a massive expansion of the academic literature exploring the potential of CBD (excluding THC due to the aforementioned concern, and due to THC being considered illegal in many jurisdictions) as a therapy in DRE . In turn, prospective studies of CBD in DRE were conducted.…”

Section: Introductionmentioning

confidence: 99%

A prospective open‐label trial of a CBD/THC cannabis oil in dravet syndrome

McCoy

Wang

Zak

et al. 2018

Ann Clin Transl Neurol

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IntroductionBoth Δ9 Tetrahydrocannabidiol (THC) and cannabidiol (CBD) components of cannabis, have been shown to have anticonvulsant effects. Cannabis oils are used to treat seizures in drug‐resistant epilepsy (DRE). Recent trials provide data on dosing, side effects, and efficacy of CBD, yet there is a paucity of information on THC in epilepsy. Primary objective was to establish dosing and tolerability of TIL‐TC150 ‐ a cannabis plant extract produced by Tilray®, containing 100 mg/mL CBD and 2 mg/mL THC‐ in children with Dravet syndrome. Secondary objectives were to assess impact of therapy on seizures, electroencephalogram (EEG) and quality of life.MethodsTwenty children received add‐on therapy with TIL‐TC150. The dose ranged from 2 to 16 mg/kg/day of CBD and 0.04 to 0.32 mg/kg/day of THC. Patients were monitored for tolerability and adverse events, and secondary objectives.ResultsNineteen participants completed the 20‐week intervention. Mean dose achieved was 13.3 mg/kg/day of CBD (range 7–16 mg/kg/day) and 0.27 mg/kg/day of THC (range 0.14–0.32 mg/kg/day). Adverse events, common during titration included somnolence, anorexia, and diarrhea. Abnormalities of liver transaminases and platelets were observed with concomitant valproic acid therapy. There was a statistically significant improvement in quality of life, reduction in EEG spike activity, and median motor seizure reduction of 70.6%, with 50% responder rate of 63%.Conclusions TIL‐TC150 was safe and well tolerated in our subjects. TIL‐TC150 treatment resulted in a reduction in seizure counts, spike index on EEG, and improved quality of life measures. This study provides safety and dosing information for THC‐containing cannabinoid preparations.

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“…23 The availability of artisanal preparations of cannabidiol in the last decade, the minimization of psychotropic activity due to plants that have been cross-bred to reduce overall THC concentrations, and interest by caretakers and patient advocate groups have led to great excitement and widespread use, but controlled scientific studies regarding efficacy were still lacking. 24,25 In 2017, Devinsky et al published a double-blind, placebocontrolled, randomized study that evaluated the effects of Epidiolex, a pharmaceutical-grade cannabidiol preparation, as an adjunct medication in 120 patients with Dravet's syndrome. They found a decrease in the median frequency of monthly convulsive seizures from 12.4 to 5.9 in the cannabidiol arm compared with a decrease from 14.9 to 14.1 in the placebo arm, which represents a 23% difference in the cannabidiol arm compared with the placebo arm (p ¼ 0.01).…”

Section: Cannabidiolmentioning

confidence: 99%

Advances in the Treatment of Drug-Resistant Pediatric Epilepsy

González-Giraldo

Sullivan

2020

Semin Neurol

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Epilepsy is a common disorder in children and adults that causes significant morbidity and affects many aspects of a patient's lives. Two-thirds of patients with epilepsy are controlled with established antiseizure medications, leaving a significant number of patients searching for other options. The purpose of this review is to provide an overview of recent advancements in the management of treatment-resistant epilepsy in pediatric patients. Recent publications have shown the efficacy of new pharmaceutical options such as fenfluramine and cannabidiol, some of which have been tested specifically in patients with childhood-onset epilepsy syndromes such as Dravet's syndrome and Lennox–Gastaut's syndrome. Furthermore, recent approval by the U.S. Food and Drug Administration of stiripentol has made available a previously difficult-to-obtain option for patients with Dravet's syndrome. Finally, implanted responsive neurostimulation devices for direct cortical stimulation and deep brain stimulation have shown efficacy in adult patients and may represent a thrilling new horizon for pediatric patients.

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Cannabinoids for epilepsy: What do we know and where do we go?

Cited by 36 publications

References 28 publications

Effects of cannabidiol on brivaracetam plasma levels

Effects of cannabidiol on brivaracetam plasma levels

A prospective open‐label trial of a CBD/THC cannabis oil in dravet syndrome

Advances in the Treatment of Drug-Resistant Pediatric Epilepsy

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