The significant genetic associations between cannabis initiation and AN are novel, yet consistent with the negative genetic association between cannabis use and BMI, and with observational (Pasman et al., 2018) and experimental (Di Marzo and Matias, 2005, Volkow et al., 2017) studies regarding the role of endocannabinoids in appetite regulation, energy expenditure, stress, and reward. One of the principal psychoactive agents of cannabis, delta-9-tetrahydrocannabinol (THC), a partial agonist of the endogenous cannabinoid 1 (CB1) receptor, is presumed to be orexigenic and may acutely increase appetite and food intake, contributing to its potential role as an appetite stimulant in patients with an anorexia or cachexia syndrome (Reuter and Martin, 2016) due to a disease (e.g., HIV AIDS) or in response to treatment (e.g., chemotherapy). An antagonist of the CB1 receptor was previously tested as a highly promising anti-obesity medication (Rimonabant, SR141716). Further, the endocannabinoid anandamide has been shown to be elevated in individuals with acute AN (Monteleone and Maj, 2013), indicating disruption in food-related reward and eating behavior regulation. Animal and human studies have also provided initial evidence for the therapeutic
