“Cannabis extracts, particularly those rich in cannabinoids like cannabidiol (CBD), have shown potential anti-inflammatory properties and are being examined in managing conditions involving inflammation.

One proposed mechanism is their modulation of chemokine expression and function in immune cells. C-X-C chemokine receptor type 4 (CXCR4) plays a pivotal role in immune cell trafficking and is implicated in the pathogenesis of inflammatory bowel disease (IBD).

Given emerging evidence that cannabinoids can influence chemokine signaling, we explored whether they could downregulate CXCR4 in immune cells.

In this study, we show that the combination of CBD and cannabidivarin (CBDV) at a 20:1 ratio significantly reduces CXCR4 expression in MOLT-4 cells, murine splenocytes and human peripheral blood mononuclear cells. This reduction in CXCR4 expression correlated with impaired chemotactic responses and suppressed actin polymerization, effects that were abrogated by CB2 receptor inhibition. In vivo, the CBD:CBDV combination ameliorated disease severity in a murine model of DSS-induced colitis, improving disease activity index, colon length, and histological outcomes. These therapeutic benefits were absent in CB2 knockout mice, confirming CB2 dependence.

Our findings support a CB2-mediated mechanism by which the CBD:CBDV combination downregulates CXCR4, providing a mechanistic basis for the entourage effect and highlighting the significance of CBDV as a modulator of the CBD effect.

Overall, this study implicates cannabinoid combinations as a promising therapeutic strategy for treating IBD.”

https://pubmed.ncbi.nlm.nih.gov/41237459

“Current therapies for inflammatory bowel disease (IBD), such as olsalazine and cyclosporine, often exhibit limited long-term efficacy and are associated with adverse effects. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, shows promise for its anti-inflammatory properties, though its effectiveness as a monotherapy remains inconclusive.

This study investigates the therapeutic potential of combining low-dose CBD (10 mg/kg) with olsalazine (50 mg/kg) or cyclosporine (2.5, 5 mg/kg) in dextran sulphate sodium (DSS)-induced acute and chronic colitis models in mice.

Disease severity was assessed via disease activity index (DAI), colon morphology, cytokine and chemokine expression, myeloperoxidase (MPO) activity, systemic inflammatory markers, and glucagon-like peptide-1 (GLP-1) regulation. Safety evaluations included haematology and plasma biochemistry. DSS-treated mice showed elevated DAI scores, colon shortening, heightened inflammation, and organ enlargement. Combination therapies significantly ameliorated colitis, reducing DAI, MPO activity, and inflammatory cytokines, while restoring colon length and GLP-1 levels-without inducing liver or kidney toxicity.

These findings demonstrate that combining a low dose of CBD with standard IBD drugs enhances therapeutic efficacy while minimizing side effects, supporting its integration into future combination strategies for more effective and safer IBD management.”

https://pubmed.ncbi.nlm.nih.gov/40869234/

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has emerged as a promising therapeutic candidate for the treatment of inflammatory conditions, including IBD. CBD’s anti-inflammatory, antioxidant, and immunomodulatory effects are mediated through multiple pathways, including the modulation of cytokine production, inhibition of oxidative stress, and interaction with the endocannabinoidome (eCBome).”

“Collectively, our data provide a strong preclinical rationale for leveraging low-dose CBD to enhance the efficacy of existing IBD therapies. The reproducible synergistic effects observed in acute and chronic colitis models—spanning clinical, morphological, molecular, metabolic, and safety domains—underscore CBD’s potential as a safer adjunct agent. CBD co-therapy with CSA or olsalazine offers a multifaceted approach to IBD treatment—achieving superior disease suppression, preserving intestinal and systemic homeostasis, and maintaining an acceptable safety profile. This strategy holds promise for improving patient outcomes while potentially reducing the doses and side effects of conventional IBD drugs. Clinical trials will be essential to confirm safety and efficacy in human IBD patients.”

https://www.mdpi.com/1422-0067/26/16/7913

“Scope: Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut, accompanied by impaired epithelial integrity, increased macrophage infiltration, and enhanced colon cancer risk.

Methods and results: Cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is supplemented into mice diet, and its beneficial effects against dextran sulfate sodium (DSS)-induced experimental colitis is evaluated. Eight-week-old mice were fed a standard diet supplemented with or without CBD (200 mg kg^-1 ) for 5 weeks. In the 4th week of dietary treatment, mice were subjected to 2.5% DSS induction for 7 days, followed by 7 days of recovery, to induce colitis. CBD supplementation reduced body weight loss, gross bleeding, fecal consistency, and disease activity index. In addition, CBD supplementation protected the colonic structure, promoted tissue recovery, and ameliorated macrophage infiltration in the colonic tissue, which was associated with the activation of cyclic AMP-protein kinase A, extracellular signal-regulated kinase ½, and AMP-activated protein kinase signaling pathways. CBD supplementation also suppressed NLRP3 inflammasome activation and related pro-inflammatory marker secretion. Consistently, CBD feeding reduced tight junction protein claudin2 and myosin light chain kinase in DSS-treated mice.

Conclusion: Dietary CBD protects against inflammation and colitis symptoms induced by DSS, providing an alternative approach to IBD management.”

https://pubmed.ncbi.nlm.nih.gov/38175840/

https://onlinelibrary.wiley.com/doi/10.1002/mnfr.202300446