Substance Use Guidelines: Xylazine Introduction
September 2023
• Xylazine, also known as tranq, is a non-opioid, unscheduled veterinary tranquilizer that is used as an additive in the illicit drug supply i In veterinary medicine, it is used as a sedative, analgesic, and muscle relaxant. It is not approved for use in humans.
• Xylazine is most notably added to heroin and fentanyl -containing products, though it has also been reported in other drugs, including cocaine. The drug can be ingested orally, inhaled/sniffed, smoked, or injected. Many people use the drug inadvertently because it is added to other drugs.
• It is believed that xylazine first emerged as an adulterant in Puerto Rico in the 2000s and then moved to Philadelphia, PA, where it rapidly became a common additive in the fentanyl supply starting in 2016/2017. In 2021, more than 90% of fentanyl samples tested in Philadelphia contained xylazine. Starting around 2020, the drug began to spread along the east coast to states including Maryland, Massachusetts, and Connecticut. Use of the drug as an additive is now spreading across the U.S.; in 2021, xylazine was found in tested drug samples in all four U.S. Census regions. ii
• Xylazine is a clonidine analog and has significant sedative effects that often outlast the effects of the substances it is mixed with. The drug’s effects cannot be reversed using naloxone, creating a need for reassessment of overdose education and response (detailed below).
• The use of xylazine has been associated with significant skin and soft tissue infections that are characterized by substantial tissue death (necrosis). The wounds are not necessarily associated with injection sites and can even be seen with smoking or snorting the drug iii, iv The wounds most commonly occur on the extremities – particularly on the forearms and lower legs.
Key Terms and Definitions
• Trauma-informed care (TIC): A patient-centered approach to care that recognizes the impacts of trauma and actively works to prevent re-traumatization and promote recovery. The principles of TIC are grounded in establishing a trusting relationship and a safe physical and psychological space in which to address needs.
• Harm reduction: A philosophical approach to care that establishes individual agency and selfdetermination as central to all efforts toward well -being. Harm reduction approaches call for the non-judgmental, non-coercive provision of services and resources to people who use substances to assist them in reducing harms related to their substance use or other health behaviors. Harm reduction-based care is collaborative, provides education on available interventions, and centers the goals of the individual in care planning.
Clinical Considerations
Physical and Behavioral Health Impacts
• As a tranquilizer and central nervous system (CNS) depressant, xylazine can cause profound and prolonged sedation (up to several hours). While sedation is the most commonly observed effect, xylazine may also cause hypotension and bradycardia. v In combination with other CNS depressants,
most notably fentanyl, xylazine use may potentiate sedation and respiratory depression, increasing the risk of overdose. vi
• Xylazine is thought to be added as an adulterant to fentanyl to prolong the drug’s effects, driven in part by fentanyl’s shorter duration of action compared to heroin. Some users report that upon awakening from xylazine-related sedation, they find themselves in early opioid withdrawal, a very undesirable effect.
• Consistent xylazine use can cause withdrawal symptoms upon decreased use or cessation, most notably significant anxiety and panic. People may also experience irritability, feelings of unease, and increased blood pressure and tachycardia. vii Longer-term symptoms after cessation may include insomnia and dysphoria.
Use of Xylazine and Experiences of Homelessness
• People experiencing homelessness (PEH) who use drugs often use xylazine inadvertently because it is an additive to other drugs, mainly fentanyl. Xylazine-related sedation puts PEH at increased risk of theft, assault, overdose, and heat or cold injuries, especially for those who are unsheltered.
• Experiences of homelessness and related trauma can make addressing substance use, getting needed supports, and coordination of care much more difficult.
• Because xylazine is associated with serious wounds, coordinated wound care is needed to address and reverse wounds. Receiving consistent and effective wound care, including frequent follow-ups, wound self-management, and even short-term hospitalization, can be very challenging for PEH due to the realities of homelessness – lack of bathroom facilities, transportation challenges, etc
Harm Reduction Strategies
• Responding to xylazine overdose: Because xylazine is most commonly mixed with fentanyl, responding to a suspected overdose should always include an assessment of respiratory status and use of naloxone, if indicated. When people are sedated or overdosing due to fentanyl and xylazine, the response to naloxone can look very different from what people may be used to. With a xylazine/fentanyl overdose, responders may see that a person regains respirations with naloxone administration but remains unconscious or heavily sedated. In this circumstance, the person does not need more naloxone; they should be put in a recovery position and monitored until emergency medical personnel arrive. The individual may require oxygen support and observation for hours; thus an emergency department or sobering center may be necessary.
• Assessing for xylazine overdose: Philadelphia service providers have found that, with xylazine sedation, assessing for responsiveness by splashing/spraying a small amount of cold water on someone’s forehead or neck is often adequate to bring them back to alertness in order to assess safety and offer support. Water should not be sprayed near or into the person’s nose or mouth and is used when the person does not respond to verbal cues.
• It is important to recognize that people’s recovery goals can vary widely, from not wanting to stop using, to seeking drugs that contain less xylazine, to wanting to decrease use or stop altogether. It is important to meet people where they are and build a co-created plan to increase safety and decrease risk.
2023
• Access to new syringes and safer use supplies is an important way to decrease risk related to xylazine use. People may need education on safer injection techniques, staggered use so that people can monitor each other, and how to recognize the early signs of a xylazine-related wound and when to seek help.
• Community education on responding to overdoses in the age of xylazine is important to prevent people from being given too much naloxone in the event that sedation persists following the return of respiration; this can cause painful precipitated withdrawal and place a person at increased risk of another overdose event as they try to manage their withdrawal.
