| Description |
The mechanisms of the anticonvulsant activity of cannabidiol (CBD) and the central excitation of delta9- -tetrahydrocannabinol (Delta9 -THC) were investigated electrophysiologically with conscious, unrestrained cobalt epileptic rats. The well-known antiepileptics, trimethadione, ethosuximide and phenytoln, were included as reference drugs. Direct measurements were made of spontaneously firing, epileptic potentials from a primary focus on the parietal cortex and convulsions were monitored visually. Ethosuximide and trimethadione decreased the frequency of focal potentials, but phenytoin and CBD exerted no such effect. Although CBD did not suppress the focal abnormality, it abolished jaw and limb clonus. Consequently, CBD may produce its anticonvulsant effect by depressing seizure spread in the CNS. In contrast, delta9-THC markedly increased the frequency of focal potentials, evoked generalized bursts of polyspikes and produced frank convulsions, 11-OH-delta9 -THC, the major metabolite of delta -THC displayed only one of the excitatory properties of the parent compound: production of bursts of poiyspikes. In contrast to delta-THC and its 11-OH-metabolite, CBD, even in very high doses, did not induce any excitatory effects or convulsions. The present study provides the first evidence that CBD exerts anticonvulsant activity against the motor manifestations of a focal epilepsy, and that the mechanism of the effect may involve a depression of seizure spread in the CNS. |
