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Disposition of smoked cannabis with high Δ(9)-tetrahydrocannabinol content: a kinetic model.
Toxicol Appl Pharmacol. 2010 Aug 01; 246(3):148-53.TA

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%).

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Authors+Show Affiliations

Hunault CC
National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
van Eijkeren JC
Expertise Center for Methodology and Information Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Mensinga TT
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.
de Vries I
National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Leenders ME
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.
Meulenbelt J
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.

MeSH

AdolescentAdultArea Under CurveCannabisCross-Over StudiesDouble-Blind MethodDronabinolHalf-LifeHumansKineticsMaleSmokeSmokingYoung Adult

Pub Type(s)

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

Language

eng

PubMed ID

20450927

Citation

Hunault, Claudine C., et al. "Disposition of Smoked Cannabis With High Δ(9)-tetrahydrocannabinol Content: a Kinetic Model." Toxicology and Applied Pharmacology, vol. 246, no. 3, 2010, pp. 148-53.
Hunault CC, van Eijkeren JC, Mensinga TT, et al. Disposition of smoked cannabis with high Δ(9)-tetrahydrocannabinol content: a kinetic model. Toxicol Appl Pharmacol. 2010;246(3):148-53.
Hunault, C. C., van Eijkeren, J. C., Mensinga, T. T., de Vries, I., Leenders, M. E., & Meulenbelt, J. (2010). Disposition of smoked cannabis with high Δ(9)-tetrahydrocannabinol content: a kinetic model. Toxicology and Applied Pharmacology, 246(3), 148-53. https://doi.org/10.1016/j.taap.2010.04.019
Hunault CC, et al. Disposition of Smoked Cannabis With High Δ(9)-tetrahydrocannabinol Content: a Kinetic Model. Toxicol Appl Pharmacol. 2010 Aug 1;246(3):148-53. PubMed PMID: 20450927.
* 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/Disposition_of_smoked_cannabis_with_high_Δ_9__tetrahydrocannabinol_content:_a_kinetic_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(10)00163-8 DB - PRIME DP - Unbound Medicine ER -
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