Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies

Study Authors Mehdi Farokhnia, Vicky Chuong, Christopher Rentsch, and Adrienne McGinn,

Featured Paper of the Month – February 2023

Published in Molecular Psychiatry with authors from the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section and Neurobiology of Addiction Section.

Summary

The steroid hormone aldosterone regulates fluid and electrolyte homeostasis mainly via its mineralocorticoid receptor. Previous studies suggest that this pathway may also modulate alcohol seeking and consumption. Spironolactone is a nonselective mineralocorticoid receptor antagonist primarily used in clinical practice to treat cardiovascular conditions. Preliminary evidence indicates that spironolactone may also reduce alcohol use. In this study, we first tested spironolactone in a mouse model of alcohol binge drinking and found that spironolactone dose-dependently reduced alcohol drinking. Using a model of alcohol dependence, we also found that spironolactone reduced alcohol self-administration in rats. Finally, in a large pharmacoepidemiologic cohort study, people who received spironolactone for conditions unrelated to alcohol drinking showed reduced alcohol consumption, compared to propensity score-matched individuals who did not receive spironolactone. This reduction in alcohol use was greater among heavy-drinking individuals and those who received higher doses of spironolactone. These convergent findings across three species indicate that spironolactone may be repurposed and further studied as a novel pharmacotherapy for alcohol use disorder.

Publication Information

Farokhnia, Mehdi; Rentsch, Christopher T; Chuong, Vicky; McGinn, M Adrienne; Elvig, Sophie K; Douglass, Eliza A; Gonzalez, Luis A; Sanfilippo, Jenna E; Marchette, Renata C N; Tunstall, Brendan J; Fiellin, David A; Koob, George F; Justice, Amy C; Leggio, Lorenzo; Vendruscolo, Leandro F

Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies Journal Article

In: Mol Psychiatry, vol. 27, no. 11, pp. 4642–4652, 2022, ISSN: 1476-5578.

Abstract | Links

@article{pmid36123420b,

title = {Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies},

author = {Mehdi Farokhnia and Christopher T Rentsch and Vicky Chuong and M Adrienne McGinn and Sophie K Elvig and Eliza A Douglass and Luis A Gonzalez and Jenna E Sanfilippo and Renata C N Marchette and Brendan J Tunstall and David A Fiellin and George F Koob and Amy C Justice and Lorenzo Leggio and Leandro F Vendruscolo},

url = {https://pubmed.ncbi.nlm.nih.gov/36123420/},

doi = {10.1038/s41380-022-01736-y},

issn = {1476-5578},

year  = {2022},

date = {2022-11-01},

urldate = {2022-11-01},

journal = {Mol Psychiatry},

volume = {27},

number = {11},

pages = {4642--4652},

abstract = {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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pubstate = {published},

tppubtype = {article}

}