(The Center Square) – Synthetic opioids estimated to be 10 times more potent than fentanyl are creeping into the illicit drug market in the U.S., according to new research. 

"Synthetic opioids, such as the fentanyl analog and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department with illicit opioid overdose," researchers warned in a paper published Tuesday in JAMA Network Open.

Nitazenes were developed in the 1950s as opioid analgesics, but were never approved to market, according to another study published this summer. That paper notes that "a characteristic of nitazenes is their high potency (e.g., hundreds to thousands fold more potent than morphine and other opioids and tenfold more potent than fentanyl)." 

"Clinicians should be aware of these opioids in the drug supply so they are adequately prepared to care for these patients and anticipate needing to use multiple doses of naloxone," according to the JAMA Network Open study by Alexandra Amaducci, Kim Aldy, Sharan Campleman and others. 

In the study of 537 overdose patients in the U.S. from 2020 to 2022, researchers found nine people tested positive for nitazenes such as brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene. That's about 1.7 percent of the total. Of the 537 patients, 11 were found to only test positive for fentanyl – about 2 percent.

Why nitazenes are showing up in the illicit drug supply is unclear, but researchers said it may be the result of changing regulations.

"The exact motivation to produce nitazenes and brorphine are unclear," according to the study. "The increased regulation of fentanyl and fentanyl analogues throughout the last decade may have led to a change in the chemical precursors required for clandestine laboratory production that were not yet regulated. This change in chemical precursors may have led to these newer and more potent opioids."

The study found that people who overdosed on nitazenes and other novel potent opioids may require more naloxone to reverse overdose symptoms.

"These findings suggest that [novel potent opioids] may have a higher potency than fentanyl due to the observed naloxone administration in the clinical setting of overdose," according to the study. It also noted that "further study is warranted to confirm these preliminary associations."

"Furthermore, this preliminary data underscores the urgent need to study [novel potent opioids] in a larger, future cohort," the authors wrote. "These data suggest that [novel potent opioids] may have higher potency than fentanyl and by extension heroin."