Clinical Relevance of Drug Interactions with Cannabis: A Systematic Review

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 and twenty-six were included. Overall, 19 pairs of drug interactions with medicinal or recreational cannabis were identified in humans. According to severity and probability, 1, 2, 12, and 4 pairs of cannabis–drug interactions were classified at levels 1 (very high risk), 2 (high risk), 3 (medium risk), and 5 (without risk), respectively. Cannabis–warfarin was classified at level 1, and cannabis–buprenorphine and tacrolimus at level 2. This review provides evidence for both the low probability of the occurrence of clinically relevant drug interactions and the lack of evidence regarding cannabis–drug interactions.

Genetic Analysis of Clozapine Metabolism in a Patient With Subtherapeutic Clozapine Plasma Concentrations—The Importance of CYP3A5

“…This phenomenon has been reported before, but only where activity of CYP1A2 was lower than expected 3 . Our patient had normal CYP1A2 activity and was a smoker of tobacco and cannabis (the latter only when not hospitalized)—both CYP1A2 inducers 14 …”

Cannabis Pharmacogenomics: A Path to Personalized Medicine

“…CBD can be involved in strong drug interactions mediated by CYP2C9, 2C19, and 3A and moderate drug interactions mediated by CYP1A2 and 2D6. THC may participate in strong CYP2C9 and weak CYP1A2 and 3A mediated drug interactions [ 282 , 283 , 284 ]. For example, the oral administration of CBD with the anticonvulsant clobazam led to a significant increase in the plasma concentrations and AUC of its active metabolite N-desmethylclobazam, which is metabolized predominantly by CYP2C19 [ 285 , 286 , 287 ].…”

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