Cannabis has been used to treat epilepsy for millennia, with such use validated by recent regulatory approval of the cannabis constituent cannabidiol (CBD) to treat Dravet syndrome. Here, we examined the anticonvulsant effects of seven other plant-derived phytocannabinoids against hyperthermia-induced seizures in the Scn1a+/- mouse model of Dravet syndrome. Cannabigerolic acid (CBGA), the major biosynthetic precursor in the cannabis plant, exhibited anticonvulsant properties, as did cannabidivarinic acid (CBDVA) and cannabigerovarinic acid (CBGVA). CBGA also potentiated the anticonvulsant effects of the first-line treatment clobazam. However, CBGA alone did not ameliorate spontaneous seizures in Scn1a+/- mice and had divergent effects in conventional seizure models. CBGA exhibited inhibitory action at GPR55 and affected other epilepsy-relevant targets such as GABAA receptors, Cav3.1 channels and TRPV1. CBGA shows some promise as an anticonvulsant and has a range of pharmacological actions consistent with observed anticonvulsant effects.

Turning over a new leaf in the search for cannabis-based therapeutics for childhood epilepsy

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.