PROJECT ABSTRACT The Big South/West Node of the NIDA Clinical Trials Network (CTN) has been a part of the CTN since 2005 (originally as the Texas Node, expanding to the Big South/West Node in 2020). The Node is led by the shared leadership of Madhukar H. Trivedi, MD of University of Texas Southwestern Medical Center (UTSW), providing expertise in multisite clinical trials, and Steven Shoptaw, PhD of University of California Los Angeles (UCLA), providing internationally recognized expertise in stimulant use disorder (StUD). This fourth competing renewal application builds on our successful track record of leading CTN trials, being excellent network partners by providing exceptional sites for multi-site studies, high productivity in publishing, and training the next generation of scientists. During the 2020-2025 funding cycle, our team completed the largest pharmacotherapy trial for the treatment of methamphetamine use disorder to date (CTN-0068, ADAPT-2), which now has six publications and three additional manuscripts under review. We also developed and led four large randomized controlled concepts for novel interventions in adults with stimulant use disorders (CTN-0108 STIMULUS, CTN-0109 CURB-2, CTN- 0110 MURB, CTN-0132 KMD) and three implementation study concepts for: improving recruitment of Black Americans in substance use clinical trials (CTN-0109-A-1, I-DREM), universal screening and measurement- based care for buprenorphine treatment (CTN-0090, MBC4OUD), and remote methadone monitoring (CTN- 0120, RMIST). For this renewal application, we capitalize on the experience of the PIs, who collectively have expertise in the treatment of StUD, treatment of and public health response to the opioid crisis, and treatment and care of comorbid conditions. Additional investigators bring content expertise spanning addiction science and clinical care, translational science, dissemination and implementation science, and trial implementation. Our geographical region is unique in that the South and West are experiencing a public health crisis of overdose deaths that involve stimulants. Furthermore, we have incredibly diverse patient populations (e.g., diverse racial and ethnic groups; underinsured; underserved; Native American and immigrant groups) within diverse settings (e.g., rural, urban). We will continue our efforts to conduct large multi-site studies on StUD treatments. In addition, our existing partnerships with primary care networks, emergency settings, and medical specialty care settings (i.e. HIV and cardio-pulmonary clinics) will allow us to scale up efficacious treatments in these healthcare settings. Our research agenda includes 1) conducting clinical trials on new and repurposed treatments for StUD; 2) implementing efficacious treatments in clinical settings to address comorbid conditions; 3) conducting implementation science to disseminate research findings and impact policy; and 4) exploring biomarkers to improve StUD treatments. Our team has experience with innovative study designs that target all areas of the translational science continuum and equip our Node to successfully and significantly improve the care of persons with StUD.

PROJECT NARRATIVE Substance use, particularly the use of stimulants, is a major public health problem, with stimulants being involved in over 50% of deaths due to overdose in 2021. Research is needed to develop new stimulant use disorder (StUD) treatments and to determine how to best broadly disseminate the treatments that are currently available and effective. The National Institute on Drug Abuse’s National Drug Abuse Treatment Clinical Trials Network (CTN) and the Big South/West Node will contribute their expertise to finding solutions for the substance use problems impacting our South/West region as well as nationally.