Background In the United States, opioid overdose has been a persistent issue for four decades, with the “fourth wave” of the overdose crisis characterized by increased polysubstance use such as between fentanyl and potent sedative adulterants. Xylazine, a veterinary sedative, has appeared commonly in the unregulated fentanyl supply since the early 2000s, and poses significant challenges for addressing and managing overdose events, withdrawal, and symptom management. Since 2022 the Opioid Data Lab, a public service of the University of North Carolina at Chapel Hill, has provided anonymous drug checking services across the United States in partnership with 193 programs across 43 states. Better understanding the relationship between xylazine and fentanyl helps to inform clinical withdrawal management, overdose prevention and intervention strategies, and community awareness of and responses to drug supply shifts. This study’s objective was to explore the relationship between xylazine adulterated fentanyl and reported sample associated overdose within North Carolina (NC) using the Opioid Data Lab database. The primary aim of this analysis is to determine whether xylazine significantly increases the likelihood of a reported overdose event when present in a fentanyl sample. Methods Samples are collected voluntarily and anonymously and mailed to the Opioid Data Lab for component analysis by gas chromatography–mass spectrometry. Self-reported data including sample-associated overdose accompany the sample. Samples included in the primary analysis were collected between January 2022 and July 2025, had fentanyl as a major component and reported overdose as yes or no (non-missing). Xylazine positive fentanyl samples were defined as xylazine as a trace or major component included in the sample. Logistic regression analysis adjusted for the region of NC (East, Central, Western) was used to evaluate the relationship between xylazine adulteration of fentanyl samples and reported-overdose. Results For fentanyl-positive xylazine-positive samples, the odds of being associated with an overdose event was 1.24 (95% Confidence Interval 0.86, 1.77) when adjusting for the NC region of sample origin. Considering all samples from North Carolina in the same time period, the odds of xylazine positivity being associated with an overdose event was 2.32 (95% Confidence Interval 1.69, 3.19) when adjusted for NC region of origin. Conclusions The lack of association of xylazine adulterated-fentanyl samples and reported overdose events in this study may have resulted from several factors including changes in drug use behavior and dosing, pharmacologic ceiling effect of fentanyl, changes in drug composition due to the introduction of xylazine, sample size, and the impact of harm reduction practices and drug checking services in regions of North Carolina. The association of xylazine and reported overdose in all of the samples regardless of fentanyl content, suggests that xylazine adulteration of the unregulated drug supply is still an important health issue in North Carolina. Furthermore, fentanyl overdose rates remain a critical public health concern.
Dmitri Fisher (Sat,) studied this question.