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

Spiritual experiences are rare but salient states of consciousness that can promote sustained well-being and resilience, yet their neuronal correlates remain poorly understood because such experiences are infrequent and unpredictable. Earlier research has focused largely on traits that predispose individuals to transcendent experiences, and recent placebo-controlled pharmacological studies have shown that the serotonergic hallucinogen psilocybin can dose-dependently elicit profound spiritual experiences, unity, insightfulness and bliss. Neuronal oscillations and their phase synchronization are proposed mechanisms of neuronal integration that shape conscious states; previous animal and human work with serotonergic hallucinogens (and related preparations such as ayahuasca/DMT) has suggested decreases in low-frequency oscillatory power, particularly in the alpha band, but whether oscillatory power or interregional phase relationships specifically underpin spiritual experiences is unresolved. This study by Kometer and colleagues set out to characterise how psilocybin alters the spatial distribution of neuronal oscillatory power and the dynamic coordination of oscillations across brain regions, and to test whether these electrophysiological changes correlate with psilocybin-induced spiritual experiences and insightfulness. Using a double-blind, placebo-controlled, within-subject design in healthy volunteers, the investigators recorded high-density EEG during eyes-open and eyes-closed resting states, computed intracerebral current source density and lagged phase synchronization across frequency bands, and related these measures to scores on the validated 5D-ASC questionnaire assessing altered states of consciousness.

Fifty-five healthy volunteers were recruited and screened by physical exam, electrocardiography, blood analyses, psychiatric interviews and urine drug testing; five were excluded for EEG-artifact contamination, leaving 50 participants (28 males, 22 females; mean age 24.8 ± 4.0 years) for analysis. The study pooled data from three parallel double-blind, placebo-controlled, within-subject pharmacological studies in which each participant completed four sessions (placebo+placebo, placebo+psilocybin, drug1+placebo, drug1+psilocybin) with sessions separated by at least 2 weeks. For the present analyses only the two placebo-controlled sessions (placebo+placebo and placebo+psilocybin) were used. Psilocybin doses were moderate: 170 μg/kg p.o. for most subjects and 215 μg/kg p.o. in one subgroup, administered 1 hour after the first capsule; the choice of moderate dosing was motivated in part by the need to minimise facial-muscle artefacts in the EEG. EEG was recorded from 64 scalp electrodes (BioSemi ActiveTwo) at 512 Hz in a shielded room 60 minutes after administration. Resting-state recordings comprised eyes-open (gaze fixed on a central cross) and eyes-closed conditions, presented in randomised order; each eyes condition lasted 2 min in study 1 and 2.5 min in studies 2–3. Vigilance was monitored and investigators intervened if strong drowsiness appeared. Subjective effects were measured after drug effects subsided using the 5D-ASC questionnaire (11 subscales including spiritual experience, experience of unity, insightfulness and blissful state). EEG preprocessing included filtering (low cutoff 0.5 Hz), removal of ocular and muscle artifacts via infomax ICA, interpolation of bad channels, average re-reference, segmentation into 2-s epochs and visual inspection to remove residual artefacts. Mean artifact-free epoch counts per condition were reported (≈116–124 epochs) and did not differ significantly between drug or eyes conditions. eLORETA source localisation was applied to compute three-dimensional intracerebral current density across 6,239 voxels (5×5×5 mm resolution) restricted to cortical grey matter and hippocampus. Eight frequency bands were analysed: delta (1.5–4 Hz), theta (4–8 Hz), alpha1 (8–10.5 Hz), alpha2 (10.5–13 Hz), beta1 (13–20 Hz), beta2 (20–30 Hz), gamma1 (30–45 Hz), and gamma2 (55–100 Hz). Voxel-wise dependent t tests compared current source density between placebo and psilocybin for each band and condition, with 5,000 permutations used to estimate the empirical null distribution and correct for multiple comparisons. Interregional coordination was assessed via lagged phase synchronization computed in eLORETA source space. Lagged phase synchronization quantifies the phase relationship between two regions after removing zero-lag contributions, thereby reducing volume-conduction and instantaneous-artifact confounds; the analysis used centroids of 42 Brodmann areas per hemisphere as regions of interest and calculated pairwise lagged phase synchronization across all ROI pairs for each frequency band and eyes condition. Dependent-samples t tests with 5,000 permutations corrected for multiple comparisons were used to test drug effects on lagged phase synchronization, and product-moment correlations (with permutation-based thresholding) related lagged phase synchronization values in the psilocybin condition to the 11 5D-ASC subscale scores.

