7. Project Summary/Abstract The goal of this proposal is to (1) examine patterns of methamphetamine (MA) use and related harms (including MA use disorder and MA overdose) in the context of an entrenched and ongoing opioid use epidemic, and (2) identify promising prevention, treatment, and harm reduction approaches for communities disproportionately affected by drug-related harms. Our team has an established collaboration and research infrastructure, and has conducted preliminary research that informs the current application. Using a combination of structured epidemiological interviews, biological testing, and qualitative timeline follow-back interviews, this proposal is designed to understand how MA and polydrug use patterns influence health outcomes, with a focus on groups underrepresented in drug use research, especially now when research and program efforts are almost exclusively confined to problematic opioid use. The aims of this proposal are: 1. To estimate prevalence of and identify risk and protective factors associated with current MA use, and MA-related harms among people who use drugs. a. Describe the frequency and quantity of MA use, and associations between MA use and other drugs, including prescription (Rx) stimulants, opioids, and other polydrug use patterns. MA use will be identified by self-report and by urine-toxicology screening. b. Identify associations between MA use and (i) risk factors, (ii) protective factors, (iii) health and social consequences (e.g.,self-reported HIV, HCV status, soft-tissue infections, OD, substance use disorder). c. Examine moderating impact of socioeconomic status (SES), ethnicity, and stigma. 2. To qualitatively describe the experiences of and rationale for MA use, polydrug use, and progression to misuse and dependence using lifetime drug use history interviews. a. Describe patterns of initiation, transition between MA and other drugs, social and structural factors that influence MA use (including Rx opioid and stimulant availability), social networks, and economic forces that structure drug use and related harms. 3. To examine the feasibility and acceptability of promising prevention, treatment, and harm reduction strategies for people who use MA. a. Assess the feasibility and acceptability of potential biomedical interventions, such as pharmacotherapies to treat MA use disorder that are currently in the clinical pipeline. b. Assess feasibility and acceptability of harm reduction strategies for people who use MA. This proposal responds directly to RFA-CD-21-002 Objective 2. It contains a detailed translation and dissemination plan that will facilitate rapid implementation of actionable findings, and leverages a successful existing multidisciplinary collaboration among investigators and community partners.