Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol

Abstract The two most important and studied phytocannabinoids present in Cannabis sativa L. are undoubtedly cannabidiol (CBD), a non-psychotropic compound, but with other pharmacological properties, and Δ9-tetrahydrocannabinol (Δ9-THC), which instead possesses psychotropic activity and is responsibl...

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Autores principales:	Pasquale Linciano, Cinzia Citti, Fabiana Russo, Francesco Tolomeo, Aldo Laganà, Anna Laura Capriotti, Livio Luongo, Monica Iannotta, Carmela Belardo, Sabatino Maione, Flavio Forni, Maria Angela Vandelli, Giuseppe Gigli, Giuseppe Cannazza
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2be800a38e640f98a7de8fd6927174c
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spelling	oai:doaj.org-article:e2be800a38e640f98a7de8fd6927174c2021-12-02T13:58:15ZIdentification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol10.1038/s41598-020-79042-22045-2322https://doaj.org/article/e2be800a38e640f98a7de8fd6927174c2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79042-2https://doaj.org/toc/2045-2322Abstract The two most important and studied phytocannabinoids present in Cannabis sativa L. are undoubtedly cannabidiol (CBD), a non-psychotropic compound, but with other pharmacological properties, and Δ9-tetrahydrocannabinol (Δ9-THC), which instead possesses psychotropic activity and is responsible for the recreative use of hemp. Recently, the homolog series of both CBDs and THCs has been expanded by the isolation in a medicinal cannabis variety of four new phytocannabinoids possessing on the resorcinyl moiety a butyl-(in CBDB and Δ9-THCB) and a heptyl-(in CBDP and Δ9-THCP) aliphatic chain. In this work we report a new series of phytocannabinoids that fills the gap between the pentyl and heptyl homologs of CBD and Δ9-THC, bearing a n-hexyl side chain on the resorcinyl moiety that we named cannabidihexol (CBDH) and Δ9-tetrahydrocannabihexol (Δ9-THCH), respectively. However, some cannabinoids with the same molecular formula and molecular weight of CBDH and Δ9-THCH have been already identified and reported as monomethyl ether derivatives of the canonical phytocannabinoids, namely cannabigerol monomethyl ether (CBGM), cannabidiol monomethyl ether (CBDM) and Δ9-tetrahydrocannabinol monomethyl ether (Δ9-THCM). The unambiguously identification in cannabis extract of the n-hexyl homologues of CBD and Δ9-THC different from the corresponding methylated isomers (CBDM, CBGM and Δ9-THCM) was achieved by comparison of the retention time, molecular ion, and fragmentation spectra with those of the authentic standards obtained via stereoselective synthesis, and a semi-quantification of these cannabinoids in the FM2 medical cannabis variety was provided. Conversely, no trace of Δ9-THCM was detected. Moreover, CBDH was isolated by semipreparative HPLC and its identity was confirmed by comparison with the spectroscopic data of the corresponding synthetic standard. Thus, the proper recognition of CBDH, CBDM and Δ9-THCH closes the loop and might serve in the future for researchers to distinguish between these phytocannabinoids isomers that show a very similar analytical behaviour. Lastly, CBDH was assessed for biological tests in vivo showing interesting analgesic activity at low doses in mice.Pasquale LincianoCinzia CittiFabiana RussoFrancesco TolomeoAldo LaganàAnna Laura CapriottiLivio LuongoMonica IannottaCarmela BelardoSabatino MaioneFlavio ForniMaria Angela VandelliGiuseppe GigliGiuseppe CannazzaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pasquale Linciano Cinzia Citti Fabiana Russo Francesco Tolomeo Aldo Laganà Anna Laura Capriotti Livio Luongo Monica Iannotta Carmela Belardo Sabatino Maione Flavio Forni Maria Angela Vandelli Giuseppe Gigli Giuseppe Cannazza Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol
description	Abstract The two most important and studied phytocannabinoids present in Cannabis sativa L. are undoubtedly cannabidiol (CBD), a non-psychotropic compound, but with other pharmacological properties, and Δ9-tetrahydrocannabinol (Δ9-THC), which instead possesses psychotropic activity and is responsible for the recreative use of hemp. Recently, the homolog series of both CBDs and THCs has been expanded by the isolation in a medicinal cannabis variety of four new phytocannabinoids possessing on the resorcinyl moiety a butyl-(in CBDB and Δ9-THCB) and a heptyl-(in CBDP and Δ9-THCP) aliphatic chain. In this work we report a new series of phytocannabinoids that fills the gap between the pentyl and heptyl homologs of CBD and Δ9-THC, bearing a n-hexyl side chain on the resorcinyl moiety that we named cannabidihexol (CBDH) and Δ9-tetrahydrocannabihexol (Δ9-THCH), respectively. However, some cannabinoids with the same molecular formula and molecular weight of CBDH and Δ9-THCH have been already identified and reported as monomethyl ether derivatives of the canonical phytocannabinoids, namely cannabigerol monomethyl ether (CBGM), cannabidiol monomethyl ether (CBDM) and Δ9-tetrahydrocannabinol monomethyl ether (Δ9-THCM). The unambiguously identification in cannabis extract of the n-hexyl homologues of CBD and Δ9-THC different from the corresponding methylated isomers (CBDM, CBGM and Δ9-THCM) was achieved by comparison of the retention time, molecular ion, and fragmentation spectra with those of the authentic standards obtained via stereoselective synthesis, and a semi-quantification of these cannabinoids in the FM2 medical cannabis variety was provided. Conversely, no trace of Δ9-THCM was detected. Moreover, CBDH was isolated by semipreparative HPLC and its identity was confirmed by comparison with the spectroscopic data of the corresponding synthetic standard. Thus, the proper recognition of CBDH, CBDM and Δ9-THCH closes the loop and might serve in the future for researchers to distinguish between these phytocannabinoids isomers that show a very similar analytical behaviour. Lastly, CBDH was assessed for biological tests in vivo showing interesting analgesic activity at low doses in mice.
format	article
author	Pasquale Linciano Cinzia Citti Fabiana Russo Francesco Tolomeo Aldo Laganà Anna Laura Capriotti Livio Luongo Monica Iannotta Carmela Belardo Sabatino Maione Flavio Forni Maria Angela Vandelli Giuseppe Gigli Giuseppe Cannazza
author_facet	Pasquale Linciano Cinzia Citti Fabiana Russo Francesco Tolomeo Aldo Laganà Anna Laura Capriotti Livio Luongo Monica Iannotta Carmela Belardo Sabatino Maione Flavio Forni Maria Angela Vandelli Giuseppe Gigli Giuseppe Cannazza
author_sort	Pasquale Linciano
title	Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol
title_short	Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol
title_full	Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol
title_fullStr	Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol
title_full_unstemmed	Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol
title_sort	identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e2be800a38e640f98a7de8fd6927174c
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Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol

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