Regular cannabinoid use and inflammatory biomarkers: Systematic review and hierarchical meta-analysis

Background Cannabis use is rising, with both therapeutic and harmful uses that might involve inflammation. Preclinical studies and findings in humans are inconsistent. It remains unclear whether cannabinoids affect inflammation in healthy populations or individuals with psychiatric disorders. We examined the association between cannabinoid use and peripheral inflammatory biomarkers. Methods We systematically searched multiple databases from inception to October 2025. Eligible studies compared inflammatory biomarkers between cannabinoid users and non-users. Bayesian multilevel cross-classified meta -analyses were used to pool effect sizes, accounting for clustering within studies and biomarkers. Results We included 46 studies (54,382 participants); 190 effect sizes from 40 studies were pooled in three meta - analyses (n = 178 effects from cross-sectional and case-control studies, n = 2 prospective studies, n = 10 RCTs). In observational studies, cannabis use was associated with higher levels of anti-inflammatory (Standardized Mean Difference (SMD) = 0.298; 95% CrI, 0.052, 0.536, PD = 99%) and pro-inflammatory biomarkers (SMD = 0.166; 95% CrI, 0.122, 0.209, PD = 100%), with credible differences by demographic factors, study design, synthetic cannabinoids and recency of use. RCTs of cannabidiol suggested small increase of pro-inflammatory markers (SMD 0.15; 95% CrI, −0.07 to 0.36; PD 90.9%). No consistent effects were observed in prospective studies. There was no evidence of major publication bias. Conclusions Cannabinoid use is associated with concurrent pro- and anti-inflammatory modulation in non-medical populations, consistent with immunomodulatory effects rather than a uniform pro- or anti-inflammatory shift. Understanding the immunological impact of cannabinoids remains critical to anticipate long-term health consequences and guide therapeutic development.