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Expert Opin Investig Drugs. 2018 Aug;27(8):667-675. doi: 10.1080/13543784.2018.1501471. Epub 2018 Aug 1.

N-acetyl cysteine in the treatment of alcohol use disorder in patients with liver disease: Rationale for further research.

Author information

1
a University of Sydney, Faculty of Medicine and Health, Central Clinical School , NHMRC Centre of Research Excellence in Mental Health and Substance Use , Sydney , NSW , Australia.
2
b NHMRC Centre of Research Excellence in Mental Health and Substance Use, Faculty of Health Sciences , University of Sydney , Sydney , NSW , Australia.
3
c Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
4
d Faculty of Medicine and Health, Discipline of Pharmacology , University of Sydney, Clinical Pharmacology and Toxicology Research Group , Sydney , NSW , Australia.
5
e South Carolina Clinical and Translational Research Centre , Medical University of South Carolina , Charleston , United States of America.
6
f Department of Psychiatry and Behavioral Sciences , Medical University of South Carolina , Charleston.
7
g The University of Sydney, Centenary Institute , Camperdown , NSW , Australia.
8
h Faculty of Medicine and Health, Discipline of Pathology , University of Sydney , Sydney , NSW , Australia.
9
i Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse , National Institutes of Health , Bethesda , MD , USA.
10
j Center for Alcohol and Addiction Studies , Brown University , Providence , RI , USA.
11
k Drug Health Services , Royal Prince Alfred Hospital , Camperdown , NSW , Australia.

Abstract

INTRODUCTION:

Alcoholic liver disease (ALD) is the leading cause of alcohol-related death and one of the most common forms of liver disease. Abstinence from alcohol is crucial to reducing morbidity and mortality associated with the disease. However, there are few pharmacotherapies for alcohol use disorder suitable for those with significant liver disease.

AREAS COVERED:

This paper presents a rationale for investigating the use of N-acetyl cysteine (NAC) to promote abstinence or reduce heavy alcohol consumption for patients with an alcohol use disorder, particularly in the presence of liver disease. NAC is an antioxidant with glutamatergic modulating and anti-inflammatory properties. Evidence is emerging that oxidative stress, neuro-inflammation and dysregulation of glutamatergic neurotransmission play a key role in alcohol use disorder. Similarly, oxidative stress is known to contribute to ALD. We outline the studies that have investigated NAC to reduce alcohol consumption including preclinical and clinical studies. We also review the evidence for NAC in other addictions as well as psychiatric and physical comorbidities associated with alcohol use disorders.

EXPERT OPINION:

NAC is low cost, well-tolerated and could have promise for the treatment of alcohol use disorder in the presence of liver disease. Clinical trials directly examining efficacy in this population are required.

KEYWORDS:

Alcoholic liver disease; N-acetyl cysteine; alcohol use disorder; comorbidity; pharmacotherapy

PMID:
30019966
DOI:
10.1080/13543784.2018.1501471
[Indexed for MEDLINE]

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