Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention.
Frederick S. Barrett, Samuel R Krimmel, Roland R. Griffiths, David A Seminowicz, Brian N. Mathur
Neuroimage September 1, 2020 DOI: 10.1016/j.neuroimage.2020.116980 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subjects pharmacological intervention Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Healthy human participants |
| Intervention | Psilocybin |
| Dose | 10 mg/70 kg |
| Duration | 100 minutes after oral administration |
| Topics | Psilocybin |
| Keywords | Psychedelics Serotonin 2a receptor Claustrum connectivity Psychedelic effects Resting State FMRI |
| Citations | 191 |
| Key points | Psilocybin modulates claustrum function by decreasing BOLD signal amplitude and variance and altering its functional connectivity with cortical networks. |
Abstract
Psychedelic drugs, including the serotonin 2a (5-HT2A) receptor partial agonist psilocybin, are receiving renewed attention for their possible efficacy in treating a variety of neuropsychiatric disorders. Psilocybin induces widespread dysregulation of cortical activity, but circuit-level mechanisms underlying this effect are unclear. The claustrum is a subcortical nucleus that highly expresses 5-HT2A receptors and provides glutamatergic inputs to arguably all areas of the cerebral cortex. We therefore tested the hypothesis that psilocybin modulates claustrum function in humans. Fifteen healthy participants (10M, 5F) completed this within-subjects study in which whole-brain resting-state blood-oxygenation level-dependent (BOLD) signal was measured 100 min after blinded oral administration of placebo and 10 mg/70 kg psilocybin. Left and right claustrum signal was isolated using small region confound correction. Psilocybin significantly decreased both the amplitude of low frequency fluctuations as well as the variance of BOLD signal in the left and right claustrum. Psilocybin also significantly decreased functional connectivity of the right claustrum with auditory and default mode networks (DMN), increased right claustrum connectivity with the fronto-parietal task control network (FPTC), and decreased left claustrum connectivity with the FPTC. DMN integrity was associated with right-claustrum connectivity with the DMN, while FPTC integrity and modularity were associated with right claustrum and left claustrum connectivity with the FPTC, respectively. Subjective effects of psilocybin predicted changes in the amplitude of low frequency fluctuations and the variance of BOLD signal in the left and right claustrum. Observed effects were specific to claustrum, compared to flanking regions of interest (the left and right insula and putamen). This study used a pharmacological intervention to provide the first empirical evidence in any species for a significant role of 5-HT2A receptor signaling in claustrum functioning, and supports a possible role of the claustrum in the subjective and therapeutic effects of psilocybin.
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 142
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine Journal of Neuroscience November 30, 2020
- The Therapeutic Potential of Psilocybin Molecules May 15, 2021
- Default Mode Network Modulation by Psychedelics: A Systematic Review The International Journal of Neuropsychopharmacology October 21, 2022
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
and 137 more in the library
Cites 53
- 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
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled 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
- 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
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