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Review
, 7 (2), 61-76
eCollection

Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?

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Review

Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?

Emilio Perucca. J Epilepsy Res.

Abstract

The interest in cannabis-based products for the treatment of refractory epilepsy has skyrocketed in recent years. Marijuana and other cannabis products with high content in Δ(9) - tetrahydrocannabinol (THC), utilized primarily for recreational purposes, are generally unsuitable for this indication, primarily because THC is associated with many undesired effects. Compared with THC, cannabidiol (CBD) shows a better defined anticonvulsant profile in animal models and is largely devoid of adverse psychoactive effects and abuse liability. Over the years, this has led to an increasing use of CBD-enriched extracts in seizure disorders, particularly in children. Although improvement in seizure control and other benefits on sleep and behavior have been often reported, interpretation of the data is made difficult by the uncontrolled nature of these observations. Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of three high-quality placebo-controlled adjunctive-therapy trials of a purified CBD product in patients with Dravet syndrome and Lennox-Gastaut syndrome. In these studies, CBD was found to be superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut syndrome. For the first time, there is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes. Based on currently available information, however, it is unclear whether the improved seizure control described in these trials was related to a direct action of CBD, or was mediated by drug interactions with concomitant medications, particularly a marked increased in plasma levels of N-desmethylclobazam, the active metabolite of clobazam. Clarification of the relative contribution of CBD to improved seizure outcome requires re-assessment of trial data for the subgroup of patients not comedicated with clobazam, or the conduction of further studies controlling for the confounding effect of this interaction.

Keywords: Cannabidiol; Cannabis; Epilepsy; Review; Seizures.

Figures

Figure 1
Figure 1
Number of articles retrieved in PubMed by using the search terms ‘cannabis and epilepsy’, grouped by year of publication.
Figure 2
Figure 2
Chemical structure of cannabidiol and 9-Δ-tetrahydrocannabinol.
Figure 3
Figure 3
Proportion of patients reporting beneficial anti-seizure effects from cannabis products in relation to whether patients’ family resided originally in Colorado or moved to Colorado in order to access cannabis therapy.
Figure 4
Figure 4
Median percent reduction in seizure frequency in the three randomized adjunctive-therapy placebo-controlled efficacy trials of cannabidiol (CBD) reported to date in patients with Dravet syndrome and Lennox-Gastaut syndrome., For patients with Dravet syndrome, seizure frequency refers to convulsive seizures. For patients with Lennox-Gastaut syndrome, seizure frequency refers to drop seizures. P values refer to comparisons between each CBD group and corresponding placebo group. n refers to number of patients randomized into each group. For further details, see text.

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