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Nitazenes are a group of powerful synthetic opioids that were created nearly 60 years ago as potential pain relief medications. However, they were never approved for therapeutic use in the United States. They are µ-opioid receptor agonists that produce psychoactive effects comparable to morphine, heroine, and oxycodone.

In the past few years, several nitazenes have been detected in the illicit recreational drug supply in North American and Europe. Some nitazenes (isotonitazene, protonitazene, and etonitazene) are 20 times more potent than fentanyl and have caused fatal overdoses. 

Nitazenes are available in powders, counterfeit tablets, or liquids and may be mixed with inert substances and/or combined with other drugs. They have most frequently been combined with fentanyl but may also be used with benzodiazepines, cocaine, heroin, methamphetamine, and tramadol.

The lethal doses for nitazenes in humans, particularly in combination with other drugs, are not known. Many factors influence overdose-related morbidity and mortality, including not only the drug, but also the amount taken, the route of administration, possible drug-drug interactions or drug-alcohol interactions, body weight, opioid tolerance, and underlying health status.

The emergence of nitazenes creates additional concern as people with substance use disorder seek more potent drugs to satisfy their addiction. Routine illicit drug tests do not detect nitrazenes. Physicians treating treating people with drug-induced respiratory depression may not be aware of the presence of nitazenes.

In theory, some nitazenes can be antagonized by the opioid receptor antagonists, such as naloxone and nalmefene, but it is not clear if the high potency and impurities of the nitazenes might limit their effectiveness.


Pergolizzi J et al. Old Drugs and New Challenges: A Narrative Review of Nitazenes. Cureus, 2023 Jun; 15(6): e40736. Published online 2023 Jun 21. doi: 10.7759/cureus.40736

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