A new international study led by scientists at Cornell University has uncovered fascinating clues about how psilocybin, the active chemical in magic mushrooms, changes the way the brain connects and communicates.
For years, researchers have known that psilocybin can ease symptoms of depression, sometimes after just a single dose.
People who take the drug in controlled clinical settings often describe feeling freed from cycles of dark and repetitive thoughts. But until now, scientists still did not fully understand how this powerful substance reshapes the brain’s wiring.
The new research offers an important step toward answering that question. Psilocybin belongs to a group of chemicals called psychedelics, which can alter perception, mood, and thinking. In recent years, these substances have gained attention as potential treatments for mental health conditions such as depression and anxiety.
Unlike regular antidepressants, which must be taken daily, psilocybin has shown surprisingly long-lasting effects even after only one guided session. This makes it a promising option for people whose depression does not respond well to other treatments.
Past work from Cornell professor Alex Kwan and his team showed that psilocybin can increase the brain’s structural plasticity. This means the brain becomes more capable of forming new connections, almost like opening new pathways inside a city’s road system.
But although earlier studies revealed that new connections were forming, researchers still didn’t know where these “new roads” were leading or which parts of the brain were being rewired.
To solve this puzzle, the team used a clever and unusual strategy. Instead of looking at individual connections with powerful microscopes, they paired psilocybin with the rabies virus. Although the virus is dangerous in nature, scientists can weaken and modify it so that it becomes a safe tracing tool.
The virus naturally moves from one brain cell to another. When engineered carefully, it can mark the exact paths along which signals travel. It works like a tracker that highlights the routes inside the brain’s complex communication map.
In this study, researchers first gave mice a single dose of psilocybin. A day later, they injected the modified rabies virus, which carried a glowing marker so scientists could see which neurons were connected.
After a week, when the virus had traveled through the brain, the team examined the patterns of glowing cells. They compared these patterns with the brains of mice that did not receive psilocybin.
The results showed two major changes. First, psilocybin weakened certain communication loops inside the brain’s cortex. These loops are thought to reinforce repetitive thinking.
When these loops are too strong, a person may get stuck in cycles of negative thoughts, something often seen in depression. Weakening these loops may explain why psilocybin helps people break out of unhealthy patterns of rumination.
Second, the study found that psilocybin strengthened connections between sensory regions of the brain and deeper areas responsible for turning sensations into actions. This may explain why people under psilocybin often describe clearer perceptions and stronger emotional responses to the world around them.
What made the findings even more surprising was how widespread the changes were. The entire brain seemed to reorganize, not just one or two regions. The team also discovered that the level of activity in a brain region affected how strongly it rewired under psilocybin.
When they artificially changed the activity of a brain area, they were able to influence which pathways psilocybin strengthened or weakened. This suggests that in the future, doctors might guide or enhance psilocybin’s positive effects by pairing it with other treatments that adjust brain activity.
Overall, the study shows that psilocybin does far more than create temporary changes in mood or perception. It appears to produce deep and lasting changes in how different parts of the brain communicate. These results help explain why psilocybin may offer long-term relief for people with depression.
At the same time, the research shows that these changes are complex and happen throughout the brain, opening the door for future studies to explore how to use this knowledge safely and effectively.
While more research is needed, this work provides strong scientific support for the idea that psychedelics may one day become important tools in mental health treatment.
If you care about mental health, please read studies about how dairy foods may influence depression risk, and 6 foods you can eat to improve mental health.
For more mental health information, please see recent studies about top foods to tame your stress, and Omega-3 fats may help reduce depression.
The study is published in Cell.
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