Psilocybin desynchronizes the human brain

Area of Science:

• Neuroscience
• Psychopharmacology
• Neuroimaging

Background:

• Psilocybin, a psychedelic, shows rapid therapeutic effects in humans and induces neuroplasticity in animals.
• The relationship between brain network alterations and the lasting effects of psychedelics remains unclear.

Purpose of the Study:

• To investigate individual-specific brain network changes following psilocybin administration using longitudinal functional mapping.
• To correlate these brain changes with subjective experiences and assess their persistence.

Main Methods:

• Longitudinal precision functional mapping (fMRI) in healthy adults before, during, and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg).
• Assessed functional connectivity (FC) changes, network distinctions, and connectivity between the anterior hippocampus and default mode network.
• Tracked participants for 6-12 months for a second psilocybin dose and assessed persistent effects.

Main Results:

• Psilocybin caused significant, dose-dependent disruption of cortical and subcortical functional connectivity, exceeding methylphenidate's effects.
• Brain desynchronization reduced network distinctions, with the most pronounced changes in the default mode network.
• Individual differences in FC changes correlated with subjective psychedelic experiences.
• A persistent decrease in FC between the anterior hippocampus and default mode network was observed for weeks after psilocybin administration.

Conclusions:

• Psilocybin profoundly disrupts brain functional connectivity, driving network desynchronization and altering network distinctions.
• Persistent reduction in hippocampal-default mode network connectivity may underlie the proplasticity and therapeutic potential of psychedelics.
• Individual brain responses to psilocybin are linked to subjective effects, suggesting personalized therapeutic mechanisms.