title: Disposition of smoked cannabis with high Δ(9)-tetrahydrocannabinol content: a kinetic model.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  Large inter-individual variability was observed in the pharmacokinetic parameters. The median pharmacokinetic parameters generated by the model were Cmax=175ng/mL, Tmax=14min, and AUC0-8h=8150ng×min/mL for the 69.4mg 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 69.4mg dose, respectively. Within the restriction of 8h of observation, the apparent terminal half life of THC was 150min.
  
  
  CONCLUSIONS
  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%).
authors.affiliation: National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Claudine C
authors.initials: CC
authors.lastname: Hunault
authors.affiliation: Expertise Center for Methodology and Information Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Jan C H
authors.initials: JC
authors.lastname: van Eijkeren
authors.affiliation: National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Clinic for treatment of drug addiction in Northern, Vondellaan 71-73, 9721 LB, Groningen, The Netherlands.
authors.forename: Tjeert T
authors.initials: TT
authors.lastname: Mensinga
authors.affiliation: National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Irma
authors.initials: I
authors.lastname: de Vries
authors.affiliation: National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Division of Perioperative and Emergency Care, University Medical Center Utrecht, 3584 CX, The Netherlands.
authors.forename: Marianne E C
authors.initials: ME
authors.lastname: Leenders
authors.affiliation: National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Division Intensive Care Center, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands; Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Meulenbelt
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002188:Cannabis / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000097:blood* / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D012906:Smoke; D012907:Smoking / Q000097:blood* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012906:Smoke; D013759:Dronabinol