Weight Loss Drugs May Also Curb Substance Use Disorders

GLP-1 drugs affect reward circuits to reduce alcohol, opioid, and nicotine use.

Key points

GLP-1 drugs show potential to treat substance use disorders.
These effects appear to be mediated at least in part through the modulation of reward pathways in the CNS.
Early results show reductions in cravings, substance use, and other related outcomes.

Glucagon-like peptide-1 (GLP-1) is a hormone responsible for most of the insulin release after consuming a meal. Its effects are mediated by activation of GLP-1 receptors (GLP-1Rs) in the central nervous system, which help regulate hunger signals that prompt people to eat when hungry and stop when satisfied (Fig. 1). The introduction of GLP-1 therapeutics has revolutionized the treatment of type 2 diabetes and obesity, with other potential indications under investigation.

One such additional indication is the treatment of substance use disorder. Because reward pathways that contribute to pathological overeating and obesity are also implicated in addiction (Fig. 1), scientists have begun to explore GLP-1 therapeutics as possible treatments for substance use disorders. Early studies suggest that these drugs may lower cravings and use for alcohol, tobacco, and even opioids. These studies are described in a recent review published in the Journal of the Endocrine Society.

Alcohol

Studies in rodents and nonhuman primates show that the GLP-1R agonists dulaglutide, liraglutide, semaglutide, and exendin-4 reduce alcohol intake and other alcohol-related outcomes.
Anecdotal evidence and pharmacoepidemiological studies in humans report reduced alcohol use by patients using GLP-1RAs for other indications.
In a randomized controlled trial, the GLP-1R agonist exenatide showed reduced alcohol intake in a subgroup of people with both obesity and alcohol use disorder.
More recently, another randomized controlled trial showed that a low dose of the GLP-1R agonist semaglutide reduced alcohol consumption and craving in people with alcohol use disorder. A subgroup analysis also showed a reduction in the number of cigarettes smoked per day among those individuals with alcohol use disorder who were also smokers.

Opioids

In animal models, several GLP-1R agonists have been shown to reduce self-administration and relapse behavior for heroin, fentanyl, and oxycodone.
Two pharmacoepidemiological analyses using electronic health records have reported that use of GLP-1R agonists is associated with lower rates of opioid overdose.

Tobacco

Animal studies indicate that GLP-1R agonists reduce nicotine self-administration, relapse, and other nicotine-related outcomes.
A study of social media posts showed that around 23 percent of posts about nicotine mentioned a cessation in use in conjunction with GLP-1R agonists.
A pharmacoepidemiological study analyzed electronic health records from people with both type 2 diabetes and tobacco use disorder and found that semaglutide was associated with improved smoking-related outcomes.
Results from initial clinical trials suggest that GLP-1 medications promote smoking abstinence, reduce nicotine craving and withdrawal, and prevent weight gain that frequently occurs with smoking cessation.

Psychostimulants

Several animal studies have shown that GLP-1R agonists reduce cocaine-seeking behavior, relapse, and other related outcomes.
Other animal studies have found that GLP-1R agonists reduce amphetamine use and amphetamine-induced hyperlocomotion.

Next Steps

Although more research is needed to confirm how effective GLP-1 medications are in treating addiction, researchers are optimistic. "This research is very important because alcohol and drug addiction are major causes of illness and death, yet there are still only a few effective treatment options," said lead researcher Lorenzo Leggio, MD, Ph.D., of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. "Finding new and better treatments is critically important to help people live healthier lives."

Ed Ergenzinger, J.D., Ph.D - blog