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New insights into the involvement of serotonin and BDNF-TrkB signalling in cannabidiol's antidepressant effect.
Guldager, Matti Bock; Biojone, Caroline; da Silva, Nicole Rodrigues; Godoy, Livea Dornela; Joca, Sâmia.
Affiliation
  • Guldager MB; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Biojone C; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • da Silva NR; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Godoy LD; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil.
  • Joca S; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: sjoca@biomed.au.dk.
Article in En | MEDLINE | ID: mdl-38762160
ABSTRACT
Cannabidiol (CBD) is a phytocannabinoid devoid of psychostimulant properties and is currently under investigation as a potential antidepressant drug. However, the mechanisms underlying CBD's antidepressant effects are not yet well understood. CBD targets include a variety of receptors, enzymes, and transporters, with different binding-affinities. Neurochemical and pharmacological evidence indicates that both serotonin and BDNF-TrkB signalling in the prefrontal cortex are necessary for the antidepressant effects induced by CBD in animal models. Herein, we reviewed the current literature to dissect if these are independent mechanisms or if CBD-induced modulation of the serotonergic neurotransmission could mediate its neuroplastic effects through subsequent regulation of BDNF-TrkB signalling, thus culminating in rapid neuroplastic changes. It is hypothesized that a) CBD interaction with serotonin receptors on neurons of the dorsal raphe nuclei and the resulting disinhibition of serotonergic neurons would promote rapid serotonin release in the PFC and hence its neuroplastic and antidepressant effects; b) CBD facilitates BDNF-TRKB signalling, especially in the PFC, which rapidly triggers neurochemical and neuroplastic effects. These hypotheses are discussed with perspectives for new drug development and clinical applications.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cannabidiol / Signal Transduction / Serotonin / Brain-Derived Neurotrophic Factor / Receptor, trkB / Antidepressive Agents Limits: Animals / Humans Language: En Journal: Prog Neuropsychopharmacol Biol Psychiatry Year: 2024 Document type: Article Affiliation country: Dinamarca Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cannabidiol / Signal Transduction / Serotonin / Brain-Derived Neurotrophic Factor / Receptor, trkB / Antidepressive Agents Limits: Animals / Humans Language: En Journal: Prog Neuropsychopharmacol Biol Psychiatry Year: 2024 Document type: Article Affiliation country: Dinamarca Country of publication: Reino Unido