Nitazenes -- a class of highly potent synthetic opioids -- are rapidly emerging as a major contributor to the overdose crisis, according to a Pain Medicine review published on Sept 14 by authors from Vanderbilt University Medical Center and the University of Pittsburgh Medical Center.
Originally developed in the 1950s but never approved for clinical use, these substances are over 20 times more potent than fentanyl and hundreds to thousands of times more potent than morphine.
They can come in liquid, pills or powder form and have been found in substances sold via social media and on the illicit drug market since 2019.
Created as a potential pain reliever but never approved for medical use in humans or studied in a clinical trial, nitazenes are an illegal Schedule I drug that can be difficult to detect with standard drug tests and are often mixed into counterfeit pills or other street drugs.
"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.
The Tennessee State Unintentional Drug Overdose Reporting System (TN SUDORS) identified a total of 92 nitazene-involved fatal drug overdoses among Tennessee residents from 2019-2023.
In Tennessee, naloxone was administered in only one in three deaths involving nitazenes, and in all nitazene-involved deaths the drug was laced with other substances, most commonly 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.
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-authorTrent Emerick, MD, associate professor of Anesthesiology and Perioperative Medicine and Bioengineering at the University of Pittsburgh's School of Medicine, said 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.