FDA-approved heart medication shows promise as treatment for alcohol use disorder

2022

Challenge

Despite the high burden associated with alcohol use disorder (AUD), currently available drug therapies are limited and underutilized. Given the complexity of biological processes that contribute to this chronic disease, a broader spectrum of medications is needed for AUD treatment. The steroid hormone aldosterone and its related mineralocorticoid receptor (MR) are best known for regulating fluid and electrolyte balance in the body, but previous studies suggested that aldosterone and the MR are also involved in alcohol seeking and consumption. Therefore, blocking the MR may be a novel approach to treating AUD.

Advance

IRP researchers led by Leandro Vendruscolo, Ph.D., Pharm.D., M.Sc., and Lorenzo Leggio, M.D., Ph.D., conducted a series of experiments in mouse and rat models of excessive alcohol drinking and found that an MR blocker called spironolactone reduced alcohol intake in male and female animals in direct relationship with the dose given. The drug, which is approved by the FDA for treating heart failure and hypertension, did not cause movement or coordination problems, nor did it affect food or water intake in treated animals. In a large clinical study in collaboration with Dr. Amy Justice from the Yale School of Medicine, the scientists also found a significant reduction in Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores among individuals taking spironolactone for any reason, compared with individuals who did not receive the drug. The largest effect was observed among heavy drinkers and those who received the highest dose of spironolactone.

Impact

Convergent evidence from three species and different study designs support the theory that spironolactone may be repurposed for the treatment of AUD. Pending randomized controlled trials, this medication could represent a novel medication option for people with AUD.

Publications

Farokhnia M, Rentsch CT, Chuong V, McGinn MA, Elvig SK, Douglass EA, Gonzalez LA, Sanfilippo JE, Marchette RCN, Tunstall BJ, Fiellin DA, Koob GF, Justice AC, Leggio L, Vendruscolo LF. (2022). Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies. Mol Psychiatry. Nov;27(11):4642-4652. doi: 10.1038/s41380-022-01736-7.

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This page was last updated on Friday, September 15, 2023