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 effectiveness of cannabinoid agonists in treating eating disorders (Andries et al., 2014, Avraham et al., 2017). It is also likely that individuals with high genetic liability to AN are less likely to experiment with a substance that has a documented hyperphagia component. Thus, there is evidence of a complex biological relationship between cannabis use and eating disorders, as well as BMI. Nonetheless, the preliminary MR analyses did not provide persuasive support for causal relationships, in either direction, between genetic liability to cannabis initiation and AN. The small number of SNPs used as instruments, due to the low number of independent genome-wide significant loci and exclusion of overlapping SNPs that were not ambiguous and palindromic, may have significantly limited power to make causal inferences. Nonetheless, in the absence of strong causal evidence, several hypotheses regarding the negative genetic correlation between cannabis initiation and AN are possible.
