Summary: Higher opioid activity in the brain may help explain appetite loss and the emotional symptoms that accompany anorexia nervosa. In a PET study, people with anorexia showed increased mu-opioid receptor availability—indicating elevated opioidergic tone—compared with healthy controls. At the same time, global brain glucose uptake was preserved despite severe malnutrition, suggesting the brain prioritizes maintaining energy supply and function. These findings link reward and mood circuitry with feeding behavior in anorexia and point to potential targets for future treatment development.
Anorexia nervosa is a serious psychiatric disorder defined by restrictive eating, intense fear of weight gain, and distorted body image, often accompanied by severe physical undernutrition, anxiety, and depression. The new study from Turku PET Centre investigated two key aspects of brain function in anorexia: the brain’s opioid system, which influences appetite, pleasure and mood, and brain glucose metabolism, which reflects energy use.
Key Facts:
- Elevated opioidergic tone: Individuals with anorexia nervosa showed higher mu-opioid receptor availability in several brain regions involved in reward processing compared with healthy controls.
- Energy use preserved: Brain glucose uptake measured during a controlled metabolic clamp was similar in patients and controls, indicating maintained cerebral energy consumption despite low peripheral energy reserves.
- Mood and reward link: Because opioid signaling affects both reward and mood, altered opioid function may contribute to the anxiety, low mood, and altered appetite seen in anorexia nervosa.
Source: University of Turku
Study overview
Researchers at Turku PET Centre, working with Turku University Hospital and collaborators in South Korea, used positron emission tomography (PET) to compare brain opioid receptor availability and glucose uptake in 13 patients with anorexia nervosa (AN) and 13 matched healthy control subjects (HC). The study combined PET imaging of mu-opioid receptor (MOR) availability using [11C]carfentanil with measurements of brain glucose uptake (BGU) using [18F]FDG PET during a standardized hyperinsulinemic-euglycemic clamp. Functional MRI and comprehensive clinical assessments were also performed to characterize participants.
Lead investigators note that the endogenous opioid system helps control both homeostatic and hedonic aspects of eating: it contributes to the drive to eat when energy is needed and to the pleasurable aspects of food consumption. In this study, MOR availability was higher in the caudate and putamen of patients with AN, with trends toward higher availability in the nucleus accumbens and thalamus as well. No brain regions showed lower MOR availability in the patient group.
Despite pronounced underweight and reduced peripheral energy stores, brain glucose uptake measured during the clamp did not differ between groups. This indicates that, even during severe malnutrition, the brain preserves its glucose consumption and may redirect available resources to protect neural function. The investigators propose that this metabolic preservation supports essential cognitive and regulatory processes during prolonged nutritional stress.
The authors also report negative correlations between MOR availability and BGU in several reward-related regions (caudate, nucleus accumbens, and thalamus), suggesting an interplay between opioid signaling and regional energy metabolism. Because opioid signaling is also implicated in mood regulation, elevated MOR availability in AN may help account for the frequent co-occurrence of anxiety and depressive symptoms in these patients.
Taken together, the results suggest that altered endogenous opioid function is a plausible neural substrate underlying the disturbed appetite, altered reward processing, and emotional symptoms characteristic of anorexia nervosa. Understanding these mechanisms could help guide the development of targeted treatments that address both the motivational and affective dimensions of the disorder.
About this neuroscience and eating disorders research news
Author: Tuomas Koivula
Source: University of Turku
Contact: Tuomas Koivula, University of Turku
Image: Image credited to Neuroscience News
Original Research: Lauri Nummenmaa et al., “Anorexia nervosa is associated with higher brain mu-opioid receptor availability,” Molecular Psychiatry. DOI: 10.1038/s41380-025-02888-3. (Closed access)
Abstract
Anorexia nervosa is associated with higher brain mu-opioid receptor availability
Anorexia nervosa (AN) is a severe psychiatric disorder marked by restrictive eating, intense fear of weight gain, and a distorted body image. The mu-opioid receptor (MOR) is a central component of the endogenous opioid system and contributes to both homeostatic and hedonic control of eating. In this study, 13 patients with AN and 13 healthy control subjects underwent multimodal imaging: MOR availability was measured with [11C]carfentanil PET, brain glucose uptake (BGU) was measured with [18F]FDG PET during a hyperinsulinemic-euglycemic clamp, and neural activity was assessed with blood-oxygen-level-dependent functional MRI.
All participants completed a screening visit that included physical examination, anthropometric measurements, fasting blood samples, an oral glucose tolerance test, psychiatric evaluation, and medical history. Body fat percentage and whole-body insulin sensitivity (M value) were determined.
Results showed higher MOR availability in the caudate and putamen of patients with AN, with trends toward increased availability in the nucleus accumbens and thalamus. No brain regions exhibited reduced MOR availability in the AN group. Brain glucose uptake did not differ significantly between patients and controls. Across reward-related regions, MOR availability and BGU were negatively correlated, with significant associations in the caudate, nucleus accumbens, and thalamus and a similar trend in the putamen.
In conclusion, anorexia nervosa is associated with increased MOR availability in brain regions involved in reward processing while global brain glucose uptake remains unaltered. These findings implicate the endogenous opioid system as a potential key contributor to the pathophysiology of AN and may inform future therapeutic strategies.