This week’s NDEWS Weekly Briefing highlights two veterinary α2-adrenergic agonists—xylazine and medetomidine—that are increasingly implicated in the US illicit opioid supply. Xylazine, long used as a fentanyl adulterant, has come under heightened scrutiny in recent years due to rising overdose deaths and detection in toxicology reports. In cities like Philadelphia, however, a recent regulatory ban has led to a decline in xylazine exposure, with medetomidine—a more potent but less understood analog—quickly emerging in its place.

Recent reports from medical examiners, media outlets, and local harm reduction networks indicate that medetomidine is now linked to a growing number of fatal overdoses and is presenting new clinical challenges, including severe withdrawal and nonresponsiveness to naloxone. These overdoses reflect an evolving and increasingly polysubstance-driven drug landscape that demands real-time surveillance and adaptive public health responses.

This issue presents recent findings from toxicology, forensic science, and emergency medicine alongside original data from NDEWS web monitoring and 911 dispatch signals.

As always, we welcome input from the field to strengthen our collective understanding. Any drug information shared with NDEWS is crucial to our surveillance mission. Please share via the form linked below.

NDEWS highlights observations from biospatial.io detailing the EMS encounters for xylazine- and medetomidine-related overdoses in the US from Q1 2023 to Q1 2025. The data shows that counties were located throughout the eastern region of the US. Among states with at least 75% coverage, there were 1,233 EMS encounters.

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What is Medetomidine? Medetomidine, also known as "Domitor®", is a highly potent alpha-2 adrenergic receptor agonist primarily used as a veterinary sedative and analgesic. Medetomidine has a rapid onset of action and produces significant sedative, amnestic, and analgesic effects.

What was found? Reddit data shows a consistent increase in medetomidine since December, and discussions of this drug are at an all-time peak on Reddit.

Previous NDEWS Reports:
June 14th, 2024

How is it being discussed? Online discussions suggest that medetomidine is used in combination with opioids for recreational purposes. Reddit users report that the drug's potent sedative effects are an order of magnitude greater than those of xylazine. The combined CNS depression of a fentanyl-medetomidine mixture, often referred to as "rhino tranq", is highlighted by commenters as a major danger, potentially leading to severe respiratory depression and overdose. The discussion also notes that the potency difference between medetomidine and other sedatives like xylazine may not be well understood, leading to unintentional overdoses. Since the last report there has been increased discussion about negative withdrawal symptoms, including tremors and cardiovascualar instability, that, in some cases, reportedly required intensive hospital care. Discussants also are referring to new symptoms more recently including hallucinations and peripheral cyanosis (blue skin without hypoxia) Recent discussion also notes the availability of medetomidine specific test strips.

Drug Terms: Medetomidine, Domitor®

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A recently published commentary in The Lancet Regional Health – Americas by Zhu and NDEWS Co-Director Dr. Palamar details the rise of medetomidine, a potent veterinary sedative, as a novel adulterant in the US illicit opioid supply. First detected in Maryland in 2022 and now linked to overdose clusters in cities like Philadelphia and Chicago, medetomidine—200–300 times more potent than xylazine—often appears alongside fentanyl and xylazine, complicating overdose treatment. The authors urge expanded surveillance, citing efforts by NDEWS and forensic networks, and recommend distributing BTNX test strips for early detection.

Read more here.

A recently published brief report in The American Journal on Addictions by Sood details the rise of medetomidine—a potent veterinary sedative over 100x stronger than xylazine—in fentanyl supplies across at least 18 US states. Linked to seizures and fatal overdoses, medetomidine often co-occurs with xylazine and fentanyl but is not reversed by naloxone. The report highlights outbreaks in Philadelphia and Michigan, urges expanded testing, and notes emerging treatments like methadone plus clonidine and possible reversal with atipamezole, though not yet studied in humans. 

Read more here.

