Nitazenes: Deadly New Opioids Up to 20 Times the Strength of Fentanyl Emerge in U.S. Illicit Drug Supply

Nitazenes, a little-known class of synthetic opioids, have begun appearing in the U.S. illicit drug supply, with some variants up to 20 times more potent than fentanyl, doctors say. Developed in the 1950s to relieve pain, nitazenes were never approved for clinical use because of overdose risk. In recent years, illegal production has surged, and the drugs are pressed into counterfeit pills, liquids or powders and sold through social media and street markets.

Counterfeit products often carry nitazenes unknowingly; buyers may believe they are taking legitimate drugs such as Xanax or oxycodone. The substances can be manufactured in labs in China and India and then trafficked to the United States, Europe and elsewhere, where they are mixed with heroin, fentanyl or methamphetamine. Because standard toxicology screens do not detect the many nitazene analogs, clinicians may miss a diagnosis or misinterpret an overdose, complicating treatment.

Since 2019, nitazene-related materials have appeared in at least 4,300 law-enforcement drug seizures, but officials say the true scale is likely higher because many tests miss the compounds. Analogs vary in potency: butonitazene and etodesnitazene are 25% to 50% as strong as fentanyl, while isotonitazene is five to 10 times stronger. The most potent forms, N-pyrrolidino protonitazene and N-pyrrolidino etonitazene, can be up to 25 times and up to 43 times stronger than fentanyl, respectively. Public health officials say nitazenes often appear as adulterants in pills sold as other opioids, increasing the risk that users won’t know what they are taking.

In Tennessee, state data show 92 nitazene-involved fatal overdoses among residents from 2019 through 2023, according to the Tennessee State Unintentional Drug Overdose Reporting System. Naloxone was administered in only about one in three of those deaths, and all involved other substances, most commonly fentanyl and methamphetamine. In Pennsylvania, nitazenes have contributed to 45 deaths since 2023. From May 2024 to 2025, Houston, Texas, DEA agents reported 15 nitazene overdose deaths in people aged 17 to 59, and 11 seizures of nitazene from November 2024 to February 2025. In May, Andrew Renna, Assistant Port Director for Cargo Operations at JFK Airport in New York City, revealed the agency seized almost a pound of nitazene that was going to a private residence in South Carolina. Renna said nitazenes are seen at JFK at least several times a week in quantities ranging from a few grams to more than a pound.

Dr Shravani Durbhakula, study co-author and associate professor of anesthesiology at Vanderbilt University Medical Center, said: 'For patients, especially those with opioid use disorder or those exposed to illicit substances, nitazenes pose a serious and often hidden threat. Because these drugs may not show up on routine toxicology screens, clinicians could miss a critical piece of the diagnosis during overdose treatment. Patients may also need higher or repeated doses of naloxone to reverse their effects.'

Dr Ryan Mortman, corresponding study author and resident at the University of Pittsburgh Medical Center, added: 'Nitazenes are an emerging class of synthetic opioids that are even more potent than fentanyl and often undetected by routine drug tests. Their rapid spread in the illicit drug market, combined with the difficulty of reversing overdoses, underscores the urgent need for public awareness, early recognition, and expanded access to harm-reduction tools such as naloxone.'

The researchers note that the drug’s raw chemicals are believed to originate in China and India, where chemical companies can produce the compounds at scale in a few steps before traffickers move them to the United States, Europe and beyond. They say the United States has the widest range of nitazene analogs and the most fatalities. 'We also want to stress that this is not just a drug issue; it is a public health emergency,' Durbhakula said, calling for collaboration among clinicians, public health officials, law enforcement and community organizations to implement harm-reduction strategies, support addiction treatment, and raise awareness about evolving threats.

Nitazene overdose can cause severe respiratory depression, slowed breathing, and other life-threatening symptoms. One to two doses of Narcan nasal spray can usually reverse an overdose when given early, but clinicians fear some patients may require additional doses due to the drugs’ potency. Mortman and Durbhakula say the next steps include analyzing clinical data to assess nitazene-specific risks and how these drugs respond to naloxone, while health systems prepare for a potentially ongoing wave of overdoses as the crisis continues to evolve.