A team of researchers from the United States conducted an unusual experiment on mice to find out how psilocybin—the active compound found in so-called ‘magic mushrooms’—affects brain function and whether it can help alleviate depressive states. To monitor changes in neural connections, the scientists used a modified rabies virus, which allowed them to visualize exactly how the chains between different brain regions are reorganized after administration of the substance.
The results were unexpected: after a single dose of psilocybin, the animals showed a significant strengthening of connections between areas responsible for processing sensory information and motor activity. At the same time, within the cerebral cortex—where persistent negative thoughts are formed—the number of connections actually decreased. According to experts, this effect may explain why, after psilocybin therapy, people are less likely to dwell on anxious and depressive thoughts.
Mechanisms of action
During the experiment, mice were first given either psilocybin or a placebo. A day later, they received a virus that spread through their neurons, leaving glowing traces behind. After a week, researchers compared how the structure of neural connections had changed among the different groups. It turned out that psilocybin doesn’t simply strengthen or weaken individual connections—it literally reconfigures entire neural networks, making them more flexible and less prone to forming closed loops of negative experiences.
Researchers paid particular attention to the cerebral cortex, where so-called “loops” of negative thinking often develop in humans. After exposure to psilocybin, they observed a decrease in internal connections in this region, which, according to the study’s authors, could help disrupt pathological patterns and ease depression symptoms.
Therapeutic Potential
Depression remains one of the most common causes of disability worldwide, and existing treatments are often not effective enough. Many patients experience side effects or fail to achieve the desired results with traditional antidepressants. This is why the search for new approaches, including the use of psychedelics, is becoming increasingly important.
Psilocybin, in addition to its psychoactive properties, also exhibits anti-inflammatory effects, expanding its potential applications in medicine. Previous studies have shown that a single dose of this compound can stimulate the growth of new neural connections. Now, scientists have discovered that the nature of these changes depends on brain activity at the moment the drug is administered. This opens up possibilities for combining psilocybin with other methods, such as magnetic stimulation, to specifically target desired areas of the brain.
Limitations and prospects
Despite the impressive results, the study’s authors emphasize that the findings are currently limited to animal data. Not all mechanisms identified in mice can be directly extrapolated to humans. Nevertheless, the results align well with observations of patients undergoing psilocybin therapy and provide a strong basis for further clinical trials.
In the future, researchers plan to explore how psychedelics can be combined with neuromodulation techniques for more precise and safer effects on the brain. This approach could mark a breakthrough in treating resistant forms of depression that do not respond to standard therapies.
If you weren’t aware, psilocybin is a naturally occurring psychoactive compound found in certain types of mushrooms, and in recent years it has been actively researched as a potential treatment for depression and other mental disorders. Leading laboratories around the world, including a team of biomedical engineers from Cornell University, are studying its effects on the brain. In 2025, the journal Cell published a study detailing the mechanisms of neural rewiring triggered by psilocybin. Research is ongoing, and scientists hope that in the coming years new effective therapies based on this compound will emerge.