A recently published commentary in American Journal of Public Health by Aronowitz and Reed argues that the US has entered a “fourth wave” of the overdose crisis—marked by widespread polysubstance use and the emergence of potent sedatives like medetomidine and etomidate in street drug supplies. Drawing on Philadelphia as a sentinel site, the authors note xylazine's rapid replacement by medetomidine and emphasize the lack of national investment in drug-checking infrastructure. 

Read more here.

A recently published commentary in Journal of Pharmacy Technology by Datta et al. warns that naloxone alone may be insufficient for overdoses involving xylazine and medetomidine, which increasingly adulterate fentanyl and do not respond to opioid antagonists. The authors recommend pharmacists advise patients to carry multiple naloxone kits (≥10 mg total), use 1-way valve CPR masks for rescue breathing, and call 911 immediately—citing over 160 medetomidine-related hospitalizations in Philadelphia within 3 days as evidence of the growing risk. This concern is echoed in recent media coverage, including his own article in The Conversation, which calls for revised overdose protocols: initiating 911 calls before naloxone administration and emphasizing rescue breathing when sedation persists.

Read more here.

Media Coverage:
- Animal tranquilizers found in illegal opioids may suppress the lifesaving medication naloxone − and cause more overdose deaths - The Conversation

A recently published study in The Journal of Applied Laboratory Medicine by Scott et al. evaluated seven commercially available xylazine test strips (XTS) for use in harm reduction and forensic settings. All strips demonstrated stable performance across urine pH levels and extreme temperature storage over six weeks. However, cross-reactivity with common adulterants—including lidocaine, levamisole, methamphetamine, and cetirizine—varied by brand, raising concerns about false positives. The 12PanelNow strips were most sensitive (LOD = 750 ng/mL), while strips from BTNx, WiseBatch, MD-Bio, and WaiveDx showed higher selectivity. The authors recommend cautious interpretation of XTS results and emphasize the need for standardization in field-based drug-checking tools.

Read more here.

Lean more here on how to use xylazine test strips

Submit any information concerning medetomidine or xylazine use in your area, here.

Is there any other information NDEWS should know about related to substance use, overdoses (fatal or nonfatal) or other drug-related trends in your area, including trends associated with polysubstance or co-use?

A recent Axios Philadelphia article reveals that medetomidine—a potent veterinary sedative—is rapidly replacing xylazine in Philadelphia’s fentanyl supply following a statewide xylazine ban. Once present in 99% of samples, xylazine dropped to 42% by late 2024, while medetomidine was detected in 46 fatal overdoses. Experts warn medetomidine is much stronger than xylazine and linked to severe withdrawal symptoms, elevated heart rate, and blood pressure spikes. Emergency physicians report revising treatment protocols to manage the new clinical challenges, as the city’s drug supply becomes increasingly volatile and harder to monitor.

Read more here.

A recent article in The Conversation by London and Alexander reports that medetomidine has overtaken xylazine as the dominant fentanyl adulterant in Philadelphia, now appearing in twice as many samples. Detected in 46 fatal overdoses by the end of 2024, medetomidine’s high potency and lack of response to naloxone complicate overdose management. Clinicians note an unprecedented rise in severe withdrawal cases—marked by hypertension, confusion, and vomiting—requiring new treatment protocols beyond those used for xylazine.

Read more here.

📅 Date: Wednesday, April 30, 2025

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If you miss or want to learn more about NDEWS Original Content, you can find our archived content on the NDEWS website:

     • NDEWS Hotspot Alerts using substance-related EMS data
     • NDEWS Rapid Street Reporting (RSR) survey data reports
     • NDEWS Web Monitoring Team Reddit Alerts
     • NDEWS Sentinel Site Reports
     • Previous issues of the NDEWS Weekly Briefings

The Weekly Briefing is a newsletter published each week by the National Drug Early Warning System (NDEWS) Coordinating Center, which is funded by the National Institute on Drug Abuse (U01DA051126) to the University of Florida (MPI: Cottler (contact), Co-Is: Goldberger, Nixon, Striley), New York University (MPI: Palamar), and Florida Atlantic University (Co-I: Barenholtz). Any item may be reproduced provided the source is acknowledged.