Highlights Substance use disorders are currently a major public health crisis in the US. The prevalence of cannabis use disorder is rising due to legalization of cannabis. This study built models to predict the risk of cannabis use disorder for a user. Risk factors include personality traits, impulsivity and initial smoking enjoyment.

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Dampened behavioral inhibition and overactive behavioral approach motivation systems (i.e. BIS/BAS) are associated with cannabis use disorder (CUD), although the underlying neural mechanisms of these alterations have not yet been examined. The brain’s executive control network (ECN) plays a role in decision-making and is associated with BIS/BAS. In this study, we tested the hypothesis that altered ECN resting-state functional connectivity (rsFC) underlies dysfunctional behavioral inhibition and approach motivation in cannabis users. To that end, we collected resting-state functional magnetic resonance imaging scans in 86 cannabis using adults and 59 non-using adults to examine group differences in the relationship between ECN rsFC and BIS/BAS. Our results showed that BIS was positively correlated with left ECN rsFC in cannabis users, while it was positively correlated with right ECN rsFC in non-users. There was a trend-level moderation effect of group on the association between BIS/BAS and ECN rsFC, showing a weaker association in BIS/BAS and ECN rsFC in cannabis users compared to non-users. An exploratory mediation analysis found that the severity of CUD mediated the relationship between users’ BIS scores and left ECN rsFC. These findings suggest that cannabis use may lead to dysregulation in typical ECN functional organization related to BIS/BAS.