Disposition of smoked cannabis with high Δ(9)-tetrahydrocannabinol content a kinetic model.
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 69mg THC). Twenty-four male non-daily cannabis users smoked cannabis cigarettes containing 29.3mg, 49.1mg, and 69.4mg THC. Blood samples were collected over a period of 0-8h and serum THC concentrations were measured. A two-compartment open model was fitted on the individual observed data. Large inter-individual variability was observed in the pharmacokinetic parameters. The median pharmacokinetic parameters generated by the model were Cmax175ngmL, Tmax14min, and AUC0-8h8150ng×minmL for the 69.4mg THC dose. Median model results show an almost linear dose response relation for CmaxDose2.8×10(-6)mL and AUC0-8hDose136×10(-6)minmL. However, for increasing dose level, there was a clear decreasing trend CmaxDose3.4, 2.6 and 2.5×10(-6)mL and AUC0-8hDose157, 133 and 117×10(-6)minmL for the 29.3, 49.1 and 69.4mg dose, respectively. Within the restriction of 8h of observation, the apparent terminal half life of THC was 150min. 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 8h after smoking cannabis with a high THC content (up to 23%).