{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:12:39Z","timestamp":1788955959507,"version":"build-2803163510"},"reference-count":51,"publisher":"Royal College of Psychiatrists","issue":"4","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"unspecified","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["202203PJT"],"award-info":[{"award-number":["202203PJT"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["BJPsych open"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec id=\"S2056472423005355_sec_a1\">\n\t    <jats:title>Background<\/jats:title>\n\t    <jats:p>Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472423005355_sec_a2\">\n\t    <jats:title>Aims<\/jats:title>\n\t    <jats:p>To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone).<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472423005355_sec_a3\" sec-type=\"methods\">\n\t    <jats:title>Method<\/jats:title>\n\t    <jats:p>In a 4-week, three-arm, \u2018double dummy\u2019 trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472423005355_sec_a4\" sec-type=\"results\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>This trial will advance the understanding of psilocybin's mechanism of antidepressant action.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472423005355_sec_a5\" sec-type=\"conclusions\">\n\t    <jats:title>Conclusions<\/jats:title>\n\t    <jats:p>This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1192\/bjo.2023.535","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T08:30:42Z","timestamp":1690273842000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":47,"title":["Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial"],"prefix":"10.1192","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5771-5750","authenticated-orcid":false,"given":"Muhammad Ishrat","family":"Husain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8422-5818","authenticated-orcid":false,"given":"Daniel M.","family":"Blumberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Castle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Ledwos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Fellows","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3248-1059","authenticated-orcid":false,"given":"Brett D. 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