In a recent research discovery published in the journal Addiction Neuroscience, scientists at the University of North Carolina at Chapel Hill found that xylazine is a kappa opioid receptor agonist, meaning it activates kappa opioid receptors in the same way fentanyl activates opioid receptors. This result was surprising because previously xylazine was thought to only bind to the α2-adrenergic receptor, and this finding could hint as to why withdrawal from fentanyl in combination with xylazine is so severe.

This research, led by the lab of Zoe McElligott, PhD, associate professor of psychiatry and pharmacology at the UNC School of Medicine, provides important insights into the subtle cellular mechanisms underlying opioid use – especially in light of the added anesthetic xylazine to fentanyl – and naloxone, the leading treatment used to prevent death from fentanyl overdose. She is senior author of the Addiction Neuroscience paper.

“Many people thought xylazine operated exclusively through a different mechanism in the nervous system,” said McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies. “But because we show xylazine is an agonist at kappa opioid receptors in the brain and body, in addition to acting at other targets, we may have gleaned insight into why withdrawal from the combination of fentanyl and xylazine is so harsh.”

Read the full article, detailing this research here.