Chronic pain is a major health problem around the world, affecting more than 1.5 billion people.
It often comes with mental health issues like depression and anxiety, creating a difficult cycle that can make life feel unbearable.
But now, a new study from the University of Pennsylvania offers fresh hope. Researchers have found that psilocybin—the active compound in psychedelic mushrooms—may help ease both pain and mood problems.
The study was led by doctors and scientists at Penn Medicine and was published in the journal Nature Neuroscience. The research team was particularly interested in how psilocybin affects the brain.
They found that it interacts with specific brain circuits linked to pain and emotions. These circuits may be key to managing chronic pain without relying on addictive painkillers like opioids.
In experiments using mice that had long-term nerve or inflammation-related pain, the researchers gave a single dose of psilocybin. The results were promising: the mice had less pain and showed fewer signs of anxiety and depression. Even more exciting, these benefits lasted for almost two weeks.
Psilocybin works by gently activating certain brain signals called serotonin receptors. These signals help control mood and how we feel pain. Unlike other drugs that might completely block or fully turn on these signals, psilocybin acts more like a dimmer switch. It adjusts the signal to just the right level, offering a more balanced effect.
To find out exactly where psilocybin works in the brain, researchers used glowing dyes and special microscopes to watch brain activity.
They discovered that when the drug was injected directly into a brain area called the anterior cingulate cortex (ACC)—a region involved in processing both pain and emotions—it provided the same pain relief and mood boost as giving psilocybin to the entire body. But when the drug was injected into the spinal cord, it didn’t work the same way.
This suggests that psilocybin may work by affecting the brain’s processing of pain rather than the source of the pain itself. In other words, instead of numbing the pain in the body, it changes how the brain responds to it—helping people feel both less pain and more emotionally balanced at the same time.
The researchers believe these findings could lead to new treatments not only for chronic pain and depression but also for conditions like PTSD or addiction that involve similar brain circuits. However, more studies are needed to learn how long the benefits last and whether repeated doses are needed to keep the brain “rewired” in a healthier way.
The research team at Penn now plans to test different doses and study the long-term effects in mice. They hope to eventually find safe and effective ways to use psilocybin as a non-addictive treatment option for chronic pain.
If you care about mental health, please read studies about cannabis use disorder linked to increased risk of mental diseases and some mental health drugs can cause rapid weight gain.
For more health information, please read studies that one sleepless night can reverse depression for days and scientists find better treatment for older adults with depression.
The study is published in Nature Neuroscience.
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