Antidepressant‐like effects of cannabidiol in mice: possible involvement of 5‐HT1Areceptors
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BACKGROUND AND PURPOSE: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT(1A) receptors. As 5-HT(1A) receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF). EXPERIMENTAL APPROACH: Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg*kg(-1)), imipramine (30 mg*kg(-1)) or vehicle and were submitted to the forced swimming test or to an open field arena, 30 min later. An additional group received WAY100635 (0.1 mg*kg(-1), i.p.), a 5-HT(1A) receptor antagonist, before CBD (30 mg*kg(-1)) and assessment by the forced swimming test. BDNF protein levels were measured in the hippocampus of another group of mice treated with CBD (30 mg*kg(-1)) and submitted to the forced swimming test. KEY RESULTS: CBD (30 mg*kg(-1)) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behaviour in the open field arena. WAY100635 pretreatment blocked CBD-induced effect in the forced swimming test. CBD (30 mg*kg(-1)) treatment did not change hippocampal BDNF levels. CONCLUSION AND IMPLICATIONS: CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT(1A) receptors.
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CBD has antidepressant-like effects observed in the forced swimming stress, Wistar-Kyoto and bulbectomy models.
“These effects could be associated with the antidepressant-like effects of CBD observed in the forced swimming stress, (33, 34), Wistar-Kyoto (35) and bulbectomy models (36).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [33]
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Monoamine involvement in the antidepressant-like effect induced by P2 blockade
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The endocannabinoid system in social anxiety disorder: from pathophysiology to novel therapeutics
Ahmed, M., Boileau, I., Le Foll, B., Carvalho, A. F., & Kloiber, S. (2022) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2021-1926 · Cited by 11 · see citing works
- Authors
- Zanelati, T., Biojone, C., Moreira, F., Guimarães, F., & Joca, S.
- Affiliations
- Universidade de São Paulo (BR)
- ORCID
- Biojone, C
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2010-01
- Volume
- 159
- Issue
- 1
- Pages
- 122-128
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2823358
- OpenAlex
- W1497893548
- Cited by
- 366
- References
- 69
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 28 · 2023: 34 · 2022: 36 · 2021: 47 · 2020: 22 · 2019: 22 · 2018: 26 · 2017: 16 · 2016: 15 · 2015: 19 · 2014: 5 · 2013: 14 · 2012: 18
- FWCI
- 10.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Keywords
- cannabidiol, antidepressant-like effects, 5-HT1A receptor, forced swim test, imipramine, WAY-100635, brain-derived neurotrophic factor, hippocampus, anxiolytic effects, antipsychotic effects, Cannabis sativa
- MeSH terms
- Animals, Antidepressive Agents, Cannabidiol, Cannabis, Depression, Disease Models, Animal, Dose-Response Relationship, Drug, Hippocampus, Imipramine, Male, Piperazines, Pyridines, Swimming, Brain-Derived Neurotrophic Factor, Receptor, Serotonin, 5-HT1A, Mice
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