Xylazine in Fentanyl Overdose Deaths, 2019–2022

This page summarizes a CDC report covering deaths from January 2019 to June 2022, published in 2023.

In 2022, provisional data showed that more than two thirds (68%) of the 107,081 drug overdose deaths reported in the United States involved synthetic opioids other than methadone, mainly illicitly manufactured fentanyls (IMFs). Increasingly, those drugs were being mixed with xylazine, a nonopioid sedative that is not approved for human use and has no known antidote. The few studies available suggest xylazine can depress the central nervous system and breathing and slow the heart and lower blood pressure in people; long-term use may cause severe withdrawal and skin ulcers.

Researchers from CDC and the University of Florida used CDC's State Unintentional Drug Overdose Reporting System (SUDORS), which draws on death certificates, medical examiner and coroner reports and toxicology results, to look at fentanyl-involved deaths with and without xylazine.

A fast-rising share

In 21 jurisdictions (20 states and the District of Columbia), the monthly share of fentanyl-involved deaths in which xylazine was detected rose 276%, from 2.9% in January 2019 to 10.9% in June 2022. The number of such deaths each month in which xylazine was listed as a cause rose from 12 to 188. Nearly all deaths with xylazine (99.5%) also involved fentanyl.

In 32 jurisdictions from January 2021 to June 2022, xylazine was detected in 4,859 (9.0%) of 53,969 fentanyl-involved deaths and listed as a cause of death in 3,735 (6.9%).

Some states were left out because too few deaths had toxicology reports, yet their death certificates still showed xylazine involvement. New York recorded 735 such deaths.

Where and who

Xylazine was concentrated in the Northeast: 49.9% of fentanyl deaths with xylazine were there, compared with 28.5% of those without it, while only 1.1% were in the West, compared with 16.5%. The authors note that fentanyl deaths rose earlier in the Northeast, where fentanyl is mostly sold as powder, than in the West, where counterfeit pills are more common. In 2022 the Drug Enforcement Administration found xylazine in 23% of seized fentanyl powder and 7% of seized fentanyl pills.

Otherwise, deaths with and without xylazine looked much alike in the victims' demographics, the other drugs involved and the circumstances. Two differences stood out: fewer of the deaths with xylazine had no pulse when first responders arrived (53.3% versus 62.2%), and more had evidence of injection drug use (28.6% versus 19.5%).

Different rulings on cause of death

Where xylazine was detected, whether it was listed as a cause of death ranged from none of the deaths to 90% or more, depending on the jurisdiction. Medical examiners and coroners may disagree about whether xylazine raises the risk of a fatal overdose, or may be unfamiliar with it. That is why the authors stress collecting toxicology results for every drug found, not just those on the death certificate.

What it means

The rise may reflect both more testing and more xylazine in the drug supply; with testing still uneven, it is probably undercounted. In April 2023 the White House Office of National Drug Control Policy declared fentanyl mixed with xylazine an emerging threat, and some jurisdictions were moving to make xylazine a controlled substance. Because banned drugs have been replaced by similar substances before, the authors urge watching for other sedatives, such as medetomidine, that have recently appeared.

Responding to an overdose. Naloxone cannot reverse xylazine's sedation, but it should still be given when an overdose is suspected, because xylazine is mainly found alongside fentanyl, which naloxone does reverse. Anyone suspected of an overdose involving opioids, xylazine or both needs immediate additional medical care; breathing and circulatory support can address xylazine's nonopioid sedative effects.

Harm reduction. Repeated xylazine injection has been linked to skin lesions, ulcers and abscesses. Prevention messages for people who inject drugs could promote safer injection and proper wound care, and xylazine test strips, used with fentanyl test strips, can reveal what a drug contains.

Limitations: the jurisdictions studied are not nationally representative, and testing for xylazine was not uniform across places or over time, which probably understates how common it is and may overstate how much it increased.

The authors call for routine xylazine testing in suspected overdose deaths, more research on its potency and effects in people, and study of why it is added to fentanyl and whether people seek it out.

Sources

• Kariisa M, O'Donnell J, Kumar S, Mattson CL, Goldberger BA. "Illicitly Manufactured Fentanyl–Involved Overdose Deaths with Detected Xylazine — United States, January 2019–June 2022." MMWR 72(26). https://www.cdc.gov/mmwr/volumes/72/wr/mm7226a4.htm
• DEA, "The Growing Threat of Xylazine and its Mixture with Illicit Drugs": https://www.dea.gov/sites/default/files/2022-12/The%20Growing%20Threat%20of%20Xylazine%20and%20its%20Mixture%20with%20Illicit%20Drugs.pdf
• The report's charts and map are not reproduced here because it was prepared jointly with a university.