The study found that carriers of the FAAH 385 A mutant alleles have significantly elevated plasma levels of AEA and related N‐acylethanolamines (NAEs) compared to wild‐type carriers, indicating endocannabinoid system activation. This elevation was particularly notable in severely obese individuals, suggesting a link between the FAAH 385 A allele and severe obesity. These findings highlight the potential of targeting the endocannabinoid system for novel obesity treatments. Here, FAAH is linked to obesity due to melanocortin 4 receptor deficiency.