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Model‐based analysis on systemic availability of co‐administered cannabinoids after controlled vaporised administration
Author(s) -
Liu Zheng,
Galettis Peter,
Broyd Samantha J.,
Hell Hendrika,
Greenwood LisaMarie,
Krey Peter,
Steigler Amy,
Zhu Xiao,
Schneider Jennifer,
Solowij Nadia,
Martin Jennifer H.
Publication year - 2020
Publication title -
internal medicine journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.596
H-Index - 70
eISSN - 1445-5994
pISSN - 1444-0903
DOI - 10.1111/imj.14415
Subject(s) - cannabidiol , medicine , pharmacokinetics , cannabis , pharmacology , dosing , population , dronabinol , drug , crossover study , cannabinoid , tetrahydrocannabinol , placebo , psychiatry , receptor , environmental health , alternative medicine , pathology
Background The most important two medicinal cannabinoids are Δ 9 ‐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 co‐administered with CBD, the influence of CBD on the pharmacokinetics, especially the systemic availability of THC after vaporised administration, is unknown. Aims To investigate the influence of different doses of co‐administered 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. Methods 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. Results 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. Conclusions 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.