A powerful and little-known group of synthetic opioids called nitazenes is emerging as a dangerous new player in the overdose crisis, according to a new review published in Pain Medicine by researchers from Vanderbilt University Medical Center and the University of Pittsburgh Medical Center.
Nitazenes were first developed in the 1950s as potential painkillers but were never approved for medical use.
Now, decades later, they have reappeared on the illicit drug market.
What makes them especially alarming is their strength: nitazenes are more than 20 times more potent than fentanyl and hundreds to thousands of times stronger than morphine.
These drugs have been sold illegally since 2019, often through social media and street markets.
They can appear in pill, powder, or liquid form and are usually mixed with other substances.
Because they are not approved medications, nitazenes are classified as Schedule I drugs—illegal with no accepted medical use.
What makes nitazenes particularly dangerous is that they are often hidden. Standard drug tests usually cannot detect them, meaning overdoses involving nitazenes may go unrecognized.
This complicates treatment for doctors and emergency responders.
According to Dr. Shravani Durbhakula, an anesthesiologist at Vanderbilt, patients overdosing on nitazenes may require higher or repeated doses of the antidote naloxone to survive.
Recent data from Tennessee highlight just how deadly these drugs can be. Between 2019 and 2023, the Tennessee State Unintentional Drug Overdose Reporting System recorded 92 deaths involving nitazenes.
In all of those cases, nitazenes were mixed with other drugs, most often fentanyl and methamphetamine. Naloxone was used in only one-third of the cases, underscoring the challenge of responding to such overdoses.
“Many people consuming nitazenes don’t even know they are taking them,” Dr. Durbhakula said. “These substances are often mixed into counterfeit pills or disguised as other opioids. That makes public awareness more important than ever.”
Experts stress that the rise of nitazenes is not just another drug issue—it is a public health emergency.
Tackling it will require a coordinated effort from healthcare providers, law enforcement, public health officials, and community organizations. Expanding harm-reduction strategies, providing take-home naloxone, and raising awareness about counterfeit pills will all be critical.
Dr. Ryan Mortman of the University of Pittsburgh added that nitazenes’ extreme potency and ability to evade routine testing make them especially worrisome.
“Their rapid spread in the illicit drug market, combined with the difficulty of reversing overdoses, underscores the urgent need for public awareness and early recognition,” he said.
Researchers are calling for more studies to understand nitazenes, including their long-term health impacts and how best to treat overdoses.
As Dr. Trent Emerick from the University of Pittsburgh put it, “The opioid crisis continues to evolve. A thorough understanding of nitazenes is crucial for physicians and communities alike.”
