Yekhtin Zhanna, Petukhov Dmytro, Khuja Iman, Kogan Natalya M, Or Reuven, Almogi-Hazan Osnat
Laboratory of Immunotherapy and Bone Marrow Transplantation, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Molecular Biology, Institute of Personalized and Translational Medicine, Ariel University, Ariel, Israel.
Front Immunol. 2025 Jun 17;16:1605474. doi: 10.3389/fimmu.2025.1605474. eCollection 2025.
B lymphocytes play a crucial role in immunity but also contribute to the pathogenesis of various diseases. Cannabis plants produce numerous biologically active compounds, including cannabinoids. The two most studied phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These cannabinoids exert diverse and potent biological effects primarily through the endocannabinoid system (ECS), which also plays a key role in mature B-cell function. Both the immune system and the ECS undergo age-related changes that lead to a clinically significant decline in function.
This study compares the effects of THC and CBD on B-cell activity in young and aged mice. Murine B lymphocytes were activated using lipopolysaccharide (LPS) and interleukin-4 (IL-4), and the impact of cannabinoid treatments was assessed in terms of cell phenotype, proliferation, antibody secretion, tumor necrosis factor-alpha (TNFα) secretion, extracellular signal-regulated kinase (ERK) phosphorylation, and the cellular metabolome.
Both THC and CBD exhibited dose-dependent inhibitory effects on B-cell activation in young and aged mice. However, we show here, for the first time, that the treatments induce distinct metabolic profiles. Although some metabolites, such as glucose-6-phosphate, pentose phosphate pathway (PPP) and nucleotide metabolites, were reduced by both cannabinoids, THC selectively reduced the levels of a distinct set of amino acids, while only CBD increased the levels of Citrulline and Allantoin. Additionally, the effects of THC and CBD differed between young and aged B cells, suggesting that age-related changes in the ECS may influence cannabinoid sensitivity.
These findings provide insights into the distinct mechanisms by which THC and CBD regulate immune activation and may open the door for investigating the mechanisms behind cannabinoids effects on the immune system. They also highlight the need for further research into phytocannabinoid-based therapies, particularly in age-specific contexts. Given the immunoregulatory properties of cannabinoids, especially CBD, tailored therapeutic strategies may enhance their clinical applications.
B淋巴细胞在免疫中起关键作用，但也参与多种疾病的发病机制。大麻植物产生多种生物活性化合物，包括大麻素。研究最多的两种植物大麻素是Δ9-四氢大麻酚（THC）和大麻二酚（CBD）。这些大麻素主要通过内源性大麻素系统（ECS）发挥多种强大的生物学效应，而该系统在成熟B细胞功能中也起关键作用。免疫系统和ECS都会经历与年龄相关的变化，导致功能出现临床上显著的衰退。
本研究比较了THC和CBD对年轻和老年小鼠B细胞活性的影响。使用脂多糖（LPS）和白细胞介素-4（IL-4）激活小鼠B淋巴细胞，并从细胞表型、增殖、抗体分泌、肿瘤坏死因子-α（TNFα）分泌、细胞外信号调节激酶（ERK）磷酸化和细胞代谢组等方面评估大麻素处理的影响。
THC和CBD对年轻和老年小鼠的B细胞激活均表现出剂量依赖性抑制作用。然而，我们首次在此表明，这些处理会诱导不同的代谢谱。尽管两种大麻素都会降低一些代谢物的水平，如6-磷酸葡萄糖、磷酸戊糖途径（PPP）和核苷酸代谢物，但THC选择性地降低了一组独特氨基酸的水平，而只有CBD会增加瓜氨酸和尿囊素的水平。此外，THC和CBD对年轻和老年B细胞的影响有所不同，这表明ECS中与年龄相关的变化可能会影响大麻素的敏感性。
这些发现为THC和CBD调节免疫激活的不同机制提供了见解，并可能为研究大麻素对免疫系统作用背后的机制打开大门。它们还强调了对基于植物大麻素的疗法进行进一步研究的必要性，特别是在特定年龄背景下。鉴于大麻素，尤其是CBD的免疫调节特性，量身定制的治疗策略可能会增强它们的临床应用。
