This application is for the Career Development Transition Award (CDTA). As a psychiatrist and clinical researcher, Dr. Yoon has designed and conducted several clinical trials and translational research driven by neuroscience-based hypotheses. The main goal of his research is to evaluate and develop medications for addictive and psychiatric disorders. He is a recipient of the VA Career Development Award (CDA-2) and the Merit Review Award. Dr. Yoon has tested novel approaches for the treatment of addictive and psychiatric disorders, particularly focusing on alcohol use disorder (AUD) and major depressive disorder (MDD). Many of his studies are the first to translate a novel observation in preclinical research to human therapy for these disorders. Addictive and psychiatric disorders produce enormous morbidity and mortality, and are very costly to the VA. The pharmacological approach he is testing has enormous potential to help patients suffering from addictive and psychiatric disorders. His current Merit Review award project is being conducted to evaluate whether the combination of ketamine (NMDA glutamate receptor antagonist) and naltrexone (opioid receptor antagonist) is effective in reducing depression and alcohol consumption. This study is highly innovative by asking important questions on (a) whether opioid receptor stimulation contributes to the antidepressant effects of ketamine and (b) whether the combination of naltrexone and ketamine might be a strategy to reduce addiction risk while rapidly treating depression. Since adequate treatment of MDD and AUD is of major clinical importance, the ketamine plus naltrexone approach may have a transformative impact on patients suffering from this condition. The CDTA will extend his capabilities beyond the current Merit Review Award project and lead his growth and development as a clinical researcher. His research plans during the CDTA period include: (a) conduct of six clinical trials that are currently funded (Project 1-6), (b) resubmission of two NIH R01 applications (Project 7-8), and (c) submission of two new grant applications (Project 9-10). Building on the findings from these projects, his long-term goal is to develop new and more effective pharmacological interventions for addictive and psychiatric disorders. In addition to these research activities, he will participate in training activities. Dr. Yoon is actively collaborating with VA and Yale researchers. They have collected data, shared research techniques, published papers, and submitted grant applications. There are three objectives. Aim #1: To conduct six clinical trials that are currently funded (Project 1-6). Aim #2: To resubmit two NIH R01 applications (Project 7-8) and submit two new grant applications (Project 9- 10) Aim #3: To participate in training activities in (1) ketamine and psychiatric research, (2) neuroscience and drug discovery, (3) addiction research, (4) clinical trials and research methodology, (5) neuroimaging, (6)...