Cited by 255Cannabis and Cannabinoid ResearchNausea and vomiting managementGastrointestinal motility and disorders

Cannabidiol, a non‐psychotropic component of cannabis, attenuates vomiting and nausea‐like behaviour via indirect agonism of 5‐HT1A somatodendritic autoreceptors in the dorsal raphe nucleus

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Rock, EM, Bolognini, D, Limebeer, CL, Cascio, MG, Anavi‐Goffer, S, Fletcher, PJ, Mechoulam, R, Pertwee, RG +1 more·2012·British Journal of Pharmacology

Abstract

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 http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.

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  • For CBD to be fully effective as an anxiolytic, there would need to be basal 5-HT1A-R occupancy.

    “This would mean that for CBD to be fully effective as an anxiolytic there would need to be basal 5-HT1A-R occupancy (Rock et al., 2012).”

    From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Rock et al., 2012

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Research works printed but not linked: 3

  1. Leslie RA, Reynolds DJM (1992). Functional anatomy of the emetic circuitry in the brainstem. In: Bianchi AL, Grelot L, Miller AD, King GL (eds). Mechanisms and Control of Emesis. London: Colloqu INSERM, pp. 19-27.
  2. Paxinos G, Watson C (1986). The Rat Brain in Sterotaxic Coordinates, 2nd edn. Academic Press: New York.
  3. Pertwee RG (2004). The pharmacology and therapeutic potential of cannabidiol. In: Di Marzo V (ed.). Cannabinoids. Kluwer Academic/Plenum Publishers: New York, pp. 32-83.

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Authors
Rock, E., Bolognini, D., Limebeer, C., Cascio, M., Anavi‐Goffer, S., Fletcher, P., Mechoulam, R., Pertwee, R., & Parker, L.
Affiliations
  • University of Guelph (CA)
  • University of Aberdeen (GB)
  • Hebrew University of Jerusalem (IL)
Corresponding author
Parker, LA
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2012-03-23
Volume
165
Issue
8
Pages
2620-2634
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
OpenAlex
W1593785499
Cited by
255
References
74
Citations by year
2026: 10 · 2025: 16 · 2024: 20 · 2023: 24 · 2022: 28 · 2021: 26 · 2020: 27 · 2019: 8 · 2018: 13 · 2017: 18 · 2016: 17 · 2015: 12 · 2014: 9 · 2013: 15 · 2012: 9
FWCI
7.97
Type
journal article
Language
en
Open access
Locations
  • British Journal of Pharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • GW Pharmaceuticals
  • Natural Sciences and Engineering Research Council of Canada
  • National Institute on Drug Abuse (R37DA003672, P01DA009789, DA‐03672, DA 09789, R01DA003672)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Surgery › Nausea and vomiting management
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
cannabidiol, 5-HT1A receptor, somatodendritic autoreceptors, dorsal raphe nucleus, WAY-100635, 8-OH-DPAT, cisplatin-induced vomiting
MeSH terms
Animals, Antiemetics, Behavior, Animal, Cannabidiol, Cannabis, Female, Male, Nausea, Piperazines, Pyridines, Raphe Nuclei, Shrews, Vomiting, Rats, Sprague-Dawley, 8-Hydroxy-2-(di-n-propylamino)tetralin, Receptor, Serotonin, 5-HT1A, Rats, Serotonin 5-HT1 Receptor Agonists, Serotonin 5-HT1 Receptor Antagonists

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