Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors

 “Extracts of the Cannabis sativa plant elicit in humans a complex subjective experience that includes euphoria, heightened sensitivity to external stimuli and relaxation. This plant contains more than 400 different compounds, of which 66 are termed cannabinoids. Δ9-tetrahydrocannabinol (Δ9-THC), one of the major constituents of C. sativa extracts is thought to account for most of the effects of cannabis through the activation of cannabinoid CB1 receptors in the brain….The major endogenous agonists of the CB1 receptor are anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids…”

“It has recently been suggested that the endocannabinoid system may be involved in the pathophysiology of depression. This is supported by several pieces of evidence showing that endocannabinoids and CB1 receptors are widely distributed in brain areas that are often related to affective disorders and that their expression is regulated by antidepressant drugs. Moreover, administration of inhibitors of anandamide uptake or metabolism, as well as CB1 receptor agonists induces antidepressant-like effects in different animal models. In accordance with these preclinical results, many patients report benefits from cannabis use in depressive syndromes…”

“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT1A receptors. As 5-HT1A receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT1A receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF).”

“Conclusion and implications:

CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT1A receptors.”

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