Model‐based analysis on systemic availability of co‐administered cannabinoids after controlled vaporised administration

• Published in: Internal medicine journal Vol. 50; no. 7; pp. 846 - 853
• Main Authors: Liu, Zheng, Galettis, Peter, Broyd, Samantha J., Hell, Hendrika, Greenwood, Lisa‐Marie, Krey, Peter, Steigler, Amy, Zhu, Xiao, Schneider, Jennifer, Solowij, Nadia, Martin, Jennifer H.
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01.07.2020; Wiley Subscription Services, Inc
• Subjects: Cannabidiol; cannabinoid; Cannabinoids; Cannabis; Cross-Over Studies; Dosage; Dronabinol; Drug delivery; Ethanol; Health risk assessment; Humans; Inhalation; Marijuana; medicinal cannabis; Pharmacokinetics; population pharmacokinetics model; Population studies; Tetrahydrocannabinol; THC; Δ9‐tetrahydrocannabinol; cannabidiol; pharmacokinetics; Δ9-tetrahydrocannabinol; population pharmacokinetics model; cannabinoid; medicinal cannabis
• ISSN: 1444-0903; 1445-5994
• DOI: 10.1111/imj.14415

Background 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 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.