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

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2020-11, Vol.198, p.173037-173037, Article 173037
• Main Authors: Stoops, William W., Strickland, Justin C., Hays, Lon R., Rayapati, Abner O., Lile, Joshua A., Rush, Craig R.
• Format: Article
• Language: English
• Subjects: Acetylcysteine - administration & dosage; Acetylcysteine - pharmacology; Adult; Alcohol; Alcoholism - drug therapy; Alcoholism - etiology; Behavioral economic demand; Blood Pressure - drug effects; Double-Blind Method; Drug-Seeking Behavior - drug effects; Ethanol - administration & dosage; Ethanol - adverse effects; Female; Free Radical Scavengers - administration & dosage; Free Radical Scavengers - pharmacology; Glutamic Acid - metabolism; Heart Rate - drug effects; Humans; Male; Middle Aged; n-Acetylcysteine; Pharmacotherapy; Reinforcement, Psychology; Self Administration; Subjective effects; Time Factors; Treatment Outcome; Young Adult
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2020.173037

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. 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. 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. Alcohol produced prototypic effects (e.g., increased breath alcohol concentration, increased ratings of Feel Drink). n-Acetylcysteine did not alter the effects of alcohol. 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). •This human laboratory study tested how n-acetylcysteine treatment influenced alcohol effects.•n-Acetylcysteine did not change alcohol effects.•More work is needed to evaluate n-acetylcysteine as an adjunct alcohol treatment.