Researchers identify off switch for alcoholism

Researchers from Monash University and the Florey Institute have made a potential breakthrough in the ability to treat alcohol addiction with a simple drug.

A study led by the Monash Institute of Pharmaceutical Sciences (MIPS) and the Florey Institute of Neuroscience and Mental Health uncovered a potential therapeutic target to treat alcohol use disorder (AUD) by targeting a specific receptor in the brain.

The researchers found that by targeting the muscarinic M4 receptor in the brain, both habitual drinking and the likelihood to relapse could be improved in those suffering from alcohol addiction.

The team, led by Dr Chris Langmead from MIPS and Professor Andrew Lawrence and Dr Leigh Walker from the Florey, performed genome-wide RNA sequencing and protein expression studies in human tissue samples from people with AUD and non-drinkers to identify potential therapeutic targets.

Dr Langmead said: “The findings from our study show a lot of promise in how we can work to treat alcohol addiction in the future.”

“Alcohol misuse is a huge burden not just for individuals, but for families, communities and the economy. By identifying a potential therapeutic target, we’re one step closer to developing a new pharmacotherapeutic option for alcohol use disorder.”

Professor Lawrence explains: “We were able to confirm that the regulation of muscarinic M4 receptors occurred in the same brain region in an animal model of alcohol intake, which gave us confidence to investigate a small molecule that activates M4 receptors and ultimately show it could reduce alcohol consumption and prevent relapse to alcohol seeking.”

The study, published in the journal Biological Psychiatry, along with collaborators from China, Thailand and the United States, paves the way forward to addressing one of Australia’s more pressing public health concerns.

Misuse of alcohol in Australia has economic costs of over $14 billion dollars every year. Recent reports show that one in six Australians drink enough alcohol to place them at lifetime risk of alcohol-related disease.

Professor Arthur Christopoulos, Dean of the Faculty of Pharmacy and Pharmaceutical Sciences and a co-author of the study, added: “We have had a long-standing interest in the M4 receptor as a novel therapeutic target in the brain. Now that we know this protein can ameliorate habitual drinking patterns and the risk of relapse, we can move towards the next step, which is translating our findings into drug development.”

Read the full publication here and the commentary here.

Visit Monash Lens to read more on this research https://lens.monash.edu/@chris-langmead/2021/02/22/1382862/the-protein-with-the-potential-to-rewire-the-alcohol-addicted-brain