Mounjaro and the brain: Why cravings fade at first, then return later

A rare brain-recording study found tirzepatide briefly muted activity linked to 'food noise'; months later the signals and intrusive thoughts returned, hinting at limits to its effect

What if a weight-loss drug could quiet the part of your brain that keeps thinking about food, only for that silence to shatter months later?

 

A new case study suggests that is exactly what happened to one woman taking tirzepatide, the blockbuster drug sold as Mounjaro and Zepbound.

 

Published in Nature Medicine, the study titled Brain activity associated with breakthrough food preoccupation in an individual on tirzepatide offers an unprecedented look inside the human brain. Using implanted electrodes, researchers showed that tirzepatide temporarily dampened activity in the nucleus accumbens, which is the brain’s reward hub closely linked to food cravings and compulsive eating, before those signals resurfaced months later.

 

 

According to the researchers, the findings raise questions about how long these drugs can truly silence ‘food noise’ and whether more targeted treatments are needed.

What is ‘food noise’, and why does it matter?

Food noise refers to the constant, intrusive thoughts about food that many people with obesity and eating disorders experience, even when they are not physically hungry.

 

It can feel like an endless mental loop: thinking about what to eat next, fighting urges to snack, or feeling pulled towards specific foods. Studies suggest up to 60 per cent of people with obesity experience this kind of food preoccupation, which can fuel binge eating, emotional distress, and loss of control.

 

Crucially, food noise is not just about willpower. It is linked to altered signalling in brain regions that govern reward, motivation, and impulse control.

Which brain region drives food cravings?

At the centre of this study is the nucleus accumbens (NAc), a deep brain structure that plays a key role in reward, pleasure, and motivation.

 

In people with obesity and binge eating disorder, activity in the NAc can become dysregulated. Instead of responding appropriately to hunger and fullness, the brain’s reward system becomes hypersensitive to food cues, especially highly palatable foods rich in sugar, fat, or salt.

 

Previous research has linked abnormal electrical rhythms in this region to compulsive eating behaviours.

 

The participant in the study, a 60-year-old woman with severe obesity, type 2 diabetes, and persistent loss-of-control eating, had electrodes implanted in her nucleus accumbens as part of an experimental trial using responsive deep brain stimulation.

 

This allowed researchers to observe, in real time, how her brain’s craving circuits behaved while she was taking tirzepatide.

How did tirzepatide change brain activity and cravings?

When the participant’s tirzepatide dose was increased to its maximum, her obsessive thoughts about food disappeared. At the same time, recordings showed a quieting of abnormal low-frequency brain activity, known as delta–theta waves, in the nucleus accumbens. These signals had previously appeared just before intense food preoccupation.

 

For several months, her brain activity during craving moments looked no different from her brain at rest. Subjectively, she reported feeling free from food noise.

Why did cravings return after months?

After about five months, the calm did not last.

 

The same abnormal brain rhythms began to re-emerge in the nucleus accumbens, despite the participant continuing on the highest dose of tirzepatide. Soon after, her intrusive thoughts about food returned, along with episodes of severe food preoccupation.

 

The timing was striking. The brain signals appeared before her symptoms fully returned, suggesting the drug’s effect on craving circuits may weaken over time.

Does this mean Mounjaro stops working on cravings?

Not exactly. According to the researchers, tirzepatide remains highly effective for blood sugar control and weight loss, the indications for which it is approved. However, this study suggests its effects on food preoccupation and compulsive eating may not be permanent, at least for some individuals.

 

Researchers caution against calling GLP-1 and GIP drugs ‘miracle treatments’ for conditions like binge eating disorder until their long-term effects on the brain are better understood. 

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This content is for informational purposes only and is not a substitute for professional medical advice.