Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substan...

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Autores principales:	Kenneth B. Walsh, Amanda E. McKinney, Andrea E. Holmes
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Cannabis sativa minor cannabinoids TRP channel endocannabinoids therapeutics CB1–CB2 cannabinoid receptors Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6b487f3a30f84fcbbf4cde21f7bdcadb
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spelling	oai:doaj.org-article:6b487f3a30f84fcbbf4cde21f7bdcadb2021-12-01T14:23:00ZMinor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses1663-981210.3389/fphar.2021.777804https://doaj.org/article/6b487f3a30f84fcbbf4cde21f7bdcadb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.777804/fullhttps://doaj.org/toc/1663-9812The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substance. A major breakthrough in understanding the pharmacology of cannabis came with the isolation and characterization of the phytocannabinoids trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This was followed by the cloning of the cannabinoid CB1 and CB2 receptors in the 1990s and the subsequent discovery of the endocannabinoid system. In addition to the major phytocannabinoids, Δ9-THC and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor and/or rare cannabinoids. These cannabinoids are produced in smaller amounts in the plant and are derived along with Δ9-THC and CBD from the parent cannabinoid cannabigerolic acid (CBGA). While our current knowledge of minor cannabinoid pharmacology is incomplete, studies demonstrate that they act as agonists and antagonists at multiple targets including CB1 and CB2 receptors, transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPARs), serotonin 5-HT1a receptors and others. The resulting activation of multiple cell signaling pathways, combined with their putative synergistic activity, provides a mechanistic basis for their therapeutic actions. Initial clinical reports suggest that these cannabinoids may have potential benefits in the treatment of neuropathic pain, neurodegenerative diseases, epilepsy, cancer and skin disorders. This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds.Kenneth B. WalshAmanda E. McKinneyAmanda E. McKinneyAndrea E. HolmesAndrea E. HolmesFrontiers Media S.A.articleCannabis sativaminor cannabinoidsTRP channelendocannabinoidstherapeuticsCB1–CB2 cannabinoid receptorsTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cannabis sativa minor cannabinoids TRP channel endocannabinoids therapeutics CB1–CB2 cannabinoid receptors Therapeutics. Pharmacology RM1-950
spellingShingle	Cannabis sativa minor cannabinoids TRP channel endocannabinoids therapeutics CB1–CB2 cannabinoid receptors Therapeutics. Pharmacology RM1-950 Kenneth B. Walsh Amanda E. McKinney Amanda E. McKinney Andrea E. Holmes Andrea E. Holmes Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses
description	The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substance. A major breakthrough in understanding the pharmacology of cannabis came with the isolation and characterization of the phytocannabinoids trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This was followed by the cloning of the cannabinoid CB1 and CB2 receptors in the 1990s and the subsequent discovery of the endocannabinoid system. In addition to the major phytocannabinoids, Δ9-THC and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor and/or rare cannabinoids. These cannabinoids are produced in smaller amounts in the plant and are derived along with Δ9-THC and CBD from the parent cannabinoid cannabigerolic acid (CBGA). While our current knowledge of minor cannabinoid pharmacology is incomplete, studies demonstrate that they act as agonists and antagonists at multiple targets including CB1 and CB2 receptors, transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPARs), serotonin 5-HT1a receptors and others. The resulting activation of multiple cell signaling pathways, combined with their putative synergistic activity, provides a mechanistic basis for their therapeutic actions. Initial clinical reports suggest that these cannabinoids may have potential benefits in the treatment of neuropathic pain, neurodegenerative diseases, epilepsy, cancer and skin disorders. This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds.
format	article
author	Kenneth B. Walsh Amanda E. McKinney Amanda E. McKinney Andrea E. Holmes Andrea E. Holmes
author_facet	Kenneth B. Walsh Amanda E. McKinney Amanda E. McKinney Andrea E. Holmes Andrea E. Holmes
author_sort	Kenneth B. Walsh
title	Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses
title_short	Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses
title_full	Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses
title_fullStr	Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses
title_full_unstemmed	Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses
title_sort	minor cannabinoids: biosynthesis, molecular pharmacology and potential therapeutic uses
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6b487f3a30f84fcbbf4cde21f7bdcadb
work_keys_str_mv	AT kennethbwalsh minorcannabinoidsbiosynthesismolecularpharmacologyandpotentialtherapeuticuses AT amandaemckinney minorcannabinoidsbiosynthesismolecularpharmacologyandpotentialtherapeuticuses AT amandaemckinney minorcannabinoidsbiosynthesismolecularpharmacologyandpotentialtherapeuticuses AT andreaeholmes minorcannabinoidsbiosynthesismolecularpharmacologyandpotentialtherapeuticuses AT andreaeholmes minorcannabinoidsbiosynthesismolecularpharmacologyandpotentialtherapeuticuses
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Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

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