How brain's appetite control center responds to endocannabinoids

This review examines how specialized neurons in the brain's hypothalamic ventromedial nucleus (VMN) act as a critical control center for appetite, integrating signals from both the homeostatic energy balance system (which monitors nutritional needs) and the hedonic reward system (which responds to food palatability). The neurons in question express pituitary adenylate cyclase-activating polypeptide (PACAP) and respond to diverse signals including hormones like leptin and insulin, as well as endocannabinoids, the body's natural cannabis-like molecules. These VMN PACAP neurons essentially serve as a master switch that coordinates hunger-driven eating with pleasure-driven eating.

The research reveals that these neurons work through two distinct pathways to suppress both types of feeding behavior. They project to the arcuate nucleus where they regulate hunger-promoting and hunger-suppressing neurons to reduce homeostatic feeding, and simultaneously project to the ventral tegmental area where they inhibit dopamine neurons to diminish reward-driven eating. Importantly, the paper highlights that endocannabinoids are among the key neuromodulators that influence these neurons' activity, suggesting a neurobiological mechanism for how cannabis affects appetite and food reward.

This integration occurs in a manner dependent on sex hormones and current energy state, meaning the system's response varies based on whether the body is fed or fasted and differs between males and females. Understanding how endocannabinoids modulate this critical appetite control center provides insight into why cannabis users experience changes in eating behavior and may help explain the notorious "munchies" phenomenon through disruption of these coordinated feeding circuits.