Urinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC), and their Metabolites Following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration.

Abstract

The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g., 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (∆9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including 3 formulations: gelcap, pharmacy-grade syrup, or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n=18). A subset of participants (n=6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 hours after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50, 100 ng/mL) for ∆9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC-MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n=18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n=18), and oral dose formulation significantly impacted mean Cmax (Epidiolex=1274 ng/mL, capsule=776 ng/mL, syrup=151 ng/mL, n=6/group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to ∆8- or ∆9-THC in any route or formulation in which pure CBD was administered. Following acute administration of vaporized CBD-dominant cannabis, 3 of 18 participants provided a total of 6 urine samples in which ∆9-THCCOOH concentrations ≥15 ng/mL. All 6 specimens screened positive at a 20 ng/mL IA cutoff, and 2 of 6 screened positive at a 50 ng/mL cutoff. These data show that absorption/elimination of CBD is impacted by drug formulation, route of administration, and gastric contents. Although pure CBD is unlikely to impact drug testing, it is possible that hemp products containing low amounts of ∆9-THC may produce a cannabis-positive urine drug test.