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

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 , Philadelphia , and Pittsburgh from mid-2023 to mid-2024. By late July 2024, medetomidine had been detected in drug samples and biological specimens from people who use illegal opioids in at least 18 states and the District of Columbia .

The geographic spread of medetomidine appears to be expanding; the number of reports submitted to the National Forensic Laboratory Information System (NFLIS) , which captures forensic laboratory findings from law enforcement drug seizures, increased by 950% from 247 in 2023 to 2,616 in 2024, followed by a further 215% increase to 8,233 in 2025. Medetomidine reports comprised <1% of all NFLIS drug reports across the United States in 2025. They were most concentrated in the Northeast (52%) and Midwest (31%), followed by the South (17%) and the West (<1%).

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 , found that 10 of 20 sentinel sites detected medetomidine in almost 35% of opioid positive samples during July 2025-December 2025 (Figure). These sites were most often located in Northeastern states (n=5 of 5 sites), followed by Midwestern states (n=4 of 6 sites), and Southern states (n=1 of 4 sites). All five sites in the Western states detected medetomidine in their opioid positive samples, but at low levels, ranging from 2% to 8%. Eight sites detected medetomidine in more than 50% of opioid-positive samples. Among drug product samples (e.g., powder or pills) with positive test results for medetomidine (n=995) from July 2025-December 2025, 98% had fentanyl co-detected, consistent with reports of medetomidine being mixed into products sold as fentanyl, as noted in local advisories.

Figure: Percentage of opioid-positive drug product and paraphernalia samples also positive for medetomidine across 20 sentinel sites^a: 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.

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.

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) . ONDCP develops the National Drug Control Strategy to coordinate government efforts to reduce the supply of and demand for illicit drugs, and tracks and communicates about evolving and emerging threats.