Severe withdrawal cases point to growing medetomidine use

by Perelman School of Medicine at the University of Pennsylvania

edited by Sadie Harley, reviewed by Robert Egan

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A powerful veterinary sedative, medetomidine, is increasingly appearing in street supplies of the already deadly opioid fentanyl, and the number of patients suffering from medetomidine withdrawal has quadrupled in recent years, according to a new analysis by researchers at the Perelman School of Medicine at the University of Pennsylvania.

The work, published in JAMA Internal Medicine, confirms the observations of medical professionals who have been treating the drug's particularly severe withdrawal with specialized care, including infused medications and intensive care unit (ICU) stays.

"You can't address something you can't see," said the study's co-first author, Tyler Boyce, MD, a fellow in pulmonary and critical care medicine. "Showing how an increase in severe withdrawal cases is a reflection of this drug's emergence in the opioid supply will likely prove valuable to hospitals and public health officials trying to appropriately plan responses."

Hundreds of times more powerful

Used as an anesthetic for larger animals, medetomidine is 100 to 200 times more powerful than xylazine, another drug mixed into the illicit opioid supply in recent years. Withdrawal from medetomidine happens quickly and can cause tachycardia (a severely elevated heartbeat), extreme anxiety, nausea and vomiting, among other symptoms. There have also been reports of organ damage associated with severe, untreated withdrawal.

To treat severe cases of medetomidine withdrawal, patients often need a medication called dexmedetomidine, an infused treatment that requires ICU stays because it can cause low heart rates and blood pressure and requires careful monitoring.

Because treating these withdrawal symptoms is complex, knowing how many people are exposed to medetomidine and suffer from its withdrawal could help hospitals and their communities better allocate resources.

"Patients are coming to us very sick, and we have had to rapidly adapt our treatments to serve the patients in front of us," said senior author Margaret Lowenstein, MD, an assistant professor of general internal medicine and research director for the Penn Center for Addiction Medicine and Policy. "Understanding the impact of this new adulterant and helping clinicians and hospitals prepare to care for affected patients is critical."

Data from two hospitals reveal spread

The researchers examined data from two Philadelphia hospitals covering 2020 through September 2025. Patients with opioid use disorder who received dexmedetomidine were classified as having severe medetomidine withdrawal.

Medetomidine's emergence in fentanyl supplies has been traced anecdotally to mid-2024, so the researchers divided the data into periods before and after that time to measure the drug's spread.

In the "pre-medetomidine period," dexmedetomidine was administered to just shy of 6% of patients with opioid use disorder. In the "post-medetomidine period," roughly 20% of these patients required dexmedetomidine. In the last three months observed, that rate climbed to approximately 32% of those treated.

"Historically, heroin withdrawal without these adulterants could be managed in outpatient or minimally monitored inpatient settings," said co-first author Ashish Thakrar, MD, an assistant professor of general internal medicine.

"It was striking that, in the last quarter of our study, a third of patients required intensive care unit management for withdrawal from fentanyl mixed with medetomidine. Clinically, we recognize that we are in a new era of withdrawal management."

Patients require more intensive treatment

In addition to dexmedetomidine, patients suspected of having medetomidine withdrawal were significantly more likely to need other medications and higher doses to help with their treatment, further suggesting that their severe withdrawal was attributable to medetomidine, not untreated fentanyl withdrawal.

For instance, 79% received methadone (a long-acting medication that helps blunt withdrawal effects and opioid cravings), compared with 50% of patients with opioid use disorder who didn't also require dexmedetomidine. Similarly, 36% of patients with medetomidine withdrawal received buprenorphine (another agonist medication), compared with 26% of patients without medetomidine-related withdrawal.

Patients who received dexmedetomidine also spent more time in the ICU, on average, than other patients with opioid use disorder.

Who is affected

The research team found that patients who required dexmedetomidine were younger and more likely to be on Medicare than other patients with opioid use disorder.

The researchers believe more analysis is needed to identify risk factors that make patients more likely to suffer medetomidine withdrawal and to inform potential policies or public health interventions.

Publication details

Tyler G. Boyce et al, Dexmedetomidine Use and Intensive Care Unit Admissions for Patients With Medetomidine Withdrawal, JAMA Internal Medicine (2026). DOI: 10.1001/jamainternmed.2026.4568

Journal information: JAMA Internal Medicine

Key medical concepts

MedetomidineDexmedetomidineFentanylOpioids and Opioid Use Disorder (OUD)

Clinical categories

Critical care medicineClinical pharmacologyHospital medicinePulmonary medicineCommon illnesses & Prevention Provided by Perelman School of Medicine at the University of Pennsylvania Who's behind this story?

Sadie Harley

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Robert Egan

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