A drugs referred to as spironolactone might assist the therapy of alcohol use dysfunction, in line with a brand new research printed in Molecular Psychiatry. The analysis was led by scientists on the U.S. National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
“Alcohol use disorder (AUD) affects 14.5 million people in the United States alone, yet less than 10% of people with AUD receive any treatment, despite the availability of behavioral treatments and three medications approved for AUD,” defined research creator Lorenzo Leggio, a physician-scientist and senior investigator at NIAAA and NIDA, who additionally serves because the NIDA deputy scientific director and appearing scientific director.
“As such, one of our critical missions is to develop new safe and effective treatments for AUD. Our previous preclinical research suggests that the mineralocorticoid receptor (MR) may play a role in alcohol consumption and craving. Furthermore, we previously found that aldosterone, an endogenous hormone that acts on the MR, is correlated with alcohol consumption and craving in patients with AUD.”
“Based on these observations, we have hypothesized that spironolactone, a medication used in clinical practice for hypertension and heart disease, may reduce alcohol consumption, given that it is an MR blocker,” Leggio mentioned. “Therefore, our hypothesis is that spironolactone (and/or other medications acting on the MR) represents a new potential medication for AUD, hence allowing us to increase the armamentarium of options to treat patients with AUD.”
In experiments performed in mouse and rat fashions of extreme alcohol consuming, the researchers discovered that spironolactone decreased the consumption of sweetened and unsweetened alcohol options with out affecting meals or water consumption. It did so in a dose-dependent method, which means that larger doses of spironolactone resulted in larger reductions in alcohol consumption.
Leggio and his colleagues additionally analyzed information from greater than 45,000 people from the U.S. Veterans Affairs healthcare system. Alcohol consumption was measured by the Alcohol Use Disorders Identification Test-Consumption, a typical screening instrument. They discovered that individuals who had been prescribed spironolactone tended to cut back their alcohol consumption greater than matched controls who weren’t prescribed spironolactone. Consistent with the rodent research, they discovered a dose-dependent impact of spironolactone in people.
“We showed, through experiments performed in mice and rats, that spironolactone decreases alcohol consumption,” Leggio informed PsyPost. “Moreover, in a complementary analysis of health records of a large sample of people from the U.S. Veterans Affairs healthcare system, we found that individuals who had been prescribed spironolactone (for reasons such as heart problems or high blood pressure) were more likely to self-report reduced alcohol consumption.”
“We were happily surprised that the effects of spironolactone on alcohol consumption were observed in a consistent matter across mice, rats, and humans, and across different animal procedures and different clinical database. This level of consistency and replication gives us assurance that spironolactone and/or other medications acting on MR are worth further investigations, as part of our broader efforts of developing new treatments for AUD.”
“Of note, the latter results found in humans are consistent with another recent study we conducted in a different healthcare system database, in collaboration with Kaiser Permanente North Carolina,” Leggio added.
The outcomes from the present research are significantly related, the researchers mentioned, as a result of they had been discovered amongst U.S. veterans, who’ve an elevated chance of creating AUD. Importantly, the most important results had been noticed amongst those that reported hazardous/heavy episodic alcohol consumption earlier than beginning spironolactone therapy.
However, Leggio famous that “it is also important to keep in mind that these findings are preliminary, and we cannot conclude that spironolactone is an effective treatment for AUD.”
“What we can say for sure is that spironolactone is a promising new medication, hence the importance of continuing this line of research,” he defined. “The ultimate goal is that, similar to other chronic medical diseases, practicing clinicians will have a larger menu of treatment options to choose from, when they treat a patient with AUD.”
Additional analysis is important earlier than spironolactone may be authorised as a therapy for AUD.
“This work should be seen as preliminary and a first step of a more complex pathway that is needed to understand whether this medication may be effective in patients with AUD,” Leggio defined. “Chiefly, this work argues for conducting future randomized, placebo-controlled studies of spironolactone in people with AUD. Furthermore, we need additional work to understand the mechanisms related to the role of the MR in AUD and how spironolactone reduces alcohol drinking.”
“It is important to see this work as part of our larger mission of developing new treatments, including new medications, for patients with AUD. In fact, at present, only three medications are approved in the U.S. to treat AUD. Not all people with AUD will respond to available medications, but for a subset of individuals, they can be an important tool in their treatment. Scientists are working to develop a larger menu of treatments that could be tailored to individual needs.”
“Future work will also need to understand who the patients are, if any, that may respond to spironolactone, among those people with AUD,” Leggio mentioned. “In fact, AUD is a complex heterogenous disorder, and ‘one size does not fit all,’ so our efforts in developing new medications for AUD need to include research aimed at identifying precision medicine approaches.”
The research, “Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies“, was authored by Mehdi Farokhnia, Christopher T. Rentsch, Vicky Chuong, M. Adrienne McGinn, Sophie Ok. 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.
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