Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies
Open accessAbstract
Evidence suggests that spironolactone, a nonselective mineralocorticoid receptor (MR) antagonist, modulates alcohol seeking and consumption. Therefore, spironolactone may represent a novel pharmacotherapy for alcohol use disorder (AUD). In this study, we tested the effects of spironolactone in a mouse model of alcohol drinking (drinking-in-the-dark) and in a rat model of alcohol dependence (vapor exposure). We also investigated the association between spironolactone receipt for at least 60 continuous days and change in self-reported alcohol consumption, using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), in a pharmacoepidemiologic cohort study in the largest integrated healthcare system in the US. Spironolactone dose-dependently reduced the intake of sweetened or unsweetened alcohol solutions in male and female mice. No effects of spironolactone were observed on drinking of a sweet solution without alcohol, food or water intake, motor coordination, alcohol-induced ataxia, or blood alcohol levels. Spironolactone dose-dependently reduced operant alcohol self-administration in dependent and nondependent male and female rats. In humans, a greater reduction in alcohol consumption was observed among those who received spironolactone, compared to propensity score-matched individuals who did not receive spironolactone. The largest effects were among those who reported hazardous/heavy episodic alcohol consumption at baseline (AUDIT-C ≥ 8) and those exposed to ≥ 50 mg/day of spironolactone. These convergent findings across rodent and human studies demonstrate that spironolactone reduces alcohol use and support the hypothesis that this medication may be further studied as a novel pharmacotherapy for AUD.
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A drinking-in-the-dark (DID) test was used to model binge-like drinking in mice.
“A drinking-in-the-dark (DID) test was used to model binge-like drinking in mice (119, 120).”
From The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission (2023) · cites this paper as [120]
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- Authors
- Farokhnia, M., Rentsch, C. T., Chuong, V., McGinn, M. A., Elvig, S. K., Douglass, E. A., Gonzalez, L. A., Sanfilippo, J. E., Marchette, R. C. N., Tunstall, B. J., Fiellin, D. A., Koob, G. F., Justice, A. C., Leggio, L., & Vendruscolo, L. F.
- Affiliations
- National Institutes of Health (US)
- United States Department of Veterans Affairs (US)
- Yale University (US)
- Corresponding author
- Leggio, Lorenzo
- Vendruscolo, Leandro F.
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2022-09-20
- Volume
- 27
- Issue
- 11
- Pages
- 4642-4652
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC10231646
- OpenAlex
- W4296335928
- Cited by
- 41
- References
- 90
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 13 · 2023: 13
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (ZIA-DA-000635, ZIA-DA000602-06)
- U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (ZIA-AA000218, R01-AA023733, U24-AA020794, U01-AA020790, and U10-AA013566)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- spironolactone, alcoholism, pharmacotherapy, mineralocorticoid receptor antagonists, alcohol self-administration, alcohol seeking, alcohol consumption, pharmacoepidemiology, AUDIT-C, sex differences
- MeSH terms
- Alcohol Drinking, Ethanol, Alcoholism, Animals, Female, Humans, Male, Rodentia, Spironolactone, Cohort Studies, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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