Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders
Open accessAbstract
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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The anti-inflammatory action of CBD could be related to its antipsychotic properties.
“This result suggests that the anti-inflammatory action of CBD (see (30), for a review), could be related to its antipsychotic properties and is consonant with recent findings that anti-inflammatory drugs such as minocycline could be useful in the treatment of schizophrenia (74).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [30]
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Self-citationTargeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors
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The Pharmacological Basis of Cannabis Therapy for Epilepsy
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Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
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Development of a Novel Nanoemulsion Formulation to Improve Intestinal Absorption of Cannabidiol
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Snapshot of the cannabinoid receptor 1-arrestin complex unravels the biased signaling mechanism
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Self-citationMolecular Targets of Cannabidiol in Experimental Models of Neurological Disease
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Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?
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A User’s Guide to Cannabinoid Therapies in Oncology
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Self-citationEffects of cannabidiol in males and females in two different rat models of depression
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Psychiatric Disorders and TRP Channels: Focus on Psychotropic Drugs
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Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid
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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
- 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
- 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
- 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 › 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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