Psilocybin Breaks Depressive Cycles by Rewiring The Brain, Study Suggests

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Psilocybin Breaks Depressive Cycles by Rewiring The Brain, Study Suggests
Tessa Koumoundouros
Mon, December 15, 2025 at 6:50 PM EST
3 min read



Psilocybin Breaks Depressive Cycles by Rewiring The Brain, Study Suggests


Scientists have used a specially engineered virus to help track the brain changes caused by psilocybin in mice, revealing how the drug could be breaking loops of depressive thinking.

This may explain why psilocybin keeps showing positive results for people with depression in clinical trials.

"Rumination is one of the main points for depression, where people have this unhealthy focus, and they keep dwelling on the same negative thoughts," says Cornell University biomedical engineer Alex Kwan.

"By reducing some of these feedback loops, our findings are consistent with the interpretation that psilocybin may rewire the brain to break, or at least weaken, that cycle."

Depression is a leading global cause of disability, with more than 300 million people impacted by the mood disorder.

Many people find current treatments have challenging side effects or do not work for them at all, so there is an ongoing search for alternative solutions, such as psilocybin.



How psilocybin changes the connections between mouse neurons. (Jiang et al., Cell, 2025)


Derived initially from magic mushrooms, psilocybin is a hallucinogenic compound that is being investigated for its anti-inflammatory properties in addition to its potential as an antidepressant.

In 2021, Kwan's laboratory showed that psilocybin reshapes brain connections, finding these changes could last for a long time. But why some neurons grew more connections, while others reduced them, was a mystery.

In their new study led by biomedical engineer Quan Jiang, the researchers took a closer look at which brain circuits were being rewired and how, using an engineered rabies virus to track changes in brain connections.

In its natural form, the rabies virus spreads through neurons, jumping across synapses.

"Here we use the rabies virus to read out the connectivity in the brain," explains Kwan.

The virus trailed paths of fluorescent proteins through the mouse brains. Mice received a single dose of psilocybin or a placebo and then, one day later, the virus. One week later, the researchers compared the viral 'trails'.

Scans revealed areas of the brain associated with sensory processing became more connected with the part of the brain that takes action.

What's more, connections within the cortex, where negative thought feedback loops take place in humans, were reduced.

Jiang and team also found that brain activity seems to direct where psilocybin rewiring occurs, opening the prospect of using methods like magnetic stimulation to modulate targeted neural activity.

Of course, these findings still need to be confirmed in humans, as not all findings from research in mice translate across species.

But the results would explain some of the results of human observation studies, and one of the most compelling ideas about how psychedelics work.

"Our study hints at an exciting avenue for future research to combine neuromodulation with psychedelics to precisely target [and rewire] specific circuits," the researchers conclude.

This research was published in Cell.


https://www.yahoo.com/news/articles/psilocybin-breaks-depressive-cycles-rewiring-235005518.html