PROJECT SUMMARY/ABSTRACT: Substance use disorders are prevalent, are associated with serious morbidity and are common causes of preventable death. Although providers have at their disposal a number of evidence-based treatments, such treatments tend to be of near-moderate effect size, leaving some patients as non-responders. Work is needed to enhance existing or develop new treatments with higher effects sizes. This mid-career investigator award in patient-oriented research would enable Joseph Sakai, MD release from clinical and administrative duties to allow continued career development activities, to expand his lab’s work on neuromodulation and addiction and to provide high-quality mentorship to early career investigators. Dr. Sakai is involved in several medication trials for the treatment of alcohol use disorder and is contact PI for a UG3 award to test deep brain stimulation for treatment refractory methamphetamine use disorder utilizing a crossover design. This mid-career award, if funded, would allow Dr. Sakai’s lab to test the safety and feasibility of an accelerated transcranial magnetic stimulation treatment protocol for methamphetamine use disorder. In addition, this trial would allow effect size estimation to power a future trial. Each project allows key opportunities for trainee participation and mentorship as described in the application. Dr. Sakai is director of the CU-Pathways resident research track, which seeks to develop research-oriented physician scientists in the Department of Psychiatry. Because of that program’s successes, CU was awarded an R25 to support that track and match 2 residents per year through the NRMP (Sakai MPI). Dr. Sakai has also been very active with the DPRG T32 post-doctoral research fellowship training program which was renewed in 2022 (Sakai is associate director, and is primary mentor for 2 post-docs in that program). Thus, Dr. Sakai has formalized roles within major departmental mentorship programs with a specific focus on physician scientists; all programs emphasize and value recruitment of individuals from backgrounds under-represented in medicine.