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Cannabis use is associated with working memory (WM) impairments; however, the relationship between cannabis use and WM neural circuitry is unclear. We examined whether a cannabis use disorder (CUD) was associated with differences in brain morphology between control subjects with and without a CUD and between schizophrenia subjects with and without a CUD, and whether these differences related to WM and CUD history. Subjects group-matched on demographics included 44 healthy controls, 10 subjects with a CUD history, 28 schizophrenia subjects with no history of substance use disorders, and 15 schizophrenia subjects with a CUD history. Large-deformation high-dimensional brain mapping with magnetic resonance imaging was used to obtain surface-based representations of the striatum, globus pallidus, and thalamus, compared across groups, and correlated with WM and CUD history. Surface maps were generated to visualize morphological differences. There were significant cannabis-related parametric decreases in WM across groups. Similar cannabis-related shape differences were observed in the striatum, globus pallidus, and thalamus in controls and schizophrenia subjects. Cannabis-related striatal and thalamic shape differences correlated with poorer WM and younger age of CUD onset in both groups. Schizophrenia subjects demonstrated cannabis-related neuroanatomical differences that were consistent and exaggerated compared with cannabis-related differences found in controls. The cross-sectional results suggest that both CUD groups were characterized by WM deficits and subcortical neuroanatomical differences. Future longitudinal studies could help determine whether cannabis use contributes to these observed shape differences or whether they are biomarkers of a vulnerability to the effects of cannabis that predate its misuse.

Cannabis-Related Working Memory Deficits and Associated Subcortical Morphological Differences in Healthy Individuals and Schizophrenia Subjects