Year: 2026
Type: preprint
Abstract: Background Medetomidine, a potent sedative, is increasingly present in fentanyl-related hospitalizations and deaths. Multiple states have passed legislation to control xylazine—a pharmacologically similar sedative in the illicit opioid supply. Medetomidine may function as a highly potent substitute for xylazine with significant overdose risk and withdrawal potential. Medetomidine has previously been described mostly in eastern U.S. fentanyl markets. Here, we characterize medetomidine-containing drug samples obtained in Southern California 2023–2026. Methods Anonymous participants in Southern California voluntarily provided drug products to a community-based drug checking program. All samples underwent direct-analysis-in-real-time mass spectrometry (DART-MS). A subset was quantified by liquid-chromatography tandem mass spectrometry (LC-MS/MS). A smaller subset underwent enantiomeric analysis. We calculated other compounds co-present with medetomidine, the prevalence of medetomidine in fentanyl over time, the concentration of medetomidine, and the enantiomer makeup of medetomidine. Results The quarterly prevalence of medetomidine co-present with fentanyl rose from ≈6 % in May 2025 (month of first detection) to ≈25 % by August 2026. The average medetomidine concentration was 0.4 % mass fraction. The most common co-detected substances with medetomidine were fentanyl and adulterants such as lidocaine and xylazine. All medetomidine samples that underwent enantiomeric analysis (n = 13) were identified as racemic. Conclusion Medetomidine represents a rapidly emerging adulterant in the Southern California fentanyl supply. All samples assessed for enantiomer status were racemic medetomidine, suggesting they were not diverted from human pharmaceutical or medical supplies. Given its high potency, a small amount (<1.5%) is likely still a physiologically significant quantity of the drug. Highlights - Medetomidine is an emerging adulterant in the Southern California fentanyl supply. - The share of fentanyl with medetomidine rose from 6% in May 2025 to 25% in Aug 2026. - Nearly all medetomidine samples were detected in the presence of fentanyl. - Medetomidine was found in two samples of DMT obtained via the dark web. - The mean concentration of medetomidine was 0.4 % mass fraction among 22 cases. - All tested medetomidine was racemic, not diverted dexmedetomidine.
Source: medRxiv
Language: English
Subfield: Toxicology
Domain: Life Sciences
Open Access status: green
Funders: James B. Pendleton Charitable Trust, National Institutes of Health, Centers for Disease Control and Prevention, National Institute on Drug Abuse, National Center for Injury Prevention and Control, National Center for Advancing Translational Sciences, Clinical and Translational Science Institute, University of California, Los Angeles, UCLA AIDS Institute, Center for AIDS Research, University of California Los Angeles
