For over five decades, a large group of productive investigators at VA Commonwealth University (VCU) has made significant contributions to our understanding of drugs of abuse. The interests of these scientists encompass synthesis, pharmacokinetic, neurochemical, molecular, behavioral and pharmacological characterization of most classes of abused drugs. While productive collaborations have always existed among these investigators, the drug abuse research effort at VCU has been enhanced by the creation of this NIDA Center. The primary objective of the Center is to foster multifaceted basic science research. The Center also will continue to provide a mechanism for uniting scientists from many other disciplines in order to share information and new research ideas regarding abused drugs. In this regard, the Center serves a coordinating role for all drug abuse grants at VCU, including numerous NIDA R01 grants, contracts, a training grant, several individual training awards and a program project. Another major contribution continues to be the training and development of young scientists in drug abuse research. The role of the Core is to provide program management and resources, and to facilitate interaction and cooperation through its administration, drug supply, shared instrumentation, and mouse knock-out facility sub-cores. In addition, a Small Grants Program provides a mechanism to attract established scientists in other fields to drug abuse research and to allow for pilot investigations in response to new drug abuse problems by all junior and senior scientists. The Center serves as a national resource through extensive collaborations and shared information with scientists at the national and international level. In addition, the Center maintains an inventory of cannabinoid analogs that we distribute to scientists at VCU and to NIDA-sponsored researchers throughout the US and the world. Of course, basic research will continue to be the primary focus of the Center. The five proposed projects address the mechanisms through which endocannabinoids produce a blockade of morphine tolerance, decrease seizure threshold following chronic cannabinoid administration, and affect the reward and withdrawal of chronic nicotine. These efforts are complemented by studies to understand the plasticity of cannabinoid receptors and characterization of cannabinoid properties of orphan G-protein coupled receptors. Coordination among the projects is directed toward the nature of ligand receptor interactions, roles of receptor-associated proteins, receptor phosphorylation states, characterization of new receptor subtypes, and signal transduction mechanisms. We are also investigating the interactions between the endocannabinoid system and opioids and nicotine. The roles of the nicotinic receptor subtypes in the development of reward and dependence will also be addressed. This center has much significance on human health since additional knowledge of this endogenous system will improve our ability to treat disease. CENTERS CHARACTERISTICS