NAC, PTSD, And Alcohol use

This study suggests that the use of NAC may reduce the amount of alcohol used by those diagnosed with PTSD who drink. As NAC is protective of alcohol toxicity anyway ( I always pop a few NAC caps when drinking…), may decrease the urge for drinking too, so win win:

“Effects of N-acetylcysteine treatment on frontal glutamate and GABA levels and associations with drinking quantity in people with co-occurring posttraumatic stress disorder and alcohol use disorder”

Abstract

Rationale

Though half of people with posttraumatic stress disorder (PTSD) develop alcohol use disorder (AUD), co-occurring PTSD and AUD (PTSD + AUD) is associated with more severe clinical outcomes relative to either alone and little remains known about the pathophysiology of PTSD + AUD. PTSD and AUD have each been associated with marked dysfunction in brain glutamate and GABA systems, making these systems promising targets for pharmacological intervention, including N-acetylcysteine (NAC), which restores extracellular glutamate concentrations via GLT-1 and System Xc-.

Objectives and Methods

Based on promising results from our pilot study of NAC, we recently completed a 12-week, randomized, double-blind, placebo-controlled clinical trial of NAC for PTSD + AUD. As part of this trial, we acquired proton MR spectroscopy (1H-MRS) data at pretreatment and ~ 8-weeks posttreatment in a subsample of (n = 44) participants to evaluate whether NAC significantly affects frontal glutamate levels (i.e., represented by Glx, glutamate + glutamine), with exploratory evaluation of GABA and glutathione levels, and whether NAC-related changes in neurometabolite levels correspond to decreased drinking and/or PTSD symptoms, in people with PTSD + AUD.

Results

We found that NAC was associated with significantly higher frontal Glx (t = 2.45, p = 0.017), and significantly lower GABA (t = -2.82, p = 0.007) but equivalent glutathione (t = -1.00, p = 0.321), levels relative to placebo. Finally, lower NAC-related GABA, but not Glx or glutathione, levels were significantly associated with decreased drinks per drinking day (t = 2.57, p = 0.014), but not percent drinking days or PTSD symptoms (ps > 0.10).

Conclusions

Though preliminary, these findings are consistent with the mechanistic hypothesis that NAC reduces drinking quantity through its effects on excitatory and inhibitory neurotransmission in people with PTSD + AUD.

https://link.springer.com/article/10.1007/s00213-025-06932-6