Awards: LIMITING OVERDOSE THROUGH COLLABORATIVE ACTIONS IN LA COUNTY - LOS ANGELES COUNTY (LAC) IS CURRENTLY EXPERIENCING THE HIGHEST RATE OF OVERDOSE DEATHS IN OUR HISTORY DRIVEN BY FENTANYL AND METHAMPHETAMINE. WE PROPOSE A DATA-DRIVEN RESPONSE FOCUSED ON IMPROVING LINKAGE TO AND RETENTION IN CARE, EXPANDING OF HARM REDUCTION SERVICES TO THE PRIORITY POPULATIONS DESCRIBED BELOW, AND IMPROVING CLINICIAN AND HEALTH SYSTEMS PRACTICES THAT ALIGN WITH CDC GUIDELINES ON PRESCRIBING CONTROLLED SUBSTANCES AND ASAM, SAMHSA, AND OTHER APPLICABLE PRACTICE GUIDELINES ON LOW-THRESHOLD INITIATION OF CLINICALLY EFFECTIVE TREATMENT FOR OUD (SUCH AS MOUD) AND INITIATION OF TREATMENT CLINICALLY EFFECTIVE FOR STIMULANT USE DISORDER (STUD) INCLUDING CONTINGENCY MANAGEMENT AND OFF-LABEL MEDICATIONS FOR STUD. THE PROPOSED HARM REDUCTION SERVICES AND LINKAGE TO CLINICAL INTERVENTIONS FOR OUD AND STUD PRIORITIZES: (1) PEOPLE WHO USE OPIOIDS AND/OR SIMULANTS AND WHO ARE CURRENTLY NOT RECEIVING SPECIALTY SUD TREATMENT, (2) PEOPLE RECENTLY RELEASED FROM INCARCERATION, (3) PEOPLE EXPERIENCING HOMELESSNESS, AND (4) ANYONE WHO HAS EXPERIENCED A NON-FATAL OVERDOSE. THESE ARE THE PRIORITY POPULATIONS REFERENCED ELSEWHERE WITHIN THIS PROPOSAL. PROPOSED ACTIVITIES WILL DEPLOY INTERVENTIONS IN COMMUNITY, PUBLIC SAFETY, AND HEALTHCARE SETTINGS. FOR THE PRIORITY POPULATIONS DESCRIBED ABOVE, LA COUNTY PROPOSES TO REDUCE THE NUMBER OF OVERDOSE DEATHS IN LA COUNTY IN COMMUNITY, PUBLIC SAFETY, AND HEALTHCARE SETTINGS THROUGH: (1) EXPANDING PROGRAMMING THAT INCREASES THE INITIATION OF LOW THRESHOLD MEDICATIONS FOR OPIOID USE DISORDER (MOUD) AND THE FORTHCOMING AMERICAN SOCIETY OF ADDICTION MEDICINE AND IMPROVES ENGAGEMENT AND LINKAGE OF PRIORITY POPULATIONS WITHIN LA COUNTY TO CONTINUITY SUD TREATMENT AND MEDICAL, MENTAL HEALTH, AND SOCIAL SERVICES; (2) EXPANDING THE AVAILABILITY OF HARM REDUCTION SERVICES TO PRIORITY POPULATIONS IN EACH SETTING; (3) IMPROVING CLINICIAN AND HEALTH SYSTEMS ADHERENCE TO CDC GUIDELINES ON SAFER PRESCRIBING OF CONTROLLED SUBSTANCES AND ADOPTION OF BEST PRACTICES THAT INCLUDE THE LOW-THRESHOLD INITIATION OF MOUD IN ACCORDANCE WITH ESTABLISHED NATIONAL GUIDELINES, AND MANAGEMENT OF STUD IN ACCORDANCE WITH THE (FORTHCOMING) AMERICAN SOCIETY OF ADDICTION MEDICINE NATIONAL PRACTICE GUIDELINE INTERVENTIONS FOR STIMULANT USE DISORDER (ASAM STUD NPG), SPECIFICALLY INCLUDING NALOXONE PRESCRIPTION AND DISTRIBUTION AND REFERRAL TO COMMUNITY HARM REDUCTION SERVICES; (4) LAUNCHING A HARM REDUCTION FOCUSED ANTI-STIGMA MEDIA CAMPAIGN INVOLVING THE COMMUNITY, HEALTH CARE SYSTEMS, FIRST RESPONDERS, AND PWUD THAT LIFTS THE VOICES OF PWUD, INCREASES THE ACCEPTABILITY OF HARM REDUCTION POLICIES, SERVICES, AND PRACTICES, AND THAT REDUCES THE STIGMA FACING PWUD; (5) ENHANCED LAC DPH-SAPC’S OVERDOSE SURVEILLANCE INFRASTRUCTURE TO PERFORM DATA ABSTRACTION TO INFORM TIMELY AND ACTIONABLE OVERDOSE RESPONSIVE INITIATIVES; (6) CONDUCTING TOXICOLOGY TESTING OF DRUG PRODUCT AND/OR PARAPHERNALIA AT LA COUNTY CONTRACTED AND CERTIFIED HARM REDUCTION SYRINGE SERVICES PROGRAMS AS DESCRIBED IN COMPONENT B. APPLYING FOR SURVEILLANCE COMPONENT B FUNDING. NOT APPLYING FOR COMPONENT C FUNDING, G1447258349, Predicting fatal and non-fatal overdose in Los Angeles County with Rapid Overdose Surveillance Dashboard to target street-based addiction treatment and harm reduction services, J. NRSA Training Core
OpenAlex ID: W7223199337