• Alessio Maria Monteleone, Vincenzo Di Marzo, Teresa Aveta, Fabiana Piscitelli, Riccardo Dalle Grave, Pasquale Scognamiglio, Marwan El Ghoch, Simona Calugi, Palmiero Monteleone, and Mario Maj.
• From the Department of Psychiatry, Second University of Naples, Naples, Italy (AMM, PS, PM, and MM); the Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy (VDM, TA, and FP); the Department of Eating and Weight Disorders, Villa Garda Hospital, Garda, Verona, Italy (RDG, MEG, and SC); and the Neuroscience Section, Department of Medicine and Surgery, University of Salerno, Salerno, Italy (PM).
• Am. J. Clin. Nutr. 2015 Feb 1;101(2):262-9.

BackgroundA dysregulation of reward mechanisms was suggested in the pathophysiology of anorexia nervosa (AN), but the role of the endogenous mediators of reward has been poorly investigated. Endocannabinoids, including anandamide and 2-arachidonoylglycerol, and the endocannabinoid-related compounds oleoylethanolamide and palmitoylethanolamide modulate food-related and unrelated reward. Hedonic eating, which is the consumption of food just for pleasure and not homeostatic need, is a suitable paradigm to explore food-related reward.ObjectiveWe investigated responses of endocannabinoids and endocannabinoid-related compounds to hedonic eating in AN.DesignPeripheral concentrations of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, and palmitoylethanolamide were measured in 7 underweight and 7 weight-restored AN patients after eating favorite and nonfavorite foods in the condition of no homeostatic needs, and these measurements were compared with those of previously studied healthy control subjects.Results1) In healthy controls, plasma 2-arachidonoylglycerol concentrations decreased after both types of meals but were significantly higher in hedonic eating; in underweight AN patients, 2-arachidonoylglycerol concentrations did not show specific time patterns after eating either favorite or nonfavorite foods, whereas in weight-restored patients, 2-arachidonoylglycerol concentrations showed similar increases with both types of meals. 2) Anandamide plasma concentrations exhibited no differences in their response patterns to hedonic eating in the groups. 3) Compared with 2-arachidonoylglycerol, palmitoylethanolamide concentrations exhibited an opposite response pattern to hedonic eating in healthy controls; this pattern was partially preserved in underweight AN patients but not in weight-restored ones. 4) Like palmitoylethanolamide, oleoylethanolamide plasma concentrations tended to be higher in nonhedonic eating than in hedonic eating in healthy controls; moreover, no difference between healthy subjects and AN patients was observed for food-intake-induced changes in oleoylethanolamide concentrations.ConclusionThese data confirm that endocannabinoids and endocannabinoid-related compounds are involved in food-related reward and suggest a dysregulation of their physiology in AN. This trial was registered at ISRCTN.org as ISRCTN64683774.© 2015 American Society for Nutrition.

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