Treatment and Supportive Services
• While there are currently no FDA-approved medications for xylazine withdrawal, symptom management may include close monitoring of cardiac status, replacement therapy with alpha-2 adrenergic agonists, and using medications to directly address pain, insomnia, and anxiety. Medications used include clonidine, tizanidine, guanfacine, gabapentin, NSAIDS, opioids, hydroxyzine, and benzodiazepines. viii
• People who are starting treatment for opioid use with medications such as buprenorphine or methadone may need additional support for xylazine withdrawal symptoms. This is also true for people who are receiving opioid withdrawal support or treatment in a hospital setting.
• Wound identification and management are vital components of supporting people who use xylazine. Wound care should be consistent and promote debridement of necrotic tissue, address exudate, and work for the patient. In terms of self-management, patients should avoid injecting into the wound, if possible, keep the wound covered, and avoid harsh cleansers like peroxide, bleach, or alcohol. Following the core principles of infection control and basic wound care, such as gentle cleansing and daily dressing changes, can result in healed wounds.
• Antibiotics may be indicated for infected wounds, and clients should be monitored for signs of a systemic infection. It is important to note that not all xylazine-related wounds require antibiotics, even with the presence of necrotic tissue; providers should assess for signs of rapid wound worsening, local, and systemic infection when determining the need for antibiotics.
• Include clients in wound care planning and assess clients’ goals and current use practices to develop a plan that will work. For example, for people who are injecting into their wounds, which they might do to address their pain or because of a desire to spare other parts of their body from wound development, dressings should be easy to remove and replace, so that use does not result in the wound going uncovered.
• Xylazine wounds can be severe, with significant portions of arms or legs being covered with necrotic tissue. People can be ashamed to reveal their wounds and may keep them hidden until they are very advanced. In areas where xylazine is being used as an adulterant, conversations with people who use drugs about the possibility of wounds, and the availability of help, are important. It is important to educate people that these wounds are not necessarily associated with injection sites.
• Equally important are conversations about the potential for wound healing. Clients presenting to emergency departments or other care settings may be told they will require a skin graft or amputation, however, with proper assessment and consistent treatment, many xylazine wounds can heal without these interventions.
Models of Care Delivery
• Leveraging an interdisciplinary model is vital for supporting people who use xylazine, especially if they have wound care needs. Clients may need coordination of primary care, wound care, substance use treatment, psychiatric care, and hospital care, in addition to housing and other social supports Peers, community health workers, and case management services are key to providing patientdriven care.
• Medical outreach and Street Medicine models of care are particularly important for providing care and services for PEH who are using xylazine. Many people who need wound care, substance use treatment, and other primary health services may not be able or comfortable accessing care in more traditional settings. Meeting a person where they are and offering medical support along with necessities like clothes, food, and water, is essential.
• Medical respite may be a vital resource for supporting someone who needs additional assistance with wound care following a hospitalization, or who needs a place to recover other than street or shelter.
Additional Resources
• HHRC Webinar: Xylazine: An Introduction for Service Providers Working with Unhoused Individuals
• Philadelphia Department of Public Health, Division of Substance Use and Harm Reduction: Health Update: Xylazine (tranq) exposure among people who use substances in Philadelphia
• Philadelphia Department of Public Health: Xylazine/Tranq
• National Harm Reduction Coalition: Xylazine
References
i Thangada, S., Clinton, H. A., Ali, S., Nunez, J., Gill, J. R., Lawlor, R. F., & Logan, S. B. (2021). Notes from the field: Xylazine, a veterinary tranquilizer, identified as an emerging novel substance in drug overdose deaths Connecticut, 2019–2020. MMWR. Morbidity and Mortality Weekly Report, 70(37), 1303–1304. https://doi.org/10.15585/mmwr.mm7037a5
ii U.S. Drug Enforcement Agency. (2022). The growing threat of xylazine and its mixture with illicit drugs: DEA joint intelligence report. Retrieved from: https://www.dea.gov/documents/2022/2022-12/2022-12-21/growing-threatxylazine-and-its-mixture-illicit-drugs
iii Malayala, S. V., Papudesi, B. N., Bobb, R., & Wimbush, A. (2022). Xylazine-induced skin ulcers in a person who injects drugs in Philadelphia, Pennsylvania, USA. Cureus. https://doi.org/10.7759/cureus.28160
iv Philadelphia Department of Public Health. (2022). Health update: Xylazine (tranq) exposure among people who use substances in Philadelphia. Retrieved from: https://hip.phila.gov/document/3154/PDPHHAN_Update_13_Xylazine_12.08.2022.pdf/
v National Institute on Drug Abuse. (n.d.) Fact sheet: Xylazine. Retrieved from: https://nida.nih.gov/researchtopics/xylazine
vi Kariisa, M., Patel, P., Smith, H., & Bitting, J. (2021). Notes from the field: Xylazine detection and involvement in drug overdose deaths United States, 2019. MMWR. Morbidity and Mortality Weekly Report, 70(37), 1300–1302. https://doi.org/10.15585/mmwr.mm7037a4
vii Philadelphia Department of Public Health, Division of Substance Use Prevention and Harm Reduction. (2020). Xylazine (tranq). Retrieved from: https://www.substanceusephilly.com/tranq#
viii Philadelphia Department of Public Health. (2022). Health update: Xylazine (tranq) exposure among people who use substances in Philadelphia. Retrieved from: https://hip.phila.gov/document/3154/PDPHHAN_Update_13_Xylazine_12.08.2022.pdf/