{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T19:24:40Z","timestamp":1773257080451,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["L\u2010023032"],"award-info":[{"award-number":["L\u2010023032"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Ketamine assisted psychotherapy is a promising new treatment for alcohol use disorder (AUD). The psychoactive effects of repeated intravenous (IV) ketamine infusions in people with AUD and their mechanistic role in treating AUD are largely unknown. This study aimed to (1) quantify the subjective, psychoactive effects of IV ketamine in people with AUD, (2) investigate how these effects change over three dosing sessions and (3) test whether these effects mediate ketamine's therapeutic benefits in reducing alcohol consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Secondary analysis of the randomised, parallel\u2010arm, double\u2010blind, placebo\u2010controlled, phase 2 \u2018KARE\u2019 clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Two clinical research facilities in England.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>96 adults (35 women) aged 18\u201364\u2009years with moderate\u2010to\u2010severe AUD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Three weekly infusions of either ketamine (IV 0.8\u00a0mg\/kg over 40\u2009minutes) or placebo (saline solution).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>Psychoactive drug effects experienced were self\u2010reported pre\u2010, during\u2010 and post\u2010infusion, every 20\u2009minutes (eight times\/infusion) on Likert scales (1\u201310), for: Effects of Drug, Liking of Drug, Altered Reality, Out of Body Experiences, Visual Distortion, Sound Distortion and Altered Time Perception. For each scale, we calculated area\u2010under\u2010the\u2010curve (AUC) scores for each infusion and the AUC average across three infusions. The clinical outcome was percentage of days abstinent from alcohol in the 6\u00a0months after infusions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Ketamine produced strong psychoactive effects on every scale, relative to placebo (all\n                      <jats:italic>P<\/jats:italic>\n                      values &lt; 0.001). Ketamine's psychoactive effects were moderated by infusion number (infusion 2 vs. infusion 1) for: Liking of Drug (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001), Altered Reality (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.030) and Out of Body Experiences (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.033), with small\u2010to\u2010moderate effect sizes. The remaining four psychoactive effects were not statistically significantly changed by repeated dosing. No psychoactive effect statistically significantly mediated the relationship between drug treatment and percentage days abstinent (all\n                      <jats:italic>P<\/jats:italic>\n                      values\u2009=\u20090.075\u20130.935).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>People with alcohol use disorder experience alterations in consciousness from 0.8\u00a0mg\/kg intravenous ketamine administration. Ketamine's effects appear to be broadly consistent across three repeated infusions. Ketamine\u2010related reductions in alcohol consumption do not appear to be mediated by the acute psychoactive effects of ketamine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70320","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:01:23Z","timestamp":1771286483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The psychoactive effects of repeated ketamine infusions and their mechanistic role in the treatment of alcohol use disorder: Secondary analysis of a randomised controlled trial"],"prefix":"10.1111","author":[{"given":"Cassie","family":"Bloy","sequence":"first","affiliation":[{"name":"Department of Psychology Institute of Psychiatry Psychology and Neuroscience (IoPPN), King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ananya","family":"Sarma","sequence":"additional","affiliation":[{"name":"Department of Psychology Institute of Psychiatry Psychology and Neuroscience (IoPPN), King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethan","family":"Marsh","sequence":"additional","affiliation":[{"name":"The Psychopharmacology and Addiction Research Centre (PARC), Department of Psychology University of Exeter  Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorna","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Health and Community Sciences University of Exeter  Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meryem","family":"Grabski","sequence":"additional","affiliation":[{"name":"Frankfurt University of Applied Sciences  Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merve","family":"Mollaahmetoglu","sequence":"additional","affiliation":[{"name":"School of Psychology University of Sheffield  Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Shotton","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shamhethan","family":"Bhaskaran","sequence":"additional","affiliation":[{"name":"Bedfordshire Hospitals NHS Foundation Trust  Luton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-3453","authenticated-orcid":false,"given":"Anne","family":"Lingford\u2010Hughes","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Brain Sciences Imperial College London, Hammersmith Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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