Medetomidine Infiltrates the US Illicit Opioid Market

The opioid crisis, driven by synthetic opioid use, has continued to lead to tens of thousands of deaths per year.¹ Although deaths appear to have begun to level off or slightly decline, the crisis has become increasingly complicated due to the emergence of comixtures of synthetic opioids (primarily fentanyl) with other central nervous system depressants, including animal tranquilizers. The recent addition of xylazine, a veterinary sedative, complicated the fentanyl overdose situation, making overdoses difficult to reverse²; and in recent months, rashes of opioid overdoses involving a new tranquilizer have been increasing.³ This new addition to illicit opioid concoctions is medetomidine, a potent α₂-adrenergic receptor agonist. Medetomidine, a racemic mixture of dexmedetomidine and levo-medetomidine, is commonly used to produce sedation and analgesia in veterinary medicine, whereas dexmedetomidine is a Food and Drug Administration–approved drug for human administration and is commonly used in hospital settings.⁴

Medetomidine, sometimes referred to as “rhino tranq” or simply “mede” among people who use illicit opioids, complicates the continuing opioid crisis because people who use illicit fentanyl tend to be unknowingly exposed, and naloxone, which can reverse fentanyl overdoses, is not fully effective in reversing overdoses when exposure to nonopioids such as xylazine or medetomidine keep the individual unconscious.³ After researchers and public health practitioners worked for months to help communities who use illicit fentanyl become more aware of xylazine (with xylazine test strips having become available), medetomidine has become the newest toxic adulterant increasingly added to illicit opioids in various parts of country. Not only is it difficult for both researchers and people who use drugs to detect medetomidine in drug products but also this substance tends to be mixed with xylazine and other adulterants, such as tetracaine.

Medetomidine is significantly more potent than xylazine, with longer duration of sedation and analgesia.⁴ Research studies suggest medetomidine is approximately 200 to 300 times more potent than xylazine. Medetomidine is not approved for use in humans, and animal studies have shown that use is associated with bradycardia, reduced cardiac output, and decreased respiration, and that combined exposure to multiple tranquilizers potentially can lead to a synergistic effect.⁴ This possibility is particularly alarming because medetomidine is typically found in combination with xylazine and fentanyl. The effects of medetomidine in hospital settings reportedly last for 2 to 3 hours; however, recreational use has been associated with longer periods of sedation and recovery times sometimes requiring hospital admission, in large part due to higher dosages consumed and coexposure with other central nervous system depressants.⁵ Clinical use of dexmedetomidine has been associated with withdrawal symptoms,⁶ and it is hypothesized that recreational use of medetomidine would be as well, similar to xylazine’s recent linkage to withdrawal.

The Spread of Medetomidine

The National Drug Early Warning System has been monitoring various data sources for shifts in medetomidine poisonings. Through July 2024, medetomidine has been detected in drug samples and biospecimens of people who use illicit opioids in at least 18 states plus the District of Columbia (Figure). Medetomidine in drug products was first detected by the US Drug Enforcement Administration’s National Forensic Laboratory Information System (NFLIS) program in 2021.⁷ The substance was present in 12 drug submissions in 2021, 10 from Ohio and 2 from Virginia. In 2022, medetomidine was detected in 262 submissions reported to NFLIS, again with most from Ohio(63.7%,n = 167), followed by Virginia(27.1%,n = 71) and Maryland (9.2%,n = 24). In July 2022, the Center for Forensic Science Research & Education’s NPS Discovery program began to detect the presence of medetomidine in biospecimens associated with the Maryland drug supply and it began to appear more regularly mixed with fentanyl, xylazine, and other drugs.³ Medetomidine, regularly mixed with fentanyl, began to become associated with suspected opioid overdoses in mid to late 2023 not only in Maryland but also in Pennsylvania, Missouri, and as far west as Colorado and California. In 2023, NFLIS received 235 submissions that tested positive for medetomidine; most (79.1%) submissions were again from Ohio (n = 186), followed by Virginia (11.1%, n = 26), Maryland (3.0%, n = 7), the District of Columbia (2.1%, n = 5), New Jersey (1.3%, n = 3), West Virginia (1.3%, n = 3), Pennsylvania (0.9%, n = 2), Indiana (0.9%, n = 2), and Florida(0.4%,n = 1).⁷ By early 2024, medetomidine combined with fentanyl and xylazine also became present in Toronto and then Vancouver, as reported by their drug checking programs.³ In late April 2024, medetomidine mixed with fentanyl and xylazine began to appear in Philadelphia,⁵ leading to an outbreak of adverse events and overdoses largely characterized by unexpected clinical toxidromes and notable bradycardia not previously observed with fentanyl and xylazine only. Within weeks, this concoction began to be associated with overdoses in Chicago, where samples containing medetomidine alongside heroin were also discovered. Recent alerts from local departments of health suggest that the drug has also begun to be detected in Michigan and New York.

Figure. States in Which Medetomidine Has Been Detected in Drug Products and in Biospecimens of People Who Use Drugs, January 12021-July 2024.

A few years ago, xylazine exposures also began in select states and then the drug slowly became detected throughout most US states.⁷ Current trends in medetomidine exposure appear to be linked to states in which detection of xylazine is most prevalent. Specifically, in 2023, of the 19 457 NFLIS drug submissions testing positive for xylazine, most were from Ohio (21.5%, n = 4177) and Pennsylvania (20.2%, n = 3928).⁷ Monitoring xylazine trends may help forecast where medetomidine will begin to appear in the illicit opioid supply.

Monitoring and Public Health Response Is Needed

Multiple modes of surveillance are needed to monitor the rapidly shifting medetomidine situation. Widespread biospecimen testing capable of detecting medetomidine is sorely needed. Furthermore, toxicology testing that allows for differentiation of dexmedetomidine and levomedetomidine is necessary to distinguish hospital administration from potential veterinary or clandestine sources. Such tests are also needed to detect the presence of medetomidine in drug products for surveillance and to inform people who use drugs when the substance is present, and tests are needed to provide information on exposure among decedents and people who overdose.

Information is needed regarding the source of the medetomidine being added to illicit opioids. Medetomidine is a legal, widely used veterinary tranquilizer and it is not currently scheduled. Better monitoring of this drug within veterinary clinics might be needed, although medetomidine appearing in opioids might have other sources. For example, although xylazine can be diverted from veterinary clinics, illicit xylazine appears to be largely imported from other countries. An online search of medetomidine powder for sale renders many results.

Clinicians and people who use illicit opioids need to be aware that medetomidine can be present in the drug supply, and education is needed regarding how to respond after an exposure. For example, exposure can lead to heightened sedation, bradycardia, and unconsciousness, which are not able to be reversed by naloxone. Medical intervention may be necessary in severe cases of medetomidine toxicity. In any cases in which opioids and adulterants are expected or suspected, it is essential for the individual to be monitored to ensure clear airways and that there is enough oxygen intake.

We believe that it is inevitable that medetomidine exposure will continue to spread among people who use illicit opioids, and continued monitoring and educational efforts are needed.