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To elucidate clinical utility and clinical mechanisms of these novel treatments, research should carefully assess medication\u2010related changes in AUD symptomatology, including craving and negative mood, over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This is a secondary analysis of a 12\u2010week randomized clinical trial of ibudilast for AUD. Participants were 102 individuals (40% female, average age 44\u2009years) seeking treatment for AUD and randomized to ibudilast (50\u2009mg twice\u2010daily) or matched placebo. Clinical symptom measures of alcohol craving, depression, and anxiety were collected monthly. Growth models compared rates of change in clinical symptomatology between treatment groups and tested whether changes were moderated by sex. A subsample (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200925) completed a functional magnetic resonance imaging scan with an alcohol cue\u2010reactivity task at week four to assess a brain\u2010based craving marker.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At pretreatment, participants reported moderate craving symptoms and nonclinically elevated negative mood symptoms, on average. Participants taking ibudilast showed significantly steeper reductions in craving during the trial, as compared with placebo (1.32 vs. 0.52 points lower per month;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035). At treatment endpoint, female participants taking ibudilast reported lower craving than female participants taking placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Greater cue\u2010elicited brain activation in bilateral insula, bilateral orbitofrontal cortex, and right precuneus (\n                      <jats:italic>p'<\/jats:italic>\n                      s\u2009&lt;\u20090.02) was detected among the placebo subsample, compared to ibudilast. Rates of change for depression and anxiety did not differ between medication conditions, nor were they moderated by sex. Depression symptoms decreased during the trial, while anxiety symptoms remained relatively stable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Consistent with prior research, ibudilast reduced neurobiological and self\u2010report markers of craving, with female participants showing a stronger treatment response by trial endpoint. Despite shared neuroimmune correlates between negative mood and addiction, ibudilast did not alleviate negative mood symptoms beyond placebo effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70178","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T05:09:11Z","timestamp":1759468151000},"page":"2604-2618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Variations in alcohol craving and negative mood during a clinical trial of ibudilast for alcohol use disorder"],"prefix":"10.1111","volume":"49","author":[{"given":"Lindsay R.","family":"Meredith","sequence":"first","affiliation":[{"name":"Department of Psychology University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5528-4918","authenticated-orcid":false,"given":"Erica N.","family":"Grodin","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences University of California  Los Angeles California USA"},{"name":"Brain Research Institute University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig K.","family":"Enders","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California  Los Angeles California 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"},{"name":"Department of Psychiatry and Biobehavioral Sciences University of California  Los Angeles California USA"},{"name":"Brain Research Institute University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14992"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2023.5483"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666170828163048"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0976-10.2010"},{"key":"e_1_2_8_6_1","unstructured":"Andersson J.L.R. 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