Federal and state agencies, local health departments, and health care providers across the country have become increasingly concerned about the rise of xylazine, an adulterant often found in combination with fentanyl and also mixed with heroin, stimulants like methamphetamine and cocaine, and other substances. It is often reported with two or more drugs present. A non-opioid sedative, analgesic, and muscle relaxant approved for veterinary use, but not for humans, xylazine can complicate diagnosis of overdose related to polysubstance use, interfere with treatment of opioid use disorder (OUD), and cause severe necrotic skin ulcerations.1
What are its effects and why is it dangerous?
The Drug Enforcement Administration (DEA) warns that xylazine can increase the chances of overdose deaths when mixed with synthetic opioids like fentanyl because it has similar pharmacological effects and can increase respiratory depression. Users have reported effects similar to opioids.2 The FDA warns that xylazine exposure may delay diagnosis and management of overdoses involving multiple drugs, cause severe, necrotic skin ulcerations, and hinder treatment of OUD.3 Another danger of xylazine is that patients can become incapacitated for a long period of time, making them susceptible to assault or other harms such as hyperthermia.4
Testing for xylazine
Xylazine may be more widespread than testing indicates. Routine toxicology screens do not detect it, and with the additional analysis required, it may still be missed because it is eliminated from the body rapidly.5 Xylazine test strips are emerging but have not been validated yet.6
Patterns of distribution
Xylazine has been found in all four census regions, having appeared first in the Northeast, then the South, then the Midwest and West (similar to the movement of fentanyl). Its use as an adulterant is expected to increase, including in fentanyl. As of October 2022, xylazine powder could be bought online for around $6 to $20 per kilogram, a low cost that may make it lucrative as an adulterant mixed with fentanyl or heroin.7
What can be done?
Naloxone may be less effective when xylazine is present because it is not an opioid itself. But administering naloxone can still save lives by addressing the effects of opioids.8 If patients present with overdose and do not respond to naloxone, health care providers should consider exposure to xylazine. If withdrawal symptoms do not respond to traditional OUD treatments, it may also be a sign of exposure to xylazine.9 For harm reduction, providers can warn patients that xylazine is heavily present in street drugs, lasts longer than opioids do, and is found in stimulants as well as opioids. Skin ulcerations from injecting xylazine, which can be in the area of injection or elsewhere on the body, should be treated right away.10
Selected resources on xylazine
Overviews from federal and state agencies
The Centers for Disease Control and Prevention (CDC) analyzed data on overdose deaths from the State Unintentional Drug Overdose Reporting System (SUDORS) in 38 states and the District of Columbia. An article in Morbidity and Mortality Weekly Report provides data on overdose deaths in which xylazine was detected or involved, including by census region and co-occurring substances. The U.S. Food and Drug Administration (FDA) issued a three-page letter to stakeholders in November 2022 warning about the risk of xylazine exposure to humans and providing guidance for clinical professionals. The FDA also issued a press release about an action to restrict unlawful import of xylazine. The National Institute on Drug Abuse (NIDA), as part of its effort to clarify trends in the illicit drug supply, published a concise advisory on xylazine. The Drug Enforcement Administration published a four-page summary on the dangers of xylazine to humans, its mixture with other substances, geographical trends, and outlook. The Biden-Harris Administration designated fentanyl combined with xylazine as an emerging threat to the United States. The degree to which xylazine has played a part in overdose deaths nationwide prompted the administration to make the designation for the first time in U.S. history. The Substance Abuse and Mental Health Services Administration (SAMHSA) issued a letter alerting providers and grantees about the risks of xylazine. The letter provides information about the consequences of xylazine exposure, how to reduce harm, and what SAMHSA is doing to address the emerging public health challenge. The South Carolina Department of Health and Environmental Control published a four-page health advisory about an increase in overdose deaths and health hazards associated with xylazine, with background and recommendations for providers and community stakeholders. Provisional estimates from the department suggest a 379% increase in deaths involving xylazine from 2020 to 2021. In-depth studies, webinars, podcasts, and news articles
Rural Communities Opioid Response Program–Technical Assistance (RCORP-TA) provides an overview on xylazine that includes its prevalence in the U.S. drug supply, health effects and clinical messages, and resources for further information. The 2022 paper “Xylazine Spreads Across the U.S.: A Growing Component of the Increasingly Synthetic and Polysubstance Overdose Crisis” provides information on health risks posed by xylazine, geographical distribution in the U.S., xylazine’s growing presence in overdose deaths, and its combination with other substances. The first author of the article, Joseph Friedman, PhD, also presented the webinar “Xylazine (“Tranq Dope”) and the Illicit Drug Supply: Epidemiology, Drug Interactions, Treatment, and Prevention,” which provides in-depth information on xylazine, including its use and risks, involvement in overdoses by jurisdiction, geography, combinations, and implications for substance use disorder treatment. The University of Vermont Center on Rural Addiction hosted the webinar “Illicit Drug Supply: Fentanyl and Xylazine.” Richard Rawson, PhD, research professor at the Vermont Center for Behavior and Health at UVM and professor emeritus at the UCLA Department of Psychiatry, presents on fentanyl and xylazine including information on supply, pharmacology, clinical effects, medical impacts, harm reduction, and treatment. Dr. Rawson discusses considerations for rural communities. “One of the largest analyses of xylazine-involved deaths in a predominantly rural state,” this West Virginia-based study published in December 2022 documents the increase in xylazine use and its combination with other drugs from 2019 to mid-2021. In the podcast “What We Know About Xylazine,” produced by the Conversations with Clinical Education Initiative of the New York State Department of Health AIDS Institute, department experts Dr. Sharon Stancliff and Lisa Skill discuss xylazine trends, use, and effects and offer clinical and harm reduction guidance. A collaborative article published by National Public Radio and Kaiser Health News discusses the growth of xylazine in the drug supply in rural areas of Massachusetts, its effects on people who are using it, and how providers are responding. References
[1] Drug Enforcement Administration (DEA). (2022, October). The growing threat of xylazine and its mixture with illicit drugs. U.S. Department of Justice; U.S. Food and Drug Administration (FDA). (2022, November 8). FDA warns about the risk of xylazine exposure in humans [Letter to stakeholders].
[2] DEA. (2022, October).
[3] FDA. (2022, November 8).
[4] Walker, W. (Host), Stancliff, S., & Skill, L. (Guests). (2023, February 9). What we know about xylazine [Audio podcast episode]. In Conversations with CEI. Clinical Education Initiative, New York State Department of Health AIDS Institute.
[5] FDA. (2022, November 8).
[7] DEA. (2022, October).
[8] DEA. (2022, October).
[9] FDA. (2022, November 8).
[10] Walker et al. (2023, February 9).
