This center for Research on Substance Abuse includes a Core and eight major projects organized into three Divisions for medication development: 1. preclinical neurobiology, 2. human laboratory studies and 3. clinical trials. The Core has stimulated novel approaches to cocaine neurobiology and pharmacotherapy by coordinating research efforts across Psychiatry, Pharmacology, Nuclear Medicine and Laboratory Medicine. It has developed innovative research ideas into current Center proposals (e.g. buproprion pilot, cocaine cue reactivity, place preference in animals), as well as into projects that were later independently funded (e.g. HIV dementia, flupenthixol pilot, desipramine in methadone pilot). Core resources have also provided technical and material assistance in trainee' research projects that have led to independently funded research (e.g. mazindol pilot, amantadine pilot). Proposed pilot studies in the Core (e.g. disulfiram for alcoholic cocaine abusers, anxiety disorders and cocaine) should continue this tradition. Three of the eight major projects are continuations of our previous work: 1. the neurobiology of cocaine withdraw, 2. cocaine challenges during maintenance pharmacotherapies, 3. metabolic studies of cocaine focusing on the interaction of cocaine with alcohol. The other original Center projects have led to independently funded grants such as the three current buprenorphine studies, and no longer need Center funding. Five new projects evolved from Core pilot work: 1. animal models to screen medications and to understand the molecular mechanisms of cocaine's actions, 2. SPECT imaging of stimulant effects on dopamine neurobiology in primates and humans, 3. human laboratory studies of cocaine cue reactivity during neurotransmitter manipulation and during maintenance pharmacotherapy, and 4,5. clinical trials with buproprion and carbamazapine. Two new clinical sites have been added to increase the investigator and subject pools for studies: West Haven V.A. and the University of Connecticut. Thus, both continuity with our current Center and major new initiates towards a broad based medication development program have been incorporated into the continuation of our Research Center.