Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity

Abstract Limited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an “entourage effect” whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sati...

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Autores principales:	Justin E. LaVigne, Ryan Hecksel, Attila Keresztes, John M. Streicher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b6a8c60272aa4418b9b955283c91678f
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spelling	oai:doaj.org-article:b6a8c60272aa4418b9b955283c91678f2021-12-02T15:51:15ZCannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity10.1038/s41598-021-87740-82045-2322https://doaj.org/article/b6a8c60272aa4418b9b955283c91678f2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87740-8https://doaj.org/toc/2045-2322Abstract Limited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an “entourage effect” whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches. We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action. These behavioral effects were selectively additive with WIN55,212, suggesting terpenes can boost cannabinoid activity. In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets. Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.Justin E. LaVigneRyan HeckselAttila KeresztesJohn M. StreicherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Justin E. LaVigne Ryan Hecksel Attila Keresztes John M. Streicher Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity
description	Abstract Limited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an “entourage effect” whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches. We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action. These behavioral effects were selectively additive with WIN55,212, suggesting terpenes can boost cannabinoid activity. In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets. Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.
format	article
author	Justin E. LaVigne Ryan Hecksel Attila Keresztes John M. Streicher
author_facet	Justin E. LaVigne Ryan Hecksel Attila Keresztes John M. Streicher
author_sort	Justin E. LaVigne
title	Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity
title_short	Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity
title_full	Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity
title_fullStr	Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity
title_full_unstemmed	Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity
title_sort	cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b6a8c60272aa4418b9b955283c91678f
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Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity

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