Assessment of the Anticonvulsant Effects and Tolerability of GW Pharmaceuticals’ Cannabidiol in the Anticonvulsant Screening Program (P2.038)

Objective: To characterize the effects of cannabidiol (CBD) in a battery of well-established rodent seizure models. Background: Previous investigations have reported anticonvulsant effects of CBD in various preclinical animal models (Jones et al., 2010, 2012), and suggest it is a promising candidate for the control of seizures warranting systematic investigation. Here, the anticonvulsant and tolerability profile of plant-derived CBD (GW Pharmaceuticals) was investigated in the Anticonvulsant Screening Program (ASP) to verify and further characterize CBD’s effects in a battery of well-established rodent seizure models. Methods: CBD was investigated in several rodent models of seizure: 6Hz “psychomotor” tests of therapy-resistant partial seizures, subcutaneous Metrazol seizure threshold test (scMET) of clonic forebrain seizures, and maximal electroshock test (mES) of generalized tonic-clonic seizures. Additionally, CBD’s effect on minimal muscular and neurological impairment was assessed in mice using the rotarod test. Rats were examined in a battery of tests (gait and stance test, placing response test and righting reflex test) to determine any neurological deficits of CBD. Results: The ASP demonstrated that CBD exerted significant anticonvulsant effects in the 6Hz (32 mA) test (ED 50 = 144 [102-194] mg/kg), 6 Hz (44 mA) test (ED 50 = 173 [136-213] mg/kg), mES (ED 50 = 80 [65-96] mg/kg) and scMET (ED 50 = 120 [99-146] mg/kg) models in mice, and the mES model (ED 50 = 53 [39-67] mg/kg) in rats. Moreover, CBD was well tolerated by both mouse (TD 50 = 272 [241-303] mg/kg) and rat (TD 50 = >500 mg/kg) in toxicity tests. Conclusions: CBD produces significant anticonvulsant effects in a number in vivo seizure models and is well-tolerated in both rodent species in the ASP. These data validate previous results from GW Pharmaceuticals’ preclinical program and suggest that CBD may be a novel therapeutic candidate for a diverse range of human epilepsies, with a potentially favorable tolerability profile. Disclosure: Dr. Jones has received personal compensation for activities with GW Pharmaceuticals as an employee. Dr. Hill has received personal compensation for activities with GW Pharmaceuticals as an employee. Dr. Stott holds stock and/or stock options in GW Pharma Ltd. Dr. Wright holds stock and/or stock options in GW Pharmaceuticals.