From the Departments of Plastic and Maxillofacial Surgery.
Biology, University of Virginia, Charlottesville, VA.
Ann Plast Surg. 2023 Jun 1;90(6S Suppl 4):S408-S415. doi: 10.1097/SAP.0000000000003547. Epub 2023 May 31.
Patients suffering from arthritis have limited treatment options for nonoperative management. In search of pain relief, patients have been taking over-the-counter cannabinoids. Cannabidiol (CBD) and cannabichromene (CBC) are minor cannabinoids with reported analgesic and anti-inflammatory properties and have been implicated as potential therapeutics for arthritis-related pain. To this end, we utilized a murine model to investigate the effectiveness of and mechanism by which CBC alone, CBD alone, or CBD and CBC in combination may provide a reduction in arthritis-associated inflammation.
Forty-eight mice were included in the study, which were separated into 4 groups: control group (n = 12), treatment with CBD alone (n = 12), treatment with CBC alone (n = 12), and treatment with CBD + CBC (n = 12). We induced inflammation in each mouse utilizing the collagen-induced arthritis model. At scheduled timepoints, mice were clinically assessed for weight gain, swelling, and arthritis severity. In addition, inflammation-associated serum cytokine levels were analyzed for each animal.
Thirty-five of 48 mice survived the duration of the study resulting in the following group numbers: control group (n = 8), treatment with CBD alone (n = 9), treatment with CBC alone (n = 9), and treatment with CBD + CBC (n = 9). Animals treated with CBC and CBD + CBC showed significant weight gain between 3 and 5 weeks. Irrespective of treatment, regression analysis comparing all cytokine measurement and physical outcomes found a significant positive correlation between levels of 5 individual cytokines and both arthritis scores and swelling. Animals treated with CBD + CBC showed a significant decrease in swelling between 3 and 5 weeks compared with the control group. Cannabinoid treatment selectively affected the gene expression of eotaxin and lipopolysaccharide-induced CXC chemokine with combined treatment of CBC + CBD.
Treatment with cannabinoids resulted in decreased clinical markers of inflammation. Further, the anti-inflammatory effect of CBC and CBD in conjunction was associated with a greater anti-inflammatory effect than either minor cannabinoid alone. Future work will elucidate the possibility of synergistic or entourage effects of minor cannabinoids used in combination for the treatment of arthritis-related pain and inflammation.
患有关节炎的患者在非手术治疗方面选择有限。为了缓解疼痛，患者一直在服用非处方类大麻素。大麻二酚（CBD）和大麻色烯（CBC）是含量较少的大麻素，具有报告的镇痛和抗炎特性，并被认为是关节炎相关疼痛的潜在治疗药物。为此，我们利用一种小鼠模型来研究单独使用 CBC、单独使用 CBD 或 CBD 和 CBC 联合使用是否可能减轻关节炎相关炎症。
本研究纳入了 48 只小鼠，将其分为 4 组：对照组（n = 12）、单独使用 CBD 治疗组（n = 12）、单独使用 CBC 治疗组（n = 12）和 CBD + CBC 联合治疗组（n = 12）。我们利用胶原诱导性关节炎模型在每只小鼠中诱导炎症。在预定的时间点，对小鼠的体重增加、肿胀和关节炎严重程度进行临床评估。此外，还对每个动物的炎症相关血清细胞因子水平进行了分析。
48 只小鼠中有 35 只在研究期间存活下来，最终分为以下几组：对照组（n = 8）、单独使用 CBD 治疗组（n = 9）、单独使用 CBC 治疗组（n = 9）和 CBD + CBC 联合治疗组（n = 9）。接受 CBC 和 CBD + CBC 治疗的动物在 3 至 5 周之间体重明显增加。无论是否接受治疗，对所有细胞因子测量和身体结果进行回归分析发现，5 种细胞因子的水平与关节炎评分和肿胀均呈显著正相关。与对照组相比，接受 CBD + CBC 治疗的动物在 3 至 5 周之间肿胀明显减少。大麻素治疗选择性地影响了嗜酸性粒细胞趋化因子和脂多糖诱导的 CXC 趋化因子的基因表达，而 CBC + CBD 的联合治疗则与更大的抗炎作用相关。
大麻素治疗可降低炎症的临床标志物。此外，CBC 和 CBD 的联合抗炎作用与单独使用任何一种含量较少的大麻素相比，具有更大的抗炎作用。未来的研究将阐明联合使用这些含量较少的大麻素治疗关节炎相关疼痛和炎症的协同或增效作用的可能性。
