A growing number of parents of children with autism say they are considering treating their children with medical marijuana because of anecdotal reports of medical benefits of marijuana in subjects with autism. The first step in testing this theory is to examine the effects of the active principle in marijuana, ∆9-tetrahydrocannabinol, to see how it interacts with receptors in the brain that are thought to be involved in social interactions. Preliminary studies used a safe agent that enhances a marijuana-like chemical already produced in the brain, known as anandamide, that regulates mood and cognition. These studies found that enhancing anandamide completely corrects abnormal anandamide signaling and the social deficits observed in two well-established mouse models of autism. In this ASF-funded study, the researcher aims to test: (a) whether dysfunctional anandamide signaling contributes to asocial behavior; (b) how the biochemical signaling of anandamide causes its pro-social behavioral effects. This research will have important implications for both understanding the neurobiology of social deficits as well as the development of novel therapies for autism spectrum disorders.