PROJECT ABSTRACT Violence exposure substantially increases substance use and abuse, doubling the risk of developing a substance use disorder and contributing substantially to overall use levels and relapse, yet the individual mechanisms that account for violence-related increases in substance use are not well examined. The proposed research will focus on three candidate mechanisms by which violence exposure maintains and exacerbates substance use: negative affect, craving, and stress dysregulation. Each mechanism has been individually linked to violence exposure and substance use in prior research. However, that research has focused almost exclusively on urban populations or users of alcohol or nicotine. The present study will address these gaps by focusing on rural populations and users of cocaine, amphetamines, and opiates. Three specific aims will be achieved: delineate the role of negative affect as a proximal predictor of illicit drug use and a mediator between violence exposure and substance use among a sample of active drug users by using EMA methods (Aim 1); delineate the role of craving as a proximal predictor of illicit drug use and a mediator between negative affect and substance use in the same population by using EMA methods (Aim 2); and delineate the role of stress regulation in substance use frequency among this population by combining lab-based procedures and EMA methods (Aim 3). To achieve these aims, this project will recruit a subsample (n=75) of a larger longitudinal cohort of rural drug users for lab-based research and follow-up monitoring. Participants will complete controlled procedures for assessing stress dysregulation, followed by real-time assessments of craving, negative affect, and substance use over a period of five weeks. This research will take the innovative step of combining lab-based procedures with validated ecological measures to provide novel data on the basic behavioral and cognitive processes operating in situ in an individual drug user’s environment. To set the stage for future research, the project will also combine multiple measures of stress and stress responding, including self-report and objective physiological data via novel data collection technology that links real-time physiological data with real-time self-report measures, thus substantially expanding current research capabilities focused on rural drug use. This project sets the stage for a long-term goal of developing a complete model of the effects of violence exposure on rural addiction, and, in turn, more targeted interventions for this pressing national problem. These long-term goals fulfill multiple priority focus areas of the National Institute on Drug Abuse strategic plan for 2016-2020 by investigating “how social and environmental stimuli can interact with [biological] networks to perturb their balance” (Focus Area 1), “the common underlying substrates and biological mechanisms that contribute to common comorbidities” (Focus Area 3), and “potential mechanisms and processes that may provide targets for intervention” (Focus Area 4).