The Endogenous Opioid System in Compulsive Eating

Background/Objectives: The rates of obesity and binge-eating disorder (BED) have increased markedly over the last few decades. The onset of these conditions has been associated in part with the disruption of neural pathways that regulate food reward. Existing literature has implicated the endogenous opioid system as an important mediator of pleasure and reinforcing behaviors associated with food intake. While the relationship between opioids and food intake has been studied extensively, how dysregulated opioid signaling contributes to compulsive eating still remains unclear. Therefore, the aim of this review is to analyze the role of opioid peptides and receptors, and their interactions with dopamine in hedonic feeding. Methods: We conducted a narrative review of preclinical and clinical trials, incorporating studies that were relevant to opioid-mediated feeding and food reward. Results: β-endorphins appear to modulate the hedonic value of food, but their effects appear to be context-dependent. Enkephalins may influence motivational drive toward food, while nociceptin signaling has been linked to the preferential consumption of palatable foods under binge-like conditions. Consistent with these findings, NOP antagonism has been reported to reduce binge-like intake of a high-fat diet (HFD) without affecting homeostatic eating patterns. Lastly, chronic mu-opioid receptor (MOP) activation by palatable foods may induce neuroadaptive changes, including receptor desensitization, dopamine D2 receptor downregulation, and reward hypofunctionality, which overlap with mechanisms associated with substance use disorders. Conclusions: Altered MOP signaling may disrupt the hedonic and behavioral mechanisms that regulate feeding behavior. Pharmacological therapies targeting opioid and opioid-dopamine interactions may show promise for treating obesity and BED. However, additional research is still needed to clarify peptide-specific mechanisms, sex differences, and long-term neurobiological consequences associated with hedonic and compulsive eating.