N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study

Biol Psychiatry. 2007 Sep 15;62(6):652-7. doi: 10.1016/j.biopsych.2006.11.021. Epub 2007 Apr 18.


Background: Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. N-acetyl cysteine (NAC), an amino acid, seems to restore extracellular glutamate concentration in the nucleus accumbens and therefore offers promise in reducing addictive behavior.

Methods: Twenty-seven subjects (12 women) with DSM-IV PG were treated in an 8-week open-label trial of NAC with responders (defined as a > or = 30% reduction in Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling [PG-YBOCS] total score at end point) randomized to 6 weeks of double-blind NAC or placebo.

Results: The PG-YBOCS scores decreased from a mean of 20.3 +/- 4.1 at baseline to 11.8 +/- 9.8 at the end of the open-label phase (p < .001). Sixteen of 27 subjects (59.3%) met responder criteria. The mean effective dose of NAC was 1476.9 +/- 311.3 mg/day. Of 16 responders, 13 entered the double-blind phase. Of those assigned to NAC, 83.3% still met responder criteria at the end of the double-blind phase, compared with only 28.6% of those assigned to placebo.

Conclusions: The efficacy of NAC lends support to the hypothesis that pharmacological manipulation of the glutamate system might target core symptoms of reward-seeking addictive behaviors such as gambling. Larger, longer, placebo-controlled double-blind studies are warranted.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use*
  • Adult
  • Aged
  • Behavior, Addictive / diagnosis
  • Behavior, Addictive / drug therapy
  • Behavior, Addictive / psychology
  • Dopamine / metabolism
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Gambling / psychology*
  • Glutamates / drug effects
  • Glutamates / metabolism
  • Humans
  • Male
  • Middle Aged
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Personality Inventory
  • Pilot Projects
  • Placebos
  • Psychiatric Status Rating Scales
  • Treatment Outcome


  • Glutamates
  • Placebos
  • Dopamine
  • Acetylcysteine