Nitazenes: synthetic opioids more potent than fentanyl

The emergence and impact of Nitazenes in the illicit drug market

Nitazenes, a class of synthetic opioids, were originally developed in the 1950s with the intention of being used as pain relievers. However, they never received approval for marketing for various reasons, including their extremely high potency and potential for abuse. Despite their initial development decades ago, nitazenes largely remained obscure outside of academic research until recently, when they began to appear in the illicit drug supply. Their resurgence is alarming due to their potency, which is significantly higher than many opioids, including morphine, and even fentanyl, making them a public health concern.

Chemical and pharmacological properties of Nitazenes

Chemically, nitazenes are characterized by their benzimidazole structure, which sets them apart from the phenanthrene structure of morphine and the piperidine structure of fentanyl. This unique structure contributes to their high affinity for the µ-opioid receptor, resulting in potent analgesic and psychoactive effects. The most well-known compound of this class, isotonitazene, exemplifies the general properties of the group, including its high potency and selectivity for the µ-opioid receptor.

Pharmacologically, nitazenes act as µ-opioid receptor agonists, similar to other opioids but with significantly greater potency. This interaction induces deep analgesia, euphoria, and, at higher doses, respiratory depression, which can lead to fatal overdoses. The pharmacodynamics of nitazenes, including their receptor binding affinity and efficacy, contribute to their dangerous profile, especially when used without medical supervision.

Differences between Nitazenes and Fentanyl

Although both nitazenes and fentanyl are potent synthetic opioids, nitazenes are often much more potent than fentanyl, with some analogs being tens or hundreds of times more potent. This higher potency means that even small doses can cause severe respiratory depression and overdose. Additionally, the pharmacokinetic profiles of nitazenes, including their metabolism and elimination, are not as well known as those of fentanyl, adding an extra level of risk due to unpredictable effects and possible interactions with other substances.

Potential issues arising from Nitazene use in Europe and North America

The emergence of nitazenes in the illicit drug markets of Europe and North America has led to a series of public health issues. The main concern is the increase in overdose deaths attributed to their use, often in combination with other opioids like fentanyl. The clandestine nature of their manufacturing and distribution complicates efforts to monitor and control their spread. Moreover, the lack of awareness among users about the potency and risks associated with nitazenes contributes to accidental overdoses. The presence of nitazenes in street drug supplies also complicates overdose treatment strategies, as the usual opioid reversal agents, such as naloxone, may be less effective.

Public health strategies to address Nitazene-related issues

Mitigating the risks associated with nitazenes requires comprehensive public health strategies, including:

  • Increased Surveillance and Regulation: Monitoring the presence of nitazenes in the drug supply and implementing regulations to control their distribution.
  • Public Education Campaigns: Informing the public, especially drug users, about the risks of nitazenes and how to recognize and respond to overdoses.
  • Healthcare Professional Training: Educating medical professionals and first responders on identifying and treating nitazene overdoses, including the potential need for higher doses of naloxone.
  • Research and Development: Encouraging the study of nitazenes to better understand their pharmacology and develop more effective treatment and reversal strategies.
  • Support and Treatment Services: Expanding access to addiction treatment services and harm reduction programs to support individuals struggling with substance use disorders.


The reemergence of nitazenes in the illicit drug market poses significant public health challenges in Europe and North America. Their high potency and the lack of public and professional awareness about these substances amplify the risks of overdose and death. Addressing this issue requires a multifaceted approach that includes increased surveillance, public education, professional training, and expanded research, along with the enhancement of treatment and harm reduction services. Only through concerted effort can the dangers posed by nitazenes be mitigated, protecting communities from the devastating impact of these potent opioids.

Pergolizzi, J., Jr, Raffa, R., LeQuang, J. A. K., Breve, F., & Varrassi, G. (2023). Old drugs and new challenges: A narrative review of nitazenes. Cureus15(6).