Clinicians first noticed medetomidine in the Philadelphia drug supply during the spring of 2024. There was a cluster of overdoses one weekend, leaving patients more sedated and with lower heart rates than normal after receiving the reversal medication naloxone.
It raised some red flags, but amid a constantly changing drug supply, not many. None of the patients died, and most went home from the hospital the same day. It wasn’t until autumn, when patients started coming in with excruciating withdrawal symptoms, that doctors knew something had dangerously shifted.
“It took a while for our patients to consistently have a supply that was exposing them to this enough so that when they stopped, they would rapidly develop withdrawal,” said Jeanmarie Perrone, an emergency medicine physician and director of the Penn Medicine Center for Addiction Medicine and Policy. “It’s the withdrawal that has caused so many problems.”
While clinicians in Pennsylvania and other hotspots are now familiar with the signs of medetomidine withdrawal, the American Society of Addiction Medicine this week released the first national guidance for recognizing and treating patients who have taken the sedative. Technically, the document consists of “considerations,” not guidelines, since researchers have not yet conducted larger studies that could validate the inferences clinicians are making on the ground.
If people are using medetomidine, it’s nearly always in combination with illicit opioids, experts say. That means naloxone should still be the first step if somebody appears to be overdosing. But it also means the patient may not be responsive even after they start breathing again. When it comes to acute medetomidine intoxication, low heart rate and low blood pressure can be treated with IV fluids and other basic care, the guidance notes.
The first symptoms of medetomidine withdrawal tend to be nausea and vomiting, without the diarrhea that accompanies opioid withdrawal, said Perrone, one of the co-authors. That’s when they recommend clonidine, a medication that, like medetomidine and xylazine before it, acts as an alpha-2 agonist. If that doesn’t help or patients can’t keep it down, they could develop very high blood pressure and a fast heart rate within a few hours. That may signal the need for the related IV medication dexmedetomidine, or Precedex.
“It’s scary. We thought we were already living in unprecedented times with the adulteration of fentanyl with xylazine,” said Kory London, an emergency physician and addiction specialist at Thomas Jefferson University. (He didn’t contribute to the considerations, but he works with many people who did.) Unlike withdrawal from other illicit drugs, coming off of medetomidine may require a stay in the intensive care unit.
“We are giving doses [of clonidine and dexmedetomidine] that, as an experienced addiction provider, I would not have given five years ago when dealing with the initial xylazine adulteration,” London said. “Unless you’re experienced with this, giving enough medications to avoid getting somebody to the ICU is really challenging.”
Before medetomidine started taking over, xylazine was the dominant adulterant in much of the American drug supply. It leaves users with horrific wounds and is such a powerful sedative that it could knock people out for hours, often leaving them vulnerable in public.
Medetomidine doesn’t seem to cause the same wounds. But as a sedative, it’s far more potent.
By the end of 2025, medetomidine had been detected in at least 18 states. It’s important for physicians to know whether medetomidine is present in the local drug supply, experts emphasize, as the symptoms may resemble other conditions, including sepsis. In general, it’s critical to stay familiar with the local supply and to consider what effects different adulterants could have on users, said Michael Lynch, a co-author of the considerations and an emergency medicine doctor specializing in medical toxicology at the University of Pittsburgh Medical Center.
“The next thing, and then the next thing, and then the thing after that are coming,” Lynch said. “We can try to predict what they’re going to be, but we can’t always.”
Not every community has the resources to do rigorous, regular drug checking. But “if we do a good job at describing our experience in places where we do have resources and have that early experience, hopefully other places can see the clinical manifestation,” Lynch said. There are drug testing strips for medetomidine.
While the clinical considerations offer doctors a blueprint for treating medetomidine withdrawal, experts say that more research is needed to understand the drug’s long-term effects and to develop better treatments.
Some patients who make it through withdrawal and begin to take medications for opioid use disorder can still experience cravings, experts said. They might think that the cravings are for opioids and begin to use again, but really, the cravings are for medetomidine.
“We’re going to have to recognize that there are now patients who are developing a sort of novel substance use disorder of alpha-2 agonist sedative addiction,” said London. “We urgently need both ways to understand that and ways potentially to help treat patients.”
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