TY - JOUR
T1 - New insights into the involvement of serotonin and BDNF-TrkB signalling in cannabidiol's antidepressant effect
AU - Guldager, Matti Bock
AU - Biojone, Caroline
AU - Rodrigues Da Silva, Nicole
AU - Dornela Godoy, Livea
AU - Joca, Sâmia
PY - 2024/7/13
Y1 - 2024/7/13
N2 - 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.
AB - 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.
KW - Antidepressant
KW - BDNF
KW - Cannabidiol
KW - Neuroplasticity
KW - Serotonin
KW - TrkB
UR - http://www.scopus.com/inward/record.url?scp=85193840059&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2024.111029
DO - 10.1016/j.pnpbp.2024.111029
M3 - Review
C2 - 38762160
SN - 0278-5846
VL - 133
JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry
M1 - 111029
ER -