Neuroimaging & Brain MeasuresSet & SettingPsilocybin

Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects

This double-blind, placebo-controlled study (n=38) found that psilocybin (22mg/70kg) in combination with mindfulness training elicited changes in the default mode network (DMN) that are associated with ego loss. These changes predicted positive outcomes four months later.

Authors

  • Milan Scheidegger
  • Franz Vollenweider
  • Matthias Kometer

Published

NeuroImage
individual Study

Abstract

Both psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition, but their combined, possibly synergistic effects on neurobiology are unknown. Accordingly, we conducted a randomized, double-blind, placebo-controlled study with 38 participants following a single administration of the psychedelic psilocybin (315 μg/kg p.o.) during a 5-day mindfulness retreat. Brain dynamics were quantified directly pre- and post-intervention by functional magnetic resonance imaging during the resting state and two meditation forms. The analysis of functional connectivity identified psilocybin-related and mental state- -dependent alterations in self-referential processing regions of the default mode network (DMN). Notably, decoupling of medial prefrontal and posterior cingulate cortices, which is thought to mediate sense of self, was associated with the subjective ego dissolution effect during the psilocybin-assisted mindfulness session. The extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later. Psilocybin, combined with meditation, facilitated neurodynamic modulations in self-referential networks, subserving the process of meditation by acting along the anterior-posterior DMN connection. The study highlights the link between altered self-experience and subsequent behavioral changes. Understanding how interventions facilitate transformative experiences may open novel therapeutic perspectives. Insights into the biology of discrete mental states foster our understanding of non-ordinary forms of human self-consciousness and their concomitant brain substrate.

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Research Summary of 'Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects'

Introduction

Smigielski and colleagues situate this study at the intersection of two approaches known to alter consciousness: serotonergic psychedelics (here, psilocybin) and contemplative meditation. Earlier research has shown that both practices can induce self-transcendent experiences and modulate large-scale brain networks, particularly the default mode network (DMN), which supports self-related cognition. However, it remains unclear which neural mechanisms underpin lasting psychological changes after psychedelic experiences and how contextual variables such as meditative training (set and setting) shape these drug effects. The introduction highlights evidence that meditation and psychedelics share phenomenological and neurodynamic features, and it frames the DMN—especially medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) coupling—as a candidate substrate linking altered self-experience to therapeutic outcomes. The present study therefore aimed to test whether a single administration of psilocybin given within a 5-day silent mindfulness retreat would produce state-dependent and lasting changes in DMN functional connectivity, subjective ego-dissolution experiences, and psychosocial behaviour. Using a randomised, double-blind, placebo-controlled, between-subject design in experienced meditators, the investigators measured brain dynamics with resting-state and two meditation-state fMRI scans before and after the retreat, and assessed acute subjective effects and persisting psychological changes up to 4 months later. The authors framed this as the first imaging study to examine the neurodynamics of a potent psychedelic administered specifically within a mindfulness retreat setting.

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