Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations

Abstract Cannabis is a complex mixture of hundreds of bioactive molecules. This provides the potential for pharmacological interactions between cannabis constituents, a phenomenon referred to as “the entourage effect” by the medicinal cannabis community. We hypothesize that pharmacokinetic interacti...

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Autores principales:	Lyndsey L. Anderson, Maia G. Etchart, Dilara Bahceci, Taliesin A. Golembiewski, Jonathon C. Arnold
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fd468edfecc4450b7a11572ec9bd513
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spelling	oai:doaj.org-article:2fd468edfecc4450b7a11572ec9bd5132021-12-02T16:26:30ZCannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations10.1038/s41598-021-94212-62045-2322https://doaj.org/article/2fd468edfecc4450b7a11572ec9bd5132021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94212-6https://doaj.org/toc/2045-2322Abstract Cannabis is a complex mixture of hundreds of bioactive molecules. This provides the potential for pharmacological interactions between cannabis constituents, a phenomenon referred to as “the entourage effect” by the medicinal cannabis community. We hypothesize that pharmacokinetic interactions between cannabis constituents could substantially alter systemic cannabinoid concentrations. To address this hypothesis we compared pharmacokinetic parameters of cannabinoids administered orally in a cannabis extract to those administered as individual cannabinoids at equivalent doses in mice. Astonishingly, plasma cannabidiolic acid (CBDA) concentrations were 14-times higher following administration in the cannabis extract than when administered as a single molecule. In vitro transwell assays identified CBDA as a substrate of the drug efflux transporter breast cancer resistance protein (BCRP), and that cannabigerol and Δ9-tetrahydrocannabinol inhibited the BCRP-mediated transport of CBDA. Such a cannabinoid-cannabinoid interaction at BCRP transporters located in the intestine would inhibit efflux of CBDA, thus resulting in increased plasma concentrations. Our results suggest that cannabis extracts provide a natural vehicle to substantially enhance plasma CBDA concentrations. Moreover, CBDA might have a more significant contribution to the pharmacological effects of orally administered cannabis extracts than previously thought.Lyndsey L. AndersonMaia G. EtchartDilara BahceciTaliesin A. GolembiewskiJonathon C. ArnoldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lyndsey L. Anderson Maia G. Etchart Dilara Bahceci Taliesin A. Golembiewski Jonathon C. Arnold Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations
description	Abstract Cannabis is a complex mixture of hundreds of bioactive molecules. This provides the potential for pharmacological interactions between cannabis constituents, a phenomenon referred to as “the entourage effect” by the medicinal cannabis community. We hypothesize that pharmacokinetic interactions between cannabis constituents could substantially alter systemic cannabinoid concentrations. To address this hypothesis we compared pharmacokinetic parameters of cannabinoids administered orally in a cannabis extract to those administered as individual cannabinoids at equivalent doses in mice. Astonishingly, plasma cannabidiolic acid (CBDA) concentrations were 14-times higher following administration in the cannabis extract than when administered as a single molecule. In vitro transwell assays identified CBDA as a substrate of the drug efflux transporter breast cancer resistance protein (BCRP), and that cannabigerol and Δ9-tetrahydrocannabinol inhibited the BCRP-mediated transport of CBDA. Such a cannabinoid-cannabinoid interaction at BCRP transporters located in the intestine would inhibit efflux of CBDA, thus resulting in increased plasma concentrations. Our results suggest that cannabis extracts provide a natural vehicle to substantially enhance plasma CBDA concentrations. Moreover, CBDA might have a more significant contribution to the pharmacological effects of orally administered cannabis extracts than previously thought.
format	article
author	Lyndsey L. Anderson Maia G. Etchart Dilara Bahceci Taliesin A. Golembiewski Jonathon C. Arnold
author_facet	Lyndsey L. Anderson Maia G. Etchart Dilara Bahceci Taliesin A. Golembiewski Jonathon C. Arnold
author_sort	Lyndsey L. Anderson
title	Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations
title_short	Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations
title_full	Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations
title_fullStr	Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations
title_full_unstemmed	Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations
title_sort	cannabis constituents interact at the drug efflux pump bcrp to markedly increase plasma cannabidiolic acid concentrations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2fd468edfecc4450b7a11572ec9bd513
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Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations

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