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Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.
Philos Trans R Soc Lond B Biol Sci. 2012 Dec 05; 367(1607):3364-78.PT

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.

Authors+Show Affiliations

Group of Neuroimmunology, Laboratory of Immunopharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23108553

Citation

Campos, Alline Cristina, et al. "Multiple Mechanisms Involved in the Large-spectrum Therapeutic Potential of Cannabidiol in Psychiatric Disorders." Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, vol. 367, no. 1607, 2012, pp. 3364-78.
Campos AC, Moreira FA, Gomes FV, et al. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci. 2012;367(1607):3364-78.
Campos, A. C., Moreira, F. A., Gomes, F. V., Del Bel, E. A., & Guimarães, F. S. (2012). Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 367(1607), 3364-78. https://doi.org/10.1098/rstb.2011.0389
Campos AC, et al. Multiple Mechanisms Involved in the Large-spectrum Therapeutic Potential of Cannabidiol in Psychiatric Disorders. Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3364-78. PubMed PMID: 23108553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. AU - Campos,Alline Cristina, AU - Moreira,Fabricio Araújo, AU - Gomes,Felipe Villela, AU - Del Bel,Elaine Aparecida, AU - Guimarães,Francisco Silveira, PY - 2012/10/31/entrez PY - 2012/10/31/pubmed PY - 2013/4/9/medline SP - 3364 EP - 78 JF - Philosophical transactions of the Royal Society of London. Series B, Biological sciences JO - Philos Trans R Soc Lond B Biol Sci VL - 367 IS - 1607 N2 - 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. SN - 1471-2970 UR - https://www.unboundmedicine.com/medline/citation/23108553/Multiple_mechanisms_involved_in_the_large_spectrum_therapeutic_potential_of_cannabidiol_in_psychiatric_disorders_ L2 - https://royalsocietypublishing.org/doi/10.1098/rstb.2011.0389?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -