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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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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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“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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Metadata
- 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
- PMC
- PMC3423241
- 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
- bronze
- doi.org
- 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 (medical) › 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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