Neural mechanisms of psychedelic visual imagery.
Devon Stoliker, Katrin H. Preller, Leonardo Novelli, Alan Anticevic, Gary F. Egan, Franz X. Vollenweider, Adeel Razi
Molecular Psychiatry April 1, 2025 DOI: 10.1038/s41380-024-02632-3 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomised, placebo-controlled, cross-over study Randomized Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Healthy adults |
| Intervention | Psilocybin |
| Dose | 0.2 mg/kg |
| Topics | Psilocybin |
| Keywords | Psychedelics Brain imaging Visual perception |
| Citations | 19 |
| Key points | Psilocybin increased self-inhibition of early visual and higher visual-association regions and reduced inhibition from visual-association areas to earlier visual areas, suggesting enhanced top-down connectivity contributes to eyes-closed visual imagery. |
Abstract
Visual alterations under classic psychedelics can include rich phenomenological accounts of eyes-closed imagery. Preclinical evidence suggests agonism of the 5-HT2A receptor may reduce synaptic gain to produce psychedelic-induced imagery. However, this has not been investigated in humans. To infer the directed connectivity changes to visual connectivity underlying psychedelic visual imagery in healthy adults, a double-blind, randomised, placebo-controlled, cross-over study was performed, and dynamic causal modelling was applied to the resting state eyes-closed functional MRI scans of 24 subjects after administration of 0.2 mg/kg of the serotonergic psychedelic drug, psilocybin (magic mushrooms), or placebo. The effective connectivity model included the early visual area, fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus. We observed a pattern of increased self-inhibition of both early visual and higher visual-association regions under psilocybin that was consistent with preclinical findings. We also observed a pattern of reduced inhibition from visual-association regions to earlier visual areas that indicated top-down connectivity is enhanced during visual imagery. The results were analysed with behavioural measures taken immediately after the scans, suggesting psilocybin-induced decreased sensitivity to neural inputs is associated with the perception of eyes-closed visual imagery. The findings inform our basic and clinical understanding of visual perception. They reveal neural mechanisms that, by affecting balance, may increase the impact of top-down feedback connectivity on perception, which could contribute to the visual imagery seen with eyes-closed during psychedelic experiences.
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
Cited by 20
- Psilocybin as Transformative Fast‐Acting Antidepressant: Pharmacological Properties and Molecular Mechanisms Fundamental and Clinical Pharmacology July 16, 2025
- Psychedelics, entactogens and psychoplastogens for depression and related disorders British Journal of Pharmacology June 15, 2025
- Neurocognitive effects of psilocybin: A systematic and comprehensive review of neuroimaging studies in humans. Neuroscience & Biobehavioral Reviews August 1, 2025
- Acute effects of psilocybin on attention and executive functioning in healthy volunteers: a systematic review and multilevel meta-analysis. Psychopharmacology June 1, 2025
- Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain Neuroscience & Biobehavioral Reviews December 16, 2025
and 15 more in the library
Cites 29
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
and 24 more in the library