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. Author manuscript; available in PMC: 2024 Oct 1.
Published in final edited form as: Int J Drug Policy. 2023 Sep 13;120:104190. doi: 10.1016/j.drugpo.2023.104190

Response to “Xylazine in the Drug Supply: Emerging Threats and Lessons Learned in Areas with High Levels of Adulteration”

Leah H Harvey 1, Traci C Green 1, Ju Nyeong Park 1, Josiah D Rich 1
PMCID: PMC10664799  NIHMSID: NIHMS1932358  PMID: 37708584

The increasing prevalence of xylazine in the drug supply is associated with greater morbidity for people who use drugs (PWUD) and may contribute to higher risk of mortality. (Kariisa et al., 2023; Reyes et al., 2012; The White House, 2023) Like other common adulterants, such as caffeine or diphenhydramine, xylazine is inexpensive, readily available, and can serve as a bulking agent to increase profits. (Drug Enforcement Administration, 21 Dec 2022; Rich & Solomon, 2023) However, xylazine can also perpetuate and augment the sedative and analgesic properties of opioids, which can be particularly desirable for some who are using it (enhanced effects) or selling it (increased profits) (Friedman et al., 2022; Reeve et al., 2023)

In this issue of The International Journal of Drug Policy, Thomas Quijano and colleagues describe the impact of xylazine adulteration utilizing multiple data sources, including mortality data, a survey of PWUD, and semi-structured interviews with harm reduction specialists in Connecticut and Pennsylvania.(Quijano T, (in press)) The results of this study highlight the severity and rapid expansion of this phenomenon. Particularly concerning is the rise in xylazine-involved deaths observed from 2021 to 2022 despite a concurrent decline in opioid and fentanyl deaths in those states. Interviews with a harm reduction service organization highlighted that xylazine-involved overdoses often have a different presentation than typical opioid overdoses, do not respond quickly to naloxone, and may therefore require use of additional strategies, such as the provision of supplemental oxygen. Interviews with PWUD demonstrated that most respondents were aware of xylazine and concerned that the drug supply was unpredictable. Notably, two-thirds of respondents were interested in having ways to detect xylazine, such as through test strips, which have significant implications for harm reduction service provision.

However, these results also highlight the need for further research to better characterize the pathophysiology and clinical manifestations associated with xylazine use, as well as a more in-depth understanding of patterns of use, effects of xylazine dose and route of administration, mitigating and preventative behaviors, geographic variation, and potential racial disparities.(Gupta et al., 2023) We call for scholarly examination of this growing phenomenon and suggest, amongst other questions, the following research agenda:

  1. Overdose Risk:
    1. What is the role of xylazine in fatal overdose?
    2. Does the presence of xylazine increase opioid mortality risk?
    3. What is the mechanism by which xylazine increases overdose risk?
  2. Pathophysiology:
    1. How do the incidence and prevalence of xylazine-induced overdose and skin wounds vary by dose, route of administration, and duration of use?
    2. How does xylazine use cause physiologic dependence and a withdrawal syndrome?
    3. How do route of administration and dose of xylazine exposure affect the incidence, location, severity, and natural history of xylazine-associated skin wounds?
    4. What are other manifestations and consequences of xylazine-induced overdose and prolonged exposed sedation (e.g., environmental exposure, rhabdomyolysis, amputation)?
  3. Use Patterns and Behaviors:
    1. Are the communities of PWUD at risk aware of xylazine and ways they can reduce harms associated with xylazine?
    2. Do clients seek out xylazine, either as an opioid adulterant or for primary use, and why?
    3. How common is xylazine seeking?
    4. Is xylazine involved in sexual assault or other criminal activity?
  4. Clinical Response and Treatment:
    1. How can we best treat complications of xylazine use, such as overdose, skin wounds, or withdrawal? Can yohimbine and other α2 antagonists be helpful?
    2. How can emergency health services and first responder agencies better respond to xylazine-involved overdoses and care for xylazine wounds?
    3. What adaptations and shifts in services do substance use treatment providers need to adopt to address xylazine withdrawal and psychosis?
  5. Harm Reduction Response:
    1. How are harm reduction service providers navigating the addition of xylazine-related service and care needs?
    2. What staffing, services, supplies and additional support are needed to continue to provide quality care and services in xylazine-affected communities?
    3. What kind of public health messaging is most effective without inciting fear and further stigmatization of PWUD?
  6. Regulation:
    1. Should xylazine be considered to be a controlled substance at the federal and/or state level and more tightly regulated by the DEA?
    2. What are possible unintended consequences of the criminalization of xylazine?
    3. What are policy alternatives (and their possible unintended consequences) to criminalization of xylazine?

We congratulate the authors on this important early step in the characterization of current practices of xylazine use, particularly given the limited published work currently available on this emerging issue. The results of this study imply there is an urgent need for more comprehensive research on xylazine use and suggest multiple potential harm reduction interventions. As the authors suggest, specialized responses to xylazine-involved overdoses and xylazine-associated skin and soft tissue infections would require additional training of first responders and other clinicians but could significantly reduce morbidity. Likewise, expanding the availability of drug checking and xylazine test strips would be highly beneficial, particularly in areas where xylazine is not currently prevalent.(Green et al., 2022; Shuda & Lam, 2022) However, we still have a ways to go in terms of optimizing access to high quality, maximally effective treatment for PWUD, including liberalizing methadone regulations and expanding low-barrier buprenorphine, and to optimizing wound care services for PWUD, in order to reduce the morbidity and mortality associated with xylazine exposure and substance use. (Benrubi et al., 2023; Ivsins et al., 2020; Krawczyk et al., 2023; Sanchez et al., 2021) These cross-cutting issues and research priorities outline an agenda to effectively combat this latest challenge to the overdose crisis.

Funding

TG, JP, and JR are funded by P20GM125507 (NIGMS). TG is also funded by UG3/UH3 DA056881-01 (NIDA) and NU17CE925012 (CDC).

Footnotes

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Disclosures

The authors have no conflicting interests to report.

Ethics

This manuscript represents the authors’ commentary only and therefore did not require IRB approval.

Declaration-of-competing-interests

The authors have no conflicting interests to report.

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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