 In this protocol, we outline studies aiming at elucidating the role of CB1 receptors in alcohol and cannabis dependence by using positron emission tomography PET and the recently developed radiotracer for CB1 receptors, 18FFMPEP-d2. The aim of this project is to explore CB1 receptor abnormalities at various stages of alcohol and cannabis dependence in humans. For the studies in alcohol dependence, the primary hypothesis is that CB1 receptors are downregulated during chronic alcohol exposure and upregulated during extended abstinence. For the studies in cannabis users, our primary hypothesis is that CB1 receptors are downregulated during chronic cannabis use and upregulated during extended abstinence. Insight into the role of CB1 receptor function in human alcoholism and in chronic cannabis use may help guide future development of pharmacotherapies. 