A brick to a bundle: A qualitative study of behavioral responses to xylazine adulteration

BACKGROUND: Xylazine, a veterinary tranquilizer, has emerged as a widespread adulterant in the U.S. illicit drug supply, detected in over 90 % of street fentanyl samples in some regions and identified in a growing number of overdose deaths. While xylazine's health risks are well-documented, little is known about how its presence influences substance use behaviors. We aimed to explore behavioral changes among people encountering xylazine in illicit drug markets. METHODS: We conducted semi-structured in-depth interviews with people with recent overdose reversal experiences in two Midwestern cities (n= 52) as part of a larger study on naloxone administration. Participants were asked about their knowledge and perceptions of local drug supply trends. Data were analyzed using the Rigorous and Accelerated Data Reduction technique. Protection Motivation Theory provided a theoretical framework. RESULTS: Participants overwhelmingly preferred opioids without xylazine. Almost all reported adjusting use toward safer practices in response to xylazine exposure: using less in amount or frequency, changing route of administration, or abstaining or seeking treatment. Behavior change was motivated by fear of negative outcomes, including physical health risks (particularly chronic wounds and limb loss), not experiencing intended opioid effects, loss of functionality due to unwanted sedation, and concerns about overdose reversibility. CONCLUSION: Findings suggest that people who use drugs are adapting consumption patterns and adopting harm reduction practices as coping responses to xylazine's adverse effects. Unlike previous major opioid market transitions that primarily differed in pharmacokinetics, xylazine introduces new risks while replacing desired psychoactive effects with undesirable ones. The widespread dissatisfaction with xylazine represents a unique opportunity to expand harm reduction interventions and explore safe supply policies while risk salience is high and user motivation for safer practices aligns with public health goals.