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At the end of 2023, the health crisis caused by fentanyl use in the United States set alarm bells ringing. However, the situation may get even worse with the emergence of another family of synthetic opioids: nitazenes.

This drug is not completely new. In the 1970s chemist Alexander Shulgin warned about the potential abuse of a family of compounds known as benzimidazoles, and half a century later, his words have proven prophetic. Nitazenes – synthetic opioids with a benzimidazole core – have emerged as one of the most dangerous classes of new psychoactive substances, causing a growing number of poisonings and deaths.

While sources are reporting alarming figures – such as the UK government recording 400 nitazene-related deaths between June 2023 and January 2025 – the lack of a specific analytical method when they first appeared means that such figures are an estimate at best.

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Nitazenes have rapidly spread into recreational drug markets for a number of reasons – high potency (which makes them easier to transport), legal status and high economic value, as well as the fact that they are relatively simple to synthesise without controlled precursors.

From the lab to the streets

The history of nitazenes began in the 1950s and 1960s, when the pharmaceutical company Ciba-Geigy developed them as potential synthetic opioid analgesics. Nitazene molecules represented the first major deviation from the characteristic chemical structure of morphine, even before Paul Janssen synthesised fentanyl in 1960.

Although many nitazenes demonstrated analgesic potency superior to morphine in animals at the time, they were never marketed as medicines because of the narrow safety margin associated with such a potent medicine.

However, from 2019 – when controls were put in place against the production of fentanyl and its analogues in China and the United States – nitazene analogues burst onto the recreational drug market. Isotonitazene was the first to appear, quickly followed by others such as methonitazene, etodesnitazene and a range of other derivatives.

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An extremely strong drug

Pharmacological research has found that many nitazenes have an exceptionally powerful effect. Although they bind to and selectively activate the same recetors as fentanyl and morphine (the mu receptors), they do so with an efficacy that is 60 times greater than fentanyl. They also activate these receptors with considerably greater strength.

Some analogues are up to 10 times stronger than fentanyl, or 100 times more potent than morphine. This high potency can have dramatic implications for public health – even tiny amounts (nanograms per millilitre) can be lethal.

Arriving directly to Europe

Nitazenes are increasingly appearing on the streets. The latest official figures indicate that, as of 2024, they had been found in Asia, Europe, North America, Oceania and South America, with Europe being the most affected region to date. Unlike fentanyl, which reached Europe via Mexico and the United States, nitazenes are arriving directly from Asia through a wider variety of distribution channels. We can expect to see more nitazenes in Europe over the coming months and years.

As well as the various health effects caused by their consumption, nitazenes are particularly harmful when they are used to replace the active ingredient in a similar medicine or drug without the consumer’s knowledge.

This can be deadly. In January 2025, a 22 year old died after taking a fake Xanax (alprazolam). Three months later the same victim’s friend, aged 21, also died after consuming fake Percocet (oxycodone). In both cases, the pills contained a nitazene.

Overdose dangers

One major problem is that it is not easy to reverse an overdose of these opioids. Naloxone (also known as Narcan) is an opioid antagonist medication that reverses and blocks the effects of heroin, morphine and fentanyl. However, it is not as effective against nitazenes.

Recent studies suggest that some nitazenes dissociate very slowly from the Mu receptors, which could mean that much higher doses of naloxone are needed to reverse these overdoses.

The challenge of detecting nitazenes

Nitazenes present several challenges for forensic toxicology. These molecules do not show up in routine tests designed to detect morphine, heroin, or fentanyl.

Because they are very potent and used in very low concentrations, they can only be detected by highly sensitive analytical methods. Given that many derivatives with very similar structures are constantly emerging, identifying a specific molecule is also complicated. This means analytical methods needs to be continuously updated.

Legislation: a game of cat and mouse

As of March 2025, only ten nitazenes had been controlled worldwide, though several countries are now beginning to implement targeted legislation. China, the main producing country, added nitazene analogues to its list of controlled substances in July 2024. However, the control of specific substances often leads to the emergence of new, uncontrolled analogues.

Generic legislation is more effective because it allows a large number of closely related substances (chemical analogues) to be controlled at once, without the need for legislation to name each one individually. However, these measures run the risk of encouraging manufacturers to develop completely new and unknown kinds of chemicals that fall outside the scope of generic control measures.

A multidisciplinary approach

The nitazene crisis is a complex problem with no easy solutions. It offers a prime example of how pharmacological innovations of the past can morph into contemporary public health threats. The Taliban’s 2022 ban on opium cultivation in Afghanistan could further accelerate the shift towards synthetic opioids in Europe, making the situation with nitazenes even more critical.

There is no single way to address this situation. It needs a coordinated response, involving unprecedented levels of cooperation between chemists, pharmacologists, forensic toxicologists, public health professionals, legislators and affected communities.

Only time will tell whether society is capable of adapting quickly enough to tackle this emerging threat. If it cannot, nitazenes will follow the path of other synthetic opioids, causing serious problems before effective control and prevention measures are put in place.

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This article is republished from The Conversation, a nonprofit, independent news organization bringing you facts and trustworthy analysis to help you make sense of our complex world. It was written by: Elena Escubedo Rafa, Universitat de Barcelona

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Elena Escubedo Rafa no recibe salario, ni ejerce labores de consultoría, ni posee acciones, ni recibe financiación de ninguna compañía u organización que pueda obtener beneficio de este artículo, y ha declarado carecer de vínculos relevantes más allá del cargo académico citado.