PROJECT SUMMARY/ABSTRACT We propose to use the Behavioral Model for Vulnerable Populations as a framework to examine the feasibility and acceptability of a community-based drug checking (CBDC) program operating through a syringe service program (SSP) to collect information about the presence of xylazine in the illicit drug supply among rural and tribal communities in Minnesota. Administrative datasets that detect xylazine are too delayed and removed from persons who use drugs to provide actionable understanding into intervention strategies or changes in use patterns. CBDC has the potential to identify emerging substances like xylazine in real time and serve as point of care to provide individuals with information about their drugs, with actionable responses and referrals to treatment and services. However, there is limited information on the feasibility and acceptability of CBDC programs in the research literature and nothing in rural settings or with tribal communities. The proposed R21, Community Mitigation Against Xylazine, will address this and is ideally situated for the NOT-DA-24-012. Minnesota legalized all drug paraphernalia in 2023, and the state provided funding to SSPs to purchase a Fourier-transform infrared spectroscopy technology (the gold standard for CBDC programs), xylazine testing strips, and wound care kits. As part of this exploratory R21, we build on a collaboration with a community- based non-profit SSP that established the first mobile community-based drug checking in the state, with a delivery area classified as rural and that includes two American Indian/Native American tribal reservations. As part of a 24-month mixed-methods study, we will examine feasibility and acceptability of the CBDC program to detect xylazine through data collected from program participants and staff, with those whose drugs test positive for xylazine recruited to complete a qualitative interview on use and health effects. To demonstrate feasibility, we will calculate the prevalence of xylazine among samples tested from a centralized database that the investigation team will develop and disseminate to local stakeholders. The proposed study has strong public health potential to mitigate harms from xylazine and future cutting agents. Our study proposes examining drug checking where legal barriers have been removed and with a highly understudied population. The investigation team has experience examining harm reduction strategies and future R01 implementation science grants will use the Behavioral Model for Vulnerable Populations to examine strategies that improve the reach and benefits of this emerging harm reduction strategy.