Anticoagulant drug-drug interactions with cannabinoids: A systematic review

This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, PscycINFO, and CINAHL from database inception through May 2023. Search terms included cannabis AND anticoagulant AND drug interactions and related keywords. The major outcome was hemorrhage or thrombosis and if available the relative change in quantitative intensity of anticoagulation after cannabinoid exposure. The search generated 959 citations. After the removal of 440 duplicates, 519 citations were screened. Overall, with the exception of warfarin, evidence supporting an interaction between cannabinoids and anticoagulants is non-existent. Seven case reports evaluating an interaction with warfarin were reported. Cannabis doses involved were either extremely high (e.g., >260 mg/day of delta-9-tetrahydrocannabidiol [THC] or >600 mg/day of cannabidiol [CBD]) or were not known. Hemorrhage was identified in 14.2% (1/7) of reports and thrombosis in 0%. Quantitative anticoagulation levels were increased in patients on warfarin (elevated International Normalized Ratio [INR]) in six of seven cases. A maximum INR change was available in five of seven reports, ranging from +0.4 to +9.61. One report found no change in INR after 4 days of medical cannabis exposure. Another report outlined two separate episodes of INR elevation associated with bleeding requiring hospitalization and reversal after marijuana smoking. Four cases involved reduction in weekly warfarin dose ranging from 22% to 31%. The Drug Information Probability Score was calculated in six cases, with a score of probable for five cases and possible for one. Very low-quality data support a potential drug-drug interaction with warfarin and both THC and CBD. Clinician recognition of this potential interaction is important. Available evidence supports the need to conduct a drug interaction study between cannabinoids and warfarin to clarify the existence of an interaction.