The Pharmacological Basis of Cannabis Therapy for Epilepsy

Recently, cannabis has been suggested as a potential alternative
therapy for refractory epilepsy, which affects 30% of epilepsy,
both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics
that would not interfere with normal function in patients with
refractory epilepsy and conditions associated with refractory
seizures. The two chief cannabinoids are D-9-tetrahyrdrocannabinol,
the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana.
Claims of clinical efficacy in epilepsy of CBD-predominant
cannabis or medical marijuana come mostly from limited studies,
surveys, or case reports. However, the mechanisms underlying
the antiepileptic efficacy of cannabis remain unclear. This article
highlights the pharmacological basis of cannabis therapy, with
an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is
anticonvulsant, but it has a low affinity for the cannabinoid
receptors CB1 and CB2; therefore the exact mechanism by which
it affects seizures remains poorly understood. A rigorous clinical
evaluation of pharmaceutical CBD products is needed to
establish the safety and efficacy of their use in the treatment of
epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other
potential treatment options.