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The GABA<jats:sub>B<\/jats:sub> agonist baclofen has been reported to reduce alcohol consumption but is associated with some undesirable side effects, including sedation. ASP8062 is a novel compound that acts as a positive allosteric modulator at the GABA<jats:sub>B<\/jats:sub> receptor and may be more tolerable than baclofen. This proof\u2010of\u2010concept human laboratory clinical trial evaluated the safety profile of ASP8062 and tested its effects on cue\u2010elicited alcohol craving and alcohol use among treatment\u2010seeking individuals with AUD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This double\u2010blind, randomized, multisite trial tested the effect of ASP8062 (25\u2009mg once daily), relative to placebo, on alcohol cue\u2010elicited craving in a laboratory setting and alcohol consumption, craving, mood, sleep, cigarette smoking, and alcohol\u2010related consequences in the natural environment over a 6\u2010week treatment period. Participants were 60 individuals (26 females and 34 males) with moderate or severe AUD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ASP8062, relative to placebo, was well tolerated, and there were no adverse events (AEs) that significantly differed between treatment groups. Most AEs were mild\/moderate, and there were no serious AEs among individuals treated with ASP8062. However, ASP8062 did not attenuate alcohol cue\u2010elicited craving compared with placebo. Moreover, exploratory analyses indicated that ASP8062, relative to placebo, did not significantly affect alcohol consumption, naturalistic alcohol craving, mood, sleep, cigarette smoking, or alcohol\u2010related negative consequences during the 6\u2010week treatment period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although ASP8062 was well tolerated with no serious AEs, the novel compound did not significantly dampen alcohol cue\u2010elicited craving or improve other AUD\u2010related outcome measures. These data indicate positive allosteric modulation of the GABA<jats:sub>B<\/jats:sub> receptor at the dose evaluated here may not blunt alcohol cue\u2010elicited craving, and preliminary drinking outcome data suggest it may not be an efficacious treatment strategy for AUD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15468","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T04:54:44Z","timestamp":1733201684000},"page":"2352-2363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of a novel <scp>GABA<\/scp>\u2010B positive allosteric modulator, <scp>ASP8062<\/scp>, on alcohol cue\u2010elicited craving and naturalistic alcohol consumption in a multisite randomized, double\u2010blind, placebo\u2010controlled trial"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-0495","authenticated-orcid":false,"given":"Joseph P.","family":"Schacht","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-9444","authenticated-orcid":false,"given":"Lara A.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-6148","authenticated-orcid":false,"suffix":"Jr.","given":"Robert","family":"Miranda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-2786","authenticated-orcid":false,"given":"Daniel E.","family":"Falk","sequence":"additional","affiliation":[{"name":"Division of Medications Development National Institute on Alcohol Abuse and Alcoholism  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan L.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Division of Medications Development National Institute on Alcohol Abuse and Alcoholism  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph T.","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Miotto","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Scott","sequence":"additional","affiliation":[{"name":"Fast\u2010Track Drugs &amp; Biologics, LLC  Poolesville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Ransom","sequence":"additional","affiliation":[{"name":"Fast\u2010Track Drugs &amp; Biologics, LLC  Poolesville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Alsharif","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development Inc.  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