Disposition of smoked cannabis with high [Delta]9-tetrahydrocannabinol content: A kinetic model.

Abstract

Introduction No model exists to describe the disposition and kinetics of inhaled cannabis containing a high THC dose. We aimed to develop a kinetic model providing estimates of the THC serum concentrations after smoking cannabis cigarettes containing high THC doses (up to 69 mg THC).Methods Twenty-four male non-daily cannabis users smoked cannabis cigarettes containing 29.3 mg, 49.1 mg, and 69.4 mg THC. Blood samples were collected over a period of 0-8 h and serum THC concentrations were measured. A two-compartment open model was fitted on the individual observed data.Results Large inter-individual variability was observed in the pharmacokinetic parameters. The median pharmacokinetic parameters generated by the model were Cmax = 175 ng/mL, Tmax = 14 min, and AUC0-8h = 8150 ng × min/mL for the 69.4 mg THC dose. Median model results show an almost linear dose response relation for Cmax/Dose = 2.8 × 10- 6/mL and AUC0-8h/Dose = 136 × 10- 6 min/mL. However, for increasing dose level, there was a clear decreasing trend: Cmax/Dose = 3.4, 2.6 and 2.5 × 10- 6/mL and AUC0-8h/Dose = 157, 133 and 117 × 10- 6 min/mL for the 29.3, 49.1 and 69.4 mg dose, respectively. Within the restriction of 8 h of observation, the apparent terminal half life of THC was 150 min.Conclusion The model offers insight into the pharmacokinetics of THC in recreational cannabis users smoking cannabis containing high doses of THC mixed with tobacco. The model is an objective method for providing serum THC concentrations up to 8 h after smoking cannabis with a high THC content (up to 23%).