Cited by 475Cannabis and Cannabinoid ResearchMedicinal Plant Extracts EffectsPsychedelics and Drug Studies

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Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

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Campos, Alline Cristina, Moreira, Fabricio Araújo, Gomes, Felipe Villela, Del Bel, Elaine Aparecida, Guimarães, Francisco Silveira·2012·Philosophical Transactions of the Royal Society B: Biological Sciences

DOI 10.1098/rstb.2011.0389PMC PMC3481531

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Abstract

Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound Δ(9)-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARγ receptors agonism, intracellular (Ca(2+)) increase, etc.), on CBD behavioural effects.

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Authors: Campos, A. C., Moreira, F. A., Gomes, F. V., Del Bel, E. A., & Guimarães, F. S.
Affiliations: Universidade Federal de Minas Gerais (BR)
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Avenue Antonio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil
Universidade de São Paulo (BR)
Faculty of Odontology of Ribeirão Preto, Department of Morphology, Physiology and Stomatology, University of São Paulo, Avenue Café s/n, 14040-904, Ribeirão Preto, São Paulo, Brazil
ORCID: Campos, Alline Cristina
Guimarães, Francisco Silveira
Venue: Philosophical Transactions of the Royal Society B: Biological Sciences
Publisher: The Royal Society
Published: 2012-12-05
Volume: 367
Issue: 1607
Pages: 3364-3378
ISSN: 0962-8436 (ISSN-L)
1471-2970
DOI: 10.1098/rstb.2011.0389
PMC: PMC3481531
OpenAlex: W2108265345
Cited by: 475
References: 135
Citations by year: 2026: 21 · 2025: 27 · 2024: 42 · 2023: 39 · 2022: 53 · 2021: 51 · 2020: 50 · 2019: 39 · 2018: 36 · 2017: 35 · 2016: 33 · 2015: 24 · 2014: 15 · 2013: 6 · 2012: 2
FWCI: 1.72
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: royalsociety.org/journals/ethics-policies/data-sharing-mining/ (tdm)
Locations: Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Keywords: cannabidiol, phytocannabinoids, anxiety, depression, psychosis, anxiolytic effects, antidepressant-like effects, 5-HT1A receptor, bed nucleus of the stria terminalis, medial prefrontal cortex, anandamide, TRPV1 channel, antipsychotic effects, bell-shaped dose-response, extinction, memory reconsolidation, adult hippocampal neurogenesis, CB1 receptor antagonism, CB2 receptor, GPR55, PPARγ
MeSH terms: Animals, Antidepressive Agents, Anxiety Disorders, Arachidonic Acids, Cannabidiol, Clinical Trials as Topic, Depression, Dose-Response Relationship, Drug, Humans, Phytotherapy, Synaptic Transmission, Psychotic Disorders, Anti-Anxiety Agents, Receptor, Cannabinoid, CB1, Receptor, Serotonin, 5-HT1A, TRPV Cation Channels, Polyunsaturated Alkamides, Neurogenesis, Endocannabinoids

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Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

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