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In this preliminary study, we examined brain metabolite levels and cognitive functioning in individuals with alcohol use disorder enrolled in a randomized controlled trial of N\u2010acetylcysteine versus placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this preliminary trial, 23 participants (average age\u2009=\u200949; 70% male) with moderate to severe alcohol use disorder (DSM\u20105) were randomized to receive 2400\u2009mg\/day of N\u2010acetylcysteine (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20099) or placebo (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200914). At baseline and follow\u2010up (\n                      <jats:italic>M<\/jats:italic>\n                      \u2009=\u200919\u2009days; SD\u2009=\u20093.73\u2009days post\u2010baseline), participants underwent proton magnetic resonance spectroscopy (\n                      <jats:sup>1<\/jats:sup>\n                      H\u2010MRS) to assess levels of glutamate (Glu), glutathione (GSH) and total N\u2010acetylaspartate (tNAA) in the anterior cingulate cortex (ACC) and completed the Stroop Color and Word Test (SCWT; a measure of distractor interference and cognitive control) and the Trail Making Test (TMT; a measure of set shifting ability).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were no significant differences between the N\u2010acetylcysteine or placebo groups in neurometabolite concentrations (GSH\/Cr:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.75, CI; \u22120.12\u20130.09, tNAAG\/Cr:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.797, CI; \u22120.10\u20130.13, Glu\/Cr:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.60, CI; \u22120.19\u20130.32), or cognitive scores (Stroop:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.57, CI; \u2212306.93\u2013172.78, TMT:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.166, CI; \u22126.62\u201336.77).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These preliminary findings indicate that N\u2010acetylcysteine may not alter brain neurometabolite levels within the ACC or show improvements in certain domains of cognitive functioning measured by the SCWT and TMT, specifically resistance to distractor interference and set\u2010shifting ability respectively, in individuals with alcohol use disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT03879759\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.70066","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T14:08:56Z","timestamp":1761228536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effect of N\u2010Acetylcysteine (\n                    <scp>NAC<\/scp>\n                    ) on Neurometabolites and Cognitive Function in Adults With Alcohol Use Disorder: A Preliminary Randomized Controlled Trial"],"prefix":"10.1002","volume":"45","author":[{"given":"Kristiane Yacou","family":"Dunbar","sequence":"first","affiliation":[{"name":"Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Edith Collins Centre for Translational Research (Alcohol, Drugs &amp; Toxicology) Royal Prince Alfred Hospital, Sydney Local Health District  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-2596","authenticated-orcid":false,"given":"Gezelle","family":"Dali","sequence":"additional","affiliation":[{"name":"Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales 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