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The proposed study is a 3-site, 12-week, feasibility, proof of concept investigation of patients who have co-occurring diagnoses of schizophrenia and current substance use disorder (alcohol, cocaine, heroin, or cannabis). The primary objectives of this study is to examine the effect of brexpiprazole treatment on the number of days of substance use in the past week as measured by the Timeline Follow Back assessment and to examine the effect of brexpiprazole treatment on substance craving using 100-mm visual analogue scale.