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

A single dose of psilocybin (315 μg/kg) combined with a 5-day mindfulness retreat altered brain connectivity in the default mode network, particularly decoupling the medial prefrontal and posterior cingulate cortices. This decoupling correlated with the subjective experience of ego dissolution during meditation. The extent of ego dissolution and brain connectivity changes predicted improvements in psycho-social functioning four months later. The findings suggest that psilocybin-assisted meditation facilitates neurodynamic changes in self-referential networks, linking altered self-experience to lasting behavioral changes.

Study at a glance

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.