What are nitazenes? What to know about the drug that can be 10 times as potent as fentanyl

https://www.cbsnews.com/news/nitazenes-fentanyl-substance-use-drug-supply-opioid-death-colorado/

A Colorado overdose death has been linked to a new formulation of nitazenes, a class of powerful opioid analgesics being increasingly seen in the illicit drug market. 

Nitazenes have been around for decades, experts told CBS News, and have been seen in multiple formulations. The person who died in Colorado had used a formulation called N-Desethyl etonitazene. The man died in mid-2023, officials said, but laboratory testing about the substance he overdosed on was not returned until recently.  

It’s believed to be the first time that formulation was found in an overdose death, according to the Boulder County Coroner’s office. 

The coroner told CBS News that while the area has seen a decrease in fentanyl overdoses, use of nitazenes has emerged — which “raises new concerns.” 

Here’s what to know about nitazenes. 

What are nitazenes? 

Nitazenes were first developed in the 1950s and early 1960s, said Claire Zagorski, a chemist, paramedic and translational scientist in Austin, Texas. At the time, they weren’t illicit drugs, but were intended to be sold commercially. That never happened, Zagorski said, and in recent years, those original formulations have been used as a backbone by illicit drug manufacturers to make new synthetic opioids amid a crackdown on substances like fentanyl. 

“When you have a backbone of one drug to start with, there is almost limitless ways to modify it,” Zagorski said. Modifications are made by adding substances to that backbone in a laboratory setting. 

The illicit use of nitazenes remains rare, according to Dr. Wilson M. Compton, the deputy director of the National Institute on Drug Abuse. However, testing for nitazenes is not conducted in every overdose death, Compton said, so “we don’t actually know the complete universe of how many deaths are due to these potentially very toxic compounds.” 

Compton said that according to reports by the Drug Enforcement Administration, nitazenes make up “much less than 1%” of the opioids that the agency seizes. However, Zagorski said she expects to see those numbers rise. 

“I wouldn’t be surprised if we see more and more nitazenes because they’re still under the radar to a lot of America and it takes time to implement advisories for law enforcement to all get on the same page of what they need to look for,” she said. 

There are multiple forms of the drug circulating, including the N-Desethyl etonitazene version seen in Colorado. Other common formulations include isotonitazenes, metonitazenes, etonitazenes and protonitzenes, according to the Alcohol and Drug Foundation.

“It really is like Whack-a-Mole. Like they just keep coming and coming and coming,” Zagorski said, because of the way the drugs are developed. Now that stopping fentanyl is a national priority, she expects to see more nitazenes being developed by illicit manufacturers and used as authorities to catch up.

“We’re seeing all of these odd chemicals kind of popping up. It’s kind of a divide and conquer strategy, and it’s hard to keep it keep track of things like that,” she said.

Are nitazenes more dangerous than fentanyl? 

Both Zagorski and Compton described nitazenes as “very potent,” but how much risk they pose varies based on the different formulations. N-Desethyl etonitazene and another formulation, etonitazene, are “about 10 times as potent as fentanyl,” Zagorski said. Fentanyl is about 50 times more potent that heroin, according to the DEA. 

“This is really going to hit with a wallop,” Zagorksi said. 

Compton said that some versions of nitazenes can be even more dangerous than carfentanil, which is a fentanyl compound that is about 100 times more potent than fentanyl itself. 

“They’re even more potent than something that we’re already quite concerned about,” said Compton. 

Nitazenes can also be mixed into other drugs that are sold illicitly, meaning people may not know that they’re consuming something so dangerous, Compton said.

“Nitazenes being mixed with other illicit drugs emphasizes the increased risk of harm or death. Illicit drug suppliers often mix drugs to increase potency or lower costs,” the Boulder County coroner’s office said. It’s not clear if the man who died in Colorado knew he was ingesting N-Desethyl etonitazene.

There also hasn’t been much research into how nitazenes interact with other substances, so there may be unexpected side effects from mixing it with other drugs or alcohol, Compton said. 

Does naloxone work on nitazenes? 

Naloxone, a medication that reverses opioid overdoses and is more commonly known by the brand name Narcan, can reverse an overdose that involves nitazenes, experts said. 

Naloxone is an opioid antagonist that binds to the same receptors in the brain that are affected by nitazenes, Zagorski said. 

Compton said that anyone who experiences a nitazene overdose and is revived with naloxone should seek medical treatment because some nitazines may be long-acting.

“There’s a concern that as the naloxone wears off, they may fall back into a coma and have respiratory depression,” Compton said. 

Naloxone also works on powerful synthetic opioids like fentanyl and carfentanil, and is available over-the-counter. 

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