The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial

J Psychopharmacol. 2017 Oct;31(10):1377-1379. doi: 10.1177/0269881117730660. Epub 2017 Sep 19.


Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation. Smoking related behaviors and neurotransmitter concentrations in the dorsal anterior cingulate cortex were assessed before and after treatment. Forty-seven non-smoking males served as baseline controls. Smokers showed higher baseline glutamate but similar gamma-aminobutyric acid concentrations than non-smokers. There were no treatment effects on dorsal anterior cingulate cortex neurotransmitter concentrations, smoking cessation, craving, or withdrawal symptoms. These results confirm glutamate disbalance in smokers, but not efficacy of N-acetylcysteine.

Keywords: N-acetylcysteine; Proton magnetic resonance spectroscopy; gamma-aminobutyric acid; glutamate; smoking cessation; tobacco dependence.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Adult
  • Craving / drug effects
  • Double-Blind Method
  • Glutamic Acid / metabolism*
  • Gyrus Cinguli / drug effects*
  • Gyrus Cinguli / metabolism
  • Humans
  • Male
  • Smoking Cessation / methods
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / metabolism*
  • Tobacco Use Disorder / drug therapy*
  • Tobacco Use Disorder / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Acetylcysteine

Associated data

  • NTR/NTR3576