Psilocybin Modulates TPJ Effective Connectivity during Out-of-Body Experiences
Devon Stoliker, Fosco Bernasconi, Olaf Blanke, Adeel Razi
medRxiv June 25, 2025 preprint DOI: 10.1101/2025.06.24.25330245 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label, baseline-controlled MRI study |
|---|---|
| Sample size | 62 |
| Population | Healthy adults |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Hallucinogen Functional connectivity Cognitive psychology |
| Citations | 1 |
| Key points | In participants reporting high-intensity out-of-body experiences, psilocybin reduced effective connectivity from the right to left anterior insula and between the right anterior insula and right temporoparietal junction. |
Abstract
Abstract Serotonergic psychedelics alter self-boundaries and can induce out-of-body experiences (OBEs)—the sense of being located outside one’s physical body. While OBEs also occur in clinical conditions and can be experimentally induced, their neural basis under psychedelics remains underexplored. In an open-label, baseline-controlled MRI study of 62 healthy adults administered psilocybin, we examined effective connectivity changes in regions implicated in clinical and induced OBEs. Spectral dynamic causal modelling (spDCM) was applied to resting-state and music-listening scans to estimate connectivity changes from baseline and assess their consistency across contexts. Participants were grouped by self-reported OBE symptom intensity at the end of the dosing day. In those reporting high-intensity OBEs, psilocybin reduced effective connectivity from the right to left anterior insula and between the right anterior insula and right temporoparietal junction (TPJ), inhibiting these connections across both scan types. These changes parallel known disruptions in TPJ–insula circuits linked to OBEs in clinical and experimental settings, particularly in the right hemisphere. Our findings highlight how psilocybin-induced disembodiment corresponds to altered effective connectivity and demonstrate the utility of spDCM for mapping causal neural dynamics underlying bodily self-consciousness.
Comparable studies
Other non-randomized and open-label trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression | 2016 | Open-label feasibility trial | n = 12 |
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Psychiatrically healthy nicotine-dependent smokers | 2014 | Open-label pilot study | n = 15 |
| Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression | 2018 | Clinical trial | n = 20 |
| Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder Subjects with obsessive-compulsive disorder (OCD) | 2006 | Controlled clinical trial |
Citations in the library
Cites 42
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Out‐of‐body experience and autoscopy of neurological origin Brain January 15, 2004
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Linking Out-of-Body Experience and Self Processing to Mental Own-Body Imagery at the Temporoparietal Junction Journal of Neuroscience January 19, 2005
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
and 37 more in the library