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.

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.“

Authors: Lukasz Smigielski, Milan Scheidegger, Michael Kometer & Franz X. Vollenweider

Summary

Psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition. A 5-day mindfulness retreat containing psilocybin altered the self-referential processing regions of the default mode network, which was associated with subjective ego dissolution and positive changes in psychosocial functioning 4 months later.

1. Introduction

Psilocybin induces profound alterations in consciousness and may be used to treat clinical conditions such as addiction, end-of-life anxiety, and depression. However, it remains unclear which neuronal underpinnings are associated with those drug-induced experiences and how extra-pharmacological variables known as set and setting may shape drug responses.

There are several similarities between psychedelic-induced and meditative states of consciousness, including self-transcendence, and a contemplative setting that facilitates mindfulness may also deepen psychedelic experiences.

Meditation is a set of mental practices for the cultivation of mindfulness, which is defined as attentiveness and non-judgmental acceptance of present-moment experience. Scientific studies highlight post-meditation neuroplastic changes, which start after a few days of practice.

The default mode network (DMN) is a large-scale network that functionally integrates distant brain nodes and mediates among other phenomena, such as wakefulness, awareness, and memory, a variety of self-related cognitions. Modulations of the DMN may facilitate states of self-transcendence, a proposed key treatment mediator in psychedelic-assisted therapies.

We administered psilocybin to experienced meditators at a 5-day retreat and measured functional connectivity in the brain before and after the retreat. We hypothesized that psilocybin-induced modulations in brain networks relevant for self-referential processing mediate acute and lasting retreat outcomes.

2.2. Study procedures

The scale measures subjective effects after placebo/psilocybin intake. It is composed of 94 visual-analogue items, clustered in five dimensions.

2.3.2. Persisting Effects Questionnaire (PEQ)

The PEQ was administered to measure follow-up effects of psychedelic experiences. The instrument was sensitive to follow-up changes in studies involving psilocybin and other psychoactive drugs.

2.5. Preprocessing

Spatial preprocessing was performed with SPM v12, including slice-time correction, realignment, segmentation of structural data, normalization into the stereotactic MNI template, and smoothing with a 6-mm full-width-at-half-maximum Gaussian kernel. Outliers were calculated using Artifact Detection Tools, and physiological noise was removed using the CompCor strategy.

2.6. Independent component analysis

ICA is a data-driven blind source separation method that generates spatial components using the principle of maximal and statistically grounded independence. The optimal number of components was estimated using the minimum description length criterion. Data were pre-normalized, a principal component analysis was performed, and an independent component analysis (ICA) was performed. GICA was used as a back-reconstruction method, and the ICA results were assessed at a FDR-corrected p 0.05 threshold.

2.8. Statistics

The 5D-ASC data were analyzed with a repeated-measures two-way ANOVA, a two-sample t-test, and a stepwise multiple regression using the forward stepwise model. Data are available upon direct request.

3.1. Acute subjective drug effects

Psilocybin significantly increased scores on the Five Dimensional Altered States of Consciousness scale compared to the placebo, but not on the Dread of Ego Dissolution or Auditory Alterations scales.

3.2. Identification of DMN components

Using independent component analysis (ICA), the posterior DMN, antero-ventral DMN, and antero-dorsal DMN were identified as the three networks of interest.

3.3. ICA spatial maps analysis

We found significant interaction effects and pre-post connectivity changes in the anterior-cingulate and medio-prefrontal cortex within the avDMN. No other statistically significant changes were found in the adDMN or pDMN at rest or in the other conditions.

4. Discussion

A 5-day psilocybin-assisted mindfulness retreat significantly potentiated positively felt states of ego dissolution (i.e., OSB) in experienced meditators, and decoupled functional connectivity between anterior (mPFC) and posterior (PCC) regions of the DMN during oceanic self-boundlessness meditation.

Psilocybin has been shown to affect brain regions involved in self-awareness, including the DMN, which is also affected by LSD, ayahuasca, and meditation. We hypothesized that psilocybin-induced states of self-transcendence specifically affect antero-posterior DMN connectivity during meditation. Although FA and OA are common mindfulness practices, they differ in the neural architecture supporting their cognitive processes. In particular, the extent of post-intervention antero-posterior DMN disintegration during OA was correlated with decreased self-referential focus under psilocybin.

The medio-prefrontal DMN is a key nexus for self-related cognition and emotion regulation, and psilocybin-related modulations at rest were mainly comprised of higher mPFC/ACC connectivity within the antero-ventral DMN. However, we failed to detect any pre-post-retreat changes in anterior DMN connectivity in our placebo group.

Psilocybin increases the variance and amplitudes of the BOLD signal in the ACC, which may be a marker of increased synchronization and wider dynamic repertoires of connectivity states. This finding may be relevant to the understanding of the neural mechanisms underlying psilocybin’s putative therapeutic effects.

Both meditation- and psychedelic-induced states of transcendence may rely on altered communication and large-scale desynchronization between the inferior parietal lobe (IPL) and other nodes of the default mode network (DMN), comprising a tripartite ‘core-self’ system.

Newberg proposed that deafferentation of the posterior parietal lobes from the prefrontal cortex is a neural correlate of mystical-type experiences. Psilocybin-assisted mindfulness practice facilitates states of self-transcendence and may decrease functional connectivity of the tripartite ‘core-self’ system during OA meditation.

Previous attempts to identify neural correlates of the self have focused on the DMN, highlighting its role in ego-identity or the narrative self. However, we did not find any modulations of DMN – MTL connectivity two days after psilocybin administration.

Psychedelic drugs can have transformative effects in healthy volunteers and may contribute to enduring psychological changes. The psilocybin experience in our study correlated with positively valued mean changes in attitudes about life, self, social behavior, mood, and spirituality.

Transformative processes might result from drug-induced alterations in functional network connectivity, which in turn increase global brain plasticity with lasting behavioral outcomes. Psilocybin increases the dynamic repertoire of DMN function, which may be a mechanism of psilocybin’s antidepressant properties. Higher DMN integration at rest is predictive of lasting behavioral outcomes at the 4-month follow-up.

The present work has some limitations, but experienced meditators did not experience any significant adverse drug reactions. A caution should be made on the use of mind-altering drugs in unprepared individuals with uncleared health histories.

Psilocybin-induced functional connectivity changes in self-referential brain networks in a group of experienced meditators after a mindfulness retreat. These effects were correlated with positively felt ego dissolution under psilocybin-assisted meditation and were predictive of behavioral outcomes 4 months later.

Acknowledgements

This study was supported by the Swiss Neuromatrix Foundation and was guided by Zen expert Vanja Palmers.