'Rhino Tranq' Withdrawal Is Rising: Are Clinicians Ready?

 Medetomidine, a veterinary sedative increasingly found in the illicit fentanyl supply, is presenting clinicians with a new challenge: a withdrawal syndrome that can emerge within hours, cause profound autonomic instability, and respond poorly to medications commonly used for opioid withdrawal.

Known on the street as "rhino tranq," "mede," or "dex," medetomidine is an alpha-2 adrenergic agonist related to xylazine and clonidine. It is not approved for human use, although its active isomer, dexmedetomidine, is widely used as a sedative in hospitals.

Amid increasing exposure to the drug and warnings from state and federal agencies, experts are urging clinicians to prepare for a likely increase in patients struggling with medetomidine addiction and withdrawal.

How Widespread Is Medetomidine Exposure?

Medetomidine was first detected in the US illicit drug supply in 2021, and surveillance data from the CDC shows how quickly the drug has spread. Reports of medetomidine submitted to the National Forensic Laboratory Information System increased 950% between 2023 and 2024, rising from 247 to 2616, respectively. Reports climbed another 215% in 2025, to 8233.

In May of 2024, the Center for Forensic Science Research and Education warned that medetomidine was "rapidly proliferating" in the US after clusters of overdoses in Philadelphia and Chicago involving fentanyl or heroin were also found to contain medetomidine, often along with xylazine and other substances.

For example, from May 2024 to March 2026, the percentage of Philadelphia dope samples with medetomidine jumped from 29% to 90%, while the percentage of samples with xylazine fell from 97% to 28%, suggesting that medetomidine is quickly overtaking xylazine in the dope supply.  

While the highest concentrations have been reported in the Northeast, medetomidine has now been detected across multiple regions of the country.  

"We know that it spread as far west as Seattle and San Diego over a year ago. However, it does not appear to be as prevalent out west, at least not yet," Joseph J. Palamar, PhD, MPH, professor of population health, NYU Langone Health in New York, told Medscape Medical News.

Research suggests that patients generally do not know they are taking it. In a 17-center US toxicology surveillance study involving 964 emergency department patients with opioid and/or stimulant overdose, medetomidine was detected in 27 patients (2.8%). None of the 24 exposed patients who completed an interview reported knowingly using the substance. 

How Severe Is Withdrawal?

In an April 2026 health advisory, the CDC warned clinicians that medetomidine can cause both severe toxicity and a potentially life-threatening withdrawal syndrome. Withdrawal also appears to have a particularly rapid onset: Symptoms may begin about 4-6 hours after the last exposure and escalate over the following 24 hours. By comparison, fentanyl withdrawal commonly begins within 12-24 hours after last use, while xylazine-associated withdrawal tends to have a faster onset, greater severity, and a more prolonged course than fentanyl withdrawal alone.

While medetomidine intoxication is marked by persistent sedation and bradycardia, sometimes with hypotension, withdrawal can look "like the opposite," Jeanmarie Perrone, MD, director of the Center for Addiction Medicine and Policy, University of Pennsylvania, Philadelphia, told Medscape Medical News. Symptoms can include rapid heart rate, severe hypertension, nausea and vomiting, and tremor.

Cara Borelli, DO, addiction medicine specialist, Yale School of Medicine, New Haven, Connecticut, described a similar clinical picture. "Patients are absolutely miserable, experiencing shaking, sweating, and vomiting with dramatic increases in heart rate and blood pressure," she told Medscape Medical News.

A brief report published in September in the Annals of Internal Medicine backs up Borelli's observations. To document what they were seeing in hospitalized patients in Pittsburgh, researchers led by Margaret Shang, MD, MS, assistant professor of medicine with University of Pittsburgh Medical Center, interviewed 16 adults with opioid use disorder and confirmed medetomidine exposure.

Patients described withdrawal as substantially worse than their previous experiences with fentanyl or fentanyl-xylazine. One said, "I could not stop throwing up. It was insane." Another patient noted, "I tried numerous times before I came to the hospital, and I could not do it by myself."

Fear of withdrawal may itself discourage treatment. One participant told investigators, "It makes me not want to get treatment because it's so hard to come off of it." Another said, "The methadone and Suboxone does not even help or touch it because it's not an opiate." Patients also described feeling powerless to avoid adulterants in the illicit drug supply.

