The anticonvulsant phytocannabinoids CBGVA and CBDVA inhibit recombinant T-type channels.

Cannabidiol (CBD) has been clinically approved for intractable epilepsies, offering hope that novel anticonvulsants in the phytocannabinoid class might be developed. Looking beyond CBD, we have recently reported that a series of biosynthetic precursor molecules found in cannabis display anticonvulsant properties. However, information on the pharmacological activities of these compounds on CNS drug targets is limited.

Epileptic encephalopathy de novo GABRB mutations impair γ-aminobutyric acid type A receptor function.

Objective: The Epi4K Consortium recently identified 4 de novo mutations in the γ-aminobutyric acid type A (GABA ) receptor β3 subunit gene GABRB3 and 1 in the β1 subunit gene GABRB1 in children with one of the epileptic encephalopathies (EEs) Lennox-Gastaut syndrome (LGS) and infantile spasms (IS). Because the etiology of EEs is often unknown, we determined the impact of GABRB mutations on GABA receptor function and biogenesis.

Methods: GABA receptor α1 and γ2L subunits were coexpressed with wild-type and/or mutant β3 or β1 subunits in HEK 293T cells.