- Cornell led team mapped how psilocybin changes connections across the brain in mice
- The drug weakened feedback loops in the cortex that may underpin rumination
- It strengthened links between sensory areas and deeper regions involved in action
Psilocybin, the active compound in so called magic mushrooms, has drawn intense interest as a potential treatment for depression.
Clinical trials have shown that a single assisted session can ease symptoms for weeks or even months.
What has been less clear is exactly how the drug reshapes brain circuits.
An international group led by Cornell University has now used an unusual tool to answer that question.
By combining psilocybin with a modified rabies virus that tracks neural connections, they mapped how networks change after a single dose.
- Psilocybin shows promise in treating major depressive disorder
- Wegovy: NHS weight loss drug is no magic pill, experts warn
The work is published in the journal Cell.
From local structural changes to whole brain wiring
Earlier research from the same laboratory showed that psilocybin causes rapid growth of tiny structures called dendritic spines.
These spines are the contact points where neurons connect, and their growth suggests increased potential for new connections.
However, that study did not reveal where the new connections led. The new project aimed to chart the broader wiring diagram after psilocybin, rather than looking at isolated synapses.
To do this, researchers gave mice a single dose of psilocybin, targeting frontal cortical neurons that are thought to play a role in mood and cognition.
One day later, they injected a variant of the rabies virus engineered to travel across one synapse and label connected neurons with fluorescent markers.
After a week, they examined the whole brain and compared these maps with those from control animals that had received the virus without psilocybin.
Breaking feedback loops and boosting sensory pathways
The maps revealed two striking patterns.
First, recurrent connections within the cortex were weakened. These feedback loops are thought to support self referential thought.
When they become overactive, they may trap people in cycles of negative thinking.
By dampening these loops, psilocybin may help loosen rigid patterns of rumination, giving the brain a chance to adopt new perspectives.
This fits with reports from patients who describe feeling less stuck in their usual thoughts after psychedelic therapy.
Second, connections between sensory areas and subcortical regions involved in linking perception to action were strengthened.
- Self-affirmations provide significant and long-lasting psychological benefits
- Skin problems could be early warning sign of serious mental health risks in those with psychosis
In simple terms, the brain seemed to become more ready to turn sensory input into behaviour.
This might help explain why colours, sounds and bodily sensations often feel more vivid and significant under psilocybin, and why therapy sessions place such emphasis on music and environment.
Activity shapes which circuits are rewired
The study also found that areas of the brain that were more active during and after psilocybin were more likely to gain or lose connections.
When the researchers artificially altered activity in a particular region, they could change how psilocybin rewired that part of the circuit.
This suggests that what a person experiences and does during a psychedelic session may influence which connections are strengthened.
It supports the idea that setting, psychological support and the participant’s focus are not side issues but central components of treatment.
