The Pleiotropic Influence of Cannabidiol and Tetrahydrocannabinol on Inflammatory Biomarkers: A Systematic Review and Meta-Analytical Synthesis

Abstract

Preclinical data suggest that cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) modulate inflammatory pathways (e.g., NLRP3, NF-κB, and PPAR-γ), but clinical translation into consistent changes in circulating biomarkers remains ambiguous. Two reviewers independently screened the studies, extracted data, and assessed risk of bias with RoB-2. Random-effects meta-analyses (RevMan 5.4.1) formed standardized mean differences (SMD) or mean differences (MD) as appropriate. The certainty of evidence was graded by means of GRADE. Thirteen studies satisfied inclusion criteria; meta-analyses were feasible for IL-6 (four studies, n ≈ 129 per arm), IL-8 (two studies, n ≈ 78 per arm), IL-10 (two studies, n ≈ 92 per arm), and TNF-α (three studies, n ≈ 105 per arm). Pooled estimates favored CBD but were trivial and imprecise: IL-6 SMD −0.17 (95% CI −0.56 to 0.23; p = 0.41; I2 = 55%); IL-8 SMD −0.30 (95% CI −0.62 to 0.01; p = 0.06; I2 = 0%); IL-10 SMD −0.10 (95% CI −0.83 to 0.63; p = 0.79; I2 = 81%); and TNF-α SMD −0.09 (95% CI −0.45 to 0.27; p = 0.62; I2 = 33%). Individual trials reported reductions in biomarkers in high-exposure or diseased populations. GRADE ratings were as follows: IL-6 very low, IL-8 moderate, IL-10 low, and TNF-α moderate. Current RCT evidence demonstrates inconsistent, often trivial effects of phytocannabinoid interventions on circulating inflammatory biomarkers.