Postdoctoral fellow University of Pittsburgh School of Pharmacy Pittsburgh, United States
Background: The use of legal cannabis is growing rapidly throughout the United States, with a projected market value of $47.5 billion by 2030. The concomitant use of cannabis with prescription and non-prescription drugs is an unknown patient safety concern given the dearth of natural product drug interaction (NPDI) research with cannabis.
Objectives: The objective of this study is to identify potential NPDIs involving cannabis based on published case reports and spontaneous reporting data.
Methods: PubMed was searched from inception to January 2023 to identify case reports analyzing potential NPDIs of cannabis sativa published in the English language. The following data were extracted from the included case reports: potential interacting drug, adverse event reported, and proposed mechanism of NPDI. Drug interaction probability scale (DIPS), a tool used to evaluate drug interactions cases, was applied for each case report. A query of the VigiBase database from November of 1967 through August of 2022 was completed using a list of known cannabis names to identify spontaneous reports with either the term “interacting” in the drug name list or “interacting drug” in the Medical Dictionary for Regulatory Activities label, suggesting potential NPDIs where cannabis was described as having an interacting role. The identified reports were summarized using descriptive statistics for demographics, outcomes, and concomitant medications.
Results: A total of 51 case reports were identified from the PubMed search and 30 met the inclusion criteria. There were 20 different potentially affected drugs reported in the literature. Warfarin was the most reported prescription drug to interact with cannabis (5/30, 16.7%). Four out of the five case reports (80%) were determined to have a DIPS score of at least probable. This NPDI resulted in an increase in international normalized ratio (INR) through CYP2C9 inhibition. Other common adverse events with cannabis and object drugs included increased object drug levels, confusion, and tachycardia. A total of 188 cannabis-related reports were detected in VigiBase. After removing 20 suspected duplicates (10.6%), there were 168 NPDI reports. Nine reports contained warfarin (9/168, 5.4%) and five of them (55.6%) mentioned an increased INR. Out of 168 reports, 20 reported outcomes (11.9%) were known to be fatal. Other common interacting drugs included antidepressants, where eight out of the 30 published case reports (26.7%) contained an antidepressant as the object drug.
Conclusions: Cannabis, a natural product, was reported to interact with frequently utilized prescription medications. Warfarin was the most common medication to have a NPDI with cannabis in both published literature and VigiBase; therefore, concomitant use should be used with caution.
