Epilepsy, characterized by spontaneous seizures, is one of the most common neurological disorders. Approximately 30% of patients continue to have seizures despite taking currently available medications, making it important to identify new treatments for these individuals. Recent research has demonstrated that cannabinoids, a class of chemicals that act in the brain, can reduce seizures in patients with epilepsy. Cannabinoids exert their effects through cannabinoid receptors, which may represent a promising target for new therapies. Drugs which activate the Cannabinoid 2 Receptor (CB2R) have shown to protect against induced seizures in mice. Further, our data shows that mice lacking CB2Rs are more susceptible to acute seizures, and drugs which block CB2Rs increase seizure susceptibility. Together, this evidence suggests that drugs acting at CB2Rs may be promising therapies for the treatment of epilepsy, although this has not yet been investigated. In this proposal, I will determine whether administration of JWH-133, a drug acting at CB2Rs, can prevent several of the disease-contributing changes that occur in a mouse model of epilepsy. I will also test whether JWH-133 can prevent the development of spontaneous seizures and behavioral abnormalities in mice. This study has the potential to establish that drugs acting at CB2Rs may provide a potential new approach to the treatment of epilepsy.
