“Two Young Men Die From Street Drug That’s 43 Times Stronger Than Fentanyl. It’s Taking Hold in the US.” —People
“Stronger Than Fentanyl: A Drug You’ve Never Heard of Is Killing Hundreds Every Year” —Wall Street Journal
“This Little-Known Synthetic Opioid Is Up to 43 Times More Deadly Than Fentanyl, Resistant to Narcan and Killing Young Americans” —New York Post
These headlines are about nitazenes, the colloquial name for a category of novel synthetic opioids derived from 2-benzylbenzimidazole. They can indeed be more potent than fentanyl. And they are becoming more prevalent in the United States drug supply; we know this because more people are dying with nitazenes in their system. However, none of this means that nitazenes are killing people.
“Nitazenes” doesn’t refer to one specific substance, but to a group of substances that are chemically similar. The potency of different individual nitazenes, AKA nitazene analogs, varies quite a lot—the same way it does with fentanyl analogs. However, nitazenes tend to show up in extremely small quantities, piggybacking on fentanyl or some other drug that was ingested in larger quantities. They very rarely show up on their own.
Reports of nitazene-involved deaths overwhelmingly involve fentanyl as well, and in cases without fentanyl there was still some other psychoactive substance with potential for fatal overdose, like benzodiazepines. Invariably the information is framed in a way that invites people to assume the nitazenes caused the deaths, or at least contributed to them, but that isn’t necessarily the case. Nitazenes typically appear in trace amounts in a mixture, and—despite the fact that some are very potent—there’s no clear evidence that nitazenes are fueling any increase in overdose.
But because as an overall group they are more potent than most other known opioids, the Drug Enforcement Administration has claimed their existence in and of itself increases overdose and problematic use. The DEA did not provide comment in response to Filter’s inquiry.
“Whenever a nitazene is found, it’s found together with fentanyl,” Dr. Miao Hua, medical director and interim deputy commissioner of behavioral health at the Chicago Department of Public Health, told Filter. “It’s not the sole ingredient. Or really the main ingredient.”
Nitazenes were first synthesized in the 1950s for medical use, but were never approved by the Food and Drug Administration. They existed in relative obscurity until early 2019, when they began gaining attention in dark web drug markets. Isotonitazene was the first analog detected in the US, and remains perhaps the most recognizable name out of the bunch. More recently, metonitazene and protonitazene have emerged as some of the more commonly detected analogs.
Media outlets frequently announce the presence of nitazenes as a harbinger of a “whole new wave” in the overdose crisis, as if they will push fentanyl out of the drug supply the way that fentanyl pushed out heroin.
“Theoretically that’s always a possibility,” Hua said. “Do I see signs of that happening anytime soon? Not really.”
As reports of “fentanyl-laced cannabis” inevitably turn out to be unfounded, nitazenes aren’t likely to show up in cannabis anytime soon either. Hua said that Chicago isn’t seeing nitazenes in its cocaine or methamphetamine supplies either—even though nitazene detection has largely been in the Midwest. But this makes sense, as the presence of fentanyl in non-opioid drug supplies is frequently overstated.
However, nitazenes do show up mixed with, or sold as, benzodiazepines; this was the case with one of the deaths in the New York Post story.
“The stronger the strain, the more resistant the nitazene is to the overdose antidote Narcan,” the Post claimed.
Regardless of the potency of a particular analog, nitazenes are not “resistant” to Narcan. It’s a myth that naloxone doesn’t work on higher-potency synthetic opioids, or that more than two doses of Narcan are routinely required. Naloxone—like other opioid antagonists such as nalmefene and naltrexone—doesn’t act on the opioids themselves; it acts on the receptors the opioids bind to, so it does its job pretty much the same way for any opioid regardless of that opioid’s potency. Including nitazenes.
Naloxone should always be used when someone shows signs of opioid overdose, and it won’t make the situation worse if it turns out no opioids were involved. Often when naloxone fails to reverse an opioid overdose it was administered too late, or the overdose was complicated by something naloxone does not work on—like benzodiazepines. Usually reports of “naloxone-resistant” drugs involve drugs that aren’t opioids, and for which naloxone was never applicable in the first place.
“Naloxone is still the best tool,” Hua said. “What we find where this actually gets confounded is because there are tranquilizers.”
In addition to benzodiazepines, people who rely on street fentanyl might find their supply unexpectedly includes xylazine or medetomidine. Naloxone will still work on the fentanyl, nitazenes or other opioids causing respiratory depression in an overdose. Perhaps largely due to law enforcement misinformation, it’s a common misconception that an opioid overdose isn’t reversed until the person dramatically “wakes up.” But when non-opioid downers are in the mix, they might remain heavily sedated even after if the naloxone worked and breathing has been restored, giving onlookers the mistaken impression that they still need more naloxone.
“We very rarely see a nitazene that’s on its own.”
Erin Tracy, a research chemist with the Injury Prevention Research Center at the University of North Carolina at Chapel Hill, analyzes drug samples submitted by harm reduction programs from all over the country, and has been doing so for several years now.
The UNC program has received a handful of samples that contained a nitazene and nothing else, but this is not the norm.
“While cocaine can be cut with other things, we see plenty of cocaine on its own. We very rarely see a nitazene that’s on its own,” Tracy told Filter. “It’s usually always in combination with fentanyl and fentanyl [analogs].”
Anecdotally, some street-level sellers are advertising nitazenes. But as with most unregulated drug sales, knowledge of the actual contents comes from word of mouth, not necessarily from drug-checking. Nitazenes test strips do exist, but they’re not much use to drug-user communities. They’re prone to false positives and false negatives; they detect some nitazene analogs but not others; and they’re not widely distributed by syringe service programs.
