Xylazine was first synthesized by Bayer in 1962 and then approved as an animal medicine by the FDA in 1972. It is a non-opioid used for its sedative, pain relieving with muscle relaxant properties in animal (veterinary) medicine. It is not approved by the FDA for use in humans.

Formerly, Bayer studied xylazine for use in humans but it was found to have serious side effects like the occurrence of very low blood pressure (severe hypotension) and severe central nervous system depressants effects.

In recent years, xylazine has been found as a component of street drugs and is complicating healthcare management of overdoses that also contain opioids. Healthcare providers should be aware of its increasing presence in illicit drugs of abuse. Patients who do not respond as expected to naloxone treatment or that have unusual necrotic skin ulcers may have been exposed to this drug.

In November 2022, the FDA released a Letter to Stakeholders and a Drug Alert to healthcare providers about the risk of xylazine exposure in humans.