A team of Marshall University researchers has identified a potentially life-saving treatment strategy for overdoses involving the dangerous combination of fentanyl and xylazine. Their findings could provide emergency responders with a crucial new tool against a growing crisis that has challenged traditional overdose treatments.
The study, published May 8 in the Journal of Translational Research, demonstrates that adding a drug called atipamezole to standard naloxone treatment dramatically improves recovery in animal models of fentanyl-xylazine overdose — a combination increasingly found in America’s illicit drug supply.
This research comes at a critical moment when xylazine — a veterinary tranquilizer never approved for human use — has become a widespread contaminant in street drugs. Between 2018 and 2021, fatal overdoses involving xylazine increased 35-fold, with 99% of those deaths also involving fentanyl.
Why Traditional Overdose Reversal Falls Short
What makes xylazine particularly dangerous? Unlike fentanyl, it doesn’t respond to naloxone (commonly known as Narcan), the standard medication for opioid overdose reversal.
When someone overdoses on fentanyl contaminated with xylazine, naloxone alone often cannot fully reverse the profound sedation and other dangerous effects. This leaves patients partially unconscious with dangerously slowed breathing, heart rate, and lowered body temperature — even after receiving multiple doses of naloxone.
Could a combination approach offer better results? The Marshall research suggests so.
How the New Treatment Works
“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 Michael Hambuchen, lead author of the study and associate professor at the Marshall University School of Pharmacy.
The research team found that this drug combination doesn’t just wake patients up — it addresses multiple dangerous aspects of xylazine poisoning:
- Rapidly restores consciousness from profound sedation
- Improves dangerously slow heart rate
- Corrects blood glucose levels
- Helps normalize body temperature
These improvements tackle the complex “toxidrome” — or constellation of symptoms — that makes xylazine-fentanyl overdoses so difficult to treat with current methods.
From Lab to Street: Real-World Applications
The researchers designed their experiments to mirror actual overdose scenarios that emergency responders encounter daily across America. Xylazine’s presence in the drug supply has grown exponentially in recent years, with the DEA reporting that 30% of fentanyl powder seized in 2023 contained xylazine.
Unlike academic research that often uses simplified models, this study deliberately replicated the messy reality of street drug contamination and polysubstance use.
“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,” said Todd Davies, associate director of research and development in the Division of Addiction Sciences at Marshall University.
The Growing Xylazine Crisis
Xylazine’s rapid emergence as a drug contaminant has alarmed public health officials nationwide. Originally used solely as a large animal sedative by veterinarians, xylazine began appearing in street drugs primarily as a way to extend the euphoric effects of opioids.
But this addition comes at a devastating cost. Beyond the immediate overdose risk, chronic xylazine exposure causes severe skin ulcers that can become infected and even lead to amputation.
The economics driving this contamination are troubling. Researchers note that xylazine, once sourced domestically from veterinary suppliers, is now being imported from online Chinese suppliers at approximately $6-20 per kilogram — making it an incredibly cheap way for dealers to cut and extend their product.
Looking Forward: Questions That Remain
While promising, the study raises important questions about implementation. Atipamezole is currently only approved for veterinary use in the United States, though it has been tested safely in humans for other purposes.
The research did reveal potential side effects that would need careful monitoring in human applications. At higher doses, atipamezole could potentially intensify stimulant effects in people who have also used methamphetamine — a common scenario given the prevalence of polysubstance use.
Additionally, the researchers noted that while the combination effectively treated immediate overdose symptoms, it did not prevent skin lesions associated with xylazine exposure.
The study was supported by the Marshall University School of Pharmacy Faculty Research Support Program and the John Marshall University Scholars Award Program, highlighting the university’s commitment to addressing the overdose crisis that has particularly impacted West Virginia and surrounding Appalachian communities.
As this research advances toward potential human trials, it represents an important step forward in addressing one of the most challenging aspects of the evolving overdose crisis. For emergency responders and addiction medicine specialists on the frontlines, effective treatments for xylazine-contaminated overdoses can’t come soon enough.
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