A medication 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 their colleagues. The study presents converging evidence from experiments in mice and rats , as well as a cohort study in humans , suggesting that the drug 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 Yale School of Medicine, New Haven, Connecticut. A report of the new findings is published in Molecular Psychiatry .
Spironolactone as a potential new pharmacotherapy for alcohol use disorder: converging evidence from studies in rodents and humans Summary Evidence suggests that spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, modulates alcohol seeking and consumption. Therefore, spironolactone 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 (dark drinking) and in a rat model of alcohol dependence (vapor exposure). We also investigated the association between receipt of spironolactone for at least 60 continuous days and change in self-reported alcohol consumption, using the Alcohol Use Disorders Identification Consumption Test (AUDIT-C), in a pharmacoepidemiological cohort study in the largest integrated health system in the United States. Spironolactone dose-dependently reduced the intake of sweetened or unsweetened alcohol solutions in male and female mice. No effects of spironolactone were observed on consumption of a non-alcoholic 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 non-dependent 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 alcohol consumption at baseline (AUDIT-C ≥ 8) and those exposed to ≥ 50 mg/day spironolactone. These converging findings in rodent and human studies demonstrate that spironolactone reduces alcohol consumption and support the hypothesis that this medication can be further studied as a novel pharmacotherapy for AUD. |
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“Combining findings from three species and different types of research studies, and then seeing the similarities in that data, gives us confidence that we are onto something potentially scientifically and clinically important. These findings support further study of spironolactone as a possible treatment for alcohol use disorder, a medical condition that affects millions of people in the US.
There are currently three medications approved for alcohol use disorder in the United States, and they are an effective and important aid 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 broader 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 cravings. Preclinical research suggests that increased 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 reduced alcohol consumption in men and women without causing movement or coordination problems, and without affecting their food or water consumption.
In a parallel study that was part of this team’s collaborative efforts, researchers led by co-senior author Amy C. Justice, M.D., Ph.D., of Yale School of Medicine, examined the health records of a large sample of people from the US Veterans Affairs healthcare system to assess possible changes in alcohol consumption after spironolactone was prescribed for their current clinical indications (e.g., heart problems, blood pressure high blood pressure).
They found a significant association between spironolactone treatment and reductions in self-reported alcohol use, as measured by the Alcohol Use Disorders Identification Consumption Test, a screening tool. Of note, the largest effects were observed among those who reported hazardous/heavy episodic alcohol use before starting 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 argues for conducting randomized, controlled studies of spironolactone in people with alcohol use disorder to further evaluate its safety and potential efficacy in this population, as well as additional work to understand how spironolactone may reduce alcohol consumption.
“As with any other medical condition, people with substance use disorders deserve to have a variety of treatment options available, and this study is an exciting step in our effort to expand medications for people with substance use disorders.” alcohol,” said Nora Volkow. , MD, director of NIDA. “In addition, we must address the stigma and other barriers that prevent many people with alcohol use disorder from accessing the treatments we already have available.”
