Evidence that the plant cannabinoid cannabigerol is a highly potent α2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist

Maria Grazia Cascio, Lisa Anne Gauson, Lesley Ann Stevenson, Ruth Alexandra Ross, Roger Guy Pertwee

Research output: Contribution to journalArticle

85 Citations (Scopus)

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 Delta(9)-tetrahydrocannabinol, cannabidiol and Delta(9)-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 [S-35]GTP gamma S 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 [H-3]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 alpha(2)-adrenoceptor agonist (EC50 = 0.2 nM) and antagonized the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent K-B = 51.9 nM). At 10 mu M, 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 alpha(2)-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 alpha(2)-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 [S-35]GTP gamma S binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain. British Journal of Pharmacology (2010) 159, 129-141; doi:10.1111/j.1476-5381.2009.00515.x; published online 4 December 2009

Original languageEnglish
Pages (from-to)129-141
Number of pages13
JournalBritish Journal of Pharmacology
Volume159
Issue number1
Early online date4 Dec 2009
DOIs
Publication statusPublished - Jan 2010

Keywords

  • cannabigerol
  • CP55940
  • mouse vas deferens
  • alpha(2)-adrenoceptor
  • 5-HT1A receptor
  • CB1 receptor
  • clonidine
  • dexmedetomidine
  • maprotiline
  • R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin
  • mouse vas-deferens
  • pharmacological profile
  • CB1
  • noradrenaline
  • hashish
  • release
  • Delta(9)-tetrahydrocannabivarin
  • adrenoceptors
  • constituents
  • cannabidiol
  • cannabigerol
  • CP55940
  • mouse vas deferens
  • a2-adrenoceptor
  • 5-HT1A receptor
  • CB1 receptor
  • clonidine
  • maprotiline

Impacts

Cannabis as a source of medicines

Roger Pertwee (Coordinator), P Consroe (Coordinator), R Musty (Coordinator) & David Baker (Coordinator)

Impact: Quality of life Impacts

Cite this