Epidemiology of xylazine-associated health harms: a cohort study of people who have injected drugs

Xylazine is a veterinary sedative that has no approved human use but that has, over the past half-decade, become increasingly prevalent in the United States’ illicit drug supply, often mixed with fentanyl. In a recent warning to stakeholders, the FDA identified risks associated with xylazine use, including that: 1) xylazine can cause respiratory depression and overdose which cannot be reversed by naloxone; 2) xylazine cessation can lead to severe withdrawal, potentially impeding treatment for opioid use disorder, and 3) xylazine use has been linked to wounds and severe necrotic skin ulcerations. There is an urgent need for rigorous epidemiologic data on xylazine use and associated health effects to inform public health response, treatment, and harm reduction. However, the epidemiology of xylazine use and its associated adverse health outcomes such as wounds and overdoses are poorly characterized. Our pilot study will provide among the first rigorous estimates of the association of xylazine use with adverse health outcomes, and will examine drug use behaviors that may exacerbate or mitigate these xylazine-related harms. Our aims specifically focus on three hypothesized xylazine-associated adverse health outcomes: 1) wounds and skin necrosis; 2) drug overdose; and 3) all- cause emergency and hospital visits and the hospital bills incurred because of those visits. These aims will be accomplished with infrastructure of the ALIVE study: a 30+ year observational cohort of community-recruited adults living in the Baltimore area who have a history of injection drug use (7,8). Enrolled participants attend twice-annual study visits at which they complete questionnaires assessing substance use and health. Beginning in 2025, urine samples will be collected from all participants for rapid, on-site xylazine and fentanyl testing. Linkage to Maryland’s Health Information Exchange (HIE) allows complete ascertainment of hospital- and emergency-department based healthcare utilization including all associated dates, locations, and diagnosis and procedure codes. To this existing infrastructure, we will add: 1) a supplemental questionnaire with detailed questions about xylazine us; and 2) a standardized direct-observation wound assessment protocol developed in collaboration with an expert on wound care for people who use drugs. If successful, our pilot will facilitate future research examining trends in the epidemiology of xylazine, including the prevalence and correlates of use and health consequences, as well as harm prevention and treatment.