Influence of n-acetylcysteine maintenance on the pharmacodynamic effects of oral ethanol

William W. Stoops, Justin C. Strickland, Lon R. Hays, Abner O. Rayapati, Joshua A. Lile, Craig R. Rush

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Rationale: Glutamate systems play an important role in the abuse related effects of alcohol. n-Acetylcysteine, a drug that promotes glutamate homeostasis, attenuates a range of alcohol effects in preclinical models. Objectives: This human laboratory study determined the influence of n-acetylcysteine maintenance on alcohol self-administration using a model predictive of treatment effectiveness, along with the subjective, performance and physiological effects of alcohol. We hypothesized that n-acetylcysteine would attenuate alcohol self-administration, as well as positive subjective effects of alcohol. Methods: Nine subjects with alcohol use disorder completed this within-subjects study. Subjects were maintained on placebo, 1.2 and 2.4 g n-acetylcysteine in random order on an outpatient basis. After five days of maintenance on the target dose, subjects completed overnight inpatient experimental sessions in which the pharmacodynamic effects of alcohol were determined. Results: Alcohol produced prototypic effects (e.g., increased breath alcohol concentration, increased ratings of Feel Drink). n-Acetylcysteine did not alter the effects of alcohol. Conclusions: These results indicate that although n-acetylcysteine can safely be combined with alcohol, it does not attenuate the abuse related effects of alcohol and is unlikely to be an effective standalone alcohol use disorder treatment. However, considering study limitations, future work is needed to further understand whether and how n-acetylcysteine might be used as a treatment for alcohol use disorder (e.g., in combination with a behavioral treatment or another pharmacological agent).

Original languageEnglish
Article number173037
JournalPharmacology Biochemistry and Behavior
StatePublished - Nov 2020

Bibliographical note

Funding Information:
The authors declare no relevant conflicts of interest. The authors gratefully acknowledge research support from the National Institute on Alcohol Abuse and Alcoholism ( R21AA026129 ) and from the National Center for Advancing Translational Sciences ( UL1TR001998 ) of the National Institutes of Health . These funding agencies had no role in study design, data collection or analysis, or preparation and submission of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2020 Elsevier Inc.


  • Alcohol
  • Behavioral economic demand
  • Humans
  • Pharmacotherapy
  • Self-administration
  • Subjective effects
  • n-Acetylcysteine

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


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