Psilocybine mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects, SMIGIELSKI Lukasz et al., 2019

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


NeuroImage, 2019, 196, 207-215

Doi : 10.1016/j.neuroimage.2019.04.009



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.

Keywords : Mindfulness, Meditation, Psychedelic, Consciousness, fMRI, Default mode network


1. Introduction

Psilocybin is a preferential 1A/2A serotonin receptor agonist that dose-dependently induces profound alterations in consciousness (Preller et al., 2017; Preller and Vollenweider, 2018; Vollenweider et al., 1998). Recent research has focused on its potential to facilitate transformative experiences with lasting aftereffects (Griffiths et al., 2011) and treat clinical conditions such as addiction, end-of-life anxiety, and depression (Vollenweider and Kometer, 2010). 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. Converging evidence suggests the quality of a psychedelic experience is influenced by context, including mindset, expectations, and environmental factors (Studerus et al., 2012). Traditionally, psilocybin-induced altered states of consciousness were embedded in indigenous rituals and contemplative practices (Nichols, 2004). These setting variables may increase the drug-induced state of self-transcendence resulting from changes in 5-HT-related synaptic signaling and brain network connectivity, which may be a unique therapeutic mechanism in the action of psychedelic drugs (Preller et al., 2018). Therefore, insights into drug-induced neuronal alterations in self-referential processing and conditions facilitating such experiences may foster our understanding of self-consciousness and promote novel therapeutic approaches to improve mental health and well-being.

There are several similarities and possible synergistic interactions between psychedelic-induced and meditative states of consciousness at the levels of both phenomenology and brain dynamics. First, some subjective psilocybin effects resemble the altered modes of perception and cognition occurring in advanced meditation, including selftranscendence (Letheby and Gerrans, 2017). Second, a contemplative setting that facilitates mindfulness may also deepen psychedelic experiences (Pahnke, 1969). Third, an increase in mindfulness-related capabilities was recently shown after intake of ayahuasca containing the serotonergic psychedelic N,N-dimethyltryptamine (Soler et al., 2016), which is chemically related to psilocybin. We thus expect that mindfulness-related capabilities, such as an increased ability to focus and deepen introspection, may have a beneficial impact on outcomes of psychedelic experiences.

Meditation describes a set of mental practices for the cultivation of mindfulness, defined as attentiveness and non-judgmental acceptance of present-moment experience (Bishop et al., 2004). The therapeutic value of mindfulness techniques has been increasingly recognized owing to their proven beneficial effects on psychosomatic health and well-being (Gotink et al., 2015). Scientific studies highlight post-meditation neuroplastic changes, with lasting effects starting after a few days of practice (van Leeuwen et al., 2012). Different neural correlates have been identified during distinct meditative states such as focused attention (FA; sustained attention on a meditation object, e.g., breath) and open awareness (OA; non reactive monitoring of the content of experience) (Tang et al., 2015). Distinguishing among different styles of meditation provides a useful heuristic for delineating dissociable psychological and neurodynamic effects.

Accumulated evidence highlights common neurobiological signatures for meditative states of self-transcendence (Vago and Silbersweig, 2012) and psychedelic states of ego dissolution (Lebedev et al., 2015), in particular through modulations of activity and connectivity in the default mode network (DMN) (Brewer et al., 2011; Carhart-Harris et al., 2012; Kometer et al., 2015). The DMN (Raichle, 2015) 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 (Qin and Northoff, 2011). Abnormalities in the DMN are linked to symptom severity in various psychiatric disorders, with adaptive changes in DMN function following pharmacological treatments (Fox and Greicius, 2010). Accordingly, the DMN was proposed as a biomarker for monitoring the therapeutic effects of meditation (Simon and Engstr€om, 2015). Modulations of the cortical midline network structures involved in higher order mental processes such as self-referential processing (Qin and Northoff, 2011) may facilitate states of self-transcendence, a proposed key treatment mediator in psychedelic-assisted therapies (Garcia-Romeu et al., 2014). Interestingly, a previous study points to the utility of DMN metrics as neural predictors, by demonstrating that a difference in coupling between the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC), two main DMN hubs, predicted behavioral outcomes that rely on self-referential processing (Tompson et al., 2016).

Building upon the above lines of evidence, the present fMRI-based study aimed to investigate changes in functional connectivity as well as experiential and behavioral markers following psilocybin intake during meditation. To this purpose, we administered a single dose of psilocybin to a group of experienced meditators at a 5-day retreat using a randomized, double-blind, placebo-controlled, between-subject design. The effects of psilocybin-assisted meditation were quantified by fMRI the days before and after the retreat (pre-post intervention) during three experimental conditions: 1) resting state (RS, no meditation), 2) FA, and 3) OA meditation. Functional connectivity offers a window into the organization of large-scale, modular, spatially allocated, and functionally linked areas by analyzing linear dependencies (i.e., correlations) between blood-oxygen level-dependent (BOLD) signal fluctuations (Rogers et al., 2007). We hypothesized that drug-induced modulations in brain networks relevant for self-referential processing, particularly within the DMN, mediate acute and lasting retreat outcomes. As psychedelic drugs are known to induce transformative experiences, we hypothesized that the degree of these modulations in the brain may be predictive of long-term adaptive changes in behaviors and attitudes. To our knowledge, this is the first imaging study to investigate the neurodynamics of a potent consciousness-altering drug in a mindfulness retreat setting.