Methamphetamine (MA) use is the fastest growing drug problem in the United States, placing strain on the criminal justice and health care systems and resulting in significant public health consequences, including HIV infection. Understanding of the neurobiological, molecular, and cellular basis of MA dependence has increased, yet no medications effective for MA dependence are available. Pharmacogenomic studies have the potential to accelerate the translation of neurobiological findings into safe and effective pharmacotherapies for MA dependence by identifying genes associated with clinical phenotypes of MA dependence and response to treatment. The goal of this Mentored Patient-Oriented Research Career Development Award is to provide Keith Heinzerling, MD, MPH with the training and experience needed to become an independent clinical investigator in the area of pharmacogenomic approaches to medication development for substance abuse with an emphasis on MA use disorders. Dr. Heinzerling is currently a co investigator with the UCLA Medication Development Unit for Stimulant Abuse, under the mentorship of Drs. Steven Shoptaw & Walter Ling. The proposal will allow Dr. Heinzerling to use the abundant educational and research resources in addiction medicine available at UCLA (S. Shoptaw & W. Ling) and Baylor (T. Kosten) and in genetics at UCLA (S. Nelson & J. McCracken) to obtain advanced training in genetics, translational research, addiction pharmacotherapy, clinical trial methodology, and responsible conduct of research that will allow him to become an independent investigator using new genomic approaches to develop medications to treat substance abuse. During the award period, Dr. Heinzerling will perform a pharmacogenomic study aimed at providing preliminary support for associations between genetic polymorphisms and two important clinical phenotypes of MA dependence, baseline frequency of MA use and treatment response to bupropion, using genotypic and phenotypic data from approximately 600 MA dependent participants undergoing screening for several NIDA-funded medication trials, including 120 participants who will be exposed to bupropion. The study will allow Dr. Heinzerling to establish the infrastructure and expertise within the UCLA Medication Development Unit required to secure R01 funding for future pharmacogenomic studies of MA dependence and response to pharmacotherapy. [unreadable] [unreadable] [unreadable]