"Because public health surveillance lags behind the rapidly changing unregulated US drug supply, people who use drugs are often among the first to identify emerging adulterants and describe new patterns of toxicity and withdrawal," Shang told Medscape Medical News. Clinicians should therefore "actively listen to and take seriously patients' reports," she added. 

What's the Treatment?

While naloxone has not been shown to reverse medetomidine toxicity, Shang emphasized that it remains essential when opioid overdose is suspected because it reverses opioid-induced respiratory depression. Persistent sedation after naloxone does not necessarily mean the drug has failed, because naloxone does not reverse medetomidine-induced sedation. Clinicians should titrate naloxone to restoration of breathing rather than full consciousness, she advised.  

Medetomidine withdrawal requires additional treatment beyond standard opioid withdrawal management. Shang said their institutional protocol prioritizes scheduled oral alpha-2 adrenergic agonists, including clonidine or guanfacine, with escalation to intravenous dexmedetomidine for patients who do not respond to or cannot tolerate oral therapy. Dexmedetomidine is typically used for 24-48 hours, with transition back to oral agents, while oral alpha-2 agonists may need to be tapered over 1-4 weeks to prevent rebound symptoms.  

Shang said acute care teams should be trained to recognize the characteristic features of medetomidine exposure and withdrawal and to avoid relying solely on standard opioid withdrawal protocols when patients present with severe or atypical symptoms.

Hospitals should also establish clear protocols for evaluating and managing suspected medetomidine withdrawal, including guidance on symptom monitoring and supportive and pharmacologic management. When available, clinicians should involve addiction medicine and/or medical toxicology services early, particularly for patients with severe or refractory symptoms, Shang said.

Perrone also cautioned that in areas where medetomidine is just beginning to emerge, the first few cases may be difficult for clinicians to recognize.

What Should Clinicians Tell Patients?

Shang urged clinicians to proactively tell patients who use unregulated opioids that medetomidine has been detected in the illicit supply and can cause profound, prolonged sedation as well as potentially severe withdrawal.

Patients and bystanders should understand that naloxone remains critical whenever an opioid overdose is suspected and that they should seek emergency care even if sedation persists after naloxone, she said.

"Clinicians should also explain that medetomidine withdrawal may be substantially more difficult to manage than typical opioid withdrawal, particularly when severe autonomic symptoms, rigors, or persistent vomiting are present. Rather than attempting an unmonitored withdrawal at home, patients experiencing severe or rapidly worsening symptoms should be encouraged to seek prompt medical evaluation," Shang said.

Drug-checking can help bridge the information gap between patients and clinicians, Perrone noted. "In Philadelphia, we can offer patients test strips to test their drugs so that they can inform clinicians" whether medetomidine or another adulterant may be present, she said.

Outreach programs in Philadelphia distribute pocket-sized medetomidine "palm cards" that patients can carry to help explain medetomidine exposure and withdrawal to clinicians who may not yet be familiar with the syndrome, Perrone added. 

What Other Drugs to Watch For?

Medetomidine is not the only emerging substance in the illicit opioid supply. In a May 2026 public safety advisory, the Drug Enforcement Administration (DEA) warned that law enforcement and public health officials are seeing fentanyl mixed with other potent substances.  

One is cychlorphine, an emerging "orphine" class of synthetic opioids. The United Nations Office on Drugs and Crime reported that cychlorphine has been detected in drug seizures and fatal overdoses in multiple countries, often in combination with fentanyl, heroin, cocaine, medetomidine, or other synthetic drugs. Spirochlorphine, another orphine analogue, has also emerged in the illicit supply.

In late August 2026, DEA temporarily placed cychlorphine, spirochlorphine, and two other synthetic opioids into Schedule I of the Controlled Substances Act. The temporary order remains in effect until August 2028.

Nitazenes are another group of potent synthetic opioids that have been appearing in fentanyl powders and counterfeit pills. DEA said it has identified 22 distinct nitazene compounds since 2020; many can cause rapid respiratory depression and may require repeated naloxone dosing.  

And xylazine remains firmly in the picture.

"Medetomidine has been slowly replacing xylazine although many people are exposed to both drugs. In many respects, medetomidine is worse," Palamar said. "I'm worried about the next drug that will eventually emerge to replace medetomidine. It could be a lot more dangerous."

Shang, Palamar, and Borelli have no relevant disclosures.

https://www.medscape.com/viewarticle/rhino-tranq-withdrawal-rising-are-clinicians-ready-2026a1000zan