In a rare deep-brain recording study of a woman with severe obesity and loss-of-control eating, tirzepatide — sold as Mounjaro and Zepbound — temporarily silenced activity in a key reward region linked to “food noise,” or intrusive thoughts about food. About five months later, those brain signals and intense food preoccupation reappeared, suggesting the drug’s effects on this patient’s cravings were short‑lived.
A single-patient case study published in Nature Medicine examined how tirzepatide interacts with the brain in a 60-year-old woman with obesity, type 2 diabetes, and loss-of-control eating who reported persistent "food noise" — intrusive, unwanted thoughts about food that contributed to overeating.
According to the Perelman School of Medicine at the University of Pennsylvania, the woman had a history of treatment-resistant obesity and was using tirzepatide, marketed as Mounjaro and Zepbound, prescribed for type 2 diabetes and obesity at the time she entered a clinical trial on deep-brain stimulation for compulsive eating.
The trial, led by neurosurgeon Casey H. Halpern, MD, involved surgically implanting intracranial electroencephalography (iEEG) electrodes in the nucleus accumbens (NAc), a reward-related region that helps regulate motivation, pleasure-seeking, and impulse control. The system, similar to devices used for drug‑resistant epilepsy and Parkinson’s disease, could both record electrical activity and deliver high‑frequency stimulation when brain signals associated with food preoccupation appeared.
In this ongoing pilot study, four participants with obesity and loss-of-control eating were enrolled. Earlier work from Halpern’s group showed that in people with obesity and binge eating disorder, signaling in the NAc and its connected circuits is dysregulated, and that distinctive low‑frequency electrical activity in this region can precede episodes of intense food craving. The team’s previous pilot data also suggested that stimulating the NAc when those craving-related signals arise can reduce binge episodes.
For the participant taking tirzepatide (identified in Penn’s report as Participant 3), researchers observed that once she had reached a full dose of the medication and had the electrodes implanted, electrical activity in the NAc quieted markedly. Penn Medicine reports that her recordings showed almost no NAc signaling linked to food preoccupation, aligning with her reports of having no intrusive thoughts about food during that period.
This period of quiescent NAc activity lasted for roughly five months. After that, the case report in Nature Medicine and summaries from Penn Medicine describe a return of NAc activity to levels typical of someone with obesity and loss‑of‑control eating, accompanied by renewed, severe food preoccupation. The authors interpret this pattern as evidence that tirzepatide’s suppressive effect on this patient’s craving-related brain signals and “food noise” was temporary.
In contrast, other participants in the trial who were not taking tirzepatide showed persistently elevated NAc activity and frequent food preoccupation, consistent with prior findings from the Halpern lab. That comparison, the Penn team argues, supports the idea that tirzepatide was responsible for the temporary quieting of craving-related activity in Participant 3’s brain, although the study was not designed to prove causation and is limited to a single patient on the drug.
Tirzepatide is a dual glucagon-like peptide‑1 (GLP‑1) and glucose‑dependent insulinotropic polypeptide (GIP) receptor agonist originally developed to manage blood sugar in people with type 2 diabetes. Clinical experience and early research have suggested that drugs in this class may help with conditions involving impulse control, including binge eating disorder, but they are not approved by the U.S. Food and Drug Administration specifically to treat food preoccupation or impulsive eating behaviors.
“While many individuals taking GLP‑1 and GIP inhibitors report a reduction in food noise, these medications are not FDA-approved to treat food preoccupation and its related impulsivity,” Halpern said in a statement released by Penn Medicine. He added that it is “far too soon” to describe them as “miracle drugs” for conditions beyond type 2 diabetes and obesity.
Kelly Allison, PhD, a study investigator and professor of psychiatry who directs Penn’s Center for Weight and Eating Disorders, noted that GLP‑1 and GIP drugs are “amazing medications” for managing blood sugar in type 2 diabetes and for promoting weight loss in people with obesity, but said the new data suggest they “might be useful to manage food preoccupation and binge eating, but not in their current form.”
Co‑first author Wonkyung Choi, a PhD candidate in Halpern’s lab, said the case “provides compelling data” about how GLP‑1 and GIP inhibitors alter electrical signals in human brain reward circuits, and argued that these insights should motivate efforts to design treatments that are better tailored to impulsivity traits in obesity and related eating disorders, and that are safe and longer‑lasting.
Loss‑of‑control eating and binge eating disorder (BED) are common among people with obesity. BED is considered the most prevalent eating disorder in the United States, affecting more than 3 million individuals, according to figures cited by Penn Medicine. People with BED or significant loss‑of‑control eating often describe feeling unable to stop eating and continuing long after they feel full.
Even without a BED diagnosis, Penn researchers note that up to 60% of individuals with obesity report experiencing ongoing “food noise” — constant, intrusive thoughts about food that can cause distress and contribute to maladaptive behaviors such as bingeing or loss‑of‑control eating. Food noise is also frequently described in bulimia nervosa and anorexia nervosa. Prior research has linked binge eating with elevated suicide risk among people with obesity and eating disorders, likely related to shared impulsivity traits and emotional dysregulation.
The authors of the Nature Medicine case study and Penn’s accompanying reports emphasize that the new findings are preliminary. Because the mechanistic observations are based on a single person taking tirzepatide, the results cannot be generalized to everyone using the drug. The surgical context, electrode placement, and the absence of controlled, long‑term behavioral outcome data further limit the conclusions. Larger, carefully designed studies will be needed to determine how reliably tirzepatide and related medications affect brain reward pathways over time and whether those effects can be harnessed to treat binge eating and other impulse‑related eating behaviors.
