Pharmacokinetic Profile of Delta 9-Tetrahydrocannabinol, Cannabidiol, and Metabolites in Blood Following Vaporization and Oral Ingestion of Cannabidiol Products.

There is limited data on the comparative pharmacokinetics of cannabidiol (CBD) across oral and vaporized formulations. This within-subject, double-blind, double-dummy, placebo-controlled laboratory study analyzed the pharmacokinetic profile of CBD, Delta 9-tetrahydrocannabinol ( increment 9-THC), and related metabolites in blood and oral fluid after participants (n=18) administered 100 mg of CBD in each of the following formulations: (1) oral CBD, (2) vaporized CBD and (3) vaporized CBD-dominant cannabis containing 10.5% CBD and 0.39% increment 9-THC (3.7mg); all participants also completed a placebo condition. Oral CBD was administered in three formulations: (1) encapsulated CBD (2) CBD suspended in pharmacy-grade syrup, and (3) Epidiolex, allowing for pharmacokinetic comparisons across oral formulations (n=6 per condition). An optional fifth experimental condition was completed for 6 participants in which they fasted from all food for 12 h prior to oral ingestion of 100 mg CBD. Blood and oral fluid samples were collected immediately before and for 57-58 hrs after each drug administration. Immunoassay screening and LC-MS/MS confirmatory tests were performed, the limit of quantitation was 0.5 ng/mL for increment 9-THC, and 1 ng/mL for CBD. The mean Cmax and range of CBD blood concentrations for each product were as follows: vaporized CBD-dominant cannabis, 171.1 ng/mL, 40.0-665.0 ng/mL, vaporized CBD 104.6 ng/mL, 19.0-312.0 ng/mL, and oral CBD, 13.7 ng/mL, 0.0-50.0 ng/mL. Of the three oral formulations, Epidiolex produced the greatest peak concentration of CBD (20.5 ng/mL, 8.0-37.0 ng/mL) relative to the capsule (17.8 ng/mL, 2.0-50.0 ng/mL) and syrup (2.8 ng/mL, 0-7.0 ng/mL). increment 9-THC was detected in the blood of 12/18 participants after vaporized CBD-dominant cannabis use, but neither increment 9-THC nor its metabolite THC-COOH were detected in the blood of any participants after vaporized or oral CBD-only administration. These data demonstrate that different oral and vaporized formulations produce substantial variability in the pharmacokinetics of CBD and that CBD alone is unlikely to convert to Delta 9-THC or produce positive drug tests for Delta 9-THC or its metabolite.