Researchers have discovered a new drug infiltrating the illicit market: the powerful veterinary sedative medetomidine. Used as an anesthetic for larger animals, medetomidine is 100 to 200 times more powerful than xylazine, the so-called “zombie drug.”
This news comes just months after the U.S. Centers for Disease Control and Prevention noted a substantial decrease in fentanyl-linked overdoses within the last three years. However, this a familiar cycle during an opioid epidemic—as one drug recedes, another takes its place.
The risk of medetomidine actually comes from withdrawal. Withdrawal happens quickly and can cause tachycardia, 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 medetomidine withdrawal, patients need a medication called dexmedetomidine, an infused treatment that requires ICU stays because it can cause low heart rates and blood pressure, thus requiring careful, constant monitoring.
“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 study 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, two periods, one drug
In their study, published in JAMA Internal Medicine, Lowenstein and her team examined data from two different Philadelphia hospitals dating from early 2020 through September 2025. 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 approximately 32 percent of those treated.
Patients suspected of medetomidine withdrawal were also significantly more likely to need other medications at higher doses. For example, 79 percent received methadone compared with 50 percent of patients with opioid use disorder who didn’t also require dexmedetomidine. Similarly, 36 percent of patients with medetomidine withdrawal received buprenorphine compared with 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.
“Historically, heroin withdrawal without these adulterants could be managed in outpatient or minimally monitored inpatient settings,” said Ashish Thakrar, co-first author of the study and assistant professor of general internal medicine at Penn. “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.”
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, as well as to inform potential policies or public health interventions.
“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,” said the study’s co-first author, Tyler Boyce, MD, a fellow in Pulmonary and Critical Care Medicine.