One dose of Psilocybin modulates Brain Activity among Depressive patients : Preliminary Neuroimaging Results from the PSILODAC Study
M. Pastre, F. Pereira, T. Gibert, A. Giron, B. Goemare, Emilie Olié, Philippe Courtet, Jorge Lopez-Castroman, Ismaël Conejero
European Psychiatry June 1, 2026 DOI: 10.1192/j.eurpsy.2026.10729 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Patients meeting DSM-IV criteria for moderate to severe treatment-resistant depression |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Measures | Amplitude of Low Frequency Fluctuations (ALFF), regional homogeneity analyses |
| Topics | Psilocybin |
| Key findings | Psilocybin administration was associated with increased resting-state brain activity in the right vlPFC, right mPFC, and left IPL, with regional homogeneity analyses confirming greater signal coherence in overlapping regions. |
Abstract
Introduction: Treatment-resistant depression (TRD) remains a major clinical challenge, with limited efficacy of available therapies. Psilocybin, a serotonergic psychedelic, has shown promising antidepressant effects. As recent studies have shown altered default mode network activity following psilocybin administration, further neuroimaging research in clinical populations is needed to clarify its mechanisms of action and the neural networks associated with symptom improvement in depression.
Objectives: To investigate whether the antidepressant effects of psilocybin are associated with changes in resting-state brain activity and to assess the feasibility of conducting psilocybin trials in a French clinical population.
Methods: Patients meeting DSM-IV criteria for moderate to severe TRD underwent two fMRI sessions 2 days before and 5 days after a single oral psilocybin administration (25 mg). Amplitude of Low Frequency Fluctuations (ALFF) and regional homogeneity analyses were conducted to identify changes in resting brain activity after psilocybin.
Results: Ten patients underwent the two fMRI sessions (8 women, 1 man; mean age 42.2 years). Resting-state analyses revealed increased ALFF signal in the right Ventro-Lateral Pre-Frontal Cortex (vlPFC) (Figure 1), the right Medial Pre-Frontal Cortex (mPFC) (Figure 2), and the left Inferior Parietal Lobule (IPL) (Figure 3) after psilocybin administration. Regional homogeneity analyses confirmed greater signal coherence in overlapping regions. Image 1: Image 1: Long description. Image 2: Image 2: Long description. Image 3: Image 3: Long description.
Conclusions: Preliminary results from the PSILODAC study suggest that psilocybin modulates resting-state brain activity in patients with TRD. Upcoming analyses will include resting-state functional connectivity within positive valence circuits, as well as correlations between imagery outcomes and clinical response to psilocybin. Disclosure of Interest None Declared
Comparable studies
Other observational and cohort studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Patients with treatment-resistant depression | 2017 | Observational cohort | n = 19 |
| Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers | 2019 | Observational cohort | n = 8 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Prediction of Psilocybin Response in Healthy Volunteers Healthy volunteers | 2012 | Observational cohort | n = 409 |