{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:22:28Z","timestamp":1792452148831,"version":"4.5.0"},"reference-count":51,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Ketamine, a rapid-acting N-methyl-D-aspartate receptor antagonist used as a therapeutic for treatment-resistant depression (TRD), is usually administered intravenously or intranasally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>This randomized, double-blind, placebo-controlled, Phase 1 study investigated safety and tolerability (primary endpoint), pharmacokinetics (PK) and pharmacodynamics (PD) of an immediate-release oral ketamine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Healthy volunteers (18\u201355\u2009years) were randomized to each receive two single doses of oral ketamine (40\u2013240\u2009mg) and one oral placebo dose. Treatment-emergent adverse events (TEAEs) and PK and PD assessments (e.g., Bond and Lader visual analogue scale, Modified Observer\u2019s Assessment of Alertness\/Sedation Scale) were assessed up to 24\u2009h after dosing. Descriptive statistics were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Nineteen participants were randomized (mean age: 31\u2009years; male, 68%); 18 completed the study. Eighty mild or moderate TEAEs were reported following oral ketamine (40\u2013240\u2009mg) and five following placebo. There were no TEAE-related discontinuations. Most TEAEs (86%) were considered probably related to study drug. The most common TEAEs with oral ketamine were dissociation (26 events), dizziness (nine events) and headache (nine events). A positive relationship between increasing ketamine doses and dissociation events was observed. PK parameters (\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      , AUC\n                      <jats:sub>inf<\/jats:sub>\n                      ) of oral ketamine and its primary metabolites (2S,6S;2R,6R-hydroxynorketamine, R\/S-norketamine) were dose proportional. Transient changes in mood and dissociation were detected 1\u2009h postdose with a return to predose values after ~4\u2009h.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>There were no unexpected safety signals with oral ketamine. PK properties were consistent with those reported for other rapid-acting formulations. These findings warrant further investigation of oral ketamine capsules in TRD (EudraCT No. 2019-001019-22).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811251340925","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T05:50:26Z","timestamp":1750398626000},"page":"545-558","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["A randomized, double-blind, placebo-controlled, Phase 1 study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of an immediate-release oral ketamine capsule in healthy volunteers"],"prefix":"10.1177","volume":"39","author":[{"given":"Mutahira","family":"Qureshi","sequence":"first","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"},{"name":"South London and Maudsley NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Silman","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romayne","family":"Gadelrab","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"},{"name":"South London and Maudsley NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Christian","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"},{"name":"South London and Maudsley NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Carmellini","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"},{"name":"Division of Psychiatry, Department of Molecular and Developmental Medicine, University of Siena School of Medicine, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2597-0058","authenticated-orcid":false,"given":"Graeme","family":"Duncan","sequence":"additional","affiliation":[{"name":"Neurocentrx Pharma, Ltd., Edinburgh, Scotland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitul A","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2291-6952","authenticated-orcid":false,"given":"Allan H","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"},{"name":"South London and Maudsley NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmel","family":"Reilly","sequence":"additional","affiliation":[{"name":"Neurocentrx Pharma, Ltd., Edinburgh, Scotland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario F","family":"Juruena","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"},{"name":"South London and Maudsley NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.01.005"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000717"},{"key":"e_1_3_3_4_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association: DSM-5 Task Force (2013) Diagnostic and Statistical Manual of Mental Disorders: DSM-5\u2122 5th edn. 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