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-Delta 9-tetrahydrocannabinol (Delta 9-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 Delta 9-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 ng/mL) for Delta 9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC-MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean C-max: 734; mean T-max: 4.7 h, n = 18) versus vaporized CBD (mean C-max: 240; mean T-max: 1.3 h, n = 18), and oral dose formulation significantly impacted mean C-max (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in T-max. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Delta 8- or Delta 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 six urine samples in which Delta 9-THCCOOH concentrations >= 15 ng/mL. All six specimens screened positive at a 20 ng/mL IA cutoff, and two of six 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 Delta 9-THC may produce a cannabis-positive urine drug test.

Automated summary

The study investigated the urinary pharmacokinetics of CBD in healthy adults and found differences in CBD metabolism in different formulations. It also showed that hemp products containing low levels of Delta 9-THC may result in a positive urine drug test.