The Effect of N‐Acetylcysteine ( <scp>NAC</scp> ) on Neurometabolites and Cognitive Function in Adults With Alcohol Use Disorder: A Preliminary Randomized Controlled Trial
Bibliographic record
Abstract
ABSTRACT Background and Aims Preclinical studies have demonstrated that N‐acetylcysteine stabilizes levels of glutamate and glutathione and reduces alcohol‐seeking behaviors, indicating it as a potential pharmacotherapy for the management of alcohol use disorder. 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‐acetylcysteine versus placebo. Methods In this preliminary trial, 23 participants (average age = 49; 70% male) with moderate to severe alcohol use disorder (DSM‐5) were randomized to receive 2400 mg/day of N‐acetylcysteine ( N = 9) or placebo ( N = 14). At baseline and follow‐up ( M = 19 days; SD = 3.73 days post‐baseline), participants underwent proton magnetic resonance spectroscopy ( 1 H‐MRS) to assess levels of glutamate (Glu), glutathione (GSH) and total N‐acetylaspartate (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). Results There were no significant differences between the N‐acetylcysteine or placebo groups in neurometabolite concentrations (GSH/Cr: p = 0.75, CI; −0.12–0.09, tNAAG/Cr: p = 0.797, CI; −0.10–0.13, Glu/Cr: p = 0.60, CI; −0.19–0.32), or cognitive scores (Stroop: p = 0.57, CI; −306.93–172.78, TMT: p = 0.166, CI; −6.62–36.77). Conclusion These preliminary findings indicate that N‐acetylcysteine 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‐shifting ability respectively, in individuals with alcohol use disorder. Trial Registration ClinicalTrials.gov identifier: NCT03879759
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".