MU researchers identify promising treatment for fentanyl-xylazine overdoses
May 30—HUNTINGTON, W.Va. — Researchers at Marshall University have developed a promising treatment strategy to address overdoses involving fentanyl and the veterinary sedative xylazine, a combination increasingly linked to severe health complications and reduced effectiveness of standard overdose reversal agents.
In a new study published in The Journal of Translational Research, Michael Hambuchen, PharmD, PhD, associate professor at the Marshall University School of Pharmacy, and pharmacy graduate student Jyostna Yalakala, BVSc, MS, in collaboration with Marshall University Joan C. Edwards School of Medicine clinical researcher Todd Davies, Ph.D., associate director of research and development in the Division of Addiction Sciences, and addiction medicine fellowship team, report that combining naloxone with the investigational drug atipamezole dramatically improves recovery outcomes in animal models of fentanyl-xylazine overdose.
"Adding even a low dose of atipamezole—already tested safely in humans for other indications—to naloxone rapidly restored consciousness in rats exposed to fentanyl and xylazine," said Hambuchen, lead author of the study. "We also saw improvements in heart rate, blood glucose and body temperature, which are all severely disrupted by this dangerous drug combination."
Xylazine, a veterinary tranquilizer not approved for human use, is increasingly found as a contaminant in illicit fentanyl supplies. The combination results in profound sedation, impaired respiration, dangerously low heart rate, lowered body temperature and elevated blood glucose, and chronic use is associated with serious skin ulcers. Compounding the danger, xylazine is not an opioid and is therefore resistant to reversal by naloxone alone.
"The collaboration on this study between Addiction Sciences and the School of Pharmacy represents the kind of translational research that bridges laboratory science with real-world clinical needs," Davies said. "By replicating complex overdose scenarios in the lab, Marshall University is advancing potential treatment strategies with direct relevance to West Virginia and beyond."
The study was supported by the Marshall University School of Pharmacy Faculty Research Support Program and the John Marshall University Scholars Award Program. The article "Co-administration of atipamezole with naloxone restores consciousness and physiological parameters in a rat model of xylazine-fentanyl overdose," may be viewed in its entirety at https://doi.org/10.1080/29947448.2025.2493044
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