PEPTIDES | Cannabinoids and Epileptiform Activity

Recently there has been renewed interest in the potential antiepileptic effects of cannabinoids. Results from several different laboratories indicate that acute administration of cannabinoid agonists can suppress convulsions, although there have been indications that proconvulsant effects occur in certain circumstances. Kindling provides a flexible approach to examining the effects of drugs on seizures, because it can be used to characterize the effects of both acute and chronic administration, as well as effects on both established seizures and epileptogenesis. We have been examining the effects of treatment with the cannabinoid agonist HU210 and the antagonist AM281 on seizures kindled from the amygdala in rats. Although a single injection of HU210 can exert a weak antiepileptic effect, repeated injections produce a proepileptic effect. Acute administration of the antagonist AM281 produced modest but, at some doses, significant proepileptic effects on electrographic components of kindled seizures. When administered to naive rats during kindling, HU210 significantly accelerated the rate of seizure development, whereas AM281 was without effect. Our results indicate that, in the kindling preparation, a cannabinoid agonist exerts only weak antiepileptic effects and that, with chronic administration, proepileptic effects develop. In contrast, administration of the cannabinoid antagonist has only modest effects on kindling and kindled seizures. The findings raise serious questions about the potential usefulness of cannabinoid drugs in treatment of epilepsy.