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An experimental medication was shown to achieve strong pain relief in early studies without the risks associated with typical opioids.
The finding comes from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), which tested nitazenes, a class of synthetic opioid compounds.
“Nitazenes are a dangerous group of drugs that have no medical indication and are highly addictive,” cautioned Dr. Marc Siegel, Fox News senior medical analyst. “They can be hundreds or thousands of times more potent than morphine.”
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After being developed in the 1950s for potential pain relief, nitazenes were abandoned because of their high addictive properties and drug overdose potential, the doctor said.
“They are a big black-market drug, and they are very problematic in terms of illicit use in the U.S.,” Siegel added.
Michael Michaelides, PhD, senior author of the study and NIDA investigator, said the researchers’ goal was to study the profile, or pharmacology, of these drugs.
“We wanted to decrease the potency and create a potential therapeutic,” he said in a press release. “What we discovered exceeded our expectations.”
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Typical opioids have been linked to dangerous side effects, including respiratory depression, where breathing becomes too slow, shallow or ineffective, causing carbon dioxide to build up in the body and oxygen levels to drop. It can also cause rising tolerance and severe withdrawal, according to the researchers.
“Opioid pain medications are essential for medical purposes, but can lead to addiction and overdose,” said Nora D. Volkow, MD, director of NIH’s National Institute on Drug Abuse, in the release.
“Developing a highly effective pain medication without these drawbacks would have enormous public health benefits.”
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In the study, the team created a drug called DFNZ, a metabolite (derivative) of nitazene, which provided at least two hours of pain relief in mice after just five or 10 minutes in the brain.
It did not appear to have any of the serious risks associated with its standard opioid counterpart, such as addiction potential and depressed (slowed) breathing.
“Developing a highly effective pain medication without these drawbacks would have enormous public health benefits.”
“At preclinical therapeutic doses, DFNZ produced a moderate and sustained increase in brain oxygen rather than depressing respiration,” the authors wrote.
“Repeated doses of the drug did not result in tolerance, drug dependency or meaningful withdrawal effects.”
The only classic opioid withdrawal symptoms observed with DFNZ was irritability, they noted.
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DFNZ could potentially be used as a safer treatment for opioid use disorder, the researchers suggested, as well as for patients undergoing surgery and experiencing cancer-related or chronic pain.
“There’s a lesson here – that even a dangerous chemical can lead to a potential treatment,” Siegel noted. “This needs to be tested in humans, but I think there is potential for a much safer pain drug that is not only not addictive, but may also be a potential treatment for addiction.”
Among DNFZ’s benefits is that it was found to increase oxygen flow to the brain rather than decrease it, and that it binds tightly to the opioid receptor but doesn’t cause the feared side effects of breathing suppression or addiction, according to Siegel. “It releases dopamine more gradually, which is safer.”
The findings were published in the journal Nature.
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“DFNZ has an unprecedented pharmacology for an opioid,” Michaelides said. “It is a potent and high-efficacy analgesic, but in certain contexts it resembles partial agonists, drugs that activate the receptor with low efficacy, which is what scientists think is needed for safety.”
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“Its capacity to be administered at therapeutic doses without producing respiratory depression is very important.”
The study did have some limitations, primarily that it was conducted with animal (rat) models. The effectiveness and safety of human use is unknown.
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It also did not explore long-term impacts or rare adverse effects, the researchers acknowledged.
Clinical studies will be needed to fully understand the drug’s addictive potential.
The research team plans to conduct more preclinical studies before seeking regulatory approval to conduct human clinical trials.
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Dr. Hooman Melamed, a board-certified orthopedic spine surgeon and sports medicine expert in Beverly Hills, California, said the new research looks “promising,” but urged caution with the early findings.
“This new drug claims to release a lower-dose opioid alternative that might be able to offer pain relief without the addictive properties,” Melamed, who was not involved in the study, told Fox News Digital.
“It’s also important to note that this has not been tested on humans, and we don’t know how this will impact people in the long run.”
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Melamed also noted that there is often a “very narrow therapeutic threshold” with this class of drugs.
“In other words, a small increase in the dosage could become addictive for people, and without solid human data, we just can’t know the dependency risk,” he said.
“It’s important to note that this has not been tested on humans and we don’t know how this will impact people in the long run.”
The doctor also expressed concern that opioids could potentially harm gut health.
“Many opioids are known to slow down intestinal mobility, leading to issues like constipation and impaired digestion,” Melamed said.
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“This is part of the reason I avoid prescribing opioids, because they can potentially weaken immune function and even contribute to broader systemic issues, such as inflammation or ‘leaky gut,'” he went on. “These issues can slow down one’s recovery.”
The doctor reiterated the need for long-term data and more research into other issues that could arise, such as cognitive effects.
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