| Summary: | 碩士 === 國立臺灣大學 === 獸醫學研究所 === 93 === Marijuana is one of the commonly abused drugs worldwide. The primary active components of marijuana are cannabinoids, such as Δ9-tetrahydrocannabinol (THC) which is psychoactive. In contrast to THC, cannabidiol (CBD) is another abundant cannabinoid that is nonpsychroactive. A line of evidence indicates that THC exhibits profound immunomodulatory activities in a variety of in vivo and in vitro experimental systems. Recently, a number of pharmacological activities possessed by CBD have been reported, including anticonvulsive, anxiolytic, antipsychotic, neuroprotective, antinausea and antirheumatoid effects. Thus, the potential pharmacological application and toxicity of CBD deserve further investigation. In light of the widely demonstrated immunomodulatory properties of cannabinoid compounds, the objective of the present studies was to investigate the effects of CBD on the immune system.
The results demonstrated that administration of ovalbumin (Ova)-immunized BALB/c mice with single dose of CBD (5-20 mg/kg) markedly suppressed the serum concentrations of Ova-specific immunoglobulins in a dose dependent manner. Five consecutive daily injections of mice with the high dose of CBD (20 mg/kg) also produced the same inhibitory effect, whereas low dose of CBD (5 mg/kg) did not. To elucidate the possible underlying mechanisms by which CBD suppressed antibody production, the effects of CBD on cytokine secretion, proliferation and metabolic activity of splenocytes were examined. Both in vivo and in vitro treatment of splenocytes with CBD significantly inhibited IL-2, IL-4 and IFN-γ secretion, concanavalin A-induced proliferation, and metabolic activity of splenocytes. However, the expression of cytokine mRNA was not influenced by CBD treatment, suggesting that CBD-induced inhibition of cytokine secretion is not mediated directly by the suppression of cytokine gene expression. As splenocyte proliferation and metabolic activity were suppressed by CBD, the present studies investigated whether CBD could induce apoptosis of splenocytes. The results of flow cytometric analysis demonstrated that CBD increased the population of splenocytes that were double positive with annexin V and propidium iodide, indicating the induction of late apoptotic responses of cells by CBD. Furthermore, typical DNA laddering was observed in splenocytes treated with CBD. Further mechanistic studies showed the increased mRNA expression of bak and bax in CBD-treated splenocytes. Collectively, results of the present studies demonstrated the immunotoxicity of CBD in vivo and in vitro. CBD suppressed the antibody production by Ova-immunized mice, that is mediated, at least in part, by the inhibition of T-cell functions.
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