mk-9470 and Bulimia-Nervosa

Although of great public health relevance, the mechanisms underlying disordered eating behavior and body weight regulation remain insufficiently understood. Compelling preclinical evidence corroborates a critical role of the endocannabinoid system (ECS) in the central regulation of appetite and food intake. However, in vivo human evidence on ECS functioning in brain circuits involved in food intake regulation as well as its relationship with body weight is lacking, both in health and disease. Here, we measured cannabinoid 1 receptor (CB1R) availability using positron emission tomography (PET) with [(18)F]MK-9470 in 54 patients with food intake disorders (FID) covering a wide body mass index (BMI) range (anorexia nervosa, bulimia nervosa, functional dyspepsia with weight loss and obesity; BMI range=12.5-40.6 kg/m(2)) and 26 age-, gender- and average BMI-matched healthy subjects (BMI range=18.5-26.6 kg/m(2)). The association between regional CB1R availability and BMI was assessed within predefined homeostatic and reward-related regions of interest using voxel-based linear regression analyses. CB1R availability was inversely associated with BMI in homeostatic brain regions such as the hypothalamus and brainstem areas in both patients with FID and healthy subjects. However, in FID patients, CB1R availability was also negatively correlated with BMI throughout the mesolimbic reward system (midbrain, striatum, insula, amygdala and orbitofrontal cortex), which constitutes the key circuit implicated in processing appetitive motivation and hedonic value of perceived food rewards. Our results indicate that the cerebral homeostatic CB1R system is inextricably linked to BMI, with additional involvement of reward areas under conditions of disordered body weight.

Topics: Adolescent; Adult; Aged; Amygdala; Anorexia Nervosa; Body Mass Index; Brain; Bulimia Nervosa; Case-Control Studies; Cerebral Cortex; Cerebrum; Dyspepsia; Female; Frontal Lobe; Humans; Linear Models; Male; Mesencephalon; Middle Aged; Neostriatum; Obesity; Positron-Emission Tomography; Prefrontal Cortex; Pyridines; Radiopharmaceuticals; Receptor, Cannabinoid, CB1; Weight Loss; Young Adult

The endocannabinoid system is a possible target in the treatment of eating disorders. We used positron emission tomography to investigate the type 1 cannabinoid receptor (CB1R) in bulimic and anorectic patients.. We investigated 16 female bulimia nervosa patients (BN) (age = 23.8 ± 7.1 years) and 14 female anorexia nervosa patients (AN) (age = 20.5 ± 3.6 years) using the selective CB1R ligand [(18)F]MK-9470. The control group consisted of 19 age-matched women (age = 25.2 ± 8.5 years). Statistical parametric mapping (p(family-wise error) < .05) and volume-of-interest analyses of CB1R availability were performed.. Global CB1R availability was significantly increased in cortical and subcortical brain areas in AN patients compared with healthy control subjects (+24.5%, p = .0003). Regionally, CB1R availability was increased in the insula in both AN and BN patients (p = .01 and p = .0004) and the inferior frontal and temporal cortex in AN patients only (p = .02).. Global CB1R upregulation in AN patients is a possible long-term compensatory mechanism to an underactive endocannabinoid system in anorectic conditions. There is a similarity in CB1R dysregulation both in AN and BN in the insular cortex, which is involved in the integration of interoceptive information, gustatory information, reward, and emotion processing.

Topics: Adolescent; Adult; Anorexia Nervosa; Brain; Bulimia Nervosa; Case-Control Studies; Female; Fluorine Radioisotopes; Functional Neuroimaging; Humans; Middle Aged; Positron-Emission Tomography; Pyridines; Radioligand Assay; Receptor, Cannabinoid, CB1; Up-Regulation