Independent lines of research linking the eCB system to stress responsiveness (Gunduz-Cinar, Hill, McEwen, & Holmes, 2013), and early life adversity to cannabis dependence risk (Duncan et al., 2008), suggest that it is important to consider the environment with regard to eCB-related genetic risk for cannabis dependence. The eCB system is modulated by stress and has reciprocal interactions with the hypothalamic-pituitary-adrenal (HPA) axis, a central regulator of stress responsiveness. Non-human animal models have demonstrated that stress exposure increases the eCB ligand 2-AG while decreasing AEA levels, with pharmacologic evidence that these changes mediate effects of stress on HPA axis activation (Hill et al., 2009; Patel, Kingsley, Mackie, Marnett, & Winder, 2009; Rademacher et al., 2008). Moreover, there is accumulating preclinical evidence that, unlike adult-onset stressors, chronic stress exposure during early life and adolescence results in sustained stress-related effects on eCB signaling and gene expression that do not recover following enrichment during adulthood (Buwembo, Long, & Walker, 2013; El Rawas et al., 2011; Lee & Hill, 2013; Malone, Kearn, Chongue, Mackie, & Taylor, 2008; Reich, Mihalik, Iskander, Seckler, & Weiss, 2013;