In samples submitted to the UNC program, often what someone had suspected of being nitazenes turned out to contain a wide range of other drugs instead.
“I generally give the benefit of the doubt that no one is trying to kill their customers,” Tracy said. “So I do think [nitazenes are] intentionally being added, but I don’t think that it’s intentionally being added to do harm.”
In her experience, when nitazenes are present it’s usually in trace amounts. And, despite reports of nitazene analogs sweeping the nation, it’s mainly isotonitazene and protonitazene showing up in certain regions.
“Other states that have not scheduled nitazene compounds may not be seeing them in forensic lab reports.”
As nitazenes gain prominence in the public consciousness, it may seem as if the discovery of emerging analogs is why more of them are being banned under the federal Controlled Substances Act or state-level equivalents. But often it’s the other way around: More are being detected because they’re being banned. Forensics labs don’t generally check for, or report, non-controlled substances.
Between 2020 and 2024, Ohio banned a total of 17 nitazene analogs, more than any other state. And then in addition to those 17 analogs scheduled individually, the state pharmacy board effectively enacted a class-wide ban, classifying “all compounds that meet the structural requirements of the 2-benzylbenzimidazole ‘nitazene’ opioids pharmacophores as Schedule I controlled substances” of the Ohio Administrative Code. The Ohio Narcotics Intelligence Center (ONIC) described the move as one of the “regulatory options” available to states attempting to keep up with emerging substances.”
“Other states that have not scheduled nitazene compounds may not be seeing them in forensic lab reports for this reason,” an ONIC representative told Filter. “[T]hey are sparsely reported before they are scheduled.”
ONIC said that nitazene analogs are being detected mixed with fentanyl, heroin, benzodiazepines, cocaine, methamphetamine and xylazine, and that they show up in pills and powder alike. It stated that nitazenes “are occasionally found by themselves,” but did not provide further detail.
“The reality is a lot of these dope samples that we are collecting … contain dozens of ingredients,” Hua said. “At this point, [it’s] hard to know what is the active compound? What is the cutting agent? What is the adulterant?”
Other recent additions to the drug supply that have begun to attract attention include medetomidine, a veterinary sedative similar to xylazine, and BTMPS, an industrial plastic preservative.
Like fentanyl analogs, nitazenes are used to stoke fear and justify harsher enforcement.
We always seem to be hearing of some powerful, frightening new drug that is unimaginably stronger than the previous one, and that has the potential to kill hundreds, thousands or tens of thousands unless certain actions are taken—actions that further the punitive policies that got us here in the first place.
Some new arrivals do stand out. Benzodiazepines have profoundly reshaped the drug supply in some communities. So has xylazine. So have synthetic cannabinoids. Fentanyl itself began gradually taking over the East Coast opioid supply around 2013, but didn’t fully push heroin out of the West Coast until the COVID-19 pandemic.
So far at least, nitazenes aren’t having that impact. Their trajectory is more like that of fentanyl analogs—used to stoke fear and justify harsher enforcement, but from a user-end perspective generally indistinguishable from fentanyl itself.
Like carfentanil, the highest-potency fentanyl analog identified to date, nitazenes are relatively minor players that get disproportionately featured in the media and other public messaging for the shock value of something “even worse than fentanyl.”
Journalists, politicians, police officers and the entrepreneurs hawking products and webinars are all motivated to portray nitazenes as the new big threat, emphasizing “parallels to the fentanyl crisis.”
Asked if nitazenes were poised to become the next fentanyl, the ONIC replied succinctly: “We cannot speculate on this.”
If heroin had never been made illegal, the market would not be veering toward highly potent, poorly understood chemicals there previously hadn’t been any demand for.
The United Nations Office on Drugs and Crime reports that each year since 2021, Europe has seen more unique new nitazenes than unique fentanyl analogs. While North America continues to see more fentanyl, the numbers of unique nitazene analogs are on par with those in Europe.
Nevertheless, while nitazenes are the subject of an unjustified media frenzy in the US, they do pose a more serious concern in the United Kingdom, which only recently began to experience the mass deaths that result from an opioid supply moving from heroin to higher-potency fentanyl.
Europe didn’t follow the same trajectory as the US in terms of the overdose crisis. For one thing, the US is the only country with a DEA. Newly restricted opioid prescribing and a reformulation of OxyContin pushed some people from pharmaceutical analgesics to heroin, and a crackdown on heroin ushered in its more potent replacement. Elsewhere in the world, continued access to quality heroin meant there was no need for fentanyl to take its place.
But as the Taliban’s crackdown on poppy cultivation has resulted in a drastic reduction in quality and availability of heroin in the UK, for example, nitazenes have begun to find a place in the supply there, too. The new kind of dope emerging as a result is far more potent than what people are acclimated to.
The appearance of nitazenes is easily and directly linked to the crackdown on fentanyl, not just in the US but globally. As the US federal government has targeted the international fentanyl supply chain, the nitazene narrative has helped fuel the vilification of all synthetic drugs, and given drug warriors another reason to blame China.
If heroin had never been made illegal, if pharmaceutical-grade diacetylmorphine were a regulated product like any other, the market would not be veering toward highly potent, poorly understood chemicals for which there hadn’t previously been any demand. And perhaps synthetic drugs would not be a scapegoat for any and all societal ills.
As the drug supply remains unregulated and therefore dangerously unpredictable, harm reduction for nitazenes means the same harm reduction people who use opioids have been practicing all along. Never use alone; start low go slow; check your drugs; always carry naloxone.
Top image via Franklin County Coroner’s Office. Inset image (cropped) via Department of Justice/Drug Enforcement Administration.
R Street Institute supported the production of this article through a restricted grant to The Influence Foundation, which operates Filter. Filter‘s Editorial Independence Policy applies.
