Abstract
<jats:p>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 attributed in part to the disruption of neural pathways that regulate food reward. Existing literature has identified 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 modulate the hedonic value of food, but their effects appear to be context-dependent. Enkephalins regulate motivational drive toward food, while nociceptin signaling preferentially promotes the consumption of palatable foods under binge-like conditions. Consistent with these findings, NOP antagonism reduces binge on a high fat diet (HFD) without affecting homeostatic eating patterns. Lastly, chronic mu opioid receptor (MOR) activation by palatable foods may induce neuroadaptive changes, including receptor desensitization, dopamine D2 receptor downregulation, and reward hypofunctionality, paralleling mechanisms associated with substance use disorders. Conclusions: Altered MOR signaling disrupts 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 of hedonic and compulsive eating.</jats:p>