{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:40:23Z","timestamp":1785328823699,"version":"3.55.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"name":"Fast-Track Drugs & Biologics, LLC","award":["HHSN275201500003I\/HHSN27500003"],"award-info":[{"award-number":["HHSN275201500003I\/HHSN27500003"]}]},{"name":"Fast-Track Drugs & Biologics, LLC","award":["HHSN275201500004I\/HHSN27500002"],"award-info":[{"award-number":["HHSN275201500004I\/HHSN27500002"]}]},{"name":"Fast-Track Drugs & Biologics, LLC","award":["HHSN275201500007I\/HHSN27500003"],"award-info":[{"award-number":["HHSN275201500007I\/HHSN27500003"]}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["75N94019D00001\/75N94019F00125"],"award-info":[{"award-number":["75N94019D00001\/75N94019F00125"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>We evaluated the safety, efficacy, and patient adherence to oral ANS-6637, a selective, reversible inhibitor of aldehyde dehydrogenase 2 (ALDH2), for treating alcohol use disorder (AUD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A 3-arm, double-blind, randomized, proof-of-concept human laboratory study embedded in a 5-week multisite clinical trial tested 200\u00a0mg and 600\u00a0mg daily doses of ANS-6637 compared to placebo in treatment-seeking adults with AUD. After 1 week of medication, participants completed an alcohol cue reactivity session. Drinking and safety assessments were measured during treatment; other exploratory outcomes were measured 1 week after treatment ended.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The study was terminated following enrollment of 43 of 81 planned participants due to clinically significant, reversible increases in liver enzymes in three women. Adverse events consistent with ALDH2 inhibition in the presence of alcohol (heart rate\/palpitations, flushing, nausea) were dose dependent. Group differences in cue-elicited craving were not significant; effect sizes (Cohen\u2019s d) comparing the 200\u00a0mg and 600\u00a0mg doses to placebo were .71 and .06, respectively. Secondary endpoints did not differ significantly between groups; Cohen\u2019s d ranged from .31 to .57 for the 600\u00a0mg dose compared to placebo for continuous drinking outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Findings of liver toxicity with ANS-6637 led to early termination and reduced power to test hypotheses. Effect size estimates are consistent with the hypothesis that selective ALDH2 inhibition may reduce craving and drinking, however these estimates may be unreliable due to the small sample size. Additional research with non-hepatotoxic selective and reversible ALDH2 inhibitors is needed to evaluate this approach to AUD pharmacotherapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/alcalc\/agaf001","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T07:57:51Z","timestamp":1737359871000},"source":"Crossref","is-referenced-by-count":5,"title":["Preliminary effects of oral ANS-6637, an ALDH2 inhibitor, on cue-induced craving, safety and alcohol consumption among adults with alcohol use disorder: a proof-of-concept, randomized, human laboratory trial"],"prefix":"10.1093","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-2369","authenticated-orcid":false,"given":"Stephanie S","family":"O\u2019Malley","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , 34 Park Street, New Haven, CT 06519 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Robert","family":"Miranda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Brown University , 121 S. Main Street, Providence, RI 02912 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah W","family":"Book","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina , 67 President Street, Charleston, SC 29425 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H","family":"Chun","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine and Pediatrics, Alpert Medical School of Brown University , Rhode Island Hospital, Claverick 2, 593 Eddy Street, Providence, RI 02903 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Liss","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , 34 Park Street, New Haven, CT 06519 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Malcolm","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina , 67 President Street, Charleston, SC 29425 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas B","family":"Muvvala","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , 34 Park Street, New Haven, CT 06519 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley Treloar","family":"Padovano","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Brown University , 121 S. Main Street, Providence, RI 02912 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P","family":"Schacht","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Colorado School of Medicine , 1890 N. Revere Court, Mail Stop F570, Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Amygdala Neurosciences, Inc. , 5214F Diamond Heights Blvd #151, San Francisco, CA 94131 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Diamond","sequence":"additional","affiliation":[{"name":"Amygdala Neurosciences, Inc. , 5214F Diamond Heights Blvd #151, San Francisco, CA 94131 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Ransom","sequence":"additional","affiliation":[{"name":"Fast-Track Drugs & Biologics, LLC , 20010 Fisher Avenue, Suite G, Poolesville, MD 20837 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan L","family":"Ryan","sequence":"additional","affiliation":[{"name":"Division of Treatment and Recovery, National Institute on Alcohol Abuse and Alcoholism , 6700 B Rockledge Drive, Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E","family":"Falk","sequence":"additional","affiliation":[{"name":"Division of Treatment and Recovery, National Institute on Alcohol Abuse and Alcoholism , 6700 B Rockledge Drive, Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raye Z","family":"Litten","sequence":"additional","affiliation":[{"name":"Division of Treatment and Recovery, National Institute on Alcohol Abuse and Alcoholism , 6700 B Rockledge Drive, Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"2025030710181585600_ref1","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1111\/j.1530-0277.1992.tb00695.x","article-title":"Techniques to enhance compliance with disulfiram","volume":"16","author":"Allen","year":"1992","journal-title":"Alcohol Clin Exp Res"},{"key":"2025030710181585600_ref2","volume-title":"Phase 1, Double-Blind, Randomized, Placebo-Controlled, First in Human Study of ANS-6637 to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Oral Doses in Healthy Smoker and Non-smoker Subjects (GS-US-272-0101)","author":"Amgdala Neurosciences Inc."},{"key":"2025030710181585600_ref3","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1111\/j.1530-0277.2009.01031.x","article-title":"Suppression of heavy drinking and alcohol seeking by a selective ALDH-2 inhibitor","volume":"33","author":"Arolfo","year":"2009","journal-title":"Alcohol Clin Exp Res"},{"key":"2025030710181585600_ref4","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0165-1781(89)90047-4","article-title":"The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research","volume":"28","author":"Buysse","year":"1989","journal-title":"Psychiatry Res"},{"key":"2025030710181585600_ref5","volume-title":"Alcohol and Public Health: Alcohol-Related Disease Impact. 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