Last week, researchers dropped a bombshell report on DFNZ, a developing new medicine derived from a class of drugs once considered too dangerous to even study.
Their proposal sounded almost too good to be true: The drug might offer patients with chronic pain and injuries the benefits of an opioid without the threat of addiction or withdrawal.
In a thorough study of the effects of DFNZ on rats, the researchers observed that the drug had an obvious “reward” effect on the subjects, but at a certain point, the rodents easily stopped going back for more.
The findings are especially timely, as Americans battle two crises that often overlap: chronic pain and opioid addiction. A 2018 scientific paper published in the Annual Review of Pharmacology and Toxicology found that more than 125 million Americans live with acute or chronic pain.
Many of those patients have been prescribed an opiate to help manage it, a common practice that’s partially contributed to a nationwide opioid epidemic that killed 80,000 people in 2023.
But doctors are buzzing over DFNZ’s potential to disrupt this tragic pattern.
In fact, Dr. Manassa Hany, MD, director of addiction psychiatry at Northwell Health’s Zucker Hillside and South Oaks hospitals, believes it could someday be the “holy grail of pain management” — offering a “much safer alternative” to drugs like fentanyl and oxycodone for post-surgical pain, cancer pain, severe chronic pain or other related conditions.
“It challenges the decades-old dogma that any opioid with high efficacy at the mu-opioid receptor must inherently be dangerous and highly addictive,” he tells The Post, referencing a clinical term for opioid pain meds.
DFNZ originates from nitazenes, a group of synthetic opioid compounds that’s considered one of the most powerful mu-opioid receptor agonists.
But DFNZ’s properties — its high efficacy at treating pain, its limited brain entry and its “distinct cellular signaling profile” — “provide a completely new blueprint for designing safer analgesics,” or pain medications, Hany says.
“This research is a remarkable example of how, through careful scientific modification, a compound from a notoriously hazardous chemical family can be engineered into a potentially valuable therapeutic agent,” he adds.
Pain relief — without the addiction risk
The properties of the drug these researchers isolated are what Hany calls “a ‘wish list’ for what we would want in a safer opioid.”
In the rodent trials, DFNZ showed promise of effective pain treatment while maintaining a “remarkable safety profile,” which Hany says is the “the most striking aspect” of the new research.
The withdrawal and tolerance that are hallmarks of other opioids — plus the respiratory depression that’s behind so many opioid overdose deaths — were nowhere to be found.
“Despite being a ‘superagonist’ (meaning it’s very powerful at the opioid receptor), it demonstrated minimal adverse effects that are the hallmark of traditional opioids,” Hany said.
“From an addiction standpoint, the results here are stunning,” he went on, noting that when the rats in the study no longer had access to DFNZ, they “immediately stopped trying to get it.”
“This is in stark contrast to heroin, where animals will continue to seek the drug for a long time, which models the powerful cravings seen in human addiction,” he explained. A “priming” dose, which “typically triggers a relapse to drug-seeking,” didn’t make them use more, either.
It also reduced how much rats sought out heroin — meaning it shows promise as a treatment for opioid use disorder, too.
While Hany says the study has produced very exciting outcomes and it offers an excellent roadmap for the next round of research, we won’t have a complete picture until we test DFNZ’s effects in humans.
“This is a study in rodents. The physiology, metabolism and the blood-brain barrier in humans can be significantly different,” he says. “A compound that is safe and effective in a mouse may not be in a person.”
It’s for this reason that much more research is needed before DFNZ can definitively take the crown for safest and most effective opioid. But there’s reason to be optimistic, Hany says.
“DFNZ is one of the most promising opioid candidates to emerge from preclinical research in a very long time.”
