How does ‘tranq’ change the effects of fentanyl?
How does ‘tranq’ change the effects of fentanyl?
March 31, 2025
Daniel Manvich and Diana Martinez (below) research the effects of fentanyl-xylazine mixtures.
Every year, millions of Americans misuse opioids and tens of thousands lose their lives to overdoses involving these drugs. Increasingly, authorities are finding one of the most potent of these substances, fentanyl, adulterated with a second drug, xylazine. However, no one fully understands how the two drugs interact.
“The fear is that the combination of these drugs may be more dangerous than either one alone,” says Daniel Manvich, an assistant professor in the Department of Neuroscience at the Rowan-Virtua School of Osteopathic Medicine.
He and his collaborator Diana Martinez, assistant professor in the Department of Biomedical Sciences at Cooper Medical School of Rowan University (CMSRU), have received funding from the National Institutes of Health to 
better understand the effects of using both drugs and how best to reverse them. The latter experiments could lay the foundation for therapies that more effectively prevent overdoses from becoming deadly.
better understand the effects of using both drugs and how best to reverse them. The latter experiments could lay the foundation for therapies that more effectively prevent overdoses from becoming deadly. Over the past decade, the synthetic opioid fentanyl and its closely related compounds have driven opioid-related overdose deaths. More recently, authorities began to document the presence of xylazine, also called “tranq,” alongside fentanyl. Both drugs have legal uses: Fentanyl is a painkiller approved by the Federal Drug Administration (FDA), while xylazine is a sedative, painkiller and muscle relaxant for animals. The FDA does not allow xylazine’s use in humans.
The two drugs activate different molecular pathways in the nervous system but produce somewhat similar effects, including sleepiness, reduced heart rate and breathing. Opioids cause death by stopping breathing altogether, and some reports suggest xylazine may enhance this fatal effect.
The idea for this project came from a meeting that Manvich, a neuroscientist who studies addiction, called in his lab, which is located on the Stratford, N.J., campus, to discuss the emergence of xylazine. During the brainstorming session, a student suggested studying how the addition of this drug affected breathing and blood flow. Manvich immediately thought of Martinez, a neuroscientist on the CMSRU campus in Camden, whose research focuses on these processes and the sleep-wake cycle.
Martinez is now applying her tools and techniques to study fentanyl and xylazine alone and together. Working with translational models, she examines how these drugs alter heart rate and blood pressure, as well as aspects of breathing, such as speed and depth.
“I’m looking forward to starting to pick apart some of the mechanisms behind this development in the opioid epidemic,” Martinez said.
Manvich’s lab, meanwhile, is addressing the appeal of adding xylazine in the first place. His experiments will test whether the combination changes the perceived effects of fentanyl, for example, by making the fentanyl feel stronger or longer lasting.
Manvich and Martinez also plan to test new approaches for decreasing the effects of fentanyl-xylazine mixtures. In their experiments, they will combine naloxone, the emergency medication now used to reverse opioid overdoses, with atipamezole, a drug used by veterinarians to reverse the sedative effects of xylazine and similar anesthetics. Some evidence suggests naloxone is less effective for overdoses involving xylazine, and the researchers suspect that adding atipamezole will improve its performance when both drugs are involved.
Researchers haven’t yet established how best to treat addiction to fentanyl-xylazine mixtures or the dangerous withdrawal symptoms that emerge among people who stop taking them. These experiments could support the development of new therapies specifically targeting the combination of these drugs.