Responses of People Who Use Drugs to the Presence of Xylazine in the Unregulated Drug Supply

"PWUD demonstrated a predominantly protective approach to xylazine emergence by modifying their drug consumption routes and reducing injection drug use, aiming to mitigate potential harms associated with xylazine adulteration. While often discussed in the context of xylazine here, this echoes a broader literature that reveals an elevated prevalence of smoking among people who previously injected opioids on the West Coast of North America [30–32].

"Xylazine use has been associated with severely necrotizing skin infections that produce wounds even distal to the injection site or when individuals are smoking [10, 12, 33]. While more research is needed on the health implications of transitioning away from injection drug use towards other routes of administration (e.g., smoking) and its consequences, it is possible that transitioning away from injecting could reduce the likelihood of tissue necrosis or subsequent SSTIs [34]. However, it is still unclear if transitioning from injecting to smoking opioids (especially those adulterated with xylazine) decreases one’s risk for overdose and what the impacts are on cardiovascular health [35].

"While clients’ reliance on alternative consumption routes and peer networks for safety highlights the importance of peer-based harm reduction approaches, increased stimulant use and ‘human testing’ practices, intended to counteract xylazine’s sedative effects and verify drug safety, raises concerns about heightened susceptibility to overdose and other adverse outcomes [3, 36]. Increased polysubstance use with stimulants may increase clients’ overall drug consumption, thereby increasing their risk for additional adverse events (e.g., cardiac arrest, overdose, and SSTIs) [37–39]. Also, reports of using drugs alone underscore the need for additional interventions to address social isolation and enhance safety while people consume unregulated substances. One such intervention that may overcome these challenges could be implementing a phone-based overdose response service, as seen in Canada [40].

"The phenomenon of clients seeking out xylazine for its unique effects challenges existing literature on individuals’ preferences for xylazine and has implications for addiction treatment in the context of an evolving drug supply [41–43]. For example, more research is needed to develop guidelines for managing buprenorphine initiation while individuals are using xylazine-adulterated opioids to help mitigate anxiety and xylazine-related withdrawal symptoms [44]. On the other hand, despite efforts to reduce exposure to xylazine, some clients reported increasing their consumption of opioids, driven by the need to counteract diminished opioid availability and withdrawal symptoms associated with xylazine’s short half-life [45]. This finding contradicts previous hypotheses suggesting xylazine’s role in extending the duration of opioids’ effects [12, 46], indicating a nuanced interplay between substance availability, dependence, and desired effects."