{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:49:04Z","timestamp":1791568144613,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"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>Psychedelic drugs may help treat alcohol use disorder (AUD). This study evaluated BPL\u2010003, a novel intranasal powder formulation of 5\u2010methoxy\u2010N,N\u2010dimethyltryptamine (5\u2010MeO\u2010DMT) benzoate salt, in people with moderate\u2013severe AUD enrolled in a standard of care, 10\u2010week programme of relapse\u2010prevention oriented Cognitive Behavioural Therapy (CBT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Open\u2010label, phase 2a, single\u2010dose, clinical trial with 12\u2010week follow\u2010up (Day 84 endpoint) with a target of 12 participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Two clinics in England between 29 March 2023 and 2 July 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Thirteen participants were enrolled. Most were male (n\u2009=\u200910; 76.9%), of White\u2010UK origin (n\u2009=\u200912; 92.3%), with a mean age of 49.3\u00a0years. Twelve participants completed the study (efficacy analysis set).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Participants received a single intranasal dose of 10\u00a0mg BPL\u2010003 in a controlled environment with psychological support. Participants received three pre\u2010dose preparation sessions and three post\u2010dose integration sessions before CBT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>Primary endpoints were safety and tolerability (by physical examination, laboratory evaluations, cardiac telemetry and treatment emergent adverse events [TEAEs]). Exploratory endpoints included Timeline Follow\u2010Back recording of alcohol use (abstinent days, units per day\/week, heavy drinking days [HDDs; defined according to the UK government definition of binge drinking: \u22657\u00a0units per day women, \u22659\u00a0units per day men]) to Week 12 follow\u2010up (study endpoint); craving, alcohol\u2010related problems; and patient\u2010 and clinician\u2010reported measures of well\u2010being and health\u2010related quality of life (HRQoL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>Over 12\u2009weeks, 41 TEAEs (all mild or moderate in severity) were reported by 11 of 12 (84.6%) participants (no TEAE\u2010related withdrawals). The most common TEAEs were study drug administration site pain (four participants; 30.8%); transient elevations in blood pressure after drug administration (four participants; 30.8%); and flashbacks (reactivations), nightmares, and nausea (two participants; 15.4%). At Week 12, the mean (standard deviation [SD]) percentage of abstinent days increased from 33.2% (22.8) at baseline to 80.8% (28.2) and HDDs reduced from 56.2% (SD 26.4) at baseline to 13.2% (SD 21.8). Six of 12 participants (50%) were continuously abstinent, three (25%) had meaningful reductions in alcohol consumption, and three (25%) had no change or a limited change in their drinking patterns. Overall, measures of the negative consequences of alcohol, craving, well\u2010being and HRQoL indicated improvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A first phase 2a clinical trial of 5\u2010methoxy\u2010N,N\u2010dimethyltryptamine (BPL\u2010003 10\u00a0mg) in the context of a 10\u2010week programme of CBT demonstrated acceptable safety and tolerability and provided preliminary evidence of efficacy for reducing alcohol craving and consumption. These findings support progression to larger, controlled trials of BPL\u2010003 for the treatment of alcohol use disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70260","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:01:10Z","timestamp":1765368070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["5\u2010Methoxy\u2010\n                    <i>N<\/i>\n                    ,\n                    <i>N<\/i>\n                    \u2010dimethyltryptamine (5\u2010MeO\u2010DMT) for alcohol use disorder: An open\u2010label, phase 2, proof\u2010of\u2010concept, clinical trial"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1307-2498","authenticated-orcid":false,"given":"John","family":"Marsden","sequence":"first","affiliation":[{"name":"Addictions Department, School of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"},{"name":"South London and Maudsley NHS Foundation Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kelleher","sequence":"additional","affiliation":[{"name":"Addictions Department, School of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"},{"name":"South London and Maudsley NHS Foundation Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Beckley Psytech  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1869-0084","authenticated-orcid":false,"given":"Anna O.","family":"Ermakova","sequence":"additional","affiliation":[{"name":"Beckley Psytech  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Mitcheson","sequence":"additional","affiliation":[{"name":"Addictions Department, School of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"},{"name":"South London and Maudsley NHS Foundation Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Roberts","sequence":"additional","affiliation":[{"name":"Beckley Psytech  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Rucker","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust  UK"},{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Scott","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Saeger","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Small","sequence":"additional","affiliation":[{"name":"Addictions Department, School of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"},{"name":"South London and Maudsley NHS Foundation Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Seynaeve","sequence":"additional","affiliation":[{"name":"Addictions Department, School of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"},{"name":"Beckley Psytech  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization.Global status report on alcohol and health. 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