Xylazine

According to the US Centers for Disease Control and Prevention, 107,735 Americans died from drug poisonings between August 2021 and August 2022, with 66% of the deaths involving synthetic opioids like fentanyl. The Sinaloa Cartel and Jalisco Cartel in Mexico, using chemicals largely sourced from China, are primarily responsible for the vast majority of the fentanyl that is being trafficked in communities across the United States.

On March 20, the US Drug Enforcement Administration issued an alert about the widespread threat of fentanyl mixed with xylazine, which is an animal tranquilizer known as tranq on the streets. It's not approved for humans but has been found in fentanyl and cocaine supplies. Xylazine surged first in some areas of Puerto Rico and then in Philadelphia. The Drug Enforcement Agency (DEA) has seized xylazine and fentanyl mixtures in 48 of 50 states. In 2022, the DEA Laboratory System detected xylazine in 23% of the fentanyl powder and 7% of the fentanyl pills that had been seized.

Xylazine is manufactured as a liquid for veterinary medicine use as a sedative with analgesic and muscle relaxant properties. Brand names of xylazine include Rompun, Sedazine, and AnaSed. It is available in liquid solutions in concentrations of 20, 200, and 300 mg/mL. Xylazine is administered to many different animal species to perform diagnostic and surgical procedures, relieve pain, or act as a local anesthetic. Although xylazine is manufactured as a liquid, it can be converted into a salt or dried into a powder,. These can be mixed into other powders or pressed into pills for illicit use. Xylazine is frequently referred to as tranq. 

On April 12, 2023, the Biden administration labeled fentanyl mixed with a powerful animal sedative called xylazine an “emerging threat to the United States”. The purpose of this designation was to prioritize federal resources to boost testing and treatment and stanch the illegal supply of the tranquilizer.

There's a lot of speculation about how and why the use of xylazine is on the rise. Xylazine is cheap and fairly unregulated. Dealers might have begun adding it as a bulking agent and then continued to do so because xylazine extended the effects of a fentanyl high. It has also been combined with stimulants such as methamphetamine and cocaine. 

The structure of xylazine is similar to phenothiazines. Xylazine is a central alpha-2 adrenergic receptor agonist that causes a rapid decrease in the release of norepinephrine and dopamine in the central nervous system. The combination of fentanyl and xylazine make drug overdoses more deadly. Xylazine may contribute to death by slowing breathing and heart rate, as well as decreasing blood pressure. Related injection of xylazine adulterated drugs can also cause severe, necrotic skin ulcerations due  to vasoconstriction and decreased tissue perfusion. 

Patients taking xylazine do not respond to naloxone, but experts recommend giving naloxone to people who may be overdosing on a drug and consider xylazine exposure if the person doesn’t respond to naloxone. When xylazine is involved in an overdose, additional support, such as supplemental oxygen, fluid resuscitation to raise blood pressure, and airway management to improve breathing. A victim’s entire body should be examined for ulcers and necrotic tissue.

Reported concentrations of xylazine in humans have varied. Concentrations from 30 to 4,600 ng/mL have been measured in non-fatal cases. Fatal case reports have reported concentrations ranging from a trace amount up to 16,000 ng/mL. Because of this variability, toxic concentrations have not been established.

Routine toxicology screens do not detect xylazine, and additional analytical techniques are required to detect xylazine when it might be involved in illicit drug overdoses. BTNX, a biotechnology company, has developed rapid test strips to detect xylazine in liquid or powder.

References

Kariisa M, Patel P, Smith H, Bitting J. Notes from the Field: Xylazine Detection and Involvement in Drug Overdose Deaths — United States, 2019. MMWR Morb Mortal Wkly Rep 2021; 70:1300–1302.

DEA Reports Widespread Threat of Fentanyl Mixed with Xylazine, March 20, 2023, https://www.dea.gov/alert/dea-reports-widespread-threat-fentanyl-mixed-xylazine

Ehrman-Dupre, R, et al. Management of Xylazine Withdrawal in a Hospitalized Patient: A Case Report. Journal of addiction medicine, 2022;16(5):595–598.