A Preliminary Pharmacokinetic Comparison of Δ-9 Tetrahydrocannabinol and Cannabidiol Extract Versus Oromucosal Spray in Healthy Men and Women

Aim: Few studies have directly compared the bioavailability of different cannabinoid formulations. Our goal was to assess the pharmacokinetic parameters and relative bioavailability of two Δ9-tetrahydrocannabinol: cannabidiol (THC:CBD) formulations: orally administered THC:CBD extract and oromucosally administered nabiximols. Methods: This pilot crossover study counterbalanced (1) 1 mL of orally administered THC:CBD extract (10 mg/mL each of THC and CBD in grapeseed oil) and (2) oromucosally administered nabiximols (four sprays of 2.7 mg THC and 2.5 mg CBD per spray, for a total dose of 10.8 mg THC and 10 mg CBD). Blood samples were obtained pre-dose and at 16 post-dose timepoints over 24 h. Pharmacokinetic parameters were calculated for THC, 11-hydroxy-tetrahydrocannabinol (11-OH-THC), and CBD. Results: Twelve occasional cannabis users (6 male, 6 female) were tested under fasting conditions. Cmax for THC and CBD was significantly higher with significantly shorter half-lives for THC:CBD extract versus nabiximols. Cmax for nabiximols was significantly higher in males compared with females. Under both treatment conditions, THC and CBD were undetectable by 24 h post-dose, and 11-OH-THC was markedly reduced from its peak. No serious adverse events were reported. Conclusions: Little is known about the comparative pharmacokinetics of commercially available cannabis products. This pilot study shows that the extract formulation achieved higher THC and CBD concentrations within a shorter time frame than nabiximols. These findings may have implications for clinical populations using these formulations therapeutically. Future studies should examine multiple doses in the context of therapeutic outcomes to characterize the relative clinical utility of these formulations.