Cannabis May Alter the Effects of Anticoagulants, Antiplatelets

A recent review published in The Journal of Clinical Pharmacology summarizes the current literature evaluating the potential risks associated with concomitant use of cannabis and antiplatelet agents or anticoagulants.

Cannabis use has exponentially increased over the past several years, and while the medical benefits are generally recognized, there is a lack of knowledge surrounding the pharmacokinetics and pharmacodynamics of specific products. Research has shown that the 2 components of medical cannabis (THC and cannabidiol) have the potential to inhibit several cytochrome P450 (CYP) hepatic isoenzymes and UDP-glucuronosyltransferases, and may also bind to P-glycoprotein. 

To better understand outcomes associated with the use of medical cannabis and antiplatelets/anticoagulants, study authors searched PubMed and EMBASE for published literature and case reports that included relevant information on possible interactions and side effects; the search yielded a total of 665 articles, of which 6 were included in the review.

The study authors reported finding several clinically significant interactions associated with concomitant cannabis and anticoagulant/antiplatelet use. A number of reports referenced a significant interaction between cannabis and warfarin. “Several case reports show cannabis may inhibit the metabolism of warfarin because of CYP2C9 interactions, resulting in increased plasma concentrations, increased international normalized ratio, and risk of bleeding,” the authors explained. 

Another significant interaction discussed in the review was between cannabis and clopidogrel. Cannabis is a known inhibitor of CYP2C19, an enzyme necessary to convert clopidogrel into its active thiol metabolite. Inhibition of this enzyme by cannabis can therefore lead to subtherapeutic concentrations of the active form of clopidogrel. 

One other interaction that the authors discussed being potentially significant was between cannabis and direct-acting oral anticoagulants (DOACs). Although no cases have been reported in the literature thus far, cannabis may significantly increase the concentration of these agents. It is important, therefore, that patients are closely monitored for adverse events. 

“Significant knowledge gaps still exist; however, until a change in the current legal status and federal schedule of medical cannabis occurs, conducting interventional clinical research involving medical cannabis and [anticoagulants] or [antiplatelets] in the United States is not feasible,” the authors concluded. They added, “As healthcare providers, it is our responsibility to establish appropriate monitoring parameters and close follow-up when adding medical cannabis to patient profiles.”

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