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

Journal: Pharmacology, biochemistry, and behavior 2021;198():173037

PMID: 32891709

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Abstract

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).

Address: Department of Behavioral Science, University of Kentucky College of Medicine, 1100 Veterans Drive, Medical Behavioral Science Building, Lexington, KY 40536-0086, USA; Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY 40509-1810, USA; Department of Psychology, University of Kentucky College of Arts and Sciences, 171 Funkhouser Drive, Lexington, KY 40506-0044, USA; Center on Drug and Alcohol Research, University of Kentucky College of Medicine, 845 Angliana Ave, Lexington, KY 40508, USA. Electronic address: [email protected].; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.; Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY 40509-1810, USA.; Department of Behavioral Science, University of Kentucky College of Medicine, 1100 Veterans Drive, Medical Behavioral Science Building, Lexington, KY 40536-0086, USA; Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY 40509-1810, USA; Department of Psychology, University of Kentucky College of Arts and Sciences, 171 Funkhouser Drive, Lexington, KY 40506-0044, USA.

DOI: 10.1016/j.pbb.2020.173037

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MeSH Terms: Acetylcysteine, Adult, Alcoholism, Blood Pressure, Double-Blind Method, Drug-Seeking Behavior, Ethanol, Female, Free Radical Scavengers, Glutamic Acid, Heart Rate, Humans, Male, Middle Aged, Reinforcement, Psychology, Self Administration, Time Factors, Treatment Outcome, Young Adult