Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations

This double-blind, placebo-controlled, within-subjects study (n=50) investigated the psilocybin-induced (12-15mg/70kg) spiritual experiences and insightfulness in healthy humans to understand the state of consciousness-related neuronal mechanisms using high-density electroencephalogram (EEG) recordings. The results identified a correlation between the intensity levels of psilocybin-induced spiritual experience and EEG measures. The study proposed that the identified mechanism may help find a way for modulating mental health considering that spiritual experiences improve well-being and psychological resilience.

Abstract

“Rationale: During the last years, considerable progress has been made toward understanding the neuronal basis of consciousness by using sophisticated behavioral tasks, brain-imaging techniques, and various psychoactive drugs. Nevertheless, the neuronal mechanisms underlying some of the most intriguing states of consciousness, including spiritual experiences, remain unknown.

Objectives: To elucidate state of consciousness-related neuronal mechanisms, human subjects were given psilocybin, a naturally occurring serotonergic agonist and hallucinogen that has been used for centuries to induce spiritual experiences in religious and medical rituals.

Methods: In this double-blind, placebo-controlled study, 50 healthy human volunteers received a moderate dose of psilocybin, while high-density electroencephalogram (EEG) recordings were taken during eyes-open and eyes-closed resting states. The current source density and the lagged phase synchronization of neuronal oscillations across distributed brain regions were computed and correlated with psilocybin-induced altered states of consciousness.

Results: Psilocybin decreased the current source density of neuronal oscillations at 1.5–20 Hz within a neural network comprising the anterior and posterior cingulate cortices and the parahippocampal regions. Most intriguingly, the intensity levels of psilocybin-induced spiritual experience and insightfulness correlated with the lagged phase synchronization of delta oscillations (1.5–4 Hz) between the retrosplenial cortex, the parahippocampus, and the lateral orbitofrontal area.

Conclusions: These results provide systematic evidence for the direct association of a specific spatiotemporal neuronal mechanism with spiritual experiences and enhanced insight into life and existence. The identified mechanism may constitute a pathway for modulating mental health, as spiritual experiences can promote sustained well-being and psychological resilience.“

Authors: Michael Kometer, Thomas Pokorny, Erich Seifritz & Franz X. Vollenweider

Summary

Abstract

In this double-blind, placebo-controlled study, 50 healthy human volunteers received psilocybin and their EEGs were recorded during eyes-open and eyes-closed resting states.

Psilocybin decreased the current source density of neuronal oscillations at 1.5 – 20 Hz and correlated with the lagged phase synchronization of delta oscillations.

Introduction

Spiritual experiences are rare but significant phenomena of consciousness, which have been the subject of countless psychological, religious, sociological, and philosophical discussions across human history. However, their neuronal correlates are largely unknown, because systematic assessment is hampered by their infrequent and unpredictable occurrence.

Recent placebo-controlled studies showed that psilocybin can be used to induce spiritual experiences, often paired with a marked experience of unity, insightfulness, and bliss. These experiences were rated as authentic and among the most spiritually significant events of their lives.

Neuronal oscillations are thought to be a key mechanism for shaping consciousness, and anesthesia-induced loss of consciousness is associated with changes in neuronal oscillations. However, whether neuronal oscillations also mediate specific states of consciousness remains unknown.

Serotonergic hallucinogens decrease neuronal oscillations across a broad frequency range in the prefrontal areas of the brain and increase oscillations in subcortical structures. These effects are independent of the association of these oscillations with identifiable conscious states.

Serotonergic hallucinogens decrease the power of lower frequency oscillations, especially alpha oscillations, and may have different functional consequences depending on the cortical area of interest. This may account for some hallucinogen-induced states of consciousness.

We administered psilocybin to 50 healthy human volunteers to alter consciousness and induce spiritual experiences. We then used electrophysiological neuroimaging methods to characterize psilocybin-induced alterations in the current source density of neuronal oscillations during eyes-open and eyes-closed resting states.

Subjects

Fifty-five healthy human subjects were enrolled. Pregnant women were excluded, and psychiatric disorders were diagnosed using a mini-interview, an expert system, and a self-report drug use questionnaire.

Subjects were informed about the procedures of the study, were asked to abstain from caffeine and other psychoactive substances, and were not allowed to drink alcohol within 48 h before measurements or to consume any illegal psychoactive substance within 3 weeks before measurements.

Substance and dosing

In three double-blind, placebo-controlled, within-subject, randomized pharmacological studies, 50 subjects received placebo, ketanserin, ergotamine, or buspirone, followed by placebo, psilocybin, on four different days. The data from these two testing sessions were used to calculate robust correlations between the psilocybin-induced altered states of consciousness and neuronal oscillations.

Experimental design

Subjects took psilocybin or placebo and were asked to keep their eyes closed or open while they were recording their EEG. The EEG was recorded for 2 min and 2.5 min and a self-reported questionnaire was given after the drugs disappeared.

Acute subjective drug effects

The 5DASC/OAV is a self-rating scale used to assess the structure and components of altered states of consciousness, including spiritual experiences.

A validated scale was developed to measure altered states of consciousness (ASCs), which can be measured across drug conditions, settings, and sexes. It includes 11 subscales, including experience of unity, spiritual experience, blissful state, insightfulness, changed meaning of percepts, disembodiment, impaired control and cognition, anxiety, elementary imagery, complex imagery, audio-visual synesthesia.

