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A single dose of psilocybin rapidly impacts brain connectivity, disrupting networks and potentially driving therapeutic effects. These changes, particularly in the default mode network, persist for weeks, offering insights into psychedelic action.

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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.