Cardiac medication shows potential as a treatment for alcohol use disorder

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

Source: NIH

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

The study presents converging evidence from experiments with 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, Conn.

A report of the new findings is published in Molecular Psychiatry.

“Combining the findings from three species and different types of research studies, and then seeing similarities in that data, gives us confidence that we’re onto something potentially scientifically and clinically 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 United States,” said Lorenzo Leggio, MD, Ph.D. , chief of the Section of Psychoneuroendocrinology and Clinical Neuropsychopharmacology, a joint laboratory of NIDA and NIAAA, and one of the senior authors.

There are currently three medications approved for alcohol use disorder in the United States, and they are effective and important aids in the treatment of people with this condition. Given the diverse biological processes that contribute to alcohol use disorder, new medications are needed to provide a broader spectrum of treatment options. Scientists are working to develop a wider menu of pharmaceutical treatments that can be tailored to individual needs.

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

The current study sought to extend 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 reduced alcohol consumption in men and men. female animals, 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 efforts, researchers led by co-senior author Amy C. Justice, MD, Ph.D., of the Yale School of Medicine, examined the records of health of a large sample of people from the Yale School of Medicine. The US Veterans Affairs health system to assess potential changes in alcohol consumption after spironolactone is prescribed for its current clinical indications (eg, 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, a screening tool.

There are currently three medications approved for alcohol use disorder in the United States, and they are effective and important aids in the treatment of people with this condition. The image is in the public domain

Of note, the largest effects were observed among those who reported episodic hazardous/heavy alcohol use prior to initiation of spironolactone treatment.

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

“Altogether, the present study argues for randomized controlled trials of spironolactone in people with alcohol use disorders to further evaluate its safety and potential efficacy in this population, as well as further work to understand how spironolactone may reduce alcohol consumption.”

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

“Also, we need to address the stigma and other barriers that prevent many people with alcohol use disorder from accessing the treatments we already have available.”

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About this neuropharmacology and AUD research news

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

Original research: Closed access
“Spironolactone as a Potential New Pharmacotherapy for Alcohol Use Disorder: Converging Evidence from Rodent and Human Studies” by Amy C. Justice et al. Molecular Psychiatry


Summary

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

Evidence suggests that epironolactone, a nonselective mineralocorticoid receptor (MR) antagonist, modulates alcohol seeking and consumption. Therefore, epironolactone may represent 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 investigated the association between receiving spironolactone for at least 60 continuous days and change in self-reported alcohol use, using the Alcohol Use Disorders Identification Test (AUDIT-C), in a pharmacoepidemiological cohort study in the largest integrated healthcare system in the USA.

Spironolactone dose-dependently reduced the intake of sweetened and unsweetened alcohol solutions in male and female mice. There were no effects of spironolactone on drinking a nonalcoholic sweet solution, 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 with propensity score-matched individuals who did not receive spironolactone. The largest effects occurred among those reporting episodic hazardous/heavy drinking at baseline (AUDIT-C ≥ 8) and those exposed to ≥ 50 mg/day of spironolactone.

These converging findings in rodent and human studies demonstrate that epironolactone reduces alcohol use and support the hypothesis that this drug may be further studied as a novel pharmacotherapy for AUD.

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