This study highlights the importance of considering the role of genotype in stress adaptation or resilience. In addition to its clearly demonstrated impact on energy regulation/obesity and pain modulation (André & Gonthier, 2010; Iversen & Chapman, 2002; Li, Jones, & Persaud, 2011; Lynch & Ware, 2015), there is considerable research underway exploring the therapeutic role of eCB signaling in treatment of mental health problems (Hill & Gorzalka, 2009), including addiction (e.g., Pava & Woodward, 2012). For example, MAGL inhibition attenuates the effects of withdrawal in opioid-, nicotine-, and THC-dependent rodents (Muldoon et al., 2015; Ramesh et al., 2011, 2013; Schlosburg et al., 2009). If eCB signaling is associated with individual differences in stress adaptation, then medications directed at enhancing these effects may be a valuable resource in the treatment arsenal. However, manipulation of the eCB system is challenging and prior failed clinical trials documenting serious adverse psychiatric events, including suicide, in cardiovascular risk patients treated with CB1 antagonist, rimonabant, serves as a cautionary tale (Boekholdt & Peters, 2010; Topol et al., 2010).
