Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis
Open accessAbstract
Psilocybin is a classic psychedelic and a candidate drug model of psychosis. This study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (FC) using functional magnetic resonance imaging (fMRI). Fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. Primary analyses focused on changes in FC between the default-mode- (DMN) and task-positive network (TPN). Spontaneous activity in the DMN is orthogonal to spontaneous activity in the TPN, and it is well known that these networks support very different functions (ie, the DMN supports introspection, whereas the TPN supports externally focused attention). Here, independent components and seed-based FC analyses revealed increased DMN-TPN FC and so decreased DMN-TPN orthogonality after psilocybin. Increased DMN-TPN FC has been found in psychosis and meditatory states, which share some phenomenological similarities with the psychedelic state. Increased DMN-TPN FC has also been observed in sedation, as has decreased thalamocortical FC, but here we found preserved thalamocortical FC after psilocybin. Thus, we propose that thalamocortical FC may be related to arousal, whereas DMN-TPN FC is related to the separateness of internally and externally focused states. We suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.
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There is some evidence to suggest that the psychedelic state produces co-activation between the DMN and task positive networks.
“There is some evidence to suggest that the psychedelic state produces co-activation between the DMN and task positive networks (a network of brain regions which activate during attention demanding tasks), two networks which are usually anti-correlated [35].”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [35]
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“between the DMN and task positive networks (a network of brain regions which activate during attention demanding tasks), two networks which are usually anti-correlated [35].”
Background
- Authors
- Carhart-Harris, R. L., Leech, R., Erritzoe, D., Williams, T. M., Stone, J. M., Evans, J., Sharp, D. J., Feilding, A., Wise, R. G., & Nutt, D. J.
- Affiliations
- University of Bristol (GB)
- Imperial College London (GB)
- Cardiff University (GB)
- Beckley Foundation (GB)
- Corresponding author
- Carhart-Harris, Robin L.
- ORCID
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-10-06
- Volume
- 39
- Issue
- 6
- Pages
- 1343-1351
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC3796071
- OpenAlex
- W2122335802
- Cited by
- 256
- References
- 43
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 20 · 2023: 20 · 2022: 22 · 2021: 18 · 2020: 17 · 2019: 32 · 2018: 12 · 2017: 17 · 2016: 30 · 2015: 14 · 2014: 13 · 2013: 9
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Schizophrenia Bulletin (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (ACF-2013-21-501, NIHR-RP-011-048)
- Medical Research Council (MR/K015192/1, MR/J00460X/1)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- psilocybin, early psychosis
- MeSH terms
- Adult, Cerebral Cortex, Female, Hallucinogens, Humans, Male, Nerve Net, Psilocybin, Psychoses, Substance-Induced, Psychotic Disorders, Thalamus, Reproducibility of Results, Cerebrum, Young Adult, Connectome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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