Xylazine is a semi-synthetic, non-opioid, sedative paralytic used in veterinary medicine as a tranquilizer. It’s an alpha agonist, similar in chemical structure to clonidine and dexmetomidine.1 It was first discovered in 1962 in Leverkusen, Germany, and used as an antihypertensive.2 It is an increasingly common additive and adulterant in illicit fentanyl, heroin, and cocaine and it’s associated with rising numbers of fentanyl and heroin overdose deaths.
Also known as anestesia de caballo (horse tranquilizer), tranq, or tranq dope (fentanyl or heroin cut with xylazine), it’s used as an adjunct to enhance and prolong the euphoric effects of fentanyl or heroin.3 It is most commonly injected intravenously, but can also be inhaled, sniffed, snorted, or ingested.
It was first reported among heroin users in Puerto Rico in the early 2000s and has now been detected with growing frequency in the U.S. Nationwide, xylazine prevalence among drug-overdose fatalities has been documented in 23 states.2 Philadelphia has been afflicted the most, with surging rates in Connecticut, Massachusetts, and Maryland.4
Xylazine does not have a reversal agent, and its effects include sedation, hypotension, bradycardia, and respiratory depression. Its effects are not mediated through opioid receptors, and it has increasingly been associated with difficult-to-treat opioid overdoses and deaths, with a lack of response to naloxone. Xylazine abuse has also been linked with difficult-to-treat, severe, necrotic, skin ulcerations and abscesses.5 In addition to directly toxic skin effects at injection sites, these skin ulcers are also seen in distant body parts, unrelated to local sites of injection. This is thought to result from vasoconstrictive effects and hypoperfusion leading to ischemia and necrosis.5 Vasoconstriction-mediated tissue hypoperfusion and reduced tissue oxygenation also lead to impaired wound healing and increased risk of acquiring infections.5 The skin ulcers are painful, require multiple debridements, and can also lead to amputations. Though the prevalence of skin ulcers is not known, they may be seen in up to 35% of xylazine users.6 Because the skin ulcers are painful, they promote further injections of xylazine mixed with opiates for their analgesic and sedative effects, which lead to a vicious cycle of abuse.
Xylazine is not classified as a controlled substance by the U.S. Food and Drug Administration. There are no established treatments or guidelines for the care of these patients. Naloxone should be administered first to treat co-occurring opioid effects from fentanyl and heroin. Subsequently, cardiovascular and respiratory supportive care is the primary treatment. Currently, testing for this illicit substance is limited to specialized toxicology testing centers, with liquid chromatography, time of flight mass spectrometry, or liquid chromatography-tandem mass spectrometry devices.7 No point-of-care testing options are giving rapid results.
It is unclear if the xylazine supply in the illicit-drug ecosystem is due to illegal production of this semisynthetic substance or diversion from the veterinary medical supply chain. Clinicians, first responders, and the general public should be aware of this emerging threat and consider the possibility of xylazine overdose and toxicity in patients with opioid overdoses not responding to traditional reversal agents, especially in those with unexplained severe skin ulcerations. Federal and state health officials should also encourage and facilitate the development of point-of-care testing kits for the detection of xylazine in blood or urine. The development of a standardized protocol for routine post-mortem testing for the presence of xylazine in all opioid overdose deaths could also be an important step.7
These measures may further enhance understanding of the true magnitude of the problem, establish trends and patterns of use and prevalence, and enable the early diagnosis and risk stratification of these patients. Another potentially beneficial step may be to label xylazine as a controlled substance. This may accelerate the surveillance of the supply and distribution of xylazine in the veterinary medical-supply chain and strengthen efforts to limit its diversion to the human illicit-drug trade.
Collaboration between state health agencies and federal agencies is crucial to identify the true scope of the prevalence of xylazine adulteration in fentanyl and heroin and to help guide mitigation efforts. Further research is needed, to characterize the synergistic toxic effects of xylazine combined with illicit opiates, to direct effective, public-policy, intervention efforts, and to facilitate the development of treatments for the acutely toxic effects and chronic sequelae.
Dr. Gowdar
Dr. Rakasi
Dr. Gowdar is a hospitalist at Baystate Medical Center, Springfield, Mass. Dr. Rakasi is a hospitalist and medical director of the oncology unit at Baystate Medical Center, Springfield, Mass. He is also the secretary of SHM’s Western Massachusetts chapter.
References
- Alexander RS, et al. Xylazine and overdoses: Trends, concerns and recommendations. Am J Public Health. 2022;112(8):1212-16.
- Reyes JC, et al. The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico. J Urban Health. 2012;89(3):519-26.
- Chhabra N, et al. Xylazine-related deaths — Cook County, Illinois. 2017–2021. MMWR Morb Mortal Wkly Rep. 2022;71(13):503-4.
- Kariisa M, et al. Notes from the field: xylazine detection and involvement in drug overdose deaths — United States, 2019. MMWR Morb Mortal Wkly Rep. 2021;70(37):1300-2.
- Malayala SV, et al. Xylazine induced skin ulcers in a person who injects drugs in Philadelphia, Pennsylvania, USA. Cureus. 2022;14(8):e28160
- Thangada S, et al. Notes from the field: Xylazine, a veterinary tranquilizer, identified as an emerging novel substance in drug overdose deaths — Connecticut, 2019-2020. MMWR Morb Mortality Wkly Rep. 2021;70(37):1303-4.
- Torruella, RA. Xylazine (veterinary sedative) use in Puerto Rico. Subst Abuse Treat Prev Policy. 2011;6:7. doi: 10.1186/1747-597X-6-7.