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

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%)

Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9-tetrahydrocannabinol (THC).

RATIONALE: Delta(9)-Tetrahydrocannabinol (THC) is the main active constituent of cannabis. In recent years, the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette (20% THC cigarettes). Acute cognitive and psychomotor effects of THC among recreational users after smoking cannabis cigarettes containing such high doses are unknown. OBJECTIVES: The objective of this study was to study the dose-effect relationship between the THC dose contained in cannabis cigarettes and cognitive and psychomotor effects for THC doses up to 69.4 mg (23%). MATERIALS AND METHODS: This double-blind, placebo-controlled, randomised, four-way cross-over study included 24 non-daily male cannabis users (two to nine cannabis cigarettes per month). Participants smoked four cannabis cigarettes containing 0, 29.3, 49.1 and 69.4 mg THC on four exposure days. RESULTS: The THC dose in smoked cannabis was linearly associated with a slower response time in all tasks (simple reaction time, visuo-spatial selective attention, sustained attention, divided attention and short-term memory tasks) and motor control impairment in the motor control task. The number of errors increased significantly with increasing doses in the short-term memory and the sustained attention tasks. Some participants showed no impairment in motor control even at THC serum concentrations higher than 40 ng/mL. High feeling and drowsiness differed significantly between treatments. CONCLUSIONS: Response time slowed down and motor control worsened, both linearly, with increasing THC doses. Consequently, cannabis with high THC concentrations may be a concern for public health and safety if cannabis smokers are unable to titrate to a high feeling corresponding to a desired plasma THC level