OBJECTIVE: Co-occurrence of substance use and bipolar disorders is both common and associated with poor treatment response and greater functional impairment than either disorder alone. The neurophysiological correlates of this co-morbidity however, remain unclear. In this pilot study, we compared brain morphometry between bipolar adolescents with co-occurring cannabis use disorders (CUD) and bipolar adolescents without any substance use disorder. METHODS: Whole-brain structural magnetic resonance imaging (MRI) scans were obtained from 14 bipolar adolescents. Seven study participants were diagnosed with CUD before and/or shortly after their MR scan was obtained, and 7 subjects were free of any substance use disorder at the time of their MR scan as well as during longitudinal follow up. Morphologic differences were calculated using voxel-based morphometry implemented using statistical parametric mapping software (SPM2). RESULTS: Bipolar adolescents with co-occurring CUD demonstrated decreased gray matter volume (GMV) in the left fusiform gyrus and increased GMV in the right caudate and precentral gyrus, as well as increased gray matter density in the right middle occipital and fusiform gyri and cerebellar vermis. CONCLUSIONS: Bipolar adolescents with CUD demonstrate evidence of greater structural abnormalities than adolescents with bipolar disorder alone in frontal and temporal cortical regions, as well as in subcortical areas linked with emotion and motivational regulation. Although the limited prescan exposure to marijuana in these adolescents tentatively suggests that these findings may reflect underlying differences, the direct effect of cannabis exposure may also be involved.