Anticonvulsant

Anticonvulsants suppress or prevent epileptic seizures. Highly purified cannabidiol (Epidiolex/Epidyolex), approved by the FDA in 2018 for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), and expanded in 2020 to tuberous sclerosis complex, is the only cannabis-derived anticonvulsant with regulatory approval. CBD's antiseizure action is independent of CB1/CB2 receptors at therapeutic concentrations; the principal mechanisms proposed by Gray & Whalley (2020, Epileptic Disorders) are antagonism of the orphan receptor GPR55 (reducing excitatory glutamate release), activity-dependent desensitization of TRPV1 channels (decreasing calcium influx), and inhibition of the equilibrative nucleoside transporter ENT1 (raising extracellular adenosine). Pivotal randomized trials by Devinsky and colleagues (2016–2018, Lancet and NEJM) demonstrated significant seizure-frequency reductions versus placebo in DS and LGS. NASEM 2017 rated evidence as insufficient at the time, but subsequent Class I trials now provide strong support for CBD's efficacy in these specific pediatric epilepsies. → See also: CBD, Epidiolex, GPR55, TRPV1.