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Intern Med J. 2019 Jul 1. doi: 10.1111/imj.14415. [Epub ahead of print]

Model-based analysis on systemic availability of coadministered cannabinoids after controlled vaporised administration.

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School of Medicine and Public Health, University of Newcastle, Hunter Medical Research Institute, Newcastle, NSW 2305, Australia.
Clinical Pharmacology, Department of Medicine, The Royal Children's Hospital, Melbourne, Australia.
Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University,Melbourne, Victoria, Australia.
The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), Newcastle, NSW 2305, Australia.
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.
School of Pharmacy, University of Otago, Dunedin, New Zealand.
School of Biomedical Sciences and Pharmacy, University of Newcastle, Hunter Medical Research Institute, Newcastle, NSW 2305, Australia.



The most important two medicinal cannabinoids are Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). Vaporised administration is superior due to its higher systemic availability, lower individual variability and faster drug delivery. Although it is common THC is coadministered with CBD, the influence of CBD on the pharmacokinetics, especially the systemic availability of THC after vaporised administration, is unknown. This study aimed to investigate the influence of different doses of coadministered CBD on the systemic availability of THC, and to compare the availability of THC and CBD in a sample of frequent and infrequent cannabis users.


The study used a randomised, double-blind, crossover placebo-controlled design. THC and/or CBD in ethanol was vaporised and inhaled. Plasma concentrations of THC and CBD were analysed. The THC data created in this study were pooled together with published THC pharmacokinetic data in order to cover all the phases of THC disposition. Population pharmacokinetic model of THC was developed based on the pooled data. The model of CBD was developed based on the data created in this study.


Population pharmacokinetic models of THC and CBD were developed. With concomitant inhalation of high dose CBD, the systemic availability of THC decreased significantly. Frequent cannabis users appeared to have higher systemic availability of THC and CBD when high dose CBD was administered.


The results observed in this study are useful for guiding future pharmacokinetic studies of medicinal cannabinoids, and for development of dosing guidelines for medical use of cannabis in the 'real world' setting. This article is protected by copyright. All rights reserved.


cannabidiol (CBD); cannabinoid; medicinal cannabis; pharmacokinetics; population pharmacokinetics model; Δ9-tetrahydrocannabinol (THC)


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