AddictionNews has spent more time covering GLP-1 agonists such as Ozempic, Monjouro, and Wegovy, than any other subject. For one thing, it’s exciting. GLP-1 agonists have only been approved for diabetes since 2017 and for obesity since 2021. Based on the experiences of those early adopters, GLP-1 drugs are now in trials for a wide swath of ailments.

Just on AddictionNews, we have covered studies involving GLP-1 and smoking cessation, nicotine use disorder, alcohol use disorder, opioid use disorder, heart disease, and dementia, among other diseases. We have tried to tease out how GLP-1 drugs work, in the gut and in the brain, but there are GLP-1 receptors in both places and it’s difficult to accurately describe what’s happening and where to cause the suppression of urges.

One study tried to determine whether it’s the brain or the gut that is the reason for weight loss:

To separate these two effects, scientists bred rats that only had GLP-1 receptors in one place or the other. The results were unequivocal: Ozempic and its relatives work in the brain.

If we have indeed found a substance that lowers the desire to eat, to indulge in alcohol or drugs, to smoke cigarettes or suck on a vape pen, to gamble or shop excessively — have we found a drug that mutes all desires? Are people on Ozempic less likely to go to Disneyland? Does it affect sexual desire? Are they less touched by music, more bored at the movies?

A fascinating study from the Max Planck Institute for Metabolism Research in Cologne, Germany, looked at the impact of GLP-1 drugs on hunger and incentive motivation. Some findings include:

• Hunger increases incentive motivation in normal-weight people but not in obese people.

• GLP-1 drugs reduce incentive motivation independently of incentive type (food or non-food).

• In humans with higher insulin sensitivity, hunger increases motivation, while poorer insulin sensitivity dampens the motivational effect of hunger.

The study involved 25 normal-weight adults (BMI 22.4 kg/m2) and 25 obese adults (BMI 35.6 kg/m2), all non-smokers with “no history of neurological, psychiatric, metabolic, or eating disorders.” A good many of the original 50 were thinned out for a variety of non-compliance reasons, arriving at 21 normal weight (9 female) and 16 obese (9 female) completing the trial.

The volunteers were involved in two testing sessions lasting two hours each, one week apart. The subjects were randomly given either a placebo or liraglutide to take the night before each session. They would then fast overnight and prior to each session. Then they were shown images of plates of snacks or plates of coins and asked to squeeze a hand grip forcefully to earn the items shown. The researchers describe the protocol:

Before each task, hunger levels were assessed via visual analogue scales and blood drawn to measure insulin and glucose. After the behavioural task, individual liking and wanting of the reward types (money and food) and the participants’ compliance were evaluated in a short debriefing.

The researchers found the GLP-1 drug reduced motivation in both normal weight and obese persons, using both financial and food incentives: “[O]ur findings suggest a role of metabolic modulation of motivated behaviour independent of incentive type (food or money).” It seems likely that GLP-1 agonists are doing something to reduce desire across the board, and that’s not always a good thing.

For example, GLP-1 drugs are not recommended for the treatment of alcohol use disorder if the patient is already underweight. Similarly, doctors are advised to consider psychiatric comorbidities before prescribing GLP-1 for obesity. Decreasing desire in someone who is depressed can lead to suicidal ideation. Sometimes, the death of desire can become the death of pleasure, and that can be deadly. 

As for how GLP-1 drugs affect the sex drive, we’ll save that for a future edition of AddictionNews.

Written by Steve O’Keefe. First published August 22, 2024.

Sources:

“Neuronal GLP1R mediates liraglutide’s anorectic but not glucose-lowering effect,” The Journal of Clinical Investigation, April 14, 2014.

“GLP-1 and hunger modulate incentive motivation depending on insulin sensitivity in humans,” Molecular Metabolism, March 2021.

“Why Does Ozempic Cure All Diseases?,” Astral Codex Ten, August 13, 2024.

Image Copyright: Grekov.