Abstract Concomitant use of cannabis with other drugs may lead to cannabis–drug interactions, mainly due to the pharmacokinetic mechanism involving the family of CYP450 isoenzymes. This narrative systematic review aimed to systematize the available information regarding clinical relevance of cannabis–drug interactions. We utilized the PubMed/Medline database for this systematic review, using the terms drug interactions and cannabis, between June 2011 and June 2021. Articles with cannabis–drug interactions in humans, in English or Spanish, with full-text access were selected. Two researchers evaluated the article’s inclusion. The level of clinical relevance was determined according to the severity and probability of the interaction. Ninety-five articles were identified...