Cannabidiol (CBD) is a major active component of the Cannabis plant, which, unlike
tetrahydrocannabinol (
THC), is devoid of euphoria-inducing properties. During the last 10 years, there has been increasing interest in the use of CBD-enriched products for the treatment of
epilepsy. In 2018, an oil-based highly purified liquid formulation of CBD (
Epidiolex) derived from Cannabis sativa was approved by the US Food and Drug Administration for the treatment of
seizures associated with
Dravet syndrome (DS) and
Lennox-Gastaut syndrome (LGS). The mechanisms underlying the antiseizure effects of CBD are unclear but may involve, among others, antagonism of
G protein-coupled receptor 55 (GPR55), desensitization of transient receptor potential of vanilloid type 1 (TRPV1) channels, and inhibition of
adenosine reuptake. CBD has complex and variable pharmacokinetics, with a prominent first-pass effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat/high-calorie meal. In four randomized, double-blind, parallel-group, adjunctive-
therapy trials, CBD given at doses of 10 and 20 mg/kg/day administered in two divided administrations was found to be superior to placebo in reducing the frequency of drop
seizures in patients with LGS and convulsive
seizures in patients with DS. Preliminary results from a recently completed controlled trial indicate that efficacy also extends to the treatment of
seizures associated with the
tuberous sclerosis complex. The most common adverse events that differentiated CBD from placebo in controlled trials included
somnolence/sedation, decreased appetite, increases in
transaminases, and
diarrhea, behavioral changes, skin rashes,
fatigue, and sleep disturbances. About one-half of the patients included in the DS and LGS trials were receiving concomitant
therapy with
clobazam, and in these patients a CBD-induced increase in serum levels of the active metabolite
norclobazam may have contributed to improved seizure outcomes and to precipitation of some adverse effects, particularly
somnolence.