Anticonvulsant potential of the phytocannabinoid, cannabidivarin, on epilepsy disease progression

Epilepsy affects about 0.8% of individuals [1]. Many treatments are available but more effective and better-tolerated antiepileptic drugs (AEDs) with new mechanisms of actions (MOAs) are needed [2, 3]. Cannabis has been historically used to treat epilepsy [4]. In our laboratory, we have demonstrated anticonvulsant effects of several cannabinoids (e.g. cannabidivarin: CBDV), major cannabis components, in animal models of seizure [5-7]. The aim of this project is to elucidate CBDV's anticonvulsive/ epileptic MOA in order to allow its further clinical development and a further drug discovery for the treatment of epilepsy with a new MOA in the future. To achieve this aim, the effects of CBDV were behaviourally evaluated in several animal models (a rat acute seizure model: pentylenetetrazole (PTZ)-induced acute seizure model, rat chronic epileptic models: pilocarpine-induced spontaneous recurrent seizure (SRS) model and PTZ-kindling model) and subsequently geneiprotein expression analyses were performed using brain tissues from test animals. In an experiment using PTZ-induced acute seizure model, CBOV significantly suppressed seizures. Moreover. suppression of PTZ-induced increases of epilepsy-related gene expressions was seen in CBDV responders. Although CBDV did not show any anti-convulsive effects in PTZ-kindling model, CBDV treatment significantly suppressed disease progression in pilocarpine-induced SRS model.