The nonpsychoactive cannabinoid cannabidiol inhibits 5-hydroxytryptamine3A receptor-mediated currents in Xenopus laevis oocytes

J Pharmacol Exp Ther. 2010 May;333(2):547-54. doi: 10.1124/jpet.109.162594. Epub 2010 Feb 16.


The effect of the plant-derived nonpsychotropic cannabinoid, cannabidiol (CBD), on the function of hydroxytryptamine (5-HT)3A receptors expressed in Xenopus laevis oocytes was investigated using two-electrode voltage-clamp techniques. CBD reversibly inhibited 5-HT (1 microM)-evoked currents in a concentration-dependent manner (IC50 = 0.6 microM). CBD (1 microM) did not alter specific binding of the 5-HT3A antagonist [3H]3-(5-methyl-1H-imidazol-4-yl)-1-(1-methylindol-3-yl)propan-1-one (GR65630), in oocytes expressing 5-HT3A receptors. In the presence of 1 microM CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 microM, in the absence and presence of CBD, indicating that CBD acts as a noncompetitive antagonist of 5-HT3 receptors. Neither intracellular BAPTA injection nor pertussis toxin pretreatment (5 microg/ml) altered the CBD-evoked inhibition of 5-HT-induced currents. CBD inhibition was inversely correlated with 5-HT3A expression levels and mean 5-HT3 receptor current density. Pretreatment with actinomycin D, which inhibits protein transcription, decreased the mean 5-HT3 receptor current density and increased the magnitude of CBD inhibition. These data demonstrate that CBD is an allosteric inhibitor of 5-HT3 receptors expressed in X. laevis oocytes. They further suggest that allosteric inhibition of 5-HT3 receptors by CBD may contribute to its physiological roles in the modulation of nociception and emesis.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Binding, Competitive / drug effects
  • Cannabidiol / pharmacology*
  • Dose-Response Relationship, Drug
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Female
  • GTP-Binding Proteins / drug effects
  • GTP-Binding Proteins / physiology
  • Imidazoles / pharmacology
  • Indoles / pharmacology
  • Membrane Potentials / drug effects*
  • Membrane Potentials / physiology
  • Oocytes / drug effects*
  • Oocytes / physiology
  • Pertussis Toxin / pharmacology
  • Receptors, Serotonin, 5-HT3 / biosynthesis
  • Receptors, Serotonin, 5-HT3 / drug effects
  • Serotonin / pharmacology
  • Serotonin 5-HT3 Receptor Antagonists*
  • Signal Transduction / drug effects
  • Xenopus laevis


  • Imidazoles
  • Indoles
  • Receptors, Serotonin, 5-HT3
  • Serotonin 5-HT3 Receptor Antagonists
  • GR 65630
  • Cannabidiol
  • Serotonin
  • Egtazic Acid
  • Pertussis Toxin
  • GTP-Binding Proteins
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid