Antidepressant‐like effects of cannabidiol in mice: possible involvement of 5‐HT _1A receptors

Background and purpose:  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‐HT_1A receptors. As 5‐HT_1A 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‐HT_1A receptors and on hippocampal expression of brain‐derived neurotrophic factor (BDNF).

Experimental approach:  Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg·kg⁻¹), imipramine (30 mg·kg⁻¹) or vehicle and were submitted to the forced swimming test or to an open field arena, 30 min later. An additional group received WAY100635 (0.1 mg·kg⁻¹, i.p.), a 5‐HT_1A receptor antagonist, before CBD (30 mg·kg⁻¹) and assessment by the forced swimming test. BDNF protein levels were measured in the hippocampus of another group of mice treated with CBD (30 mg·kg⁻¹) and submitted to the forced swimming test.

Key results:  CBD (30 mg·kg⁻¹) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behaviour in the open field arena. WAY100635 pretreatment blocked CBD‐induced effect in the forced swimming test. CBD (30 mg·kg⁻¹) treatment did not change hippocampal BDNF levels.

Conclusion and implications:  CBD induces antidepressant‐like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5‐HT_1A receptors.