New Potential Treatment for Fentanyl and Xylazine Overdose Combines Naloxone with Investigational Drug

Recent research conducted by scientists at Marshall University has revealed promising advancements in the treatment of overdoses involving fentanyl combined with xylazine, a veterinary sedative increasingly found as a contaminant in illicit drug supplies. This dangerous drug pairing often leads to severe health complications, including profound sedation, respiratory issues, dangerously low heart rates, hypothermia, and elevated blood glucose levels. Standard overdose reversal agents like naloxone are ineffective against xylazine, making this combination particularly lethal.

In a groundbreaking study published in the Journal of Translational Research, researchers led by Dr. Michael Hambuchen and pharmacy student Jyostna Yalakala explored the potential of adding atipamezole—a drug already proven safe for human use in other contexts—alongside naloxone. Their experiments in animal models demonstrated that the combination of naloxone and atipamezole significantly enhances recovery outcomes from fentanyl-xylazine overdoses. Notably, even low doses of atipamezole helped restore consciousness and stabilized vital signs such as heart rate, blood glucose, and body temperature in rats subjected to these substances.

Xylazine, not approved for human use, is increasingly contaminating illicit fentanyl, leading to more complex overdose scenarios. Because xylazine is a non-opioid, it doesn’t respond to naloxone alone, which poses a substantial challenge for emergency treatments. The study underscores the importance of developing combination therapies to address these complex overdoses effectively.

This collaborative effort between Marshall University's Addiction Sciences and School of Pharmacy highlights the translational potential of laboratory research to tangible clinical interventions. The findings could pave the way for improved treatments, especially in regions like West Virginia, where drug contamination with substances like xylazine is a growing concern.

For further details, the full study is available through the DOI: 10.1080/29947448.2025.2493044. This research not only broadens the scope of overdose treatment options but also reinforces the need for innovative approaches to combat the evolving opioid crisis.