University of Florida
Background: There are been no studies that have comprehensively reviewed safety profiles, including reported adverse drug events (ADEs), for cannabis-derived and synthetic products approved in the United States (U.S.) and internationally.
Objective: To examine ADE reports for cannabis-derived (i.e., Epidiolex), synthetic cannabis-related (i.e., Marinol, Syndros, Cesamet, and Sativex), and unspecified cannabidiol (CBD) drug products, and to describe ADE reports by characteristics, reactions, and outcomes reported.
Methods: Data from the FDA Adverse Event Reporting System were analyzed from 1985 to Q3/2019. Brand and generic product names as well as common names (e.g., “CBD”) were used to extract reports. Characteristics of the ADE were described by the cannabinoid product’s role in the event, reporter type, and country. Reactions were described by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms.
Results: After de-duplication, there were 3,445 unique ADE reports, of which 1,892 were for Marinol or Syndros, 655 for Epidiolex, 374 for Cesamet, 183 for Sativex, and 341 for unspecified CBD. The cannabinoid product’s role in the ADE was as concomitant or interacting (62.6%) more frequently than as a primary or secondary suspect drug (37.4%) with the exception of Epidiolex (primary or secondary suspect drug 96.6%). ADEs were most often reported by physicians (33.1%), other health professionals (27.9%), and consumers (28.2%). Reports originated most often in the U.S. for a majority of the ADEs, followed by Canada (11.1%) and Germany (6.5%). The most frequently reported reactions were seizure (6.0%), death (3.6%), decreased appetite (2.6%), and vomiting (2.2%). The most frequent reaction for Marinol or Syndros was death (4.9%); seizure (26.0%) for Epidiolex; therapeutic product effect incomplete (7.5%) for Cesamet; multiple sclerosis relapse (7.1%) for Sativex; and off-label use (3.8%) for unspecified CBD. Hospitalizations (40.9%) were the most frequent outcome, followed by other serious medical events (38.5%) and death (16.8%).
Conclusion: Frequently reported reactions with cannabis-derived and synthetic cannabis-related products were related to the indications for which they are approved. However, death was the second most frequent reaction overall and which accounted for one in six reported outcomes. Presence of these ADEs warrants further safety evaluation.
Co-authors: Rachel Matthews1, Amie Goodin1, Joshua Brown1
1University of Florida