Psilocybin Promotes Cell-Type-Specific Changes in the Orbitofrontal Cortex Revealed by Single-Nucleus RNA-seq
Ziran Huang, Xiaoyan Wei, Xiaobin Wang, Jing Tian, Jihui Dong, Bo Liang, Lin Lu, Wen Zhang
bioRxiv (Cold Spring Harbor Laboratory) January 7, 2024 preprint DOI: 10.1101/2024.01.07.573163 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Intervention | Psilocybin |
| Dose | a single dose |
| Topics | Psilocybin |
| Keywords | Orbitofrontal cortex Hallucinogen |
| Citations | 3 |
| Key findings | A single dose of psilocybin produces long-term genetic and functional changes in OFC neurons, with excitatory and inhibitory neurons collectively reducing circuit activity, and 5-HT2A receptor knockdown in deep-layer excitatory neurons attenuating these effects and the anti-depressant response. |
Abstract
Abstract Recent clinical breakthroughs hold great promise for the application of psilocybin in the treatments of psychological disorders, such as depression, addiction, and obsessive-compulsive disorder. Psilocybin is a psychedelic whose metabolite, psilocin, is a 5-HT 2A receptor agonist. Nevertheless, the underlying mechanisms for the effects of psilocybin on the brain are not fully illustrated, and cell type-specific and circuit effects of psilocybin are not fully understood. Here, we combined single-nucleus RNA-seq with functional assays to study the long-term effects of psilocybin on the orbitofrontal cortex (OFC), a brain region vulnerable to psychological disorders such as depression. We showed that a single dose of psilocybin induced long-term genetic and functional changes in neurons of the OFC, and excitatory and inhibitory neurons collectively reduced circuit activity of the brain region. Knockdown of 5-HT 2A receptor in deep layer excitatory neurons abated psilocybin-induced functional changes and the anti-depressant effect. Together, these results showed the cell type-specific mechanisms of psilocybin and shed light on the brain region difference in the effect of psychedelics.
Comparable studies
Other experimental studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... | 2015 | Validation study using pooled data from five laboratory experiments | n = 184 |
| Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants | 2013 | Experimental study | |
| Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... | 2020 | Long-term within-subjects follow-up analysis | n = 15 |
| Enzymatic Synthesis of Psilocybin | 2017 | Laboratory study |
Citations in the library
Cited by 3
- Psilocybin causes sex, time, and dose dependent alterations in brain signaling pathways bioRxiv (Cold Spring Harbor Laboratory) December 17, 2024
- Psilocybin decreases reward-seeking behavior accompanied by increased activity of parvalbumin neurons with perineuronal nets in the medial prefrontal cortex bioRxiv (Cold Spring Harbor Laboratory) December 26, 2025
- Persistent large-scale changes in alternative splicing in prefrontal cortical neuron types following psychedelic exposure. bioRxiv : the preprint server for biology January 16, 2025
Cites 22
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
and 17 more in the library