Evidence that the plant cannabinoid cannabigerol is a highly potent α2‐adrenoceptor agonist and moderately potent 5HT1A receptor antagonist
Open Access
- 19 January 2010
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 159 (1), 129-141
- https://doi.org/10.1111/j.1476-5381.2009.00515.x
Abstract
Background and purpose: Cannabis is the source of at least seventy phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. Experimental approach: The [35S]GTPγS binding assay, performed with mouse brain membranes, was used to test the ability of cannabigerol to produce G protein-coupled receptor activation or blockade. Its ability to displace [3H]CP55940 from mouse CB1 and human CB2 cannabinoid receptors and to inhibit electrically evoked contractions of the mouse isolated vas deferens was also investigated. Key results: In the brain membrane experiments, cannabigerol behaved as a potent α2-adrenoceptor agonist (EC50= 0.2 nM) and antagonized the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent KB= 51.9 nM). At 10 µM, it also behaved as a CB1 receptor competitive antagonist. Additionally, cannabigerol inhibited evoked contractions of the vas deferens in a manner that appeared to be α2-adrenoceptor-mediated (EC50= 72.8 nM) and displayed significant affinity for mouse CB1 and human CB2 receptors. Conclusions and implications: This investigation has provided the first evidence that cannabigerol can activate α2-adrenoceptors, bind to cannabinoid CB1 and CB2 receptors and block CB1 and 5-HT1A receptors. It will now be important to investigate why cannabigerol produced signs of agonism more potently in the [35S]GTPγS binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain.This publication has 36 references indexed in Scilit:
- α2‐Agonists as analgesic agentsMedicinal Research Reviews, 2008
- Guide to Receptors and Channels (GRAC), 3rd editionBritish Journal of Pharmacology, 2008
- The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarinBritish Journal of Pharmacology, 2008
- Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitroBritish Journal of Pharmacology, 2007
- Chemical constituents of marijuana: The complex mixture of natural cannabinoidsLife Sciences, 2005
- Plant cannabinoids: a neglected pharmacological treasure troveBritish Journal of Pharmacology, 2005
- Evidence that (−)-7-hydroxy-4′-dimethylheptyl-cannabidiol activates a non-CB1, non-CB2, non-TRPV1 target in the mouse vas deferensNeuropharmacology, 2005
- Clonidine - a potent analgesic adjuvantCurrent Opinion in Anaesthesiology, 2002
- pA2 and receptor differentiation: A statistical analysis of competitive antagonismLife Sciences, 1979
- Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reactionBiochemical Pharmacology, 1973