PHILADELPHIA— A powerful veterinary sedative, medetomidine, is increasingly infiltrating the street supplies of the already deadly opioid fentanyl, with patients suffering from its withdrawal quadrupling in recent years, according to a new analysis by researchers at the Perelman School of Medicine at the University of Pennsylvania . This work, published in JAMA Internal Medicine , confirms the observations of medical professionals, who have been treating the drug’s particularly nasty withdrawal with specialized care that includes 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 cases of 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.
Since treating these withdrawal symptoms is complex, an accurate idea of how many people are exposed to medetomidine and suffering 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.”
Two hospitals’ data reveals spread
Data from two different Philadelphia hospitals dating from 2020 through September 2025 was examined by the researchers. Patients with opioid use disorder recorded as having received dexmedetomidine were recorded as suffering from severe medetomidine withdrawal.
Medetomidine’s emergence in fentanyl supplies has been traced anecdotally to the middle of 2024, so data was split to before and after that time to measure the drug’s ascent.
In the “pre-medetomidine period,” dexmedetomidine was administered to just shy of 6 percent of patients with opioid use disorder. But in the “post-medetomidine period,” roughly 20 percent of these patients required dexmedetomidine. In the last three months observed, that rate climbed to approximate 32 percent 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.”
Resources used
In addition to dexmedetomidine, patients suspected of having medetomidine withdrawal also were significantly more likely to need other medications and higher doses of them to help with their treatment, further suggesting that their severe withdrawal was attributable to medetomidine, not untreated fentanyl withdrawal.
For instance, 79 percent received methadone (an long-acting medication that helps blunt withdrawal effects and opioid cravings) compared to 50 percent of patients with opioid use disorder who didn’t also require dexmedetomidine, and, similarly, 36 percent patients with medetomidine withdrawal received buprenorphine (another agonist medication), compared to 26 percent of non-medetomidine-related patients.
Additionally, patients who received dexmedetomidine logged more time in the ICU, on average, than other patients with opioid use disorder.
Pinning down who this affects
The patients who required dexmedetomidine were found by the research team to be younger and more likely to be on Medicare compared to other patients with opioid use disorder.
Moving forward, the researchers believe that more analysis needs to be done to uncover particular risk factors that make patients more likely to suffer medetomidine withdrawal, and to inform potential policies or public health interventions.
This work was supported by grants from the National Institute on Drug Abuse (K23DA055087 and K23DA062008).
JAMA Internal Medicine
10.1001/jamainternmed.2026.4568
Data/statistical analysis
People
Dexmedetomidine Use and Intensive Care Unit Admissions for Patients With Medetomidine Withdrawal