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Scientists may have found way to make fentanyl a less dangerous drug — and save lives

FILE - This undated file photo provided by the U.S. Attorneys Office for Utah and introduced as evidence at a trial shows fentanyl-laced fake oxycodone pills collected during an investigation. Congress has voted to temporarily extend a sweeping tool that has helped federal agents crack down on drugs chemically similar to fentanyl. The Senate on Thursday, April 29, 2021, approved legislation extending until October an order that allows the federal government to classify so-called fentanyl analogues as Schedule I controlled substances. The drugs are generally foreign-made with a very close chemical makeup to the dangerous opioid. (U.S. Attorneys Office for Utah via AP, File)
U.S. Attorneys Office for Utah
Fentanyl is sold in various forms and made to look identical to real prescription medications — including OxyContin, Percocet, and Xanax, say federal officials. A University of Florida scientist is part of a team that may have discovered a way to lessen fentanyl's deadly side effects.

A group of scientists, including a University of Florida professor, may have found a way to alter the chemical components of fentanyl — a powerful pain medication being used illegally and killing tens of thousands nationwide — to lessen its deadly side effects.

Jay McLaughlin, a neuroscientist and a professor of pharmacodynamics at the University of Florida College of Pharmacy, is working with scientistsat Washington University in St. Louis, the University of Southern California and Stanford University who've discovered a safer version of it.

Fentanyl was originally developed as a legal drug to treat intense pain for patients with cancer or coming out of surgery, but drug traffickers have used it to make it more potent.

McLaughlin told WLRN News that the team started their research by exploring ways to "re-engineer it in a way" to make fentanyl a "safer painkiller that doesn't have all the bad side effects."

He said they wanted to solve two problems at the same time: Find newer, safer compounds that would be less likely to be abused but still treat pain.

Fentanyl causes a short-term but intense feeling of pleasure, and slows respiration. The way it works is that fentanyl binds to what's called the mu-opioid receptor on nerve cells.

Jay McLaughlin, a neuroscientist at the University of Florida College of Pharmacy
University of Florida
Jay McLaughlin, a neuroscientist at the University of Florida College of Pharmacy

"The receptor has this molecular switch dead in the center, hidden inside it, that regulates its function," McLaughlin said, pointing to the research by another colleague on the team.

The scientists then decided to work on a compound that works at the normal receptor to turn it on and "produce the good painkilling benefit, but also regulates its function by acting at that second molecular switch to prevent some of the negative side effects," McLaughlin said.

In their testing, the compound they produced didn’t cause "respiratory depression," or shallow breathing. Opioid receptors are found in other parts of the brain that don't regulate pain and do regulate respiration. A drug like fentanyl will activate all of the opioid receptors.

“Some of them are going to block your pain, but some of them are also going to cause respiratory depression,” McLaughlin explained. “In the case of super potent compounds like fentanyl, that means that you get the danger of patients that stop breathing. That's actually what kills a lot of people who suffer from opioid overdose.”

The team’s altered drug engages a sodium ion binding site in the receptor that turns off a receptor before side effects like depressed breathing take place. They found evidence of this in their testing on mice.

Their study was publishedin Nature, a weekly research journal. More testing is needed by other researchers to confirm their findings and ensure it is safe, and later on would come human clinical trials.

"We're hoping this can make a contribution to help people," McLaughlin said.

If scientists can make fentanyl safer, it would literally be life-saving.

DEA: ‘Deadliest drug threat’

The U.S. Drug Enforcement Administration calls fentanyl the deadliest drug in the nation. DEA Administrator Anne Milgram has said it's "the single deadliest drug threat our nation has ever encountered.”

"Fentanyl is everywhere," she said. "From large metropolitan areas to rural America, no community is safe from this poison."

The DEA reportedlast month (December) that in 2022 it had seized more than 50 million fentanyl-laced, fake prescription pills and more than 10,000 pounds of fentanyl powder this calendar year. The seizures represent more than 379 million potentially deadly doses of fentanyl.

It is a highly addictive man-made opioid that is 50 times more potent than heroin. Just two milligrams of fentanyl, the small amount that fits on the tip of a pencil, is considered a potentially deadly dose.

Rising death toll

Two-thirds of the 107,000 overdose deaths in the United States were attributed to synthetic opioids like fentanyl, according to the latest data from the U.S. Centers for Disease Control and Prevention, or CDC.

In 2020, more than 6,150 people died from overdoses involving fentanyl and fentanyl analogs in Florida, according to the Florida Department of Health. In the first half of 2021, fentanyl caused 2,920 deaths.

The Florida Department of Law Enforcement also reports that fentanyl was the drug most frequently found in people who died from drug use.

Mexican drug cartels in recent years have produced most of the illegal fentanyl seen in the U.S., smuggling it inside vehicles or strapped to pedestrians crossing at ports of entry along the international border. DEA officials say the chemicals largely come from China.

The drug is sold in various forms and made to look identical to real prescription medications — including OxyContin, Percocet, and Xanax, say federal officials, who warn that the fake pills are peddled on social media.

"The only safe medications are ones prescribed directly to you by a trusted medical professional and dispensed by a licensed pharmacist," warns the DEA.

For now, anyone who has an overdose can be treated with Naloxone — often known by the brand name, Narcan. It takes opiates off of the brain’s receptors and, among other things, restores a person's breathing.

First responders in South Florida and across the state can request free Naloxone through a program called HEROS, or Helping Emergency Responders Obtain Support.

Last November, the Florida Department of Health in Miami-Dade County began offering free kitsthat have two Naloxone nasal sprays.

To receive the kit, you must be 18 years old or older, be at risk of experiencing an opioid overdose or be a caregiver who may witness an opioid overdose.

The Associated Press contributed to this article.

Verónica Zaragovia was born in Cali, Colombia, and grew up in South Florida. She’s been a lifelong WLRN listener and is proud to cover health care, as well as Surfside and Miami Beach politics for the station. Contact Verónica at vzaragovia@wlrnnews.org
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