Investigation of the GLP-1 receptor agonist semaglutide on alcohol effects: relevance for the treatment of alcohol use disorder

2023 Award: $70,152

Alcohol use disorder (AUD) is a devastating disease that affects many individuals and families. There is an urgent need to identify medications to help with the treatment of AUD. The goal of the present work is to determine whether semaglutide (an FDA-approved antidiabetic and weight management medication) blunts the subjective/interoceptive effects of alcohol. This is an important question as these effects have the capability to influence alcohol drinking behavior and relapse.

Need/Problem: Alcohol use disorder (AUD) is a significant health and societal burden. However, there are only three FDA-approved medications for treating AUD and while these medications work well for some, they do not work for all individuals. Therefore, there is the need to identify new medications to help treat AUD.

Grant Summary: One approach to identify new possible medications for the treatment of AUD is medication repurposing. That is, testing FDA-approved drugs as candidate AUD therapies. The present project will use the glucagon-like peptide 1 (GLP-1) agonist, semaglutide (an antidiabetic medication used for the treatment of type 2 diabetes and a medication for chronic weight management). We will test whether semaglutide blunts the subjective/interoceptive effects of alcohol in a preclinical model.

Goals & Projected Outcomes: The goal of the present project will be to determine whether acute and/or chronic treatment with semaglutide will blunt the interoceptive effects of alcohol. Data derived from this study will be important to help us understand a potential mechanism by which semaglutide may reduce alcohol consumption.

Joyce Besheer, PhD

Grant Details: We will use well-established procedures such that rats are trained to “report” whether they experience the effects of alcohol or not (based on selecting a lever to press) as a measure of the interoceptive effects of alcohol. Once animals are trained on the procedure, we will administer a single dose of semaglutide before alcohol. This will allow us to determine whether the effects of alcohol are blunted. We will next test whether the effects of semaglutide on alcohol interoceptive effects are altered following chronic semaglutide as repeated treatment is clinically relevant as these medications are taken chronically.