Profiling unknown cannabis constituents which might be potentially candidates for treating childhood epilepsy.

Title: Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy.

Journal: The British Journal of Pharmacology (2021) in press

Link: https://doi.org/10.1111/bph.15661

Comments:

Cannabis has been used to treat epilepsy. Some phytocannabinoids derived from cannabis, including cannabidiol (CBD), reduce seizures or epileptiform activity, and thus CBD is used for Dravet syndrome. Unregulated artisanal cannabis-based products used to treat children with intractable epilepsies often contain relatively low doses of CBD but are enriched in other phytocannabinoids. This paper addressed the possibility that other cannabis constituents have anticonvulsant properties.

The authors used the Scn1a+/− mouse model of Dravet syndrome to investigate the cannabis plant for phytocannabinoids with anticonvulsant effects against hyperthermia-induced seizures. By the initial screening, three phytocannabinoids, cannabigerolic acid (CBGA), cannabidivarinic acid (CBDVA), and cannabigerovarinic acid (CBGVA), were identified. The authors found that CBGA was most potent and potentiated the anticonvulsant effects of clobazam, which is used as an adjunctive therapy in epilepsy, against hyperthermia-induced and spontaneous seizures. CBGA was found to interact with numerous epilepsy-relevant targets such as GPR55, TRPV1 channels and GABAa receptors.

These results suggest that CBGA, CBDVA and CBGVA may contribute to the effects of cannabis-based products in childhood epilepsy. Although these phytocannabinoids have anticonvulsant potential and could be lead compounds for drug development programmes, several liabilities would need to be overcome before CBD is superseded by another in this class.