Conversion of Cannabidiol Following Oral Administration: Authors' Response to Grotenhermen et al. DOI: 10.1089/can.2016.0036

In a commentary, Grotenhermen, Russo, and Zuardi questioned not only the clinical relevance but also the conclusions of a recently published study by Merrick et al. on the conversion of cannabidiol (CBD) to delta-8 and delta-9-tetrahydrocannabinol (THC) in simulated gastric fluid. In response, this article aims to provide a thorough review of the in vitro and in vivo studies of gastric CBD conversion as well as potential consequences resulting from such conversion. Findings highlight (1) consistent evidence over the past half century of gastric conversion of CBD, (2) evidence from human studies, indicating the importance of testing for THC metabolites as well as a number of other cannabinoids in the detection of such conversion, and (3) THC-like effects after administration of oral CBD in humans that may not only stem from CBD's conversion to THC, but also its conversion to 9α-hydroxy-hexahydrocannabinol and 8α-hydroxy-iso-hexahydrocannabinol. These findings, coupled with a number of limitations in the existing literature, point to the need for large-scale human studies, specifically designed to explore gastric conversion and potential THC-like side effects after oral administration of CBD.