Farm to City: Xylazine as a Drug of Abuse

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Fentanyl has superseded heroin since 2015 in Philadelphia’s illicit opioid market.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.