Early life adversity increases the risk of both CS and OUD.44,59,70,82,88,101 Polymorphisms of the mu-opioid receptor gene OPRM1 may predispose individuals to CS and OUD.22,32,34,41,80 Neuroimaging has associated decreased gray matter volume in the insula and anterior cingulate cortex with CS and OUD.13,43,79 These structures are involved in affective pain processing as well as conscious urges to take drugs.47,65,79 Together, these findings suggest CS may be a promising precision medicine target for chronic pain and OUD. This evidence concerns the gene OPRM1 and Cowden syndrome 1.