NIH Finds Pain Drug With Low Addiction Risk

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Researchers at the National Institutes of Health (NIH) have identified a novel, highly potent opioid called DFNZ that shows potential as a therapy for both pain and opioid use disorder. In laboratory studies, DFNZ demonstrated high pain-relieving effects without causing respiratory depression, tolerance, or other indicators of addiction potential in humans.

Why it matters

Opioid pain medications are essential for medical purposes but can lead to addiction and overdose. Developing a highly effective pain medication without these drawbacks would have enormous public health benefits by providing a safer alternative for patients in need of pain relief.

The details

The NIH team investigated formulations of an understudied class of synthetic opioid compounds called nitazenes, which selectively engage the mu-opioid receptors in the brain and nervous system. While nitazenes had been shelved in the 1950s due to their excessive potency, the researchers revisited this class of compounds and engineered a new nitazene called DFNZ that appears to sidestep the liabilities of other opioids. At therapeutic doses, DFNZ produced pain relief without depressing respiration and did not result in tolerance, drug dependency, or meaningful withdrawal effects in animal studies.

• The research findings were published in the scientific journal Nature in April 2026.

What they’re saying

What’s next

The research team will pursue additional preclinical studies to support an application for regulatory approval to conduct studies of DFNZ in humans. They believe several patient populations may benefit from DFNZ, including those in surgical settings and with cancer-related or chronic pain who have a particularly high need for effective pain treatment.