Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

Abstract

Devinsky et al. (May 25 issue)¹ present data showing that 65% of patients in their trial of cannabidiol as treatment for seizures in the Dravet syndrome were taking clobazam. We are concerned about a potential drug–drug interaction between clobazam and cannabidiol. Cannabidiol is a potent inhibitor of CYP3A4 and CYP2C19, which can increase concentrations of several other antiepileptic drugs, including clobazam.² A previous study showed that, during cannabidiol treatment, clobazam levels increased by a mean of 60%, and levels of its active metabolite, N-desmethylclobazam, increased by a mean of 500%.³ Moreover, studies have shown that raising clobazam concentrations is likely to have an effect on seizure frequency.⁴ Thus, this interaction may lead to an overestimation of cannabidiol efficacy in patients who are receiving clobazam.