9. The anticonvulsant effects of cannabidiol examined in animal seizure models

Abstract

Cannabidiol (CBD), a major nonpsychotropic compound of Cannabis sativa, is emerging as a treatment for intractable seizures and their comorbid cognitive, behavioral and quality of life sequelae. Basic research studies in animals have started to define the anticonvulsant properties of CBD. Studies of CBD in mice and rats using maximal electroshock (MES) and pentylenetetrazol (PTZ) models of generalized clonus or myoclonus reported ED50 values of CBD as early as the 1970s – however chromatographic analysis of CBD purity was often not reported. The ED50 values for CBDs reported previously may be inaccurate for some botanical derived extracts; although historically, the ED50 values reported for MES in rats (10 mg/kg) may be an order of magnitude lower than those reported in mice. We will compare recent data derived from in vivo studies with the published data. Testing of CBD in seizure models will be interpreted in this context – including a study of CBD in ventral subiculum kindling. The latter studies provide a useful comparison with the drug-standardized amygdala kindling model – the model in which we evaluate novel drugs that may be effective against complex-partial seizures of temporal lobe origin. The systematic investigation of CBD efficacy, toxicity and pharmacokinetics may be important in view of the tendency to add CBD to other antiepileptic drug regimens for the treatment of treatment-resistant epilepsy. Better evaluation of the ED50 of CBD in animal models will form the basis for more reliable dosing in human epileptic patients.