Cited by 1,167Psychedelics and Drug StudiesTreatment of Major DepressionTryptophan and brain disorders

The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index; 7 of the 15 sources its claims cite were checked for support.

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression

Open access

Abstract

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Overview

Integrity signals

Registry

Crossref · 10.1056/nejmoa2206443

Cites

22 of 22 references verified0 citation errors · 0 not checkable

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Nothing to recompute.

Verification

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7 of 15 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

Show all 27 claims

  • Probably not a substantial claim. 18
  • It may state two separate claims as one. 30
42 of 42
  • The paper relies on this without support.

    The 1-mg dose of psilocybin is an inactive control that does not itself produce antidepressant effects.

    “1 mg (control)”
  • The paper relies on this without support.

    Participants remained unaware of their trial-group assignment (dose) during the trial.

    “This was a phase 2 double-blind, dose-finding, parallel-group, randomized clinical trial.”
  • The paper relies on this without support.

    The 1-mg dose of psilocybin is an inactive comparator that does not produce therapeutic effects.

    “The change from baseline to week 3 in the MADRS total score (primary end point) was significantly better with a 25-mg dose than with a 1-mg dose; there was not significant difference between the 10-mg dose and the 1-mg dose.”
3 of 3

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Metadata

Authors
Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., Bird, C., Blom, R. E., Brennan, C., Brusch, D., Burke, L., Campbell-Coker, K., Carhart-Harris, R., Cattell, J., Daniel, A., DeBattista, C., Dunlop, B. W., Eisen, K., Feifel, D., Forbes, M., Haumann, H. M., Hellerstein, D. J., Hoppe, A. I., Husain, M. I., Jelen, L. A., Kamphuis, J., Kawasaki, J., Kelly, J. R., Key, R. E., Kishon, R., Knatz Peck, S., Knight, G., Koolen, M. H. B., Lean, M., Licht, R. W., Maples-Keller, J. L., Mars, J., Marwood, L., McElhiney, M. C., Miller, T. L., Mirow, A., Mistry, S., Mletzko-Crowe, T., Modlin, L. N., Nielsen, R. E., Nielson, E. M., Offerhaus, S. R., O’Keane, V., Páleníček, T., Printz, D., Rademaker, M. C., van Reemst, A., Reinholdt, F., Repantis, D., Rucker, J., Rudow, S., Ruffell, S., Rush, A. J., Schoevers, R. A., Seynaeve, M., Shao, S., Soares, J. C., Somers, M., Stansfield, S. C., Sterling, D., Strockis, A., Tsai, J., Visser, L., Wahba, M., Williams, S., Young, A. H., Ywema, P., Zisook, S., & Malievskaia, E.
Affiliations
  • King's College London (GB)
  • SUNY Downstate Health Sciences University (US)
  • From COMPASS Pathfinder (G.M.G., J.C.B., L.M., S.M., S.C.S., J.T., S.W., E.M.), the Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (C. Bird, L.A.J., G.K., L.N.M., F.R., J.R., S. Ruffell, M. Seynaeve, A.H.Y.), the National Institute for Health and Care Research Clinical Research Facility, King’s College Hospital NHS Foundation Trust (K.C.-C., J.C., A.D.), and South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital (L.A.J., L.N.M., J.R., A.H.Y.), London, and the Cumbria, Northumberland, Tyne and Wear Foundation Trust and Newcastle University, Newcastle (M.W.) — all in the United Kingdom; the Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt, Baltimore (S.T.A., M.F., T.L.M., S. Rudow); Sant Joan de Déu Hospital and the Sant Joan de Déu Research Foundation, Barcelona (O.A.); SUNY Downstate College of Medicine (P.C.A.), the New York State Psychiatric Institute (D.J.H., R.E.K., R.K., M.C.M., E.M.N.), and the Depa...
  • University of California, San Francisco (US)
  • Emory University (US)
  • University Medical Center Groningen (NL)
  • Duke University (US)
Venue
New England Journal of Medicine
Published
2022-11-03
Volume
387
Issue
18
Pages
1637-1648
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W4308146982
Cited by
1,167
References
19
Citations by year
2026: 275 · 2025: 327 · 2024: 333 · 2023: 216 · 2022: 15
FWCI
203.26
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, other-oa)
  • VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
COMPASS Pathfinder Limited
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
psilocybin, treatment-resistant depression, major depressive episode, single-dose administration, dose-response relationship, antidepressant efficacy, adverse events, suicidal ideation, psychedelic therapy
MeSH terms
Adult, Antidepressive Agents, Depression, Major Depressive Disorder, Double-Blind Method, Humans, Psilocybin, Treatment Outcome, Depressive Disorder, Treatment-Resistant

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