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Medetomidine in the U.S. Illegal Fentanyl Supply Increasing Risk for Overdose and Severe Withdrawal Syndrome | HAN

Despite declines in U.S. drug overdose deaths since 2022 that continued in 2025, the illegal drug supply remains unpredictable. Illegally made fentanyl continues to be involved in most overdose deaths and is frequently mixed with other drugs, such as benzodiazepines or xylazine. Medetomidine, an alpha-2 adrenergic agonist sedative, more potent and longer-acting than clonidine and xylazine, was first identified in the illegal drug supply in 2021 and began appearing sporadically with fentanyl in multiple jurisdictions including Chicago

The geographic spread of medetomidine appears to be expanding; the number of reports submitted to the National Forensic Laboratory Information System (NFLIS)

From October 2025–January 2026, medetomidine was detected in treated wastewater every week in at least one of 14 states included in a wastewater testing program in the United States. Data from CDC’s Overdose Data to Action (OD2A) program, which funds local health departments to conduct laboratory testing of drug products and paraphernalia, and the National Institute of Standards and Technology (NIST) RaDAR program

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Figure: Percentage of opioid-positive drug product and paraphernalia samples also positive for medetomidine across 20 sentinel sitesa: US region, July 2025–December 2025 (Provisional data)b,c


a. 20 sites include Midwest (Chicago Dept. of Public Health, IL; Cuyahoga County Board of Health, OH; Hamilton County Public Health, OH; Health and Hospital Corporation of Marion County, IN; Saint Louis County Dept. of Public Health, MO; Sedgwick County Health Dept., KS), Northeast (Allegheny County Health Dept., PA; City of Hartford Health and Human Services, CT; Fund for Public Health in New York City, NY; Philadelphia Dept. of Public Health, PA; Savage Sisters Recovery [Philadelphia, PA] in collaboration with Friends Research Institute), South (Florida Dept. of Health – Broward County, FL; Delaware Department of Health and Social Services; Maryland Dept. of Health; Florida Dept. of Health – Palm Beach County, FL), West (Alameda County Health Care Services Agency, CA; Denver Dept. of Public Health and Environment, CO; Los Angeles County Dept. of Public Health, CA; Public Health – Seattle & King County, WA; Southern Nevada Health District, NV).
b. Total number of samples tested per site ranged from 102 to 1,216 (median=308) and are a convenience sample. Thus, overall percentages are not representative of drug use locally or regionally.
c. Types of samples (e.g., drug products versus drug paraphernalia) tested varies across sites. Thus, the presence of drugs in the drug market is overestimated as drug paraphernalia may be used multiple times by multiple people and drug samples can be contaminated at trace amounts due to storage or handling.

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Reported effects of medetomidine intoxication are consistent with those of alpha-2 agonists and include:

  • marked bradycardia (heart rates as low as 32 beats per minute),
  • hypotension, and
  • profound, often prolonged sedation.

Unlike xylazine, medetomidine use does not seem to be associated with development of wounds.

Because fentanyl is involved in most overdoses involving medetomidine, OORMs should be administered in an attempt to restore normal breathing in suspected overdoses. OORMs like naloxone are effective in reversing opioid effects but are not effective in reversing the effects of medetomidine or other drugs that may have been consumed. Consequently, while apnea may be reversed with naloxone, sedation may not be reversed. The frequency of respiratory support and intensive care unit (ICU) management for medetomidine-involved overdoses is comparable to that for opioid or stimulant overdoses not involving medetomidine, unless withdrawal signs are present.

Emergence of medetomidine in the illegal opioid supply has been associated with overdose clusters, including one in Chicago in May 2024 with 12 confirmed, 26 probable, and 140 suspected medetomidine-involved overdoses; fentanyl was detected in all medetomidine-positive samples. Most patients exhibited findings typical of opioid overdose and suggestive of opioid co-involvement (altered mental status, pinpoint pupils, hypoxemia). Most had significant bradycardia due to medetomidine’s alpha agonist effect, with some requiring atropine. At least 16 people were hospitalized and one died.

Stopping medetomidine following regular use can precipitate a severe withdrawal syndrome, similar to clonidine withdrawal, that can require emergency or intensive care. Withdrawal symptoms are marked by:

  • tachycardia (>100 beats per minute),
  • severe hypertension,
  • fluctuating alertness,
  • tremor,
  • chest pain, and
  • intractable nausea and vomiting.
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Withdrawal symptoms may begin within hours of last use and peak 18–36 hours later. Complications such as non-ST elevation myocardial infarction and posterior reversible encephalopathy syndrome have been associated with severe medetomidine withdrawal. Increases in emergency department visits for non-alcohol, non-nicotine, and non-cannabis withdrawal have been temporally associated with medetomidine detection in the drug supply, with sustained prevalence linked to substantial emergency department and ICU utilization. From September 2024–January 2025, 165 patients across three Philadelphia health systems were hospitalized for fentanyl withdrawal complicated by severe autonomic dysfunction. Similar presentations were reported in Pittsburgh (October 2024–March 2025), where many patients required dexmedetomidine infusions and ICU-level care, and in Maryland (July 2025–August 2025), where medetomidine-related overdoses were frequently accompanied by withdrawal signs and symptoms.

CDC supports states and local communities in detecting, preventing, and responding to health threats through ongoing technical assistance and support through CDC’s Overdose Data to Action (OD2A) cooperative agreement and the Overdose Response Strategy (ORS)


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