Journal of Cannabis Therapeutics

Journal of Cannabis Therapeutics

[IACM Homepage] [Table of contents] [Article 2002-01]

[Full Text in PDF]

Journal of Cannabis Therapeutics


Origin of Cannabinoid Receptors

Sourcing the Code: Searching for the Evolutionary Origins of Cannabinoid Receptors, Vanilloid Receptors, and Anandamide

John M. McPartland, Patty Pruitt

Abstract

Two cannabinoid (CB) receptors are known in humans, CB1 and CB2. They are phylogenetically ancient. Studies suggest CB receptors occur in mammals, birds, amphibians, fish, sea urchins, mollusks, leeches, and Hydra vulgaris. The CB receptor genes from some of these animals have been cloned and sequenced. These sequences were used to construct a phylogenetic tree of CB genes. The gene tree is rooted in an ancestral CB gene that predates the divergence of vertebrates and invertebrates. Thus the primordial CB receptor evolved at least 600 million years ago, a date broadly consistent with the Cambrian explosion.

Since then, one clade of invertebrates, the Ecdysozoa, has secondarily lost the genes coding CB receptors. There is no evidence that animals obtained CB genes from other organisms via horizontal gene transfer. We hypothesize that the primordial CB receptor diverged from a related G-protein coupled receptor, and it linked with a pre-existing ligand, anandamide. Anandamide serves as a ligand for CB receptors as well as vanilloid (VR) receptors. VR receptors regulate the sensation of pain, and may also modulate mood and memory. Our phylogenetic analysis suggests that VR receptors evolved before CB receptors, so anandamide first served as a VR ligand. We speculate that CB receptors, lacking se- lective constraints, subsequently acquired a mutation that coupled them with 2-AG. A better understanding of CB and VR receptors man enable us to combine their beneficial effects. Dual-signaling ligands such as anandamide have excellent therapeutic potential as analgesics, vasodilators, and anti-cancer agents.

Keywords. Cannabis, cannabinoids, vanilloids, G-protein coupled receptors, anandamide, horizontal gene transfer


[Full Text in PDF]

[IACM Homepage] [Table of contents] [Article 2002-01]

Webinars 2020

In October 2020 the IACM is organising a webinar series. Among the speakers are Roger Pertwee, Raphael Mechulam, Manuel Guzman, Ethan Russo and Kirsten Müller-Vahl. There will be subtitles for several languages after the webinars. Access is free for regular memebers of the IACM. Please find here the brochure for sponsors

IACM Conference 2020

The IACM will hold its 11th Conference on Cannabinoids in Medicine in collaboration with the Asociación Mexicana de Medicina Cannabinodie from 5 to 7 November 2020 in Mexico City. It will be a virtual congress

IACM Conference 2021

The 12th IACM Conference on Cannabinoids in Medicine will be held in Basel, Switzerland, from 14 to 16 October 2021.

Members only

Regular members can sign up for the new member area of the IACM to access exclusive content.

You need to become a regular member of the IACM to access the new member area.

IACM on Twitter

Follow us on twitter @IACM_Bulletin where you can send us inquiries and receive updates on research studies and news articles.