Background Recent sharp exacerbations of the US overdose crisis have been linked to systemic polysubstance use and potent synthetic compounds in numerous drug classes. Xylazine is a veterinary tranquilizer, long noted in the opioid supply of Puerto Rico, and more recently Philadelphia. Yet its national growth over time, geographic distribution, and potential role in the shifting US overdose risk environment are poorly characterized.
Conclusions We summarize evidence that xylazine is increasingly implicated in overdose deaths across the US and is linked to the proliferation of illicitly-manufactured-fentanyls. We document hypothesis-generating ethnographic accounts linking it to health risks for PWID. Nevertheless, many jurisdictions do not routinely test for xylazine, and it is not tracked in federal overdose statistics. Further efforts are needed to provide PWID with services that can help to minimize additional risks associated with a shifting drug supply.