The medication could potentially treat alcohol use disorder.
A recent study by National Institutes of Health researchers and their colleagues suggests that a medication used to treat heart issues and high blood pressure may also be useful in treating alcohol use disorder. The study presents convergent evidence from mice and rat trials, as well as a human cohort study, indicating that the medication, spironolactone, may have a role in lowering alcohol consumption.
Scientists from the National Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), both part of the NIH, and Yale School of Medicine in New Haven, Connecticut, led the study. Their findings were recently published in the journal Molecular Psychiatry.
“Combining findings across three species and different types of research studies, and then seeing similarities in those data gives us confidence that we are onto something potentially important scientifically and clinically. 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, M.D., Ph.D., chief of the Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, a joint laboratory of NIDA and NIAAA, and one of the senior authors.
There are currently three medicines that have been approved for the treatment of alcohol use disorder in the United States, and they are both effective and essential help to the treatment of those who suffer from this condition. Given the variety of biological processes involved in alcohol use disorder, new drugs are required to give a greater range of treatment options. Scientists are attempting to develop a broader range of pharmaceutical treatments that may be customized to individual need.
Previous research has shown that mineralocorticoid receptors, which are located throughout the brain and other organs and help regulate fluid and electrolyte balance in the body, might play a role in alcohol use and craving. 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 medication with multiple actions, including blocking mineralocorticoid receptors. Spironolactone is used in clinical practice as a diuretic and to treat conditions like heart problems and high blood pressure.
In experiments conducted in mouse and rat models of excessive alcohol drinking, NIAAA and NIDA researchers led by co-senior author Leandro Vendruscolo, Pharm.D., Ph.D., from NIDA found that increasing doses of spironolactone decreased alcohol consumption in male and 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, M.D., Ph.D., of the Yale School of Medicine, examined health records of a large sample of people from the U.S. Veterans Affairs healthcare system to assess potential changes in alcohol drinking after spironolactone was prescribed for its current clinical indications (e.g., heart problems, high blood pressure). They found a significant association between spironolactone treatment and reduction in self-reported alcohol consumption, as measured by the Alcohol Use Disorders Identification Test-Consumption, a screening tool. Of note, the largest effects were observed among those who reported hazardous/heavy episodic alcohol consumption 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 assess its safety and potential efficacy in this population, as well as additional work to understand how spironolactone may reduce alcohol drinking.”
“Just like for 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 medications for people with alcohol use disorder,” said Nora Volkow, M.D., 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.”
Reference: “Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies” by Mehdi Farokhnia, Christopher T. Rentsch, Vicky Chuong, M. Adrienne McGinn, Sophie K. Elvig, Eliza A. Douglass, Luis A. Gonzalez, Jenna E. Sanfilippo, Renata C. N. Marchette, Brendan J. Tunstall, David A. Fiellin, George F. Koob, Amy C. Justice, Lorenzo Leggio and Leandro F. Vendruscolo, 20 September 2022, Molecular Psychiatry.
The study was funded by the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse.