Cerebral μ-opioid and CB₁ receptor systems have distinct roles in human feeding behavior

Eating behavior varies greatly between individuals, but the neurobiological basis of these trait-like differences in feeding remains poorly understood. Central μ-opioid receptors (MOR) and cannabinoid CB₁ receptors (CB₁R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brain's opioid and endocannabinoid signaling, the variation in MOR and CB₁R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [¹¹C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [¹⁸F]FMPEP-d₂ scans of CB₁Rs from 35 subjects (all males, all also included in the [¹¹C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating-individuals with low MORs reported being more likely to eat in response to environment's palatable food cues. CB₁R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB₁Rs overlap anatomically in brain regions regulating food reward, they have distinct roles in mediating individual feeding patterns. Central MOR system might provide a pharmacological target for reducing individual's excessive cue-reactive eating behavior.