Anxiolytic and antidepressant effects of the essential oil of Moroccan Cannabis sativa in mice exposed to unpredictable chronic mild stress: Behavioral and biochemical evidences

Abstract

• Chronic treatment with Cannabis sativa effectively reversed the behavioral changes induced by chronic unpredictable mild stress. • Anxiolytic and antidepressant effects of the essential oil of Cannabis sativa . • Cannabis sativa essential oil also significantly reduced lipid peroxidation and nitrite levels, increased levels of glutathione , superoxide dismutase , and catalase activities. Cannabis sativa L. is an annual plant from the Cannabaceae family. In Morocco, it has a long-standing traditional use as a sedative and in the treatment of various neurological disorders. This study aimed to investigate the anxiolytic and antidepressant effects of Cannabis sativa essential oil (CSEO) in a mouse model of depression induced by unpredictable chronic stress. Mice were exposed to various stress paradigms to induce depression-like behaviors and were subjected to the Unpredictable Chronic Mild Stress (UCMS) protocol for 30 days. The mice received intraperitoneal doses of 2.5, 5, and 10 mg/kg body weight of CSEO daily. Anhedonia, a key symptom of depression, was assessed using a sucrose preference test, while anxiety and depression-related behaviors were evaluated. Additionally, the oxidative parameters of CSEO, including lipid peroxidation , glutathione peroxidase activity, and catalase , were measured. Results demonstrated that chronic administration of CSEO at 2.5, 5, and 10 mg/kg, effectively reversed the behavioral changes induced by UCMS. CSEO reduced the immobility period and increased sucrose preference in stressed mice, indicating an improvement in depressive symptoms. Moreover, CSEO administration positively impacted the biochemical changes associated with chronic stress, including reduced lipid peroxidation and increased levels of glutathione , superoxide dismutase , and catalase activities.