Plasma cannabinoid pharmacokinetics following the inhalation of vaporised cannabis with and without cannabidiol.

Abstract

The presence of cannabidiol (CBD) in cannabis may alter cannabinoid pharmacokinetics, however previous research has produced mixed results. Furthermore, no prior research has explored how cannabinoid pharmacokinetics are moderated by age. Using vaporised and inhaled cannabis, we aimed to (1) examine the effect of CBD on the plasma concentration of delta-9-tetrahydrocannabinol (THC) and its metabolites, and (2) compare cannabinoid plasma pharmacokinetics in adolescents and adults. We conducted a randomised, double-blind, placebo-controlled, cross-over study. We compared the effects of three vaporized, weight-adjusted cannabis preparations: 'THC-alone' (8mg THC/75kg), 'THC+CBD' (8mg THC and 24mg CBD/75kg) and placebo, in 48 participants, aged 16-17-years and 26-29-years. Blood samples were taken prior to inhalation, then 20, 30, and 160min after inhalation began. Thirty-five participants had complete pharmacokinetic datasets, which were analysed. Plasma was analysed for concentrations of THC, 11-hydroxy-THC (OH-THC) and 11-Nor-9-carboxy-THC (COOH-THC), CBD, 7-hydroxy-cannabidiol (OH-CBD) and 7-carboxy-cannabidiol (COOH-CBD). The 'THC+CBD' condition produced significantly greater THC, OH-THC, and COOH-THC plasma levels than the 'THC-alone' condition, in terms of natural-log-transformed area-under-the-curve (AUC) and peak concentration (C_max) values, with the exception of C_max for OH-THC. Geometric mean ratios showed the 'THC+CBD' condition led to higher THC plasma levels. There was no strong evidence of age-related differences. The presence of CBD in vaporised cannabis increased circulating levels of THC and THC-metabolites. However, further research is needed to understand discrepancies across studies regarding the impact of CBD on THC pharmacokinetics.