Brain cannabinoid CB1 receptor signaling modulates reward responses and inhibitory control in humans

The central endocannabinoid system, particularly the in vivo cannabinoid type 1 (CB1) receptor signaling, presents a promising target for treating eating disorders. However, its precise role in appetite control remains unclear. This study aimed to determine how CB1 receptor signaling contributes to key aspects of appetite regulation, specifically anticipatory food reward responses and inhibitory control. Forty-one healthy male participants underwent [¹⁸F]FMPEP-d2 positron emission tomography (PET) to quantify CB1 receptor availability. Functional magnetic resonance imaging (fMRI) was used to assess anticipatory neural responses to food cues, while inhibitory control was measured using a go/nogo task. Data show that individuals with higher CB1 receptor availability exhibited stronger anticipatory reward-related neural responses and reduced activation during inhibitory control. Therefore, CB1 receptor signaling plays a distinct role in modulating reward and inhibitory processes related to feeding behavior. The findings suggest that the CB1 receptor may serve as a therapeutic target for regulating appetite.