Fentanyl has been used to treat severe pain since the 1960s. But the powerful synthetic opioid has also become a major driver of addiction and overdose deaths.
San Diego County recorded 320 fentanyl overdose deaths last year.
Now, scientists at Scripps Research said they may have found a way to redesign the drug at the molecular level, keeping its powerful pain-relieving properties while reducing the dangerous breathing problems that make overdoses so deadly.
Scripps Research chemist Kim Janda said his team wanted to see if they could make fentanyl safer by slightly redesigning the drug at the molecular level. They tested the redesigned drug in mice.
“I decided to try to look at putting in a component that would basically be viewed as fentanyl by the immune system, but wouldn’t have the liabilities that fentanyl has,” Janda said. “So we did a structural alteration on fentanyl.”
For decades, scientists believed fentanyl’s molecular structure could not be modified without ruining its ability to block pain. Janda’s team focused on what he calls the drug’s core unit.
“That core unit looks like a honeycomb in shape,” Janda said. “And what we did was we changed it to look like two squares that are hooked together like paper clips. And surprisingly, we found that it still has the ability to block pain, but it doesn’t cause respiratory depression.”
Respiratory depression is that dangerous slowing of breathing that makes fentanyl overdoses fatal.
“The higher the amount that you inject in yourself, the quicker you’re going to stop breathing. And it’s potential that you could stop breathing within minutes of a large dose of fentanyl,” said Dr. Richard Clark, an emergency physician and director of toxicology at the University of California San Diego.
Clark, who was not involved in the research, said the findings are promising, if they hold up in further testing.
“My takeaway would be this research is fascinating, and if it actually holds true in humans, it has great potential,” he said.
The research remains in early laboratory stages, and the redesigned compound has not yet been tested in people. Janda said his team chose not to patent the discovery, hoping other researchers will build on the work.
“In a sense, it’s like a makeover of fentanyl, which people think is this monster,” Janda said. “We’re trying to make it more tame in terms of how it could be used therapeutically.”
He said the work could help pave the way for a new generation of opioid medications designed to lower the risk of addiction, overdose and death.
