This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to improve treatment for opioid misuse and addiction. Since joining the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) in 2015, the NorthStar Node has made significant contributions to the objectives and priorities of the CTN. The NorthStar Node and its investigators have led or co-led five CTN protocols, served as a research site for seven CTN studies, co- chaired the CTN Steering Committee and the Data Science Work Group, served on the Research Development Committee, and contributed to several special interest groups. The NorthStar Node's research portfolio includes traditional randomized controlled trials (CTN-0068), pragmatic comparative effectiveness research (CTN-0098A and CTN-0099), implementation science (CTN-0074, CTN-0098B, and CTN-0099), community-based participatory research (CTN-0096), data science (CTN-0076 and CTN-0087), and health services research (CTN-0070). In this application, the NorthStar Node has seven guiding objectives (POLARIS): 1) generating evidence that informs Policy and clinical guidelines; 2) evaluating models addressing co-Occurring SUD and medical and psychiatric conditions; 3) using principals of a Learning health system to conduct pragmatic trials; 4) using Artificial intelligence and other data sciences approaches to enhance SUD research and care; 5) Reaching understudied populations to ensure SUD research is relevant to diverse populations; 6) using Implementation science to test the integration of evidence-based SUD practices into general medical settings; and 7) testing innovative Strategies for SUD treatment. Potential studies to meet these objectives include 1) a novel therapeutic intervention for methamphetamine use disorder; 2) development of machine learning algorithms in the electronic health record to target substance use screening and enhance substance use disorder diagnoses; 3) precision/personalized medicine studies using population pharmacokinetics to better define and refine medication dosing strategies that improve treatment outcome; and 4) testing collaborative care models to address co-occurring chronic medical illnesses in specialty addiction treatment settings. Our expertise spans multi-site clinical trials, implementation science, community-based participatory research, EHR-based interventions, machine learning and natural language processing, and health services research. In addition to community partners that include urban and rural integrated health systems, federally qualified health centers serving underrepresented minorities, specialty addiction treatment programs, and pediatric and adolescent health clinics, the NorthStar Node brings affiliated research and dissemination networks into the CTN, including CTSA, SIREN, PCORNet, JCOIN, HOPE, the Network Coordi...