Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms

Trends in use, pharmacology, and clinical applications of emerging herbal nutraceuticals

“…CBD has anxiolytic effects-possibly via 5-HT 1A receptor activation-and facilitates the extinction of contextual fear memory-perhaps via indirect activation of CB 1 receptors-in rodents (Lee, Bertoglio, Guimarães, & Stevenson, 2017). Also, CBD modulates several targets involved in the neurobiology of depression, although the involvement of the serotonergic neurotransmission in the antidepressant-like effects of CBD represents the best investigated neurochemical mechanism (Silote et al, 2019). Finally, CBD strongly decreases mesolimbic dopaminergic activity and exerts effects on schizophreniarelated molecular signalling pathways that are distinct from those associated with more traditional anti-psychotic drugs (Renard, Norris, Rushlow, & Laviolette, 2017).…”

“…CBD was initially shown to be non‐euphoric, with the suggestion that it was an inactive compound (Crippa et al, ). However, later studies denied this assumption, and several investigations demonstrated that CBD causes multiple effects in the CNS (Silote et al, ). CBD exerts behavioural effects in animals predictive of anxiolytic, antipsychotic and antidepressant effects in humans (Rong et al, ).…”

Orphan G Protein Coupled Receptors in Affective Disorders

“…GPR3 is among the several GPCRs modulated by cannabidiol (CBD), which acts on GPR3 as an inverse agonist [ 134 ]. Within the last ten years, research on CBD has revealed that both acute and chronic CBD administration elicits antidepressant and anxiolytic effects in rodents [ 135 ]. Research aimed at testing the hypothesis that GPR3 mediates at least part of the antidepressant effects attributed to CBD has not yet been performed.…”

The Pro-neurogenic Effects of Cannabidiol and Its Potential Therapeutic Implications in Psychiatric Disorders

“…Consequently, CBD is an efficient anxiolytic (Fogaça et al, 2018 ) and there is evidence suggesting that it possesses anti-inflammatory (Atalay et al, 2019 ), neuroprotective (Campos et al, 2016 ), antidepressant (Sales et al, 2019 ), anti-relapse (Gonzalez-Cuevas et al, 2018 ), pro-cognitive (Osborne et al, 2017 ) and antipsychotic (Renard et al, 2017 ) effects. Accordingly, CBD has been proposed as a novel therapeutic strategy for different mental disorders such as drug addiction (Calpe-López et al, 2019 ), depression (Silote et al, 2019 ), or schizophrenia (Elsaid and Le Foll, 2020 ). Notwithstanding the foregoing, CBD has a formidably complex pharmacology, and therefore, we lack a clear understanding of the molecular and neuroplastic consequences of CBD treatments.…”