Subjective effects: Repeated-measures ANOVA on 5D-ASC scores showed a robust main effect of drug (psilocybin vs placebo; F(1,48)=64.23, p<0.00001) and of subscale (F(10,480)=20.57, p<0.00001), with no significant main effect of dose (170 vs 215 μg/kg). Post hoc tests indicated that psilocybin significantly increased scores on all 11 subscales (all p<0.05), including spiritual experience, experience of unity, blissful state and insightfulness (all p<0.00001). Higher dose produced slightly higher scores on elementary hallucinations (p<0.05) and blissful state (p<0.01), but doses were overall similar. Current source density: In the eyes-closed condition psilocybin significantly decreased intracerebral current source density across oscillations from 1.5–20 Hz (p max = 0.00020, corrected), and in the eyes-open condition decreases extended up to 30 Hz (p max = 0.00020, corrected). The most consistent reductions in low-frequency power (<20 Hz) were localised to the posterior cingulate cortex (PCC; BA23/31) and the retrosplenial cortex (RSC; BA30), with additional decreases in the anterior cingulate cortex (ACC; BA24), precuneus (BA31), cuneus (BA30), parahippocampal gyrus (BA27/30) and other RSC areas (BA29). Theta and alpha1 band decreases were more widespread and included insula (BA13), occipitotemporal cortex (BA37) and parahippocampal regions (BA35/36). In the alpha1/alpha2 bands reductions covered large posterior occipital–parietal areas (BA7, BA17–19), especially on the right. There were no significant group-level effects in the gamma1 band (30–45 Hz). High-frequency oscillations (55–100 Hz) exhibited a psilocybin-induced increase in the left RSC (BA29) during eyes-closed (p max = 0.020, corrected) and a trend-level increase in RSC during eyes-open (p max = 0.054, corrected). Correlations between current source density and subjective state were limited. Only the insightfulness subscale correlated significantly with current source density in the alpha2 band (10.5–13 Hz) in very posterior medial parieto-occipital areas during the eyes-open condition; importantly, this region was not reduced by psilocybin at the group level, suggesting that intact alpha2 power in that posterior area related to higher insightfulness when other surrounding areas were reduced. No other 5D-ASC subscales showed significant correlations with current source density after correction. Lagged phase synchronization: Psilocybin produced a small increase in interhemispheric lagged phase synchronization of delta oscillations (1.5–4 Hz) during eyes-open, reaching significance between right BA7 and left BA39 (p max = 0.017, corrected); a trend was observed in eyes-closed (p max = 0.063, corrected). Crucially, within the eyes-closed condition the intensity of insightfulness and spiritual experiences correlated strongly and specifically with lagged phase synchronization of delta oscillations within a network of deep cortical structures. Insightfulness correlated with delta lagged phase synchronization between BA27–BA34, BA29–BA34, and BA28–BA47 (p max = 0.0028, corrected), while spiritual experience scores correlated with synchronization between BA28–BA29, BA34–BA29, and BA20–BA41 (p max = 0.029, corrected). The other nine 5D-ASC subscales showed no significant correlations with lagged phase synchronization in any frequency band (p max = n.s.), indicating specificity of these associations. Some reported effects reached only trend-level significance after correction.

Kometer and colleagues interpret their findings as evidence that psilocybin decreases ongoing lower-frequency oscillations (1.5–20 Hz), especially in theta/alpha bands, within an extended network centred on PCC, RSC, ACC and parahippocampal regions—areas that overlap substantially with the default-mode network (DMN). The investigators note that similar reductions in lower-frequency power have been observed with other serotonergic hallucinogens and that 5-HT2A receptor activation mediates decreases in alpha oscillations; they therefore propose that attenuation of ongoing lower-frequency oscillations, particularly in the DMN, may be a common action of serotonergic hallucinogens. The modest increase in high-gamma power in RSC is interpreted as consistent with an excitation/inhibition (E/I) shift toward excitation, and the authors suggest that disruption of lower-frequency rhythms may perturb the temporal structure of neuronal processing and thereby alter self-referential functions associated with the DMN, contributing to experiences such as unity. However, the authors emphasise that regional power decreases were only weakly associated with subjective reports: after correction, only insightfulness correlated with alpha2 power in a posterior parieto-occipital area during eyes-open. By contrast, lagged phase synchronization emerged as the stronger electrophysiological correlate of specific subjective states. The authors highlight that increased lagged phase synchronization of delta oscillations between parahippocampal areas, the RSC and lateral orbitofrontal cortex correlated with insightfulness and spiritual experience scores, and they link these regions and frequency band to autobiographical memory retrieval, memory valence attribution and coding of self-location within a global spatial context. From this perspective, insightfulness may reflect increased retrieval and reattribution of autobiographical memories, while spiritual experiences may involve a reorganisation of the self in a broader spatial context mediated by delta-phase coupling. The investigators stress the specificity of these associations: lagged phase synchronization correlations were observed for insightfulness and spiritual experiences but not for other psilocybin-induced phenomena (for example blissful state or disembodiment), and significant correlations were found primarily in the eyes-closed condition. They therefore suggest that eyes-closed resting-state paradigms may be particularly suitable for probing the neuronal mechanisms of these experiences and note that the identified network might be a pathway through which serotonergic modulation influences mental health. The authors refer to prior reports linking spiritual experiences with sustained well-being and to emerging therapeutic findings for psilocybin in mood disorders and anxiety in terminal illness, and they propose that future studies should test whether modulation of lagged phase synchronization among RSC, parahippocampus and lateral orbitofrontal cortex can promote mental health via autobiographical memory processes and changes in self-representation. The authors acknowledge limits inherent in the data: some effects were trend-level after correction, correlations were mostly confined to eyes-closed recordings, and the identified oscillatory changes alone were not sufficient to explain the full range of altered conscious states. They further note methodological choices such as using moderate psilocybin doses to reduce artefacts and restricting analysis to the placebo versus psilocybin sessions; these design features were intended to improve EEG data quality and the robustness of correlations but also shape the generalisability of findings. Overall, the discussion frames the results as providing systematic evidence that specific spatiotemporal neuronal mechanisms—namely decreased low-frequency oscillatory power within the DMN and increased delta-band phase synchronization across parahippocampal–retrosplenial–orbitofrontal networks—are associated with psilocybin-induced spiritual experiences and insightfulness.