Marijuana is the most commonly used illicit substance in the United States and is especially prevalent among young adults.¹ Marijuana use typically emerges during adolescence, peaking in the early 20s, with 35% of 21- and 22- year-old individuals reporting past year use.² This pervasiveness may be due to low perceptions of harm,² despite the short- and long-term negative consequences³ of marijuana use. Short-term consequences include acute anxiety, paranoia, and altered perception,⁴ as well as impaired motor coordination while driving.⁵ Deficits in academic achievement⁶ and disrupted brain structure and function^7-10 suggest long-term negative consequences of marijuana use. Of particular relevance to the present study is evidence that earlier onset of marijuana use leads to a faster transition to marijuana dependence¹¹ and increases the risk of developing other substance use disorders (SUDs).¹²

The detection of threat is a role that the amygdala plays well, evidenced by its increased response to fearful faces in human neuroimaging studies. A critical element of the fearful face is an increase in eye white area (EWA), hypothesized to be a significant cue in activating the amygdala. However, another important social signal that can increase EWA is a lateral shift in gaze direction, which also serves to orient attention to potential threats. It is unknown how the amygdala differentiates between these increases in EWA and those that are specifically associated with fear. Using functional magnetic resonance imaging, we show that the left amygdala distinguished between fearful eyes and gaze shifts despite similar EWA increases whereas the right amygdala was less discriminatory. Additional analyses also revealed selective hemispheric response patterns in the left fusiform gyrus. Our data show clear hemispheric differences in EWA-based fear activation, suggesting the existence of parallel mechanisms that code for emotional face information.