Beyond Xylazine: How Medetomidine’s Rise Is Changing Overdose and Withdrawal Care

For several years, addiction medicine providers and health workers in Philadelphia have worked to adapt to a new additive in the regional drug supply. Xylazine, sometimes known by its nickname “tranq,” appeared in the fentanyl sold locally on the street and was causing new and harmful symptoms in the people who used it.  

Xylazine is what’s known as an alpha-2 agonist. It binds with a person’s alpha-2 receptors and reduces the release of norepinephrine causing a sedative effect. Its emergence has complicated care for people who use it, wittingly or not. One of the more troubling effects of xylazine’s inclusion is the appearance of wounds on people who use drugs which are slow to heal, even with attentive medical care.  

Joseph D'Orazio, MD

But according to organizations that monitor the makeup of the drug supply, xylazine’s days may be numbered. It’s being found much less frequently as another more powerful alpha-2 agonist called medetomidine has begun to take its place. In Philadelphia and Camden, addiction medicine teams report seeing this shift over the last year and a half or so.  

Both xylazine and medetomidine complicate the care that a person who uses drugs needs, but there is still much to learn about the differences.  The SNJMATCOE recently created new guidance for managing medetomidine exposure based on the best evidence available.

Joseph D’Orazio, MD, is an addiction medicine specialist with the Cooper Center for Healing and a toxicologist who follows the makeup of the local drug supply. In advance of a December 12 lecture on the topic, he answered the questions below. 

How does an alpha-2 agonist affect a person who uses illicit opioids? How does it complicate their care? 

Xylazine and other alpha-2 agonists cause a sedative effect or sometimes referred to as a "downer" colloquially much like benzodiazepines such as Xanax or Klonopin. People using a supply contaminated with alpha-2 agonists experience much more sedation. They commonly report that they use a bag and are unconscious or asleep for hours and wake up feeling opioid withdrawal symptoms. From an overdose perspective, the added sedation makes it much more difficult to manage.  

Withdrawal from xylazine has its own set of symptoms with a lot of anxiety and irritability. This makes the task of helping someone out of withdrawal much more difficult.  

We have practices to treat and manage xylazine withdrawal, but many institutions have still not changed their protocols to account for alpha-2 agonists in the supply. I hear of many patients leaving hospitals, and drug rehabs because they felt their xylazine withdrawal was unmanaged. 

Xylazine-associated wounds have made drug treatment exponentially more difficult. Besides the complexities of treating the actual wound, it is often more difficult to engage patients with levels of care like inpatient drug rehab when they are experiencing xylazine-associated wounds. Many inpatient drug rehabs and facilities are not equipped or do not know how to manage these wounds which makes getting into recovery that much more difficult. 

Over the last 10 years, many states, including New Jersey, have made it much easier to acquire naloxone, or Narcan. How do these alpha-2 agonists complicate naloxone's effectiveness at reversing overdose? 

Wide distribution of Narcan has been one of the most successful parts of the opioid epidemic response. Bystander Narcan administration has saved countless lives. Policymakers should continue to get Narcan in the hands of as many people as possible.  

Narcan continues to be a very effective treatment for opioid overdose even in the setting of contaminants like xylazine, medetomidine, and even more potent opioids than fentanyl like carfentanil. 

I’ve seen many overdoses deemed "Narcan resistant" but I think this is a bit of a misconception. We were used to giving a dose or two of Narcan and have patients quickly become alert. Now, with the added sedatives to the opioid supply, patients may not necessarily “wake up” and start talking the way they did a few years ago after Narcan, but the Narcan may still have addressed their respiratory depression, which is the most dangerous aspect of a life-threatening overdose situation.  

When I hear a patient was "Narcan resistant," that so-called resistance is usually easily explained by the other drugs in the supply rather than the opioid being resistant to naloxone reversal. 

Now medetomidine is replacing xylazine in the fentanyl supply. Where are we in that transition? 

We are seeing a significant shift from xylazine to medetomidine over the last 18 months, roughly. In the spring of 2024, Philadelphia hospitals saw a steep increase in visits associated with medetomidine overdose. Within months, health care providers started seeing patients experiencing medetomidine withdrawal.  

Here in South Jersey, we are seeing cases more frequently since the spring but still nowhere near the level that Philadelphia is seeing it. 

And when we look at the numbers from the Mid-Atlantic region, we see a drastic shift from xylazine to medetomidine. In the first quarter of 2024, 97 percent of fentanyl bags that were tested contained xylazine while no medetomidine was found. In the second quarter of 2025, just about a year later, 82 percent of fentanyl bags now contain medetomidine and only 12 percent contain xylazine.  

This is a significant change, and we are starting to see some of the same shift here in Camden. 

Xylazine has become widely known for the devastating wounds associated with its use. Is it known yet if medetomidine also makes these difficult wounds more likely? 

We don't have any data on that yet. I think it is too early to tell, but, anecdotally, I think many providers have noticed fewer wounds. There are many factors at play here, so I don’t want to draw any conclusions, but I certainly have seen a shift to fewer wounds. 

Tell me about withdrawal. Xylazine has its own withdrawal symptoms separate from symptoms traditionally associated with opioid withdrawal. How does medetomidine compare? 

Medetomidine is a much more potent alpha-2 agonist, so we see much more severe symptoms of withdrawal.  

Unlike with xylazine withdrawal, we see a lot of vital sign changes, tremors, vomiting, and altered mental status. Patients typically end up in the ICU for medetomidine withdrawal and it can be life-threatening. This is drastically different than Xylazine withdrawal.