Hedonism vs. Aversion: Finding the Right Balance with GLP1s?
- Valerie Sutherland, MD
- Dec 7
- 5 min read
At Obesity Week in Atlanta this Fall, much of the content was on common benefits and pitfalls in real-world, large scale clinical use of GLP1s. To me, the underlying concept for many of these is the balance between hedonic versus aversive signals in the brain. On the one hand, these medications quiet overly active hedonic signals that lead to overeating and overly ingesting highly palatable foods, collectively termed “food noise.” These medications even have been known to reduce cravings for other things that lead to “addictive” behaviors such as substance use, gambling, and shopping. On the other hand, there are reports of people having an aversion to eating even a minimum number of calories and reporting fatigue, depression, or lack of libido. What is happening, why is it happening, and are we talking about it enough?
What is Hedonic Eating?
Eating falls into two broad categories: eating for fuel and nutrition, and eating for pleasure. Eating for pleasure is called hedonic eating and is driven by food palatability, or how good it tastes, rather than hunger. In short, the better a food tastes, the more people eat of it. The mechanism by which it is controlled in humans is not currently understood. The primary candidate under research is dopamine and neurons that respond to dopamine and glutamine. It is obvious that this system functions very differently in different people, and the mechanism and causes for this is not understood. T
Hedonic Eating and GLP1s
To research hedonic eating and how GLP1s affect it, this study looked at differences in eating between mice treated with semaglutide and those without. They treated some mice with semaglutide and compared them to those treated with a sham injection. They measured body weight and chow intake when given access to highly palatable food (undiluted Ensure) versus lower palatability food (Ensure diluted to 20%). and then they crossed over the mice after allowing the to regain weight they had lost. They monitored dopamine neuron in the brain during this experiment. They found that with regard to the highly palatable chow, the number of eating bouts started was the same, but that the duration of eating and the amount of calories eaten was higher in the untreated mice and lower in the mice treated with semaglutide. They found that this was correlated with decreased activity of the dopaminergic neurons in the brain, implying a causative role. They also found that when they blocked these dopaminergic neurons, the increase in food ingestion following weight loss after semaglutide was stopped was decreased. Does this imply a mechanism for preventing weight regain after stopping semaglutide?
Nutritive Eating and GLPS1
Nutritive eating is eating in response to physical hunger and tends to avoid lower palatability foods. In a second portion of this study, they compared intake of lower palatability food between mice treated with semaglutide and mice not treated with semaglutide using Ensure diluted to 20%. For the lower palatability food, consumption amounts and duration were similar in mice treated and not treated with semaglutide.
When has it gone “too far?”
With the widespread, and sometime unmonitored, use of GLP1s, there is more discussion about the potential risks and downfalls of these medications. Some of it is centered around risk and harm, such as excessive weight loss or depression, and some of it is simply around high discontinuation rates and trying to understand the reasons for that. Putting aside the common gastrointestinal side effects, let’s focus on things like food aversion, fatigue, and depression as possible cases where the reduction in dopaminergic/hedonic signals may have gone “too far." In this case series, appetite suppression and food aversion were so strong that patients, for example, reduced calorie intake to 350 calories a day, or ate only one time per week. The article suggests a procedure focused on prescreening and monitoring and cautions against unmonitored use.
In another large review on depression/suicide/self-harm signals, the authors looked at the FDA Adverse Event Reporting System data looking at reviewing depression/suicide/self-harm signals. They found 8284 reports for liraglutide, 14,435 reports for semaglutide, and 15,597 reports for tirzepatide. Reports were similar across gender and more common in ages 18-64 and more common after approval for weight management (compared to diabetes). The authors note that there are no current psychiatric warnings in labeling.
*If you or someone you know is experiencing mental health challenges or thoughts of suicide, there is treatment and resources. The national Suicide and Crisis Lifeline is available 24/7 be calling or texting "988."
Finding the Balance
Oftentimes, the conversation about these medications tend to focus on the scale. People may ask how much weight have I lost? How much weight should I have lost? What should my weight be? I have tried to focus on conversation, usually with buy-in from the individual, to health outcomes. How are my blood sugar, blood pressure, cholesterol, and liver? How are my cardiometabolic risk factors? How is my pain, function, fitness, and quality of life? How is the body composition, especially excess visceral adiposity? How is the lean body mass, including skeletal muscle and bone? Perhaps we should also be “measuring”, tracking, monitoring the balance of hedonic versus aversive brain signals? What are the best questions to ask for this? Perhaps finding the right balance using the right medication at the right dose at the right time, in the right environment with the other comprehensive components, should be the target. Then, the rest will follow. After all, isn’t addressing the underlying causes and not just the weight the goal? Since there is not just one cause, and no two people are the same, that will look unique to each person.
Take Aways
Let’s develop a more mature and broad language for understanding the brain chemistry involved. We have coined the new term “food noise”, but let’s drill down and find a more diverse vocabulary for more nuanced conversations. Let’s all come to the table and learn from each other and ourselves and move forward deliberately. Let's be sure we are using these powerful tools wisely, for now and the long-term. We have come far, but we are by no means there, yet.
Take Back Your Dopamine Balance,
Valerie Hope-Slocum Sutherland, MD
AI was NOT used in this blog. The thoughts and opinions are only those of the author.
References
Zhu Z, Gong R, Rodriguez V, Quach KT, Chen X, Sternson SM. Hedonic eating is controlled by dopamine neurons that oppose GLP-1R satiety. Science. 2025 Mar 28;387(6741):eadt0773. doi: 10.1126/science.adt0773. Epub 2025 Mar 28. PMID: 40146831; PMCID: PMC12009138.
Lee S, Li M, Le GH, Teopiz KM, Vinberg M, Ho R, Au HCT, Wong S, Valentino K, Kwan ATH, Rosenblat JD, McIntyre RS. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) as treatment for nicotine cessation in psychiatric populations: a systematic review. Ann Gen Psychiatry. 2024 Nov 11;23(1):45. doi: 10.1186/s12991-024-00527-9. PMID: 39529123; PMCID: PMC11552190.
Richards JR, Khalsa SS. Highway to the danger zone? A cautionary account that GLP-1 receptor agonists may be too effective for unmonitored weight loss. Obes Rev. 2024 May;25(5):e13709. doi: 10.1111/obr.13709. Epub 2024 Feb 6. PMID: 38320760; PMCID: PMC11144546.
Wang M, Yang Z, Yan M, Liu S, Xiao S. Depression and suicide/self-injury signals for weight loss medications: A disproportionality analysis of semaglutide, liraglutide, and tirzepatide in FAERS database. J Affect Disord. 2025 Nov 15;389:119670. doi: 10.1016/j.jad.2025.119670. Epub 2025 Jun 14. PMID: 40523410.
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