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We identified 12 trials examining psychopharmacological interventions for the treatment of cannabis use disorder. Trials examined antidepressants (ie, escitalopram, fluoxetine, bupropion, nefazodone, venlafaxine, vilazodone), antipsychotics (ie, clozapine, ziprasidone), buspirone, mood stabilizers (ie, divalproex, lithium), and atomoxetine. Overall, studies found that antidepressants as a class were less effective than placebo for the achievement of abstinence (moderate SOE). There was no difference between antidepressants (moderate SOE) or buspirone (low SOE) and placebo in reducing overall cannabis use or retention in treatment. We found low strength evidence of no difference from placebo for antidepressants or buspirone on harms. Antidepressant medications did not impact secondary outcomes (low SOE). 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