Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus

Br J Pharmacol. 2012 Apr;165(8):2620-34. doi: 10.1111/j.1476-5381.2011.01621.x.


Background and purpose: To evaluate the hypothesis that activation of somatodendritic 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis.

Experimental approach: The potential of systemic and intra-DRN administration of 5-HT(1A) receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT(1A) receptors and to modify the ability of the 5-HT(1A) agonist, 8-OH-DPAT, to stimulate [(35) S]GTPγS binding in rat brainstem membranes.

Key results: CBD suppressed nicotine-, lithium chloride (LiCl)- and cisplatin (20 mg·kg(-1) , but not 40 mg·kg(-1) )-induced vomiting in the S. murinus and LiCl-induced conditioned gaping in rats. Anti-emetic and anti-nausea-like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti-nausea-like effects of systemic CBD, and (ii) CBD suppressed nausea-like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell-shaped dose-response curve) at enhancing the ability of 8-OH-DPAT to stimulate [(35) S]GTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8-OH-DPAT synergistically suppressed LiCl-induced conditioned gaping.

Conclusions and implications: These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT(1A) autoreceptors in the DRN.

Linked articles: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit To view Part I of Cannabinoids in Biology and Medicine visit

Publication types

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

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Antiemetics / therapeutic use*
  • Behavior, Animal / drug effects
  • Cannabidiol / therapeutic use*
  • Cannabis
  • Female
  • Male
  • Nausea / drug therapy
  • Nausea / physiopathology
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Serotonin 5-HT1 Receptor Agonists / pharmacology*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology
  • Shrews
  • Vomiting / drug therapy*
  • Vomiting / physiopathology


  • Antiemetics
  • Piperazines
  • Pyridines
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Receptor, Serotonin, 5-HT1A
  • WAY 100135
  • Cannabidiol
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin