Changes in self-related cognitive processes and depressive symptom severity following a single, moderate dose of psilocybin in depressed patients.
Lydia Belinger, Flora Moujaes, Robin von Rotz, Nathalie M Rieser, Xaver Funk, Klemens Egger, Lena Meinhold, Maike Renkert, Philipp Stämpfli, Marcus Herdener, Franz X Vollenweider, Katrin H Preller
Philosophical transactions of the Royal Society of London. Series B, Biological sciences November 10, 2026 DOI: 10.1098/rstb.2025.0168 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled clinical trial Peer reviewed |
|---|---|
| Sample size | 37 |
| Population | Individuals diagnosed with major depressive disorder |
| Interventions | Psilocybin psychological support |
| Dose | 0.215 mg kg-1 |
| Duration | Assessments two weeks after substance administration |
| Measures | Beck's depression inventory, Montgomery-Åsberg depression rating scale, Frankfurt self-concept scale, fMRI-based self-referential processing task |
| Topics | Depression Psilocybin Psychedelic-assisted therapy |
| Keywords | Self-concept Self-referential processing |
| Key findings | Two weeks after a single moderate dose of psilocybin (0.215 mg/kg) with psychological support, participants with major depressive disorder showed significant reductions in depressive symptoms and a significant increase in positive self-concept compared with placebo; self-concept changes correlated with decreased depressive scores. Neuroimaging showed psilocybin-associated modulation of caudate activation during externally oriented attention, contrasting with placebo-induced caudate changes during self-referential processing. |
Abstract
Psychedelic-assisted therapy, particularly with psilocybin, is increasingly proposed as a treatment for major depressive disorder, yet the neural and psychological mechanisms underlying its effects remain under investigation. In a randomized, double-blind, placebo-controlled clinical trial, individuals diagnosed with major depressive disorder received a single, moderate dose of psilocybin (0.215 mg kg-1) or placebo, with the same psychological support. We analysed N = 37 individuals with major depressive disorder undergoing assessments of depressive symptoms (Beck's depression inventory and Montgomery-Åsberg depression rating scale), self-concept (Frankfurt self-concept scale) and neural markers of self-referential processing using an fMRI-based task. Compared with placebo, the psilocybin group exhibited significant reductions in depressive symptoms and a significant increase in positive self-concept two weeks after substance administration. Changes in self-concept were significantly correlated with decreased depressive scores. Neuroimaging revealed psilocybin-associated modulation of caudate activation during externally oriented attention after two weeks, contrasting with placebo-induced caudate changes during self-referential processing. These findings extend prior evidence linking psychedelics to changes in self-referential processing and self-concept and demonstrate that such changes occur concurrently with reductions in depressive symptoms. Future research should aim to replicate and extend these results and refine therapy protocols targeting self-processing and self-concept in psychedelic-assisted therapy in major depressive disorder. This article is part of the discussion meeting issue 'From being to identity: analysis and synthesis of the self'.