- PMID: 37332213
- DOI: 10.1097/SAP.0000000000003547
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Conflict of interest statement
Conflicts of interest and sources of funding: B.R.D. received support from the SESPRS Annual Research Award in 2021. M.P.T. received partial support through funds from Trulieve VA, Inc (award no. GR016205).
References
-
- Russo EB. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers. 2007;4:1614–1648.
-
- Mlost J, Bryk M, Starowicz K. Cannabidiol for pain treatment: focus on pharmacology and mechanism of action. Int J Mol Sci. 2020;21. doi:10.3390/ijms21228870. – DOI
-
- Hill TDM, Cascio M-G, Romano B, et al. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor–independent mechanism. Br J Pharmacol. 2013;170:679–692.
-
- Naftali T. An overview of cannabis based treatment in Crohn’s disease. Expert Rev Gastroenterol Hepatol. 2020;14:253–257.
-
- Miller RJ, Miller RE. Is cannabis an effective treatment for joint pain? Clin Exp Rheumatol. 2017;35(suppl 107(5)):59–67.