xylazine

xylazine, drug used in veterinary medicine to sedate, relieve pain, and induce muscle relaxation in animals. Xylazine was discovered in 1962 by researchers at the German pharmaceutical company Farbenfabriken Bayer AG (now Bayer AG). The drug was initially investigated for its antihypertensive (blood pressure-lowering) properties in humans. However, because its effects were found to be excessive and life-threatening in human subjects, it was instead adapted for use in animals. Nonetheless, xylazine is highly sought after as an adulterant in illicit drug combinations for human use, particularly in mixtures containing opioid drugs (e.g., heroin and fentanyl), since it prolongs the euphoric effects produced by opioids. Xylazine is frequently detected in persons who have died from drug overdose.

Mechanism and veterinary use

Xylazine is classified as an alpha-2 adrenergic receptor agonist. In the central nervous system, its action at these receptors reduces the release of so-called adrenergic substances—namely, the neurotransmitters epinephrine and norepinephrine. Epinephrine and norepinephrine normally mediate the “fight-or-flight response,” and thus when their levels are decreased by the actions of xylazine, analgesia (pain relief), muscle relaxation, and sedation occur. Veterinarians typically use xylazine to sedate animals for surgery and other clinical purposes. It is commonly used in cats, dogs, cattle, and horses but may also be used in wildlife such as deer and elk.

Illicit use

In humans, xylazine causes deep sedation. Specifically, it slows heart rate and respiration and decreases blood pressure and body temperature, which can drop to dangerously low levels that result in a coma or death. In addition to life-threatening effects on major organs, other medical complications, such as pressure ulcers and blood clots, can result from users’ lying in the same position for long periods of time. In addition, xylazine causes skin lesions that resemble blisters, as well as small scabs and areas of dead tissue. These wounds usually appear on the arms and legs or at the injection site but may also be apparent elsewhere on the body; they may also develop in users who have snorted or smoked the drug. Some cases are so severe as to require limb amputation. Furthermore, individuals who use xylazine may develop a physical dependence on the drug; withdrawal symptoms can be severe and typically include sharp chest pains and seizures.

In the early 2000s, laboratory testing conducted by the U.S. Drug Enforcement Administration (DEA) found that xylazine had been used as an adulterant in drug mixtures in Puerto Rico, where it was later also found to be used on its own. The drug, in its illicit form, was first detected on the U.S. mainland in 2006. By 2022 the DEA had seized mixtures of xylazine and fentanyl in 48 states. Overdose deaths involving xylazine increased in parallel with the spread of the drug. Because xylazine is not an opioid, the administration of naloxone, which relieves potentially fatal respiratory depression caused by opioid overdose, does not reverse its effects.