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Disposition of smoked cannabis with high Δ(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 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.

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 8h after smoking cannabis with a high THC content (up to 23%).

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

    ,

    Expertise Center for Methodology and Information Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

    ,

    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.

    ,

    National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

    ,

    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.

    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.

    Source

    Toxicology and applied pharmacology 246:3 2010 Aug 01 pg 148-53

    MeSH

    Adolescent
    Adult
    Area Under Curve
    Cannabis
    Cross-Over Studies
    Double-Blind Method
    Dronabinol
    Half-Life
    Humans
    Kinetics
    Male
    Smoke
    Smoking
    Young Adult

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20450927

    Citation

    * When formatting your citation, note that all book, journal, and database titles should be italicized* Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Disposition of smoked cannabis with high Δ(9)-tetrahydrocannabinol content: a kinetic model. AU - Hunault,Claudine C, AU - van Eijkeren,Jan C H, AU - Mensinga,Tjeert T, AU - de Vries,Irma, AU - Leenders,Marianne E C, AU - Meulenbelt,Jan, Y1 - 2010/05/04/ PY - 2009/12/03/received PY - 2010/04/16/revised PY - 2010/04/26/accepted PY - 2010/5/11/entrez PY - 2010/5/11/pubmed PY - 2014/8/8/medline SP - 148 EP - 53 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 246 IS - 3 N2 - 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 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. 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 8h after smoking cannabis with a high THC content (up to 23%). SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/20450927/abstract/Disposition_of_smoked_cannabis_with_high_Delta_9__tetrahydrocannabinol_content:_A_kinetic_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(10)00163-8 DB - PRIME DP - Unbound Medicine ER -