Urinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC) and Their Metabolites following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration.
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 (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations gelcap, pharmacy-grade syrup and 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 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs 20, 50 and 100 ngmL) for Δ9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC-MS-MS. Urinary CBD concentrations (ngmL) 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 1,274 ngmL, capsule 776 ngmL, syrup 151 ngmL, n 6group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Δ8- or Δ9-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 six urine samples in which Δ9-THCCOOH concentrations ≥15 ngmL. All six specimens screened positive at a 20 ngmL IA cutoff, and two of six screened positive at a 50 ngmL cutoff. These data show that absorptionelimination 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 Δ9-THC may produce a cannabis-positive urine drug test.