Nitazenes are designer opioids, producing all the effects of drugs like heroin and fentanyl but at a much greater, and often unpredictable, strength. Never authorized or widely manufactured for legitimate use, they’ve nonetheless cropped up in illicit drug supplies, where they’re responsible for growing numbers of overdoses.
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What are nitazenes?
Nitazenes are another name for benzimidazole opioids, a class of synthetic opioids distinguished by their unusual structure.[1] Like other opioids, they bind to opioid receptors in the body, relieving pain, causing sedation, and producing euphoria and a sense of well-being.
Never approved or marketed for legitimate medical use, nitazenes are designer drugs, analogs of more restricted substances (opioids, in this case), synthesized in clandestine laboratories and circulated in drug markets. Designer drugs may also be called new psychoactive substances.
Nitazenes have earned the nickname “Frankenstein opioids.” And like Dr. Frankenstein’s monster, they’re frighteningly strong, outpacing other synthetic opioids. Laboratory testing has revealed that some types—specifically isotonitazene, protonitazene, and etonitazene—have a potency of up to ten times greater than fentanyl and several hundred times greater than morphine.[2][3] This means overdoses of nitazenes—which have occurred increasingly in North America and Europe since 2019—can be extremely deadly and difficult to reverse.
What are examples of nitazenes?
Starting in 2019, the nitazene isotonitazene has been detected in samples of illicit drugs and identified in toxicology screenings following overdoses in the United States, Canada, and Europe.[3][4] Isotonitazene is estimated to be twice to five times as strong as fentanyl.[5] It may be known by the street names "iso" or "toni."[6]
In 2021, most nitazene-involved deaths in the United States were attributed to the analog metonitazene.[3] Metonitazene is an estimated 30 to 200 times as potent as morphine.[7] It’s sometimes encountered in combination with butonitazene, a lower-potency nitazene that's nonetheless five times as strong as morphine.[8]
Over the last few years, other nitazenes have been identified in toxicology samples or drug materials, some of which have never been patented.[8] Others have been discussed in online drug forums and sold online as designer drugs.[9] These include:
- flunitazene
- etodesnitazene/etazene
- N-pyrrolidino etonitazene
- protonitazene
Prior to 2019, the best-known nitazene was etonitazene, which has sporadically been encountered on illicit drug markets, in Italy, German, Russia, and the United States, since the 1960s.[4]
What are nitazenes used for?
Nitazenes were initially synthesized by a Swiss pharmaceutical company in the 1950s as potential painkillers but were never approved for human use.[1][4]
However, their opioid-like effects and high potency make them attractive to illicit drug manufacturers and dealers, who are looking for less expensive and less tightly regulated controlled substances to fortify their products. Nitazenes can be synthesized relatively easily in underground laboratories, using ingredients that are legal and readily available.[10]
Nitazenes are usually encountered in combination with other substances: most commonly fentanyl but also methamphetamine, amphetamine, and flualprazolam (a benzodiazepine that was never marketed and has turned up as a designer drug.)[3] Many users may be unaware that the drug they’re using has been cut with or adulterated with nitazenes.
Nitazenes may also be sold masquerading as another substance. Australia recently identified protonitazene being sold as the popular party drug ketamine.[11]
People who knowingly take nitazenes are usually heavily dependent on strong opioids such as fentanyl and are looking for a stronger high.
Are nitazenes legal?
Many nitazenes are illegal but have only recently been made illegal. Following the surge in overdoses involving isotonitazene, the United States temporarily made isotonitazene a Schedule I controlled substance in August 2020 and made this designation permanent in December 2021.[12]
In December 2022, the U.S. temporarily made seven other synthetic benzimidazole-opioid substances Schedule I under the Controlled Substances Act, with the option to make the scheduling permanent. These include:[13]
- butonitazene
- metonitazene
- etodesnitazene/etazene
- flunitazene
- metodesnitazene
- pyrrolidino etonitazene/etonitazepyne
- protonitazene
Schedule I substances have no accepted medical use and are highly likely to be abused. They're illegal to manufacture, distribute, buy, or possess.
How strong as nitazenes?
Nitazenes can be tens or hundreds of times as strong as morphine and even stronger than fentanyl, the synthetic opioid that’s 100 times as strong as morphine and has been implicated in the surge of overdoses in the U.S. over the last few years.
However, their exact strength in humans isn’t always known as they either haven’t been tested or experiments were abandoned. For example, early studies of metonitazene in humans were halted after patients developed adverse effects including respiratory depression and failure and coma in response to doses of just 1mg.[14] We’re therefore limited to estimating these drugs' potencies using animal studies and other assessments.
These estimated potencies vary widely between different nitazene analogs.[14]
- flunitazene: approximately equal to morphine
- metodesnitazene: approximately equal to morphine
- butonitazene: 5 times as strong as morphine
- etodesnitazene: 70 times as strong as morphine, slightly less potent than fentanyl
- metonitazene: 100 times as strong as morphine, similar to fentanyl
- protonitazene: 200 times as strong as morphine, twice as strong as fentanyl
- isotonitazene: 500 times as strong as morphine, five times as strong as fentanyl
- etonitazene: 1,000 times as strong as morphine, ten times as strong as fentanyl
What are the risks of nitazenes?
Because nitazenes are so potent, they can easily cause overdoses, even in people who are opioid-tolerant and regularly use fentanyl. This is especially true because the potency of nitazene varies so greatly between analogs and often has never been tested in humans. Additionally, many people exposed to nitazene are unaware they’re using it much less which type of nitazene they’re using. The DEA warns that “the identity, purity, and quantity [of nitazenes] are uncertain and inconsistent, thus posing significant adverse health risks for the user.”[1]
The largest health risk is opioid overdose, which can cause respiratory depression, extreme sedation, and death. Overdoses with nitazene can be very difficult to reverse, often requiring multiple doses of the opioid antagonist naloxone (Narcan).
Although nitazenes may seem obscure, they are increasingly surfacing in illicit drug supplies, with fatal consequences. Health officials in Tennessee recently published data revealing a dramatic rise in nitazene-related deaths in the state in just a couple of years: from zero in 2019 to ten in 2020 and 42 in 2021.[3] The growing presence of nitazenes has prompted health and law enforcement officials across the U.S. to issue warnings about them.
Scientists warn that “non-fentanyl-derived ultrapotent synthetic opioids” such as nitazenes will be encountered more frequently in the illicit drug supply over the next few years and will contribute to the ongoing overdose crisis.[10]
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