Could GLP-1 receptor agonists treat addiction and dementia?

Ozempic Insulin injection pen

Medications containing semaglutide such as Ozempic, licensed for diabetes, and Wegovy, for weight loss, are being studied to see if they can treat a range of different conditions, including addiction and dementia.

Semaglutide manufacturer Novo Nordisk reported earlier this month that the drug reduces the risk of major adverse cardiovascular events by 20% in adults with overweight or obesity, as shown in the SELECT trial, an effect that was also shown in clinical trials in 2022.

It is currently under investigation in various other clinical trials, for example, as a treatment for polycystic ovary syndrome at the University of Hull, and to understand its impact on ageing at the University of Texas Health Science Center at San Antonio.

According to The Guardian, anecdotal evidence from patients taking semaglutide shows that they have overcome addictions to smoking, alcohol, and even nail-biting as a side-effect of taking the drug.

Dr Christian Hendershot, Director of the Clinical and Translational Addiction Research Programme at the University of North Carolina at Chapel Hill, is conducting one of the new trials into addiction.

He told The Guardian: “We know that drugs in this class are remarkably effective for several important health outcomes – many of which can influence longevity and quality of life. In some ways there is a sense that some of this might be too good to be true. But I think any potential benefits should be investigated.”

A treatment for addiction

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, a group which also includes exenatide, dulaglutide, liraglutide, and tirzepatide. GLP-1 is a hormone that is produced naturally in the brain and the gut in response to food ingestion. The drugs are currently approved as treatments for type 2 diabetes and weight loss.

GLP-1 receptors are found in an area of the hindbrain known as the nucleus tractus solitarius, which is linked to addiction, and also act on the mesolimbic pathway, a dopamine-based system that regulates responses to rewarding stimuli like drugs and food.

In a 2021 study in Texas, US, exenatide in combination with the nicotine replacement therapy was proved to improve smoking abstinence, reduce craving and withdrawal symptoms, and decrease weight gain among abstainers.

In June, researchers from the Sahlgrenska Academy at the University of Gothenburg in Sweden, investigated semaglutide as a treatment for alcohol use disorder (AUD). In their paper in The Lancet, they demonstrated that ‘in male and female rats, acute and repeated semaglutide administration reduced alcohol intake and prevented relapse-like drinking’.

The clinical trials conducted by Hendershot are designed to determine whether semaglutide can help smokers and people with AUD reduce their intake. “It’s an exciting area,” he told The Guardian. “The anecdotal reports that are coming in certainly suggest that there is a signal there that we should follow up on.”

Potential in dementia

GLP-1 receptor agonists (RA) are of interest as a treatment for dementia primarily because obesity and type 2 diabetes are major risk factors for developing the condition.

In February 2022, a Danish study showed that the dementia rate was lower in patients randomised to GLP-1 RAs versus placebo. The researchers concluded that treatment with GLP-1 RAs “may provide a new opportunity to reduce the incidence of dementia in patients with type 2 diabetes”.

Novo Nordisk is currently funding a study at the University of Oxford investigating the effect of semaglutide on the rate of accumulation of tau protein in the brain in Alzheimer’s disease (AD). The research also aims to explore other potential mechanisms of action and effects of semaglutide on the pathway for AD including neuroinflammation.

The manufacturer is also conducting two other trials, evoke and evoke+, to assess the effect of semaglutide versus placebo in people with early Alzheimer’s disease. It is believed the drug could affect an overall improvement of nerve cells, inflammation and vascular health that could potentially help to slow the clinical progression of Alzheimer’s disease. However, these trials won’t be complete until 2026 at the earliest.

Diana Spencer, Senior Digital Content Editor, Drug Discovery World

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