PROJECT SUMMARY Non-pharmaceutical fentanyl and other novel synthetic opioids (NSO) have contributed to unprecedented increases in overdose mortality in the U.S. A rapid surge in the availability of counterfeit pharmaceutical drugs signals a new wave of the NSO spread, and it presents unique challenges and increased risks to a broad population of users. More research is urgently needed to characterize the toxicological features and the initiation pathways, patterns of use, and overdose risk behaviors related to the use of counterfeit pills that mimic prescription opioids, benzodiazepines, and other drugs. The study will be conducted in Arizona (AZ), characterized as a “ground zero” in terms of the new waves of the evolving NSO epidemic. The study builds on a collaborative partnership with Sonoran Prevention Works, a leading grassroots harm reduction organization in AZ. The overall purpose of the proposed study is to characterize drug use experiences and overdose risks associated with the rapidly growing counterfeit pharmaceutical drug (opioids, benzodiazepines) spread in AZ. The study will recruit a sample of 60 individuals in the Phoenix, AZ metro area, stratified into two groups by their current (past 7 days) use of a) non-prescribed pharmaceutical opioids and/or counterfeit opioid pills; 2) non-prescribed benzodiazepine and/or counterfeit benzodiazepine pills (n=30). We will aim to engage ethnic minority groups to identify ethnic/racial disparities and vulnerabilities related surging availability of counterfeit drugs in AZ. The Specific Aims are: Aim 1: Characterize how local drug market conditions, individual vulnerabilities, and broader social and structural factors influence drug use experiences and overdose risks associated with counterfeit opioid and benzodiazepine pill use through in-depth qualitative interviews with persons who use illicit drugs (N=60) in Phoenix, AZ. Aim 2: Conduct urine toxicology analysis using liquid- chromatography-tandem mass spectrometry (LC-MS/MS)-based methods to identify fentanyl, fentanyl analogs, other NSOs, designer benzodiazepines, and other prescription and illicit drugs and assess the concordance with self-reported use of these drugs (N=60). Aim 3: Identify priority intervention and policy response strategies to reduce overdose-related risks of counterfeit pills through focus groups with key stakeholders (N=20), including harm reduction coordinators, grassroots organizations of persons who use drugs, treatment providers, and policymakers. The study is highly significant because it will provide timely data on the growing counterfeit pharmaceutical drug use in the U.S. The proposed research is innovative because of: a) interdisciplinary approach and partnership with a grassroots harm reduction organization, b) integration of qualitative interview data and toxicological analyses, c) compare and contrast drug use experiences and overdose risks associated with the counterfeit opioid and counterfeit benzodiaz...