A medication primarily prescribed for heart problems has shown promise as a treatment for alcohol use disorder (AUD). Combining data from animal experiments with observations in humans, the authors of a new study found that the drug spironolactone reduces drinking in multiple species, with the greatest effects seen in alcohol-dependent individuals.
Inspiration for the study came from previous research that highlighted the role of a hormone called aldosterone in alcoholism. Among people with AUD, higher aldosterone levels have been associated with anxiety, obsessive cravings, alcohol withdrawal, and increased drinking.
Though the mechanism behind this effect is unclear, it’s thought that aldosterone enhances mineralocorticoid receptor signaling, thereby altering the body’s ability to regulate fluid and electrolyte levels. Interestingly, spironolactone is known to block mineralocorticoid receptors, and is administered to counteract the effects of aldosterone and treat fluid build-up following heart failure.
To investigate whether spironolactone also helps to alleviate the symptoms of AUD, the researchers administered the drug to alcohol-dependent mice and rats. A dose-dependent effect was observed in both species, whereby the more spironolactone an animal received, the less they drank.
Experiments in mice also looked at the ability of spironolactone to attenuate binge drinking. Compared to rodents exposed to unsweetened alcohol, those that were given sugary alcoholic drinks tended to gorge themselves, achieving blood alcohol levels that are typically seen following intense drinking sessions.
Encouragingly, spironolactone helped these mice to curtail their boozing but didn’t alter their general food and water intake or decrease their appetite for non-alcoholic sugary drinks.
Turning their attention to humans, the researchers analyzed data from the US Veterans Affairs healthcare system to look for changes in alcohol use amongst those who were prescribed spironolactone for a minimum of 60 continuous days. In total, the study authors compared 10,726 spironolactone-exposed individuals to 34,461 unexposed controls, with highly encouraging results.
Using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scale to assess drinking levels, the researchers found that, on average, alcohol intake scores decreased by an extra 0.17 points among those who received the medication. Once again, this effect was found to be dose-dependent, with larger measures of spironolactone correlating with greater decreases in drinking.
Even more importantly, individuals who drank the most at baseline showed the greatest reductions in booze intake. Typically, those who were classed as heavy or hazardous drinkers prior to taking spironolactone achieved a decrease of 0.47 points more than unexposed individuals after treatment.
“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,” explained study author Lorenzo Leggio in a statement. “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 US.”
The study has been published in the journal Molecular Psychiatry.
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