Regional specificity of the cingulate cortex thickness association with the intensity of psilocybin experience: a replication study
David Greguš, Jaroslav Hlinka, Filip Tylš, Vojtěch Viktorin, Michaela Viktorinová, Anna Bravermanová, Renáta Androvičová, Veronika Andrashko, Jakub Korčák, Marek Nikolič, Petr Adámek, Michal Beneš, Tomáš Páleníček, Jiřı́ Horáček
Psychopharmacology December 13, 2025 DOI: 10.1007/s00213-025-06983-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled crossover design Peer reviewed |
|---|---|
| Sample size | 25 |
| Population | Healthy participants |
| Intervention | Psilocybin |
| Dose | 0.26 mg/kg |
| Topics | Default mode network Psilocybin |
| Keywords | Anterior cingulate cortex Association psychology Cortex anatomy Posterior cingulate Error-related negativity Magnetic resonance imaging Amygdala Brain mapping Consciousness Hypnosis |
| Data | Zenodo |
| Key points | An anterior–posterior gradient in cingulate thickness significantly predicted psychedelic experience intensity, while the previously reported association between rostral anterior cingulate cortex thickness and emotional responses did not reach statistical significance. |
Abstract
Individual variability in psilocybin response is a major challenge for psychedelic-assisted therapy, with structural brain features potentially serving as predictive biomarkers. (Lewis et al. Biomedicines 8(2):34 2020) reported that rostral anterior cingulate cortex thickness predicted emotional experiences under psilocybin, suggesting cortical morphometry as a marker of psychedelic responsivity. This study sought to replicate and extend these findings by examining associations between cingulate thickness and psilocybin-induced altered states of consciousness using comprehensive assessment and rigorous statistical control. Twenty-five healthy participants underwent a double-blind, placebo-controlled crossover design with psilocybin (0.26 mg/kg) and placebo. High-resolution T1-weighted magnetic resonance imaging (MRI) measured cortical thickness across cingulate subregions. Subjective effects were assessed with the Altered States of Consciousness (ASC) questionnaire. Analyses applied false discovery rate (FDR) correction for multiple comparisons. The primary Lewis et al. finding—that rostral anterior cingulate cortex thickness predicts emotional psilocybin responses—showed a comparable effect size (β = 0.523 vs. their range 0.324–0.572) that did not achieve statistical significance (p = 0.297), likely reflecting limited statistical power given our smaller sample (N = 25 vs. N = 55). We identified an anterior–posterior gradient in cingulate thickness that significantly predicted psychedelic experience intensity (r = 0.676, FDR p = 0.0004). Findings indicate that spatial organization within the cingulate cortex provides a neuroanatomical marker of variability in psychedelic response. Results highlight the importance of organizational patterns within the cingulate cortex, rather than focal regional measures, when predicting psychedelic effects.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cites 19
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
and 14 more in the library