(PI: Dennis Daley, Psychiatry, Pitt). This is an Appalachian Tri-State (ATS) Node of NIDA’s Clinical Trials Network (CTN). One of the goals is to study substance use disorders (SUDs) that co-occur with psychiatric and/or medical conditions. These are essential because of the high prevalence of SUDs among those who have other illnesses, and the lack of studies for many specialized clinical populations, especially patients in medical settings. Potential CTN studies could focus on screening, identifying and engaging patients with SUDs in these non-addiction settings as well as examining dissemination and cost-effectiveness of the interventions. FRP7 will benefit from research conducted by Core A. High prevalence of SUDs exists among those vulnerable groups of poly drug use, which often carries with more risk than use of a single drug, due to an increase in side effects, and drug synergy. Core A will, in collaboration with Cores B and C, collect the DA-associated chemicals, genes, proteins and pathways related with SUDS and psychiatric diseases (see also FRP1) and map out the interactions between drugs and their targets by our developed HTDocking and ligand-based TargetHunter programs. Our analyses with quantitative systems pharmacology tools developed in Core B will help elucidate the putative mechanisms of drug synergy and side effects that will be tested/validated by FRP9. Such integrated studies will help translate Core research technologies to clinical applications and design better personalized medicines.