Third, we were unable to link individual differences in amygdala habituation as a result of rs604300 and childhood trauma interplay to cannabis dependence. The extent of problematic cannabis use is limited in this college-attending sample – only 48.4% of the EA participants report using cannabis even once in their lifetime, and, of those, only 23.7% report using it >10 times, with 4 individuals meeting criteria for cannabis dependence. Because THC administration reduces anxiety in rodents and amygdala reactivity to threatening stimuli, it is possible that individuals who show prolonged amygdala response (i.e., decreased amygdala habituation), may be more sensitive to the coping-related effects of cannabis and thus more likely to develop problematic cannabis usage (Phan et al., 2009; Koob & Volkow, 2010). Evidence that fear extinction and drug-seeking extinction rely on similar neural pathways also suggests that individuals who can more readily adapt to threatening stimuli may also be more able to extinguish substance use (Peters, Kalivas, & Quirk, 2009). On the other hand, it is also entirely possible that increased amygdala habituation might lead to more exploratory behavior and exposure to substances, but not necessarily increased problematic use (Lissek et al., 2005).
