Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis

BackgroundRecent 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.MethodsIn this sequential mixed methods study, xylazine was increasingly observed by our ethnographic team over many years of intensive participant observation fieldwork in Philadelphia among drug sellers and people who inject drugs (PWID). Subsequently, we systematically searched for records describing xylazine-involved overdose mortality across the US and assessed time trends and overlap with other drugs.ResultsIn 10 jurisdictions—representing all 4 US Census Regions—xylazine was found to be increasingly implicated in overdose mortality, rising from 0.36% of deaths in 2015 to 6.7% in 2020. The highest xylazine prevalence in the recent data was observed in Philadelphia, (25.8% of deaths), followed by Maryland (19.3%) and Connecticut (10.2%). Illicitly-manufactured-fentanyls were present in 98.4% of xylazine-involved-overdose-deaths— suggesting a strong ecological link—as well as cocaine (45.4%), benzodiazepines (28.4%), heroin (23.3%), and alcohol (19.7%). PWID in Philadelphia described xylazine as a sought-after adulterant that improves euphoria and lengthens the short duration of fentanyl injections, in particular. They also linked it to increased risk of soft tissue infection and overdose.ConclusionsWe 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.