Jon E. Zibbell

Background: Xylazine, a veterinary sedative not approved for human use, has emerged as a consequential adulterant in the U.S. illicit fentanyl supply. Although a growing body of qualitative research has documented the experiences of fentanyl consumers exposed to ‘tranq’ in large Northeastern cities, little is known about how xylazine is experienced in rural or Southern regions where the evolution of the illicit drug supply often lags behind its urban equivalents. This study examines how fentanyl consumers in west-central North Carolina detect, comprehend and respond to the widespread adulteration of fentanyl markets with xylazine. Methods: Between September and December of 2025, a seasoned interviewer conducted 25 in-depth, semi-structured qualitative interviews with fentanyl consumers recruited from both fixed and mobile syringe service programs in west-central North Carolina. Interviews explored sensory discernment strategies, pharmacologic effects, and behavioral responses to the presence of xylazine. Data were analyzed using a combined deductive-inductive thematic approach in QSR NVivo 14.0. Results: Participants described a distinctive repertoire of sensory strategies for identifying xylazine in their fentanyl supply, including the appearance of drug residue on foil, bitterness and chemical odor when smoked, and altered viscosity when injected. A minority described an inability to detect xylazine through sensory cues. Participants consistently distinguished a profound involuntary sedation they called “tranq sleep” from the familiar opioid nod, characterizing it by nearly instantaneous loss of consciousness with severe withdrawal upon awakening. While nearly all participants expressed strong aversion to xylazine, a meaningful minority valued its amplifying effects to ‘improve’ a diminishing fentanyl high. Conclusions: This study offers among the first qualitative description of xylazine exposure in a rural fentanyl market. Findings extend the xylazine literature geographically and pharmacologically and underscore the urgency of harm reduction responses tailored to the distinctive harms of xylazine. In particular, adverse health outcomes that accumulate during episodes of protracted and unarousable sedation, including physical injury, victimization, and the severe withdrawal syndrome that follows upon awakening. Highlights: xylazine; tranq sleep, fentanyl; qualitative methods; harm reduction; rural drug markets; drug discernment

The United States is at an inflection point in its decades-long opioid epidemic with the recent shift toward a more toxic and synthetic illicit opioid supply. The overdose epidemic began in the lat...

The United States continues to experience an unprecedented overdose crisis. Fentanyl overdose deaths increased 525% from 3105 in 2013 to 19 413 in 2016 and then increased 45.2% from 19 413 in 2016 to 28 466 in 2017, with fentanyl overdose deaths outpacing deaths from both prescription opioids and heroin in 2016 and 2017.^1,2 The Drug Enforcement Administration³ reported a 5-fold increase in national law enforcement seizures of illicitly manufactured fentanyls, and fentanyl overdose deaths increased substantially over this period. The Centers for Disease Control and Prevention^4,5 has endorsed using law enforcement drug seizures as a proxy indicator for the illicit drug supply, and a joint investigation between the Centers for Disease Control and Prevention and the state of Ohio⁶ demonstrated concurrent increases in fentanyl overdose deaths and fentanyl seizures. Less known, however, is whether there are associations between law enforcement drug seizures and drug overdose deaths.