Drug used to treat alcoholism shows promise for anxiety, study finds

FDA-approved disulfiram can safely reduce anxiety levels in rodents, according to analysis by Tokyo University of Science and other Japanese institutes.

Disulfiram (DSF), an FDA-approved drug to treat alcoholism, may also effectively treat anxiety, according to the results of a new study by researchers from Tokyo University of Science and others. Japanese institutes.1

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

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

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

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

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

Anxious mice generally prefer to spend time in closed arms.1

In this study, some of the mice were given diazepam, a drug commonly used to treat anxiety, and others were given DSF. The mice were then placed in 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 device, indicating 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

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

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

Investigators were also surprised to find that, unlike diazepam, DSF treatment did not cause adverse effects (AEs), such as amnesia, impaired coordination, or sedation.1

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

The results of this study are among the first to show that DSF exhibits anti-anxiety properties comparable to existing benzodiazepines without exhibiting adverse effects seen with benzodiazepines.1

The inhibitory activity of DSF against the functioning of FROUNT could help to develop anxiolytic drugs in the future.1

General symptoms of anxiety disorders are highest in people between the ages of 18 and 29, and symptoms tend to decrease with age, according to the CDC.2

Reference

1. A drug that cures alcoholism could be the next anti-anxiety drug. Eurek alert. Press 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

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