Psilocybin reorganizes large-scale cortical networks in the brain, reveals groundbreaking study

A new study shows that psilocybin, a psychedelic compound found in mushrooms, is capable of reorganizing large cortical networks in the brain in a manner dependent on neuronal activity. The research used advanced neural tracking techniques to map how the substance modifies brain connections associated with perception, cognition, and emotional regulation.

The results indicate that psilocybin strengthens circuits that direct sensory information to subcortical regions, while weakening connections related to recurrent loops between cortical areas, suggesting a selective redesign of the brain's functional architecture.

How the study was conducted

Researchers applied a technique known as monosynaptic rabies tracing, which uses a genetically modified version of the rabies virus to map, with high precision, connections between neurons. The method allows the identification of which brain regions send signals directly to medial prefrontal cortex pyramidal neurons, before and after the administration of psilocybin.

Key findings

• Specific connectivity by brain network: Psilocybin does not act in a generalized manner, but promotes selective changes in specific networks.

• Strengthening of sensory and subcortical pathways: Connections from perceptive regions and the medial network — considered analogous to the default mode network in humans — were reinforced.

• Reduction of cortico-cortical feedback: Inputs associated with feedback circuits between cortical areas showed weakening.

• Activity-dependent plasticity: Synaptic reorganization depends on the electrical activity of neurons during the substance's effect; by silencing specific regions, researchers prevented the psilocybin-induced “rewiring.”

Therapeutic implications

Clinical studies have been demonstrating that psilocybin can generate lasting therapeutic effects in conditions such as major depression and treatment-resistant depression, even after a single dose. The new data help explain this phenomenon, by showing that the substance promotes long-lasting structural plasticity, such as the growth of dendritic spines — fundamental communication points between neurons.