Mounjaro May Alter Brain Signals Behind Food Cravings

Popular diabetes and weight-loss medicines, including Ozempic, Wegovy and Mounjaro, can profoundly affect the body. However, their effects on the brain remain less clear.

These treatments are believed to reduce appetite broadly and increase the sensation of fullness, yet precisely how they produce these effects in the human brain is not well understood.

Mounjaro and brain signals linked to food cravings

The first human study of its type suggests that tirzepatide, sold as Mounjaro, may alter a particular brain signal that could be associated with disordered eating.

The research involved three people with severe obesity who struggled to control their eating and had not responded to earlier weight-loss interventions.

When the participants experienced powerful food-related thoughts or cravings, researchers observed heightened delta–theta signals in an area called the nucleus accumbens. These signals form part of the mammalian brain’s reward system.

Each participant had previously undergone bariatric surgery but continued to have distressing preoccupation with food. Two participants started deep-brain stimulation targeting the nucleus accumbens, while the third had been given tirzepatide to treat type 2 diabetes.

Tracking nucleus accumbens activity

In all three participants, brain activity was recorded using electrodes implanted in the nucleus accumbens.

By coincidence, the third participant’s tirzepatide dose was increased at roughly the same time as her brain-implant operation. Across the following four months, excluding the first month, she experienced a "profoundly" small number of episodes of 'severe food preoccupation'.

Over this period, when she did experience food cravings, delta–theta activity in her nucleus accumbens could not be distinguished from activity recorded when she was not experiencing 'food noise'.

This pattern contrasted sharply with that of the other participants. Unfortunately, the apparent benefits did not continue.

Tirzepatide’s effects did not persist

Between five and seven months after the implantation procedure, the participant taking tirzepatide again began to have more cravings and intrusive food-related thoughts, despite receiving the maximum tirzepatide dose.

At the same point, delta-theta waves in her nucleus accumbens also started to intensify again.

"Our findings raise the possibility that this delta–theta band oscillation could serve as a target engagement biomarker, but its relationship to food preoccupation warrants more controlled investigation," the study authors conclude.

Like Wegovy and Ozempic, Mounjaro is part of a drug class that imitates a naturally occurring hormone in the body, reducing appetite and slowing digestion.

This research is highly preliminary. Without a control group, the conclusions scientists can draw from its findings are restricted. Nevertheless, as one of the earliest human investigations into Mounjaro’s effects on the brain, it may help shape future research.

The study was published in Nature Medicine.