A drug for heart problems and high blood pressure may also be effective for treating alcohol use disorders, 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 and a human cohort study 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 part of the NIH, and the Yale School of Medicine, New Haven, Connecticut. A report on the new findings is published in Molecular Psychiatry.
Combining insights from three types and different types of research studies, and then seeing similarities in that data gives us confidence that we are on to something that is scientifically and clinically potentially important. These results support further investigation of spironolactone as a potential treatment for alcohol use disorder, a condition that affects millions of people in the United States.
Lorenzo Leggio, MD, Ph.D., director of the Division of Clinical Psychoneuroendocrinology and Neuropsychopharmacology, a joint laboratory of NIDA and NIAAA, and one of the senior authors
There are currently three drugs approved for alcohol use disorders in the United States, and they are an effective and important aid in the management of people with the disorder. Given the diverse biological processes that contribute to alcohol use disorders, new drugs are needed to provide a broader range of treatment options. Scientists are working to develop a wider range of pharmaceutical treatments that could 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, 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 attempted to expand this line of research by testing spironolactone, a drug with multiple effects 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 on mouse and rat models of binge drinking, NIAAA and NIDA researchers led by NIDA co-senior author Leandro Vendruscolo, Pharm.D., Ph.D., found that increasing Doses of spironolactone reduced alcohol consumption in males and females in 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, examined the US Veterans Affairs health care system to assess potential changes in alcohol use after spironolactone prescribed for its current clinical indications (e.g. heart problems, hypertension). They found a significant association between spironolactone treatment and reductions in self-reported alcohol consumption. measured by the Alcohol Use Disorder Identification Test, a screening tool. Notably, the greatest effects were seen in those who reported hazardous/heavy episodic alcohol use prior to starting spironolactone treatment.
“These are very encouraging results,” said NIAAA director George F. Koob, Ph.D., a co-author of the study. “Taken together, the present study advocates conducting 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 additional work to understand how spironolactone may reduce alcohol consumption .”
“As with any other medical condition, people with substance use disorders deserve a range of treatment options available to them, and this study is an exciting step in our efforts to expand medicines for people with alcohol use disorders,” said Nora Volkow, MD, director of NIDA . “Additionally, we must address the stigma and other barriers that prevent many people with alcohol use disorders from accessing the treatments we already have available.”
NIH/National Institute on Substance Abuse
Farokhnia, M., et al. (2022) Spironolactone as a potential new pharmacotherapy for alcohol use disorders: convergent evidence from rodent and human studies. Molecular Psychiatry. doi.org/10.1038/s41380-022-01736-y.