Background Xylazine is a veterinary tranquilizer found in the unregulated drug supply in the United States. It appears alone or as an adulterant in fentanyl (“tranq dope”). Xylazine’s symptomatology is well described and includes skin and soft tissue damage, bradycardia, and loss of consciousness. However, little is known about whether and how substance use behaviors have changed as xylazine’s presence in street drugs has grown.

Methods We conducted semi-structured in-depth interviews with people with recent overdose reversal experiences in two mid-sized midwestern cities (n=52). Interviews were part of a larger study on naloxone administration behaviors. Participants were asked about their knowledge and perceptions of local drug supply trends. Transcript data were analyzed using the rigorous and accelerated data reduction technique.

Results Participants preferred fentanyl and heroin without xylazine. Most participants discussed adjusting opioid use toward safer practices: using less in amount or frequency, abstaining or seeking treatment, alternating use (e.g., ingesting xylazine only at night), or changing route of administration from injecting to smoking, snorting, or boofing (ingesting anally). Motivations for changes in use included not experiencing intended opioid agonist effects, fear of physical health risks, loss of functionality and productivity, and overdose concerns.

Conclusion Findings suggest that xylazine is encouraging reduced fentanyl and heroin use. Our results corroborate laboratory, clinical, and behavioral studies showing that xylazine, which causes severe health harms, may also, paradoxically, be protective against fatal overdose. More research is needed on this phenomenon in light of recent downward trends in overdose mortality.

The authors have declared no competing interest.

This research was supported by the US Food & Drug Administration (BAA-22-00123, grant #75F40122C00193). No funders were involved in the preparation of this manuscript or the decision to submit for publication.

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The IRB of University of North Carolina-Chapel Hill gave ethical approval for this work

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