A Closer Look at Medetomidine and Its ‘Unusual’ Patient Presentations

“The drug sample contained multiple different nitazenes, a bunch of fentanyl analogues, xylazine, diphenhydramine, caffeine, and medetomidine.”

That last word, medetomidine, stuck out to me. This was the preliminary report I received recently on a specimen I had sent for testing from a patient experiencing an overdose. While I am all too familiar with recognizing and managing overdoses — I can’t even keep track of how many thousands I have seen at this point — I had sent this for testing because this one was unusual.

Unfortunately, “unusual” presentations are becoming more and more common. In this case, the patient had presented like a classic opioid overdose, unresponsive and barely breathing, reportedly after using heroin. What was unusual was that standard treatments did next to nothing for the patient’s failure to breathe and failure to circulate blood and perfuse their organs. Although the patient ended up surviving, the toxic effects lasted much longer than normal.

The lab results confirmed what I’d be reading about in the news: another drug has entered the supply and is causing mass overdoses.

Enter Medetomidine

Medetomidine has a very similar mechanism of action as xylazine, another drug that has recently entered the drug supply, and it is also not an opioid. Like xylazine, medetomidine is used in veterinary medicine, although one of its two isomeric forms, dexmedetomidine, is approved for human use and used primarily as a sedative and anesthetic agent. The main differences between the two are just that medetomidine is much more potent and its effects last significantly longer.

I am certainly not alone in my experience dealing with medetomidine overdose, in both its unexpected nature and difficulty in managing. A recent report out of Philadelphia detailed an overdose cluster from this drug that led to 160 hospitalizations in just a few days, and it has been reported in other parts of the U.S. and Canada with increasing frequency. Not only are patients presenting with overdoses that don’t respond to standard overdose reversal measures like naloxone (Narcan), but patients can have dangerously low heart rates and blood pressure, and symptoms can last for longer than both patients and clinicians are used to. It can additionally suppress breathing to the point of completely stopping breathing if the dose is high enough.

In these situations, even under direct medical care, this can mean the difference between sending someone home or sending someone to the intensive care unit. Outside of a hospital setting, this can be the difference between life or death.

At present, there is no approved antidote for medetomidine in humans. It remains unclear whether there are additional adverse effects besides overdose, or any possible long-term effects.

Responding to Unpredictable Challenges and Drug Cocktails

Why is medetomidine showing up in street drugs, especially when they’re labeled as heroin or fentanyl, which are an entirely different class of drug? The answer to this question remains unknown.

While medetomidine has been detected in drug samples going back to 2022, it was not nearly as widespread as these recent clusters and reports now show it to be. Xylazine had a similar emergence over the past few years, showing up sporadically for a number of years before becoming commonplace in drug samples across North America. Although it may be impossible to ever get a perfect answer for why medetomidine was added to the illicit opioid supply, it seems likely the intent was to potentiate the effects of opioids — essentially to deliver an equivalent effect with less fentanyl (which has been almost ubiquitous in the street drug supply for a number of years).

With medetomidine coming into the spotlight, we can only hope such attention will increase awareness of this drug and its effects, especially for people who use drugs and the people who treat them. However, medetomidine is only one of many substances that have emerged in the opioid supply in recent years, and I can guarantee that it is far from the last.

Like my sample, street drugs often times contain unknown mixtures of multiple drugs. Nitazenes, which were also detected in my patient’s sample, are another class of opioid drug that can be more potent than even fentanyl and have increased in prevalence in overdoses and drug samples in North America and Europe over the past few years. Atypical, novel, nonpharmacologic benzodiazepines have also increased in prevalence in different regions for a number of years and remain a problem for drug users and health professionals alike.

Xylazine, the veterinary sedative with similar effects to medetomidine, has also become widely prevalent in the North American drug supply. Beyond the problems it presents in causing overdoses that defy standard treatments, we have seen xylazine associated with serious and difficult-to-treat wounds, and its own withdrawal syndrome that does not respond to standard medicines used for heroin or fentanyl withdrawal. Furthermore, these substances are difficult to detect even in medical laboratories.

The fact that we, as physicians, often don’t know what mix of drugs a patient took — and perhaps even they don’t really know — poses immense challenges to treatment.

Preventing the Next Threat

Unfortunately, attention to previous emerging drugs has mostly led to criminal justice responses, rather than to the scientific study and research needed to better manage them. Additional bans on street drugs that are already illegal actually impede the ability to study them so that we can better understand and respond. As someone who treats overdoses and substance use disorders, my job has become increasingly difficult due to the unpredictable and constantly changing drug supply that lacks evidence-based treatments, and my patients have continued to suffer increasing harms.

Meanwhile, harm reduction measures continue to polarize policymakers and the general public, despite having a strong evidence base. The scientific literature we do have, and the majority of public health professionals practicing in this space, continue to advocate not only for increased study but for expanding access to safer, regulated drugs to mitigate these risks. With more than 100,000 preventable overdose deaths in the U.S. every year now, and many other adverse outcomes besides death, hopefully our policymakers will listen before the next wave of overdoses.