Drug Used to Treat Alcoholism Shows Promise for Anxiety, Study Results Show

FDA-approved Disulfiram can safely reduce anxiety levels in rodents, analysis from the Tokyo University of Sciences and other Japan institutes finds.

Disulfiram (DSF), a drug approved by the FDA to treat alcoholism, may also effectively treat anxiety, according to the results of a new study by investigators from the Tokyo University of Sciences and other Japan institutes.1

DSF inhibits the enzyme aldehyde dehydrogenase, which is responsible for the metabolism of alcohol, but the results of recent studies have shown that DSF inhibits a cytoplasmic protein called FROUNT.1

FROUNT controls the direction in which certain immune cells migrate, and DSF blocks FROUNT from interacting with 2 chemokine recuperators, CCR2 and CCR5, which are involved in important cellular signaling pathways.1

Other study results have suggested that chemokine receptors could be involved in the regulation of emotional behavior in rodents, so investigators conducted a study examining the pharmacological properties of DSF.1

In the study published in Frontiers in Pharmacology, investigators used an elevated plus-maze (EPM) tests, which is used to screen for anxiolytic drugs, to study the effects of DSF in mice.1

The EPM apparatus consists of 4 arms set in a cross pattern and connected to a central square. Two of the arms are protected by vertical boundaries, while 2 have unprotected edges.1

Mice with anxiety usually prefer to spend time in the closed arms.1

In this study, some of the mice were given diazepam, a drug commonly used to treat anxiety, and others received DSF. The mice were then placed into the EPM, and their activity was monitored.1

Investigators found that mice treated with DSF spent significantly more time in the open arms of the apparatus, which indicated that they were less anxious.1

Additionally, the team evaluated the anxiolytic effects of a more potent FROUNT inhibitor called DSF-41 and observed similar results.1

The behavioral changes were similar to those observed in mice treated with diazepam.1

“We propose that DSF inhibits FROUNT protein and the chemokine signaling pathways under its influence, which may suppress presynaptic glutamatergic transmission in the brain,” Akiyoshi Saitoh from Tokyo University of Science said in a statement. “These results indicate that DSF can be used safely by elderly patients suffering from anxiety and insomnia and has the potential to become a breakthrough psychotropic drug.”1

Investigators were also surprised to find out that by contrast to diazepam, the DSF treatment did not lead to adverse effects (AEs), such as amnesia, coordination disorders, or sedation.1

Investigators plan to further investigate DSF’s pharmaceutical actions. Additionally, they hope to understand the exact role of the FROUNT molecule in the central nervous system.1

The results of this study are some of the first to show that DSF exhibits anti-anxiety properties comparable to existing benzodiazepines without exhibiting any AEs observed with benzodiazepines.1

DSF’s inhibitory activity against FROUNT functioning could help develop anxiolytic drugs in the future.1

General anxiety disorders symptoms are highest among those who are aged 18 to 29 years, and the symptoms tend to decrease with age, according to the CDC.2

Reference

1. A drug that cures alcoholism may be the next anti-anxiety medication. EurekAlert. News release. April 14, 2022. Accessed April 20, 2022. https://www.eurekalert.org/news-releases/949771

2. Symptoms of generalized anxiety disorder. CDC. Updated September 23, 2020. Accessed April 20, 2022. https://www.cdc.gov/nchs/products/databriefs/db378.htm