N-Acetyl Cysteine, a Glutamate-Modulating Agent, in the Treatment of Pathological Gambling: A Pilot Study

Jon E. Grant, Suck Won Kim, Brian L. Odlaug

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211 Scopus citations


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 ≥ 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.

Original languageEnglish (US)
Pages (from-to)652-657
Number of pages6
JournalBiological psychiatry
Issue number6
StatePublished - Sep 15 2007

Bibliographical note

Funding Information:
This research was supported in part by a Career Development Award (K23 MH069754-01A1) to JEG. Dr. Grant has been a consultant to Somaxon Pharmaceuticals and has received research grants from Somaxon Pharmaceuticals, Forest Pharmaceuticals, and GlaxoSmithKline.

Copyright 2010 Elsevier B.V., All rights reserved.


  • Addiction
  • amino acid
  • gambling
  • glutamate
  • pharmacology
  • treatment


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