Cannabichromene Showed Antidepressant Effects Comparable to Imipramine in Stressed Mice

CBC at 20 mg/kg significantly reduced immobility in stressed mice (comparable to imipramine 15 mg/kg) without affecting locomotor activity. Both CBC and imipramine reduced elevated plasma nitrite and corticosterone and inhibited brain monoamine oxidase-A. In silico modeling showed CBC had stronger CB2 receptor binding (docking score: -9.4) than CBD (-8.8) or THC (-9.1).

Male Swiss albino mice underwent 3 weeks of chronic unpredictable mild stress. CBC (10 and 20 mg/kg) and imipramine (15 mg/kg) administered for 21 days. Behavioral testing (forced swim, locomotor activity), plasma biochemistry (nitrite, corticosterone), and brain enzyme assays (MAO-A, catalase) performed. In silico target prediction and molecular docking complemented in vivo findings.

CBC is one of the least-studied major cannabinoids. Finding antidepressant activity comparable to a standard antidepressant, mediated through CB2 receptors rather than the psychoactive CB1 pathway, opens a potential avenue for non-psychoactive cannabinoid-based treatments for depression.

Depression treatment needs new approaches: current antidepressants fail 30-40% of patients. CBC offers a non-psychoactive cannabinoid alternative working through a novel mechanism (CB2 receptors and MAO-A inhibition). However, this is a single mouse study and must be validated in multiple models before clinical translation.

Single mouse strain (Swiss albino males only). CUMS model does not fully replicate human depression. In silico CB2 binding prediction needs experimental confirmation. 21-day treatment may not reflect chronic use effects. Dose-response showed efficacy only at 20 mg/kg, not 10 mg/kg.