〔Abstract〕 Objective To study the rapid antidepressant effects of cannabioiol(CBD) on depression-like mice and its possible mechanism. Methods Chronic restraint was used to establish a mouse depression model. The test mice were divided into 5 groups: normal control group, model group, positive control group, CBD low-dose group (25 mg/kg) and CBD high-dose group(50 mg/kg). The mice in each group were given intragastric administration one hour before the behavioral experiment. After the behavioral experiment, the hippocampus and prefrontal cortex specimens were collected, and brain-derived neurotrophic factor(BDNF), postsynaptic density protein 95(PSD-95), synaptophysin(SYP) and target of rapamycin(mTOR) were tested by ELISA.Results Compared with the model group, the central area activity distance percentage, the central area activity time percentage and total distance increased in the open field experiment in the CBD low-dose group. Compared with the model group, the percentage of immobility in the forced swimming experiment in the low-dose CBD group decreased. The ELISA test results showed that CBD could rapidly increase the concentration of BDNF and PSD-95 in the prefrontal cortex, as well as the concentration of SYP and mTOR in the hippocampus and prefrontal cortex.Conclusion CBD can rapidly improve the behavioral performance of depression-like mice, and rapidly up-regulate the level of BDNF and synaptic protein in the hippocampus or prefrontal cortex.