A new class of extremely powerful synthetic opioids known as nitazenes is quickly becoming a significant factor in the ongoing overdose epidemic, as detailed in a comprehensive review published in Pain Medicine on September 14. The study was conducted by researchers from Vanderbilt University Medical Center and the University of Pittsburgh Medical Center.
These compounds were first synthesized back in the 1950s with the intention of serving as painkillers, but they were never granted approval for use in medical settings. Nitazenes exhibit potency levels exceeding fentanyl by more than 20 times and surpass morphine by factors ranging from hundreds to thousands. Their extraordinary strength makes them particularly dangerous in uncontrolled environments.
Nitazenes are available in various forms, including liquids, tablets, and powders. Since 2019, they have been detected in products marketed through social media platforms and within the illegal drug trade. This widespread distribution has amplified their presence in the streets and online marketplaces.
Although initially designed as a possible analgesic, nitazenes have not undergone any clinical trials or received approval for human therapeutic applications. Classified as illegal Schedule I substances, they pose challenges for detection using conventional drug screening methods. Frequently, they are blended into fake prescription pills or other recreational drugs sold on the black market, heightening the risk of accidental exposure.
“For individuals battling opioid use disorder or those who encounter street drugs unknowingly, nitazenes represent a grave and frequently undetectable danger,” explained co-author Shravani Durbhakula, MD, who serves as an associate professor of Anesthesiology in the Division of Pain Medicine at Vanderbilt University Medical Center.
She continued, “Routine toxicology tests often fail to identify these substances, which means healthcare providers might overlook a vital diagnostic clue when managing overdose cases. As a result, patients could require elevated doses of naloxone or multiple administrations to counteract the effects effectively.”
Data from the Tennessee State Unintentional Drug Overdose Reporting System (TN SUDORS) reveals 92 fatal overdoses linked to nitazenes among Tennessee residents between 2019 and 2023. In these incidents within the state, naloxone was provided in just one out of every three cases. Moreover, every recorded nitazene-related death involved the substance being combined with other drugs, predominantly fentanyl and methamphetamine.
“A large number of people ingesting nitazenes are completely unaware of their presence in what they’re consuming,” Durbhakula noted. “These chemicals are commonly used as fillers in tablets misrepresented as other opioids, which underscores the critical need for widespread public education efforts.”
She emphasized further, “This situation transcends a mere drug problem; it constitutes a full-blown public health crisis. Tackling it demands joint efforts from medical professionals, public health authorities, law enforcement agencies, and community groups. Together, they must roll out harm-reduction initiatives, bolster addiction recovery programs, and heighten awareness of these developing hazards.”
The research team advocates for broader availability of specialized test strips capable of identifying nitazenes. They also call for ensuring that vulnerable populations can readily obtain take-home naloxone supplies, access to addiction therapy services, and informative resources on the perils of counterfeit medications.
“Nitazenes constitute a rising category of synthetic opioids that outmatch fentanyl in potency and frequently evade detection by standard drug testing protocols,” stated corresponding author Ryan Mortman, MD, a resident in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh Medical Center.
He added, “The swift proliferation of these drugs in underground markets, coupled with the complexities involved in reversing their overdose effects, highlights the pressing requirement for increased public knowledge, prompt identification, and greater provision of harm-reduction resources like naloxone.”
Co-author Trent Emerick, MD, an associate professor of Anesthesiology and Perioperative Medicine as well as Bioengineering at the University of Pittsburgh School of Medicine, outlined future priorities. These include collecting human clinical evidence to deepen insights into nitazenes’ physiological impacts, particularly their prolonged health consequences, metabolic processes, and reactions to interventions such as naloxone.
“As the opioid epidemic persists in transforming, developing a comprehensive grasp of nitazenes’ underlying mechanisms and associated dangers is essential for pain management specialists, anesthesiologists, and fellow healthcare practitioners,” Emerick affirmed.
