Cannabinoids as potential anti-epileptic drugs.

Cannabinoids have long been recognized as having the potential for both anticonvulsant and proconvulsant effects. The increased understanding of the cannabinoid receptors and their endogenous ligands over the last decade has provided a potential mechanism of action for these apparently paradoxical effects. Although the anticonvulsant effects of cannabinoids appear to be mediated by their action at presynaptic cannabinoid receptors, which inhibit the release of excitatory neurotransmitters such as glutamate, it is clear that they are also capable of producing proconvulsant effects through the activation of cannabinoid receptors on terminals releasing inhibitory neurotransmitters, such as gamma-amino-butyric acid. In the brain, the activation of cannabinoid receptors is carefully controlled by the rapid synthesis and degradation of endocannabinoids in a way that targets the endogenous ligands to specific sets of cannabinoid receptors. The potential problem in delivering a cannabinoid drug to treat epilepsy is the inability to control its actions at different cannabinoid receptors regulating the release of different neurotransmitters. Since the action of cannabinoids is complex, and there is a dearth of clinical trial data, it is currently unclear whether cannabinoids might be both efficacious and safe in the treatment of epilepsy.