Longitudinal associations between amygdala reactivity and cannabis use in a large sample of adolescents.

The amygdala is a key brain structure to study in relation to cannabis use as reflected by its high-density of cannabinoid receptors and functional reactivity to processes relevant to drug use. Previously, we identified a correlation between cannabis use in early adolescence and amygdala hyper-reactivity to angry faces (Spechler et al. 2015). Here, we leveraged the longitudinal aspect of the same dataset (the IMAGEN study) to determine (1) if amygdala hyper-reactivity predicts future cannabis use and (2) if amygdala reactivity is affected by prolonged cannabis exposure during adolescence. First, linear regressions predicted the level of cannabis use by age 19 using amygdala reactivity to angry faces measured at age 14 prior to cannabis exposure in a sample of 1119 participants. Next, we evaluated the time course of amygdala functional development from age 14 to 19 for angry face processing and how it might be associated with protracted cannabis use throughout this developmental window. We compared the sample from Spechler et al. 2015, the majority of whom escalated their use over the 5-year interval, to a matched sample of non-users. Right amygdala reactivity to angry faces significantly predicted cannabis use 5 years later in a dose-response fashion. Cannabis-naïve adolescents demonstrated the lowest levels of amygdala reactivity. No such predictive relationship was identified for alcohol or cigarette use. Next, follow-up analyses indicated a significant group-by-time interaction for the right amygdala. (1) Right amygdala hyper-reactivity is predictive of future cannabis use, and (2) protracted cannabis exposure during adolescence may alter the rate of neurotypical functional development.