Fentanyl ranks among the most powerful medications available for treating intense pain. However, its benefits come with serious hazards, including a high potential for addiction and respiratory depression, a dangerous slowing of breathing that can be fatal. Because of these risks, doctors must carefully restrict its use even though it is highly effective. At the same time, fentanyl is inexpensive and relatively simple to manufacture, which has led to widespread illegal production and distribution. That surge has contributed to a devastating overdose crisis that claimed more than 70,000 lives in the United States in 2023.

Researchers at Scripps Research have now redesigned fentanyl at the molecular level, creating a new version that maintains its strong pain-relieving effects while reducing its tendency to suppress breathing. The study, published in ACS Medicinal Chemistry Letters, indicates that further refinements could lead to safer opioid medications with lower risks of addiction, overdose, and death.

“For decades, the pharmaceutical industry has been constrained by the assumption that major structural changes to opioids would eliminate their analgesic properties,” says senior author Kim D. Janda, the Ely R. Callaway Jr. Professor of Chemistry at Scripps Research. “Our research has identified a different possibility—that fundamental structural redesign can preserve pain relief while improving safety.”