Growing Xylazine Supply in NC: A Community-Based Investigation of Exposure and Health Consequences - PROJECT SUMMARY/ABSTRACT We propose a community-based, longitudinal, mixed-methods study to investigate the growing crisis of xylazine exposure among people who use drugs (PWUD) in the southeastern US. The Office of National Drug Control Policy recently listed xylazine as an emerging threat and the Centers for Disease Control and Prevention (CDC) warned of xylazine’s growing involvement in fentanyl overdose deaths. Among all US regions in 2020–2021, the south experienced the largest increase in xylazine-involved overdose (OD) deaths and the largest rise in xylazine-positive drug seizures. Yet, there remains a paucity of information on adulteration patterns in local markets, the impact of (un)witting exposure among consumers, how consumers are responding to xylazine, and drug use behaviors placing people at increased risk for atypical ODs and novel wounds. CDC recommends testing illicit drugs for xylazine to clarify prevalence in drug supplies and provide actionable intelligence to inform response. Community-based drug checking (CBDC) will expand the scientific impact of the proposed study by allowing us to identify patterns of xylazine adulteration within and across drug classes without having to rely on self-report to identify study participants exposed to xylazine, thus strengthening our scientific capacity to measure its psychosocial and physiological impact. Aim 1: To employ CBDC to determine xylazine’s overall prevalence in the illicit drug supply and its relative prevalence in specific drugs consumed by study participants; Aim 2: To explore knowledge and discernment strategies among consumers of illicit drugs as they navigate an illicit drug supply increasingly adulterated with xylazine; Aim 3: To examine the drugs and drug use behaviors of PWUD to determine the psychosocial consequences, behavioral risks, and adverse sequalae associated with xylazine exposure; Aim 4: To disseminate real-time CBDC results (Aim 1) and rapidly-analyzed study findings (Aims 2–3) to the state/county health departments and community-based organizations to inform public health response . To achieve these aims, we will recruit PWUD from two study sites and their surrounding counties. The study will be led by Principal Investigator Jon Zibbell, a National Institute on Drug Abuse–funded behavioral scientist with many years of experience studying injection drug use and infectious disease risk among PWUD. The team also includes Arnie Aldridge, a National Institutes of Health–funded statistician; Bradley Ray, a research sociologist; and Sarah Duhart Clarke, an applied psychologist. Findings from the proposed study will help clarify prevalence of xylazine and illicit markets and identify associated behaviors, observations, and adverse sequalae by Drug, Set, and Setting factors. The proposed study is poised to directly inform local and national efforts for combatting harms associated with xylazine use by disseminating findings to community members and decisionmakers in real-time.