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. 2025 Aug 1.
doi: 10.1097/ADM.0000000000001560. Online ahead of print.

Severe Fentanyl Withdrawal Associated With Medetomidine Adulteration: A Multicenter Study From Philadelphia, PA

Kory S London, Samantha Huo, Lauren Murphy, TaReva Warrick-Stone, Dennis Goodstein, Maeve Montesi, Meg Carter, Sabrina Butt, Karen Alexander, Wayne Satz, Abriana Tasillo, Lin Xu, Maya Arora, Emily Casey, Rita McKeever, Margaret Lowenstein, Philip Durney, Brendan Hart, Jeanmarie Perrone

Severe Fentanyl Withdrawal Associated With Medetomidine Adulteration: A Multicenter Study From Philadelphia, PA

Kory S London et al. J Addict Med. .

Abstract

Objectives: Medetomidine, a potent veterinary α2-adrenergic agonist, has emerged as an adulterant in the illicit fentanyl supply in Philadelphia, PA. Accompanying this change, a severe withdrawal syndrome, distinct from opioid and more comparable to dexmedetomidine withdrawal, emerged. We describe it.

Methods: A multicenter case series is described across 3 hospital systems in Philadelphia between September 2024 and April 2025. The cohort included patients who reported opioids as the primary drug of choice, who presented with opioid withdrawal complicated by severe sympathetic activation and required hospitalization. Data extraction from the electronic health record included demographics, clinical outcomes, and confirmatory toxicology in a subset.

Results: Two hundred nine patients met the inclusion criteria; the median age was 38 years and 29% were female. Intensive care unit (ICU) admission occurred in 77.5%, with 20.1% requiring intubation. Symptoms were often refractory to traditional opioid withdrawal management, and 73.7% received dexmedetomidine infusion. In the cohort subset with toxicology testing (n=43), 100% had fentanyl and medetomidine metabolites, while xylazine metabolites were not always present (24, 55.8%). Severe complications included encephalopathy (35.4%), myocardial injury (28.7%), and rarely seizures (5%). Patients suffered from severe withdrawal, with a median maximum recorded Clinical Opiate Withdrawal Score (COWS) score of 23.

Conclusions: This study describes individuals experiencing severe withdrawal, temporally associated with medetomidine-adulterated fentanyl exposure. Clinicians should be alert to the limitations of standard withdrawal protocols for fentanyl or opioids and the need for aggressive α2-agonist therapies, such as dexmedetomidine. As medetomidine continues to spread in the illicit drug supply, adapting clinical and public health responses will be critical.

Keywords: alpha-2 agonists; fentanyl; medetomidine; opioid withdrawal; xylazine.

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Conflict of interest statement

The authors report no conflicts of interest.

References

    1. Schwarz ES, Buchanan J, Aldy K, et al. Detection of medetomidine among patients evaluated in emergency departments for suspected opioid overdoses—Missouri, Colorado, and Pennsylvania, September 2020–December 2023. MMWR Morb Mortal Wkly Rep. 2024;73(30):672–674.
    1. Nayani Z, Reese T, Armstrong A, et al. Medetomidine-associated opioid overdoses in Chicago, Illinois: a report of 3 cases. J Addict Med. 2025. doi:10.1097/ADM.0000000000001500. - DOI
    1. Palamar JJ, Krotulski AJ. Medetomidine infiltrates the US illicit opioid market. JAMA. 2024;332(17):1425–1426.
    1. Murphy L, Krotulski A, Hart B, et al. Clinical characteristics of patients exposed to medetomidine in the illicit opioid drug supply in Philadelphia—a case series. Clin Toxicol. 2025;63:438–441.
    1. Sood N. Rise of illicit medetomidine use: a worrisome trend. Am J Addict. 2025;34(2):123–124.

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