New insights into the involvement of serotonin and BDNF-TrkB signalling in cannabidiol's antidepressant effect.
Prog Neuropsychopharmacol Biol Psychiatry
; 133: 111029, 2024 Jul 13.
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cannabidiol
/
Signal Transduction
/
Serotonin
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Brain-Derived Neurotrophic Factor
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Receptor, trkB
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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