EEG recordings

EEG data were recorded from 64 scalp electrodes and two additional electrodes were attached to the left eye to record electroocculograms.

Preprocessing of EEG data

Data were filtered offline with a low cutoff of 0.5 Hz, interpolated using spherical splines, and inspected by a trained researcher to remove artifacts. The number of artifact free epochs did not significantly differ between drug or eyes-open/closed conditions.

Current source density of neuronal oscillations

Exact low-resolution brain electromagnetic topography (eLORETA) was applied to compute the three-dimensional intracerebral current density values of the scalp-recorded EEG rhythms. eLORETA has no localization bias even in the presence of structured noise and was found to have a slightly increase localization performance compared to the previous version, calledsLORETA.

We used eLORETA with a three-shell spherical head model registered to the digitized MRI version of the Talairach and Tournoux atlas to calculate the intracranial spectral density for eyes-open and eyes-closed conditions.

We corrected for multiple comparisons across voxels and frequencies, calculated the correlation between the current source density in the psilocybin condition and the 11 states of consciousness, and determined the cortical voxels with significant effects.

Lagged phase synchronization of neuronal oscillations

Lagged phase synchronization is a novel index based on normalized Fourier transforms that measures phase-synchronization between two regions of interests (ROIs) after removing the zero-lag contribution. It has been increasingly used in recent studies combining EEG-based lagged phase synchronization measurements with MRI-based diffusion tensor imaging.

We used a whole-brain Broadmann areas (BAs) approach to prevent bias in selecting regions of interest for lagged phase synchronization analysis.

Statistical differences in lagged phase synchronization between placebo and psilocybin conditions were assessed using dependent samples t tests, and the association between lagged phase synchronization and state of consciousness was assessed using a product-moment correlation.

Acute consciousness-altering effects of psilocybin

Psilocybin significantly increased scores on all subscales of the Altered States of Consciousness questionnaire (5D-ASC), except for elementary hallucinations and blissful states, which revealed high scores with higher doses.

Current source density of neuronal oscillations

Psilocybin significantly decreased current source density in all frequency bands up to 20 Hz in the eyes-closed condition and all frequency bands up to 30 Hz in the eyes-open condition. This effect was more widespread in the theta (4 – 8 Hz) and alpha1 (8 – 10.5 Hz) frequency bands.

Psilocybin increased high-frequency oscillations in the RSC during the eyes-closed condition and had a trend toward increasing high-frequency oscillations in the parahippocampal gyrus during the eyes-open condition.

Correlation analysis revealed that only the score of insightfulness significantly correlated with current source density of neuronal oscillations during the eyes-open condition. This is because the current source density in the alpha2 frequency band in very posterior, medial parieto-occipital areas was maximal.

Lagged phase synchronization of neuronal oscillations

Psilocybin increased lagged phase synchronization of delta oscillations between right BA 7 and left BA 39 and between BA27 and BA34, BA29 and BA34, and BA28 and BA47, and between BA20 and BA41 during the eyes-closed condition. This increased lagged phase synchronization was strongly correlated with insightfulness and spiritual experiences scores.

Discussion

The serotonergic hallucinogen psilocybin decreased ongoing oscillations in the PCC, the RSC, the anterior cingulate cortex, and parahippocampal regions during the resting state, but increased high-frequency oscillations in the RSC.

The serotonergic hallucinogenic brew ayahuasca attenuated ongoing oscillations up to 20 Hz, and psilocybin and DMT attenuated ongoing oscillations below 20 Hz, particularly theta/alpha oscillations.

Psilocybin modulated lower-frequency oscillations in the PCC, the RSC, the ACC, and parahippocampal regions, which overlapped with the default-mode network, which has been associated with altered states of consciousness.

The strong decrease in lower-frequency oscillations seen in this study may be indicative of a shift of the resting excitation/inhibition balance (E/I balance) toward excitation, which may contribute to the psilocybin-induced alterations in the state of consciousness.

Psilocybin elevates the E/I balance and disrupts the temporal structure of neuronal processes in the extended DMN, which may alter self-referential processing and thereby lead to psilocybin-induced alterations in a state of consciousness.

We found that lagged phase synchronization of delta oscillations between parahippocampal regions, between parahippocampal regions and the lateral orbitofrontal cortex, and between parahippocampal regions and the RSC was strongly associated with the psilocybin-induced state of consciousness. This finding supports the view that neural integration, rather than activity, underlies the state of consciousness.

The phenomenological descriptions of hallucinogen-induced insightfulness and spiritual experiences fit well with our interpretation that psilocybin-induced spiritual experiences are associated with a reorganization of the self within the global spatial context mediated by phase synchronization of delta oscillations.

Phase-synchronization processes were specifically associated with insightfulness and spiritual experiences, but not with other psilocybin-induced phenomena. Furthermore, the correlation was only seen during eyes-closed condition, suggesting that additional network processes are implicated in a full blown mystical/spiritual experience.

The neuronal network processes underlying spiritual experiences and insightfulness may constitute a crucial pathway that can be modulated by serotonergic receptors to regulate mental health.