Cannabis in Epilepsy: from clinical practice to basic research focusing on the possible role of cannabidivarin

Cannabidivarin (CBDV) and cannabidiol (CBD) have recently emerged amongcannabinoids for their potential antiepileptic properties, as shown in several animalmodels. We report the case of a patient affected by symptomatic partial epilepsy whoused cannabis as self-medication after the failure of countless pharmacological/surgicaltreatments. Clinical and video electroencephalogram (EEG) evaluations were periodi-cally performed, and the serum levels of CBDV, CBD, and D9-tetrahydrocannabinolwere repeatedly measured. After cannabis administration, a dramatic clinicalimprovement, in terms of both decrease in seizure frequency and recovery of cognitivefunctions, was observed, which might parallel high CBDV plasma concentrations. Towiden the spectrum of CBDV possible mechanisms of action, electrophysiologicalmethods were applied to investigate whether it could exert some effects on c-amino-butyric acid (GABA)Areceptors. Our experiments showed that, in human hippocam-pal tissues of four patients affected by drug-resistant temporal lobe epilepsy (TLE)transplanted in Xenopus oocytes, there is decrease of current rundown (i.e., reductionof use-dependent GABAAcurrent) after prolonged exposure to CBDV. This result hasbeen confirmed using a single case of Rasmussen encephalitis (RE). Our patient’s elec-troclinical improvement supports the hypothesis that cannabis could actually repre-sent an effective, well-tolerated antiepileptic drug. Moreover, the experimental datasuggest that CBDV may greatly contribute to cannabis anticonvulsant effect throughits possible GABAergic action.