Severe withdrawal cases point to growing medetomidine use

The number of patients treated for severe withdrawal linked to medetomidine—a powerful veterinary sedative increasingly found in fentanyl—quadrupled in recent years, according to a new analysis by researchers at the Perelman School of Medicine at the University of Pennsylvania. The study, published in JAMA Internal Medicine, confirms observations by medical professionals who have treated the drug’s particularly intense withdrawal symptoms 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 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 lead to low heart rates and blood pressure, requiring 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, 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.”

Leveraging two hospitals’ data to reveal spread

Data from two Philadelphia hospitals from 2020 through September 2025 showed that patients with opioid use disorder who received dexmedetomidine were recorded 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 point to measure the drug’s rise.

During the “pre-medetomidine period,” dexmedetomidine was administered to just under 6 percent of patients with opioid use disorder. During the “post-medetomidine period,” roughly 20 percent of these patients required dexmedetomidine. In the final three months studied, that rate climbed to approximately 32 percent.

“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 experiencing medetomidine withdrawal were significantly more likely to require other medications and higher doses, further suggesting that their severe withdrawal was attributable to medetomidine rather than untreated fentanyl withdrawal.

For instance, 79 percent received methadone (a long-acting medication that helps reduce withdrawal symptoms and opioid cravings), compared with 50 percent of patients with opioid use disorder who did not require dexmedetomidine. Similarly, 36 percent of patients with medetomidine withdrawal received buprenorphine (another opioid agonist medication), compared with 26 percent of patients without suspected medetomidine withdrawal.

Additionally, patients who received dexmedetomidine logged more time in the ICU, on average, than other patients with opioid use disorder.

Identifying who faces the greatest risk

Patients who required dexmedetomidine were younger and more likely to have Medicare coverage than other patients with opioid use disorder.

Moving forward, the researchers believe more research is needed to identify specific risk factors that make patients more likely to experience 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).