Using Demographic and Substance Use Features to Predict Suspected Xylazine-associated Wound Development Among People Who Use Drugs in North Carolina

Xylazine is a veterinary sedative and α-2 adrenergic agonist that is not approved for human use. In recent years, it has been increasingly detected in combination with fentanyl and other substances in illicit drug markets (Cano et al., 2024; Drug Enforcement Administration, 2024; Friedman et al., 2022). The emergence of xylazine as an adulterant in the illicit drug supply presents significant novel public health concerns in the United States. In addition to complicating overdose response due to its non-opioid pharmacology, xylazine has been associated with severe skin and soft tissue wounds among people who use drugs (Ciccarone et al., 2025; Lutz et al., 2025; Perrone et al., 2024). These wounds often begin as small lesions that may rapidly progress into large ulcerations or necrotic tissue damage and may require extensive medical treatment.

Research on xylazine-associated wounds has been on the rise. For example, Jawa et al. (2024) found that in a sample of 175 persons who used drugs in Massachusetts, 86.5% experienced xylazine wounds. The researchers reported no statistically significant demographic differences between those with and without xylazine wounds, whereas subcutaneous injections were highly associated with xylazine wounds. Other research indicated that xylazine wounds could develop quickly at both the injection sites and distant sites (Carroll, 2024; Perrone et al., 2024). Wounds have also been observed in people who only use snorting or smoking (Perrone et al., 2024). Mice experiments showed that exposure to both xylazine and fentanyl significantly delays wound closure (Bedard et al., 2025).

Although these new findings have improved the knowledge of xylazine-associated wounds, empirical research examining the factors that predict wound development remains limited. The present brief report explores the predictors of xylazine-associated wound occurrence and severity among people who use drugs in a region of North Carolina, where recent reports confirm xylazine’s continued presence in the illicit drug supply (Cumberland County Government, 2022; UNC Street Drug Analysis Lab, 2022; UNC Street Drug Analysis Lab, 2025).

Methods

Results

Table 1 presents the descriptive statistics for the xylazine-related drug use variables. In terms of xylazine exposure (i.e., time of first use), the distribution of the four lengths was relatively even. For frequency of drug use in the last 30 days, one-four times a week received the highest count, and no use had the lowest. For the main substance adulterated with xylazine, nearly 80% of the sample reported fentanyl. Regarding route of administration, the most popular method was injection.

Among participants reporting possible xylazine exposure, 42% indicated that they had experienced wounds or suspected wounds associated with xylazine use, whereas 57.9% reported no wound experience. Among those reporting wounds, 31.8% described wounds as mild, while 51.3% reported moderate wounds requiring medical treatment and 16.9% reported severe wounds involving extensive care or long-term complications.

Discussion

This report highlights a substantial burden of xylazine-associated wounds among people who use drugs in a high-prevalence region of North Carolina. Over 40% of individuals reporting xylazine exposure indicated experiencing wounds, with most of them describing moderate to severe wound severity. These findings reinforce the growing clinical significance of xylazine beyond overdose risk and identify wound-related morbidity as a critical consequence of the evolving synthetic drug supply.

This study represents one of the first efforts to examine what demographic and drug use features may predict xylazine-associated wound development. Consistent with prior research (Jawa et al., 2024), injection drug use was more strongly associated with wound occurrence than other routes of administration. However, wounds were also reported among individuals who primarily smoke or snort substances, aligning with frontline and clinical reports (Carroll, 2024; Perrone et al., 2024). These patterns indicate that wound development is not solely attributable to injection-related trauma and supports a role for systemic pharmacologic effects. A novel current finding was that injection did not have a stronger association with wound severity than other routes, suggesting that route of administration may influence wound initiation, whereas systemic mechanisms may drive progression and severity.

In contrast, frequency of drug use did not predict wound occurrence but was associated with severity with the highest frequency linked to lower reported severity, suggesting that high-frequency users may have greater tolerance to xylazine in terms of wound severity. Additionally, xylazine exposure predicted neither wound occurrence nor severity. Together, these findings are consistent with a threshold-based rather than dose-dependent model of wound development.

Substance-specific patterns displayed in the current study further underscore the complexity of xylazine-associated wounds. For instance, cocaine as the primary substance was associated with greater severity, while heroin was associated with less severe outcomes. Importantly, fentanyl users did not have a higher rate of wound occurrence or severity compared to non-fentanyl users. These findings may reflect complex pharmacological interactions associated with polysubstance use.

Demographic characteristics did not significantly predict wound occurrence or severity, consistent with prior findings (Jawa et al., 2024). This suggests that xylazine-associated harms are driven more by structural exposure within a contaminated drug supply than by individual-level demographic risk. In regions such as Cumberland County, where drug checking confirms ongoing xylazine presence (UNC Street Drug Analysis Lab, 2022, 2025), these results support population-level public health responses.

Limitations include reliance on self-reported data which may introduce recall bias or misclassification, and the absence of dosage or toxicologic confirmation. Additionally, the single-site sample may limit generalizability.

Conclusions

The increasing presence of xylazine in the illicit drug supply introduces new clinical and public health challenges beyond overdose. The current findings suggest that xylazine-associated wounds appear to represent a distinct clinical phenomenon characterized by threshold-based onset, systemic pathophysiology, and complex polysubstance interactions. Implications for practice are clear. Wound prevention efforts should extend beyond injection-focused messaging, as non-injection routes also confer risk. Broad screening and early intervention are warranted regardless of use frequency. The high prevalence of moderate to severe wounds also highlights the need for low-threshold, community-based wound care integrated into harm reduction services.

Ethics approval statement

This research received ethics approval by the Human Rights in Research Committee at Fayetteville State University (IRB # 2025–35).