Scientists at Washington University School of Medicine and Stanford University have developed a new compound that may offer pain relief without the risks linked to opioids or the mind-altering effects of cannabis.
The drug, which was tested in mice, works by mimicking a natural compound found in the cannabis plant. The results of the study were published on March 5 in the journal Nature.
About 50 million people in the U.S. suffer from chronic pain, and many rely on opioids for relief. However, opioids are addictive and can be deadly if misused. In 2022 alone, around 82,000 deaths in the U.S. were connected to opioids. That’s why researchers are working hard to find safer options.
Dr. Susruta Majumdar, senior author of the study and professor of anesthesiology at Washington University, said the compound his team created attaches to pain-relieving receptors in the body but is designed not to enter the brain. This helps avoid side effects like mood changes or addiction, which are common with opioids and cannabis.
Opioids reduce pain by acting in the brain and triggering the release of dopamine, a chemical linked to pleasure. This reward system is what makes them so addictive. Cannabis has also been used for pain for thousands of years, but its psychoactive effects have made it a less appealing option for long-term treatment.
The compound developed by the team is based on cannabinoid molecules, which are found in marijuana and bind to receptors in the body called CB1 receptors. These receptors are located both in the brain and in pain-sensing nerves.
The team modified the cannabinoid molecule so it has a positive charge. This change prevents it from crossing the blood-brain barrier, meaning it can’t reach the brain but can still reduce pain in the body.
Dr. Robert Gereau, another author of the study and director of the Pain Center at Washington University, explained that the new drug targets pain-sensing nerve cells outside the brain. As a result, it provides pain relief without the “high” associated with cannabis.
The researchers tested the drug in mice with nerve injury pain and migraine-like symptoms. The mice were given small touches that normally wouldn’t hurt, and the researchers measured how sensitive they were. The new compound reduced the pain response in both models.
One of the biggest problems with painkillers like opioids is that people build up a tolerance, meaning they need higher and higher doses over time. But the mice given the new compound twice a day for nine days did not develop tolerance. This is a hopeful sign that the drug could work long term for people with chronic pain.
Using advanced computer modeling, the researchers also discovered that the compound binds to a hidden pocket in the CB1 receptor. This pocket had been considered unreachable before. Binding at this spot reduces activity linked to developing tolerance, which could explain why the drug continues to work even after repeated use.
Dr. Majumdar said that designing drugs that reduce pain without serious side effects is very difficult. However, his team plans to keep working on this compound and hopes to eventually turn it into a pill that can be tested in human clinical trials.
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The study is published in Nature.
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