What to Know About Nitazenes, a Class of Potent Synthetic Opioids

— This unapproved drug class is turning up in more overdose deaths across the country

MedicalToday
A photo of a DEA instructor holding a bag of counterfeit pills in their purple rubber gloved hands

A class of synthetic opioids known as the nitazenes that are as potent as fentanyl -- or stronger -- have been increasingly involved in deaths in the U.S. and globally, according to reports.

"These are exceptionally dangerous molecules," Andrew Kolodny, MD, an expert in opioid policy and addiction medicine at Brandeis University in Massachusetts, told . "These drugs are entering the black market and they're being sold to people who are opioid addicted, and these individuals are losing their lives."

Nitazenes were originally developed in the 1950s as an alternative to morphine, but were never approved by the FDA. Among the drugs in this class are isotonitazene, protonitazene, etonitazene -- which are far more potent than fentanyl -- and metonitazene, which is of similar potency to fentanyl.

Reports of nitazenes being involved in overdose deaths have been cropping up across the country. In 2022, researchers that nitazine-involved fatal drug overdoses in Tennessee rose from 0 in 2019 to 10 in 2020, jumping to 42 in 2021.

Two people in Colorado died from overdoses involving nitazenes late last year, reported, noting that the state has seen 13 overdose deaths involving this drug class since 2021.

And in the U.K., officials reported 54 deaths in a recent 6-month period where nitazenes were detected in post-mortem toxicology, according to a .

While nitazenes do respond to the opioid overdose reversal agent naloxone, multiple doses are usually needed, according to the MMWR report and a .

"Drugs like fentanyl and the nitazenes are increasing mortality in people with [opioid use disorder] because the supply that they're using is becoming more dangerous," Kolodny said, noting that nitazenes are frequently manufactured in Mexico or China and can be purchased online and shipped to the U.S.

While efforts have been made to curb access to these potent synthetic opioids, the problem "is that it's been a game of whack-a-mole," Kolodny said.

For instance, the United Nations Commission on Narcotic Drugs to its Schedule I classification in 2021. While it appeared to reduce that drug's availability, Kolodny said, other formulations such as began appearing on the market after that change.

Nonetheless, Kolodny said scheduling is one mechanism for controlling the flow of these drugs into the black market. If it were used more effectively, it might make more of a difference, he said.

"We are not scheduling drugs effectively," he said. "The process is reactive and slow."

Healthcare professionals should be aware of the rising tide of nitazene use in the U.S. and should help patients with opioid use disorder get the treatment they need, Kolodny said. But the power to make real change lies with policymakers and how they approach the ongoing opioid crisis, he said.

"It's really less about what mental health professionals should be doing and more about what Congress should be doing -- and the Biden administration -- in terms of improving our treatment system," he said, "so that there's much better access to the most effective treatments like buprenorphine."

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    Michael DePeau-Wilson is a reporter on ’s enterprise & investigative team. He covers psychiatry, long covid, and infectious diseases, among other relevant U.S. clinical news.