Introduction: Recent trials using cannabidiol (CBD) have shown that most acute and prolonged adverse effects of CBD are mild to moderate, with rare serious adverse effects (SAEs). This review focused on analyzing SAEs of CBD and their possible relation to drug-drug interactions.Areas covered: We systematically analyzed the SAEs reported in randomized controlled trials (RCTs) involving the administration of oral CBD for at least one week in both healthy volunteers and clinical samples.Expert opinion: SAEs related to CBD in RCT are rare and include mainly elevated transaminases, convulsion, sedation, lethargy, and upper respiratory trait infections. Elevated transaminases are related to concomitant valproate use, while sedation, lethargy, and upper respiratory trait infections are related to concomitant clobazam use. Epileptic patients should be monitored when using CBD concomitantly with these and other antiepileptic drugs for other possible drug-drug interactions.
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