Farm to City: Xylazine as a Drug of Abuse

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Lauren Igneri
Critical care pharmacist and proud Rutgers University graduate. Enjoys rock climbing, cycling, travel, and lively discussions on the finer points of pharmacokinetics and critical care over a beer with friends.

The Pre-brief

  • Xylazine is FDA approved as a sedative with analgesic and muscle relaxing properties for veterinary use only.
      • Exerts sedative effects by acting as an alpha-2 receptor agonist, similar to clonidine and dexmedetomidine. It is given IV, IM, or orally either alone or in combination with ketamine or barbiturates. 
      • It has been shown to reduce the dose of barbiturates needed to induce anesthesia in animals.
      • Supplied in liquid solutions at 20, 100, and 300 mg/m
  • Cocaine and heroin are often mixed with other agents to increase bulk and enhance effects of the street drug
  • Xylazine as an adulterant may potentiate sedation and respiratory depression, increasing the risk for fatal overdose.
  • Xylazine has been documented in Puerto Rico’s illicit opioid supply since the early 2000s, but there has been a sharp increase seen in the continental U.S.,  particularly in the Northeast region.


Xylazine is structurally similar to phenothiazines, tricyclic antidepressants, clonidine, and dexmedetomidine. It exerts sedative effects by agonizing alpha-2 receptors, thus decreasing the synaptic release of norepinephrine and dopamine.

After IV administration, xylazine has an onset of action within minutes and peak plasma concentrations are seen between 12-14 minutes in animals. Terminal half-life ranges between 23-50 minutes, with effects typically lasting up to four hours. Xylazine is highly lipophilic and has a high volume of distribution (1.9-2.5 L/kg) in animals. While pharmacokinetic parameters do not vary significantly between different animal species, robust studies in humans are lacking. Effects have been reported ranging 8-72 hours in case reports of human overdose

Xylazine has cholinergic, serotonergic, dopaminergic, alpha-1 adrenergic, histaminergic and opiate effects. The typical toxidrome in humans is shown below:

Xylazine as a drug of abuse

Cocaine, heroin, and fentanyl may be adulterated with other agents not only to increase bulk, but to enhance illicit drug effects. Xylazine as an adulterant may potentiate the sedative effects of heroin or fentanyl and balance the sympathomimetic effects of cocaine. However, this increases the risk for respiratory depression and fatal overdose.

There were 45,676 overdose deaths in the U.S. in 2019. According to the SUDORS registry, 1.8% of patients were xylazine-positive on autopsy and xylazine was implicated as the cause of death in 1.2% of cases. While the overall rate of xylazine-associated overdose is low, deaths were reported in 25 states, with the majority (67%) occurring in the Northeast region of the country: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont.

Why is the Northeast seeing an increase in xylazine-associated overdose? It may have something to do with illicit drug pharmacokinetics.

Fentanyl has superseded heroin since 2015 in Philadelphia’s illicit opioid market. Johnson et al. found that xylazine was detected in 2% of unintentional heroin and/or fentanyl overdose deaths from 2010-2015 in Philadelphia, but this increased to 31% by 2019. When injected intravenously, fentanyl has a usual duration of action between 30-60 minutes – much shorter than heroin’s active metabolite, morphine. Focus groups of people who use drugs in Philadelphia said that when xylazine is added to fentanyl it “makes you feel like you’re doing dope (heroin) in the old days (before it was replaced by fentanyl) when the euphoric effects lasted longer” according to the study by Johnson et al.

Therefore, it is not uncommon to find xylazine in the Philadelphia illicit drug market as a single agent (street name: tranq) or mixed with heroin/fentanyl (tranq-dope). In Puerto Rico, heroin laced with xylazine is known as horse anesthesia (anestesia de caballo) or anestesia for short. It can also be found as single agent piqui-piqui. In a cross-sectional survey of drug users in Puerto Rico, Reyes et al. found that xylazine-adultered speedballs (heroin and cocaine mixtures) were the primary drug in 65% of participants. 

Treatment after xylazine exposure

As there is no specific antidote for xylazine, supportive measures focused on maintaining an airway, breathing, and circulation are of utmost importance. Advanced airways and mechanical ventilation should be implemented during initial resuscitative efforts. Hemodynamic instability should be managed with intravenous fluid and vasopressor administration, and atropine may be considered for symptomatic bradycardia. Intravenous insulin therapy should be given for hyperglycemia and electrolytes should be aggressively repleted.

Remember, xylazine is not an opioid. Therefore, naloxone may be less effective in reversing a xylazine-associated opioid overdose since the effects of xylazine may persist even after the opioid is reversed. While there is a paucity of evidence to support this practice, it may be reasonable to consider dexmedetomidine or clonidine as adjunctive therapy to manage agitation in patients withdrawing from xylazine based on their similar mechanisms of action.

Chronic xylazine users may have characteristic necrotic skin ulcerations thought to be induced by low skin oxygenation. (For those with a strong stomach, images of xylazine skin ulcerations may be found in the article by Reyes et al.) Since the ulcerations are painful, many inject directly into the site with the intent to exploit xylazine’s alpha2-receptor agonism and relieve pain. However, this contributes to abscess formation, worsening of necrosis, and decreased wound healing. Patients presenting with wounds may require surgical debridement, and in extreme cases, skin grafting.

The Debrief

  • Xylazine is an alpha2-agonist that is FDA approved as a veterinary sedative.
  • Xylazine has been increasingly implicated as an adulterant in heroin, fentanyl, and cocaine.
  • Potentiates the sedative effects of opioids and balances the sympathomimetic effects of cocaine.
  • May cause significant CNS and respiratory depression, as well as hypotension and bradycardia.
  • Following xylazine exposure, supportive treatment focused on maintaining an airway, breathing, and circulation should be implemented. 
  • Since xylazine is not an opioid, naloxone may be less effective in reversing respiratory depression in a xylazine-associated opioid overdose.


  1. Kariisa M, Patel P, Smith H, et al. Notes from the field: xylazine detection and involvement in drug overdose deaths – United States, 2019. MMWR Morb Mortal Wkly Rep. 2021; 70:1300-02.
  2. Johnson J, Pizzicato L, Johnson C, et al. Increasing presence of xylazine in heroin and/or fentanyl deaths, Philadelphia, Pennsylvania, 2010-2019. Inj Prev. 2021; 27(4):395-398.
  3. Reyes JC, Negrón JL, Colón HM, 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. 
  4. Ruiz-Colón K, Chavez-Arias C, Díaz-Alcalá JE, et al. Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature. Forensic Sci Int. 2014; 240:1-8.
  5. Xylazine: a toxic adulterant found in illicit street drugs. October 2020. Accessed 19 September 2021 from:
  6. Xylazine. Drug Enforcement Administration. February 2021. Accessed 19 September 2021 from: 


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