Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms
Open accessAbstract
Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.
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The use of open-label and crossover designs, as well as a single-dose protocol, was frequently noted.
“In terms of study design, the use of open-label 25,39,57,78-81 and crossover designs, 31-33,74,80 as well as a single-dose protocol, 31,33,39,72-77 was frequently noted.”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [78]
The Introduction identifies this as an open-label clinical trial, supporting that part of the citing sentence. It describes two psilocybin doses given one week apart, not a crossover design. The source is not cited for the sentence’s single-dose claim. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSome studies showed inconsistent application of correction for multiple testing, no consideration of confounding factors, lack of randomization, and relatively short-term follow-up periods generally between one and 6 months after one or two single active psilocybin treatments.
“In terms of methodology, some studies showed inconsistent application of correction for multiple testing, 26,74 no consideration of confounding factors, 57,78 lack of randomization, 72 and relatively short-term follow-up periods were often observed, 25,26,31-33,39,57,72-81 generally between one and 6 months after one or two single active psilocybin treatments.”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [78]
Open-label studies and two follow-up analyses supported the overall positive findings of RCTs.
“Open-label studies 25,39,57,78-81 and two followup analyses 61,62 supported the overall positive findings of RCTs.”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [78]
Carhart-Harris et al. (2017) showed rapid and sustained antidepressant effects with psilocybin in treatment-resistant depression.
“Rapid and sustained antidepressant effects”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as Carhart-Harris et al. (2017)
In patients with treatment-resistant major depression, two doses of psilocybin (10 mg followed by 25 mg 1 week apart) produced a rapid and sustained antidepressant effect.
“the results demonstrated a rapid and sustained antidepressant effect”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as Carhart-Harris et al. (2017)
Only one of 19 patients did not show a decrease in QIDS-SR16 score.
“with only one patient not showing a decrease in the QIDS-SR16 score.”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as Carhart-Harris et al. (2017)
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- Authors
- Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., Tanner, M., Kaelen, M., McGonigle, J., Murphy, K., Leech, R., Curran, H. V., & Nutt, D. J.
- Affiliations
- Imperial College London (GB)
- Hammersmith Hospital (GB)
- University of Cape Town (ZA)
- Cardiff University (GB)
- University College London (GB)
- Corresponding author
- Carhart-Harris, Robin L
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-10-13
- Volume
- 7
- Issue
- 1
- Pages
- 13187-13187
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5640601
- OpenAlex
- W2762746674
- Cited by
- 587
- References
- 64
- Citations by year
- 2026: 48 · 2025: 79 · 2024: 80 · 2023: 68 · 2022: 90 · 2021: 74 · 2020: 53 · 2019: 34 · 2018: 52 · 2017: 7
- FWCI
- 49.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (200804/Z/16/Z)
- Alexander Mosley Charitable Trust
- Medical Research Council
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- psilocybin, treatment-resistant depression, cerebral blood flow, resting-state functional connectivity, amygdala, default mode network, ventromedial prefrontal cortex, parahippocampal cortex, treatment response prediction, serotonin receptor agonists, psychedelics
- MeSH terms
- Adult, Brain, Depression, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Psilocybin
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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