The Immunomodulating Effects of THC and CBD in the Context of Inflammation and Infection: Data

The therapeutic potential of cannabinoid-based medicines has led many U.S. states and countries to authorize their clinical use. Delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), the biologically active compounds of cannabis, possess a wide range of immune regulatory properties. Macrophages are specialized immune cells that express endocannabinoid receptors which can affect inflammatory phenotypes and phagocytosis. Increasing prevalence, and legalization of cannabis, has led to regulatory findings of various aspects of physiological, behavioral, and metabolic function; however, the effects on immunological regulation in the setting of infection is less well understood. The purpose of the current study was to test the immunoregulatory effects of various THC and CBD doses in the context of infection. Secondary, THC and CBD temporal and tissue-specific cytotoxic effects were evaluated at 2 or 6 h. Macrophages were pre-treated with THC or CBD (0, 2, 5, 10, 15, 25 µg/mL) and challenged with LPS (2 h) or live Escherichia coli (E. coli) (6 h). Extracellular bacteria were eliminated, macrophage cells lysed, and intracellular bacteria quantified. Unlike CBD, THC-induced phagocytosis was significantly decreased in a dose-dependent manner. CBD-induced phagocytosis was inversely increased at 25 µg/mL. In macrophages, THC increased cytotoxicity and CBD decreased cytotoxicity at doses 15 µg/mL and greater. These findings demonstrate the multifaceted interplay between THC and CBD that affect the immunological interaction between host and microbes. Taken together, it is necessary to understand the immunoregulatory underpinnings of phytocannabinoids to maximize therapeutic potential and reduce opportunistic infections.

基于大麻素的药物治疗潜力已促使美国多州及全球多国批准其临床应用。Δ-9-四氢大麻酚（Delta-9 tetrahydrocannabinol, THC）与大麻二酚（cannabidiol, CBD）作为大麻的生物活性成分，具备广泛的免疫调节特性。巨噬细胞是一类特化免疫细胞，可表达内源性大麻素受体，该受体能够调控炎症表型与吞噬功能。随着大麻流行率攀升及合法化进程推进，学界已针对其生理、行为及代谢功能的多方面开展监管相关研究；然而其在感染状态下对免疫调节的作用仍尚未被充分阐明。本研究的核心目的为探究不同剂量THC与CBD在感染状态下的免疫调节效应；次要研究目标为在2小时或6小时的时间节点下，评估THC与CBD的时间依赖性及组织特异性细胞毒性作用。研究人员将巨噬细胞经不同浓度THC或CBD（0、2、5、10、15、25 µg/mL）预处理后，分别用脂多糖（LPS）刺激2小时，或用活大肠杆菌（Escherichia coli, E. coli）刺激6小时。去除胞外细菌后裂解巨噬细胞，对胞内细菌进行定量检测。与CBD不同，THC可呈剂量依赖性显著抑制吞噬功能；而在浓度为25 µg/mL时，CBD则可反向提升吞噬功能。在巨噬细胞中，当剂量达到15 µg/mL及以上时，THC会增强细胞毒性，而CBD则会降低细胞毒性。上述研究结果揭示了THC与CBD之间复杂的相互调控关系，该关系可影响宿主与微生物间的免疫相互作用。综上，为最大化植物大麻素的治疗潜力并降低机会性感染风险，阐明其免疫调节的内在机制具有重要意义。