In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa

Abstract The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabi...

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Autores principales:	Ayat Zagzoog, Kawthar A. Mohamed, Hye Ji J. Kim, Eunhyun D. Kim, Connor S. Frank, Tallan Black, Pramodkumar D. Jadhav, Larry A. Holbrook, Robert B. Laprairie
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a52077388f3b4632a837de46a8b03235
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spelling	oai:doaj.org-article:a52077388f3b4632a837de46a8b032352021-12-02T11:40:20ZIn vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa10.1038/s41598-020-77175-y2045-2322https://doaj.org/article/a52077388f3b4632a837de46a8b032352020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77175-yhttps://doaj.org/toc/2045-2322Abstract The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the ‘high’ associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.Ayat ZagzoogKawthar A. MohamedHye Ji J. KimEunhyun D. KimConnor S. FrankTallan BlackPramodkumar D. JadhavLarry A. HolbrookRobert B. LaprairieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ayat Zagzoog Kawthar A. Mohamed Hye Ji J. Kim Eunhyun D. Kim Connor S. Frank Tallan Black Pramodkumar D. Jadhav Larry A. Holbrook Robert B. Laprairie In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
description	Abstract The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the ‘high’ associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.
format	article
author	Ayat Zagzoog Kawthar A. Mohamed Hye Ji J. Kim Eunhyun D. Kim Connor S. Frank Tallan Black Pramodkumar D. Jadhav Larry A. Holbrook Robert B. Laprairie
author_facet	Ayat Zagzoog Kawthar A. Mohamed Hye Ji J. Kim Eunhyun D. Kim Connor S. Frank Tallan Black Pramodkumar D. Jadhav Larry A. Holbrook Robert B. Laprairie
author_sort	Ayat Zagzoog
title	In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
title_short	In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
title_full	In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
title_fullStr	In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
title_full_unstemmed	In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
title_sort	in vitro and in vivo pharmacological activity of minor cannabinoids isolated from cannabis sativa
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/a52077388f3b4632a837de46a8b03235
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In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa

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