Cannabidiol (CBD) is a non-psychotomimetic compound derived from Cannabis sativa. Preclinical and clinical studies have shown therapeutic potential of CBD in a variety of disorders. Despite several research efforts on CBD, its antidepressant activity has been poorly investigated and the exact mechanism of action remains unclear. Thus, this study aimed to further explore the mechanism of CBD after chronic administration (7 days). First, the dose level of CBD that is enough to produce antidepressant effects after chronic administration was explored. Second, the changes in key proteins and neurotransmitters through such methods as real-time polymerase chain reaction (RT-PCR), western blotting, and high-performance liquid chromatography-electrochemical detection (HPLC-ECD) were critically studied. Furthermore, correlation between behavioral phenotypes with protein and neurotransmitters was established and the possible mechanism was herein postulated. The results showed that only the high dose CBD 100 mg/kg chronic administration induced antidepressant-like effects in mice subjected to forced swim test. Chronic CBD 100 mg/kg administration resulted in significant increases in serotonin (5-HT) and noradrenaline (NA) levels in the hippocampus (HPC). Similarly, the chronic administration of CBD 30 mg/kg and CBD 100 mg/kg significantly decreased nuclear factor kappa B (NF-κB) expression in the HPC. Moreover, none of the treatments were observed to induce locomotor effects. Thus, we concluded that chronic administration of CBD (100 mg/kg) induced antidepressant-like effects by increasing 5-HT and NA levels in the HPC. These results shed new light on further discovery of the antidepressant effect of CBD.

大麻二酚（CBD）是一种源自大麻的非拟精神病化合物。临床前和临床研究表明，CBD在多种疾病中具有治疗潜力。尽管对CBD进行了数项研究，但其抗抑郁活性的研究仍很少，确切的作用机理仍不清楚。因此，本研究旨在进一步探索慢性给药（7天）后CBD的机制。首先，研究了在长期给药后足以产生抗抑郁作用的CBD剂量水平。其次，通过实时聚合酶链反应（RT-PCR），蛋白质印迹和高效液相色谱-电化学检测（HPLC-ECD）等方法对关键蛋白和神经递质的变化进行了严格研究。此外，建立了蛋白质与神经递质的行为表型之间的相关性，并在此推测了可能的机制。结果表明，仅高剂量的CBD 100 mg / kg慢性给药可在进行强迫游泳试验的小鼠中诱导抗抑郁样作用。慢性CBD 100 mg / kg给药会导致海马（HPC）的血清素（5-HT）和去甲肾上腺素（NA）水平显着增加。同样，长期服用CBD 30 mg / kg和CBD 100 mg / kg会显着降低HPC中核因子κB（NF-κB）的表达。此外，未观察到任何治疗诱导运动作用。因此，我们得出结论，长期服用CBD（100 mg / kg）可通过增加HPC中的5-HT和NA水平来诱导抗抑郁样作用。