Abstract
Introduction:
Rheumatoid arthritis (RA) is a debilitating autoimmune disease affecting approximately 1% of the global population and is associated with significant morbidity and mortality. Given the known anti-inflammatory effects of cannabinoids, we investigated the therapeutic potential of a high-CBD extract, termed CBD-X, by assessing its effects on immune cells and disease progression. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in RA.
Methods:
We evaluated the effects of CBD-X on cells involved in RA pathogenesis using macrophages and primary human neutrophils as ex vivo models. In addition, two murine models of RA were applied: collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA).
Results:
Ex vivo experiments demonstrated that CBD-X inhibited the secretion of pro-inflammatory cytokines, including IL-1β from macrophages and IL-8, IL-6, and TNF-α from human neutrophils, suggesting its potential to modulate inflammatory responses. Moreover, CBD-X attenuated NF-κB p65 and Akt phosphorylation downstream LPS-activation signal in neutrophils. To further evaluate its therapeutic effects, we employed two murine models of RA: collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA). In both models, CBD-X treatment resulted in a significant reduction of leukocyte levels in the blood, primarily through the suppression of neutrophil and monocyte populations, which play a central role in RA pathogenesis. Additionally, CBD-X reduced neutrophil migration to the joints in the CAIA model, highlighting its potential to alleviate joint inflammation. Furthermore, it modulated the neutrophil-to-macrophage ratio (NMR), an important marker of RA progression, an effect that was not observed with dexamethasone treatment, suggesting a distinct mechanism of immune regulation. Notably, CBD-X promoted the pro-resolving macrophages to the rheumatic joints. Importantly, CBD-X exerted its anti-inflammatory effect by downregulating TNF-α and MCP-1 while upregulating IL-10, a key anti-inflammatory cytokine involved in immune homeostasis.
Discussion:
These findings indicate that CBD-X has a significant potential as a therapeutic agent for RA, offering a promising approach to modulate immune responses and reduce inflammation in RA patients.