Enhanced Effects of Fentanyl-Xylazine Combinations and Limited Efficacy of Narcan in Adult Goats

Project Summary:

Opioids are highly useful clinically as a pain management tool but can be highly addictive and lethal. Tens of thousands of opioid-involved overdose (OiOD) deaths occur each year in the U.S. due primarily to fentanyl, and OiOD deaths in Wisconsin mirror the national data. In Wisconsin, more than 91.5% of all OiOD deaths included fentanyl, and these deaths occur in rural and urban counties alike. Narcan is highly effective in reversing fentanyl-induced breathing suppression. However, OiOD deaths involving fentanyl alone are rare, with increasing trends for polysubstance abuse including the illicit drug xylazine. The data suggest combined fentanyl-xylazine has a more severe effect on breathing, and Narcan is less effective making the combination more lethal. Thus, the project team will rigorously test in adult goats, which have a human-like ventilatory response to fentanyl, whether combinations of xylazine and fentanyl result in more severe compromise of breathing than fentanyl alone and if Narcan is less effective as a reversal agent, which may explain why this drug combination is highly lethal. Completing these studies will increase awareness and provide the foundation for additional testing of novel drugs that can overcome fentanyl-xylazine-induced ventilatory suppression and potentially save more lives to stem the opioid epidemic.