Heart medication shows potential as a treatment for alcohol use disorder

Overview: Spironolactone, a drug commonly used to lower blood pressure and treat heart-related problems, shows potential for treating alcohol use disorders.

Source: NIH

A drug for heart problems and high blood pressure may also be effective for treating alcohol use disorders, according to a new study from researchers at the National Institutes of Health and their colleagues.

The study presents convergent evidence from experiments in mice and rats, as well as a cohort study in humans, suggesting that the medication, spironolactone, may play a role in reducing alcohol consumption.

The research was led by scientists from the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), both parts of the NIH, and the Yale School of Medicine, New Haven, Connecticut.

A report of the new findings has been published in Molecular Psychiatry.

“Combining findings across three types and different types of research studies, and then seeing similarities in those data gives us confidence that we’re on something scientifically and clinically potentially important.

“These findings support further study of spironolactone as a potential treatment for alcohol use disorder, a medical condition that affects millions of people in the U.S.,” said Lorenzo Leggio, MD, Ph.D., chief of the Division of Clinical Psychoneuroendocrinology and Neuropsychopharmacology, a joint lab. from NIDA and NIAAA, and one of the senior authors.

Currently, three drugs are approved for alcohol use disorders in the United States, and they are an effective and important tool in treating people with this condition. Given the diverse biological processes that contribute to alcohol use disorders, new drugs are needed to provide a broader spectrum of treatment options. Scientists are working to develop a larger menu of pharmaceutical treatments that can be tailored to individual needs.

Previous research has shown that mineralocorticoid receptors, which are located in the brain and other organs and help regulate fluid and electrolyte balance in the body, may play a role in alcohol consumption and cravings. Preclinical research suggests that higher mineralocorticoid receptor signaling contributes to increased alcohol consumption.

The current study sought to expand this line of research by testing spironolactone, a drug with multiple actions, including blocking mineralocorticoid receptors. Spironolactone is used in clinical practice as a diuretic and to treat conditions such as heart problems and high blood pressure.

In experiments conducted in mouse and rat models of excessive alcohol consumption, NIAAA and NIDA researchers led by co-senior author Leandro Vendruscolo, Pharm.D., Ph.D., of NIDA found that increasing doses of spironolactone increased alcohol consumption in men and women. females, without causing movement or coordination problems and without affecting their food or water intake.

In a parallel study that was part of this team’s collaborative effort, researchers led by co-senior author Amy C. Justice, MD, Ph.D., of the Yale School of Medicine, examined health records of a large sample of people. from the US Veterans Affairs health care system to assess potential changes in alcohol consumption after spironolactone was prescribed for current clinical indications (e.g., heart problems, high blood pressure).

They found a significant association between spironolactone treatment and reduction in self-reported alcohol use, as measured by the Alcohol Use Disorders Identification Test-Consumption, a screening instrument.

Currently, three drugs are approved for alcohol use disorders in the United States, and they are an effective and important tool in treating people with this condition. Image is in the public domain

Note that the greatest effects were seen in those who reported dangerous/heavy episodic alcohol consumption prior to initiating spironolactone treatment.

“These are very encouraging findings,” said NIAAA director George F. Koob, Ph.D., a co-author of the study.

Taken together, the present study calls for conducting randomized, controlled trials of spironolactone in people with alcohol dependence to further assess its safety and potential efficacy in this population, as well as additional work to understand how spironolactone may reduce alcohol use.

“As with any other medical condition, people with substance use disorders deserve to have a range of treatment options available to them, and this study is an exciting step in our effort to expand the drugs for people with alcohol disorders. expand,” says Nora Volkow. , MD, director of NIDA.

“In addition, we need to address the stigma and other barriers that prevent many people with alcohol dependence from accessing the treatments we already have.”

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About this neuropharmacology and AUD research news

Author: NIDA Press Agency
Source: NIH
Contact: NIDA Press Office – NIH
Image: The image is in the public domain

Original research: Closed access.
“Spironolactone as a potential new pharmacotherapy for alcohol use disorders: convergent evidence from rodent and human studies” by Amy C. Justice et al. Molecular Psychiatry


Abstract

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

There is some evidence that spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, modulates alcohol seeking and consumption. Therefore, spironolactone may be a new pharmacotherapy for alcohol use disorder (AUD). In this study, we tested the effects of spironolactone in a mouse model of alcohol consumption (drinking-in-the-dark) and in a rat model of alcohol dependence (vapor exposure).

We also examined the association between spironolactone reception for at least 60 consecutive days and change in self-reported alcohol consumption, using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), in a pharmacoepidemiological cohort study in the largest integrated health care system. in the U.S.

Spironolactone dose-dependently reduced the intake of sweetened or unsweetened alcohol solutions in male and female mice. No effects of spironolactone were observed when drinking a sweet solution without alcohol, food or water intake, motor coordination, alcohol-induced ataxia, or blood alcohol content.

Spironolactone dose-dependently reduced operant alcohol self-administration in dependent and undependent male and female rats. In humans, a greater reduction in alcohol consumption was observed in those who received spironolactone, compared to individuals with the same propensity score who did not receive spironolactone. The largest effects were in those who reported dangerous/heavy episodic alcohol consumption at baseline (AUDIT-C ≥ 8) and those exposed to ≥ 50 mg spironolactone/day.

These convergent findings in rodent and human studies show that spironolactone reduces alcohol consumption and support the hypothesis that this drug could be further studied as a new pharmacotherapy for AUD.

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