Study: CBD and CBDV Combination Reduces IBD-Related Gut Inflammation by Targeting Key Immune Receptor

The research, conducted by scientists from the Technion-Israel Institute of Technology, offers evidence for a CB2-dependent cannabinoid interaction that may help explain the entourage effect The team of researchers focused on C-X-C chemokine receptor type 4 (CXCR4), a molecule that directs immune cells to sites of inflammation and is known to play a central role in IBD. Using a combination of CBD and CBDV in a 20:1 ratio, researchers found that the blend significantly lowered CXCR4 expression in multiple immune cell types, including MOLT-4 cells, murine splenocytes, and human peripheral blood mononuclear cells.

That reduction carried functional consequences. Cells exposed to the CBD-CBDV mixture showed impaired chemotaxis and decreased actin polymerization, disrupting the movement and activation of inflammatory immune cells. These effects were eliminated when CB2 receptors were blocked, pointing to a clear CB2-mediated mechanism.

The findings extended to an animal model. In mice with DSS-induced colitis—a widely used model for human IBD—the cannabinoid blend improved several disease markers, including disease activity index, colon length, and overall tissue health. Importantly, these improvements did not appear in CB2 knockout mice, reinforcing that the therapeutic action relies on CB2 signaling.

Altogether, the study provides mechanistic support for combining cannabinoids rather than relying on a single compound. By showing how CBDV enhances the anti-inflammatory activity of CBD through CB2-driven suppression of CXCR4, the researchers say the results underscore the potential for targeted cannabinoid formulations in treating inflammatory bowel disease.