Pharmacokinetic Profile of Δ9-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.

Automated summary

Limited data is available on the pharmacokinetics of cannabidiol (CBD) in different formulations. This study compared the pharmacokinetic profiles of CBD, Delta 9-tetrahydrocannabinol (9-THC), and related metabolites in blood and oral fluid after participants took 100mg of CBD in oral and vaporized forms. The results showed that oral and vaporized formulations produce significant variability in the pharmacokinetics of CBD, and CBD alone is unlikely to convert to Delta 9-THC or produce positive drug tests for Delta 9-THC or its metabolite.