Endocannabinoid signaling of homeostatic status modulates functional connectivity in reward and salience networks

Rationale: Endocannabinoids are well poised to regulate crosstalk between energy sensing of hunger and satiety and reward-driven motivation. Objectives: Here, we aimed to unravel associations between plasma endocannabinoids and brain connectivity in homeostatic and reward circuits across hunger and satiety states. Methods: Fifteen participants (7 females) underwent two counter-balanced resting-state functional magnetic resonance imaging scans, one after overnight fasting and one after consumption of a standardized filling meal (satiety). Before each scan, we drew blood to measure plasma endocannabinoid concentrations (anandamide [AEA], anandamide-derived POEA, and 2-arachidonoylglycerol [2-AG]), analyzed with liquid chromatography tandem mass spectrometry. Results: We found that AEA levels were associated with increased connectivity between the lateral hypothalamus and the ventral striatum during satiety. Furthermore, fasting AEA levels correlated with connectivity between the ventral striatum and the anterior cingulate cortex and the insula. Conclusions: Altogether, results suggest that peripheral AEA concentrations are sensitive to homeostatic changes and linked to neural communication in reward and salience networks. Findings may have significant implications for understanding normal and abnormal interactions between homeostatic input and reward valuation.