UK will study the effects of newly prevalent drug xylazine (‘tranq’)

By Elizabeth Chapin
University of Kentucky

Two University of Kentucky researchers have received a $2.65 million federal grant to study how the brain is changed by the mixture of fentanyl and xylazine, a veterinary anesthetic commonly referred to as “tranq.” It is increasingly being used to enhance the effects of fentanyl, a potent opioid that can be deadly even in small amounts.

Cassandra Gipson-Reichardt and Terry Hinds Jr. associate professors in the College of Medicine’s Department of Pharmacology and Nutritional Sciences, received the five-year grant from the National Institute on Drug Abuse to see how the drugs change the brain’s signaling pathways.

These are the only preclinical studies now funded by NIDA to address an epidemic of xylazine-fentanyl use, and will be the first to determine neurobiological and behavioral impacts of the drug combination and identify treatment targets to reverse xylazine’s effects on fentanyl.

The combination of xylazine and fentanyl caused a 1,127% increase in xylazine-positive overdose deaths in the South in 2020-21, and other problematic health effects, including tissue death from poor circulation.

Xylazine is posing other new challenges to the fight against opioids, since it decreases the usefulness of naloxone (branded as Narcan), the drug that reverses the effects of an opioid overdose.

Gipson-Reichardt and Hinds will study the brain circuits that are changed when xylazine and fentanyl are used together and see if these changes are responsible for making naloxone less effective. They have already identified unexpected pathways controlled by the combination that may reduce the actions of naloxone. In their work, they will determine if targeting these pathways could be therapeutic.

“By studying these processes in detail, we hope to better understand the ways xylazine and fentanyl interact in the brain and how they affect behavior,” said Gipson-Reichardt. “This knowledge could lead us to new strategies for treating people who are struggling with the combined use of these substances and help make naloxone more effective in saving lives.”

Gipson-Reichardt and Hinds will collaborate with Kelly Dunn of Johns Hopkins University in Baltimore to translate findings to inform the public on individual factors that may lead to worse clinical outcomes during withdrawal from the xylazine-fentanyl combination.
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