Work

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

Year: 2025

Type: article

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: H-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.

Source: Psychopharmacology

DOI: 10.1007/s00213-025-06932-6

Authors: James J. Prisciandaro, Amber M. Jarnecke, Jane E. Joseph, Kevin M. Gray, Elizabeth J. Santa Ana, Sudie E. Back

Institutions: Medical University of South Carolina, Ralph H. Johnson VA Medical Center

Language: English

Topic: Posttraumatic Stress Disorder Research

Subfield: Clinical Psychology

Field: Psychology

Domain: Social Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,390