Hill, 2013; Sciolino et al., 2010). Second, THC and CB1 agonist administration reduce subjective anxiety, blunt threat-related amygdala function, and facilitate fear extinction (Gruber, Rogowska, & Yurgelun-Todd, 2009; Phan et al., 2008; Rabinak et al., 2013). Importantly, knockout and pharmacologic manipulation studies in rodents suggest that eCB signaling is critical for fear extinction, but not conditioning, which is consistent with recent genetic work in humans linking an eCB polymorphism (rs324420 in FAAH) to amygdala habituation as well as stress-related negative emotionality (Gunduz-Cinar, MacPherson, et al., 2013). Collectively, these independent lines of research suggest that the effects of eCB-related genetic variation and stress exposure may exert behavioral effects by influencing amygdala habituation to threat-related stimuli. Such differences may lead to cannabis dependence symptoms through self-medication of cannabinoid signaling, impulsivity, and/or the removal of negative affect, consistent with recent theories of the transition to dependence (Koob & Volkow, 2010).
