Scientists at USF Health are making important progress in understanding how pain-relieving drugs known as opioids work inside the body.
Their goal is to help create safer medicines for people living with chronic pain—drugs that provide relief without the deadly side effects linked to traditional opioids like morphine or fentanyl.
The latest research, led by Dr. Laura Bohn and her team, was recently published in two top journals, Nature and Nature Communications. The studies explain how certain new opioid compounds behave differently in the body and suggest a new way to design painkillers that may be less risky.
Opioids work by attaching to special proteins called mu opioid receptors on nerve cells. When these receptors are activated, they block pain signals. This is what makes opioids effective for relieving pain.
But the same receptors can also slow breathing, which can be deadly—especially in overdose situations. That’s one of the reasons why opioids have contributed to a major health crisis in recent years.
Dr. Bohn and her team are studying new compounds that still target the mu opioid receptors but do so in a different way. Their research shows that the very first step in how these drugs work—the signaling process inside the cell—can actually move in reverse. This is something scientists did not know before.
Normally, when a drug like morphine binds to the receptor, it starts a chain reaction that leads to pain relief but also side effects like breathing problems. The team found that some new compounds prefer to reverse this chain reaction instead of pushing it forward.
When these new compounds were given along with morphine or fentanyl at very low doses, they made the pain relief stronger but did not increase the risk of slow breathing. That’s a very promising result.
These new compounds are not ready to become medicines yet. At high doses, they still cause breathing suppression, and they haven’t been tested for safety. However, they offer a helpful framework for designing better drugs in the future.
Dr. Bohn’s lab has already made progress in this area. They previously discovered a compound called SR-17018. This drug activates the same opioid receptor as morphine, but it works differently.
It does not cause tolerance (when the drug stops working over time) or breathing suppression. It also allows the body’s natural pain-relief chemicals to keep working. Researchers believe this compound and others like it could help reshape how pain is treated.
What makes this new research so exciting is that it could change how scientists think about many types of drugs—not just opioids. The reverse signaling process they discovered might also happen in other important receptors, such as the serotonin 1A receptor, which plays a role in mental health conditions like depression and psychosis.
This discovery also comes at a critical time. The opioid crisis continues to cause thousands of deaths every year. In 2024, opioids were involved in 68% of overdose deaths in the U.S., with fentanyl and similar drugs making up the majority of those cases.
Dr. Bohn is a well-known expert in the field of drug discovery. Her team’s work helps us better understand how the body responds to opioids and brings us one step closer to creating safer, non-addictive painkillers.
This research does not offer a final cure or replacement yet, but it lays the groundwork for a new generation of pain medications. In the future, patients might be able to get pain relief without facing the deadly risks that come with today’s opioid drugs.
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