The Street Drug 20x More Powerful Than Fentanyl

Nitazenes, stronger than fentanyl, are fueling overdoses. Researchers urge better detection and harm reduction.

Nitazenes, a group of extremely powerful synthetic opioids, are quickly becoming a significant factor in the overdose epidemic, according to a Pain Medicine review published by researchers at Vanderbilt University Medical Center and the University of Pittsburgh Medical Center.

These drugs were first synthesized in the 1950s but were never approved for clinical use. They are estimated to be more than 20 times stronger than fentanyl and hundreds to thousands of times stronger than morphine.

Nitazenes can appear in several forms, including liquid, pills, and powder, and since 2019 they have increasingly been identified in products sold on the illicit drug market as well as through social media.

Difficult to detect and highly dangerous

Although initially designed as potential painkillers, nitazenes were never tested in clinical trials or cleared for medical use in humans. Classified as illegal Schedule I substances, they are often mixed into counterfeit pills or other street drugs. Compounding the danger, they are not reliably detected by standard drug screening methods.

“For patients, especially those with opioid use disorder or those exposed to illicit substances, nitazenes pose a serious and often hidden threat,” said co-author Shravani Durbhakula, MD, associate professor of Anesthesiology, Division of Pain Medicine at Vanderbilt University Medical Center.

“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,” she said.

Rising deaths and overdose reports

Between 2019 and 2023, the Tennessee State Unintentional Drug Overdose Reporting System (TN SUDORS) documented 92 fatal overdoses in the state that involved nitazenes.

Data showed that naloxone was given in only about one-third of these cases. In every instance where nitazenes were present, they were combined with other drugs, most often fentanyl and methamphetamine.

“Many people consuming nitazenes don’t even know they’re taking them,” Durbhakula said. “These substances are often adulterants in pills sold as other opioids, making public education more important than ever.

“We also want to stress that this is not just a drug issue; it is a public health emergency. Addressing it will require collaboration between clinicians, public health officials, law enforcement, and community organizations to implement harm-reduction strategies, support addiction treatment, and raise awareness about these evolving threats,” she added.

Expanding awareness and next steps

The authors recommend expanding access to new test strips that can detect nitazenes and for at-risk patients to have access to take-home naloxone, addiction treatment, and education about counterfeit pills.

“Nitazenes are an emerging class of synthetic opioids that are even more potent than fentanyl and often undetected by routine drug tests,” said corresponding author Ryan Mortman, MD, a resident in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh Medical Center.

“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,” he said.

Co-author Trent Emerick, MD, associate professor of Anesthesiology and Perioperative Medicine and Bioengineering at the University of Pittsburgh’s School of Medicine, said the next steps are to generate human clinical data to better understand nitazenes’ effects, especially long-term health impacts, metabolism, and response to treatments like naloxone.

“The opioid crisis continues to evolve, and a thorough understanding of the mechanisms and risks of nitazenes is crucial for pain physicians, anesthesiologists, and other providers,” Emerick said.

Reference: “Nitazenes: Are Pain Physicians Aware of the Risks?” by Ryan Mortman, Shravani Durbhakula and Trent Emerick, 14 September 2025, Pain Medicine.
DOI: 10.1093/pm/pnaf127

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