Medetomidine Withdrawal: A Dangerous New Syndrome in Philadelphia’s Fentanyl Supply

Philadelphia's illegal opioid supply keeps changing. In the last 4 months of 2024, medetomidine — a synthetic sedative (an alpha-2 adrenoreceptor agonist) not approved for use in people — was found in 72% of opioid samples tested there, while xylazine, previously the most common additive, dropped from 98% to 31%. At the same time, hospital doctors began seeing a severe withdrawal syndrome unlike fentanyl or xylazine withdrawal.

The patients

Addiction medicine and medical toxicology physicians at three Philadelphia health systems reviewed records of patients admitted from September 1, 2024, to January 31, 2025, whose withdrawal was severe and didn't respond to the usual fentanyl and xylazine protocols. They found 165.

Signs included agitation, anxiety, severe high blood pressure, racing heart rate, tremor (without clonus or overactive reflexes) and vomiting. These persisted despite escalating doses of:

• opioids such as fentanyl, hydromorphone, methadone and oxycodone;
• sedatives including diazepam, droperidol, haloperidol, lorazepam, midazolam, phenobarbital and propofol;
• other withdrawal medicines — clonidine, ketamine, olanzapine, ondansetron and tizanidine.

At one health system, which tracked heart damage, 39 of 62 patients had a positive high-sensitivity troponin test.

Where patients went after the hospital:

What worked

The syndrome resembles what happens in intensive care patients taken off dexmedetomidine — a sedative used in ICUs and operating rooms, and the mirror-image molecule of medetomidine — after days of exposure: autonomic withdrawal with vomiting and agitation. And like that syndrome, it responded to dexmedetomidine itself, even when rising doses of the usual fentanyl and xylazine withdrawal medicines failed.

What it means

• Watch the drug supply. Changes in what's mixed into illegal opioids can change what patients look like when they arrive, and what treatment they need.
• Expect escalation. Medetomidine withdrawal is life-threatening and can require far more intensive care than typical opioid or xylazine withdrawal.
• Test locally. Public health agencies should consider testing for medetomidine in their regional drug supplies.

Sources

Based on Huo S, London K, Murphy L, et al., "Notes from the Field: Suspected Medetomidine Withdrawal Syndrome Among Fentanyl-Exposed Patients — Philadelphia, Pennsylvania, September 2024–January 2025," Morbidity and Mortality Weekly Report 74(15), Centers for Disease Control and Prevention; a work of the United States government in the public domain. An erratum has been published for this report. Original report.