# The Effect of N‐Acetylcysteine (NAC) on Neurometabolites and Cognitive Function in Adults With Alcohol Use Disorder: A Preliminary Randomized Controlled Trial

## TL;DR

This study tested if N-acetylcysteine (NAC) affects brain chemicals and cognitive function in people with alcohol use disorder, but found no significant differences compared to a placebo.

## Contribution

First study to examine the effect of NAC on metabolites in adults with alcohol use disorder.

## Key findings

- NAC did not significantly alter neurometabolite concentrations in the anterior cingulate cortex.
- No significant improvements in cognitive functioning were observed with NAC compared to placebo.

## Abstract

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.

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 (1H‐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).

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).

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.

ClinicalTrials.gov identifier: NCT03879759

First study to examine the effect of NAC on metabolites in adults with alcohol use disorder. No significant differences were observed between NAC and placebo treatment on metabolites or cognitive functioning.