Clinical Takeaway
Regular cannabinoid use shows a measurable association with changes in peripheral inflammatory biomarkers, though findings vary depending on population health status and pattern of use. Current evidence does not yet establish a clear pro- or anti-inflammatory direction for cannabinoids in healthy individuals or those with psychiatric conditions. Clinicians should interpret patient inflammatory lab results in the context of cannabinoid use history.
#5 Regular cannabinoid use and inflammatory biomarkers: Systematic review and hierarchical meta-analysis.
Citation: Belvederi Murri Martino et al.. Regular cannabinoid use and inflammatory biomarkers: Systematic review and hierarchical meta-analysis.. Brain, behavior, and immunity. 2026. PMID: 41740869.
Design: 6 Journal: 0 N: 2 Recency: 3 Pop: 2 Human: 1 Risk: -2
- Preclinical only
Methodological Considerations:
- Cross-sectional design — causal inference not possible
Abstract: 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.
What This Study Teaches Us
Cannabis use is associated with both increased pro-inflammatory and anti-inflammatory markers simultaneously in observational studies, suggesting the drug modulates the immune system in complex ways rather than simply ramping inflammation up or down. RCT data on cannabidiol alone show minimal pro-inflammatory effects, while prospective studies have not yet demonstrated consistent patterns.
Why This Matters Clinically
Clinicians advising patients on cannabis use need to move past the simple narrative that cannabis is either ‘anti-inflammatory’ or ‘pro-inflammatory.’ The immunological reality appears nuanced and context-dependent, which matters for patients with inflammatory conditions, psychiatric disorders, or chronic illness who are considering or using cannabis therapeutically.
Study Snapshot
| Study Design | Systematic review with Bayesian multilevel meta-analysis; 46 studies pooled including observational studies (cross-sectional and case-control), 2 prospective studies, and 10 RCTs |
| Population | 54,382 total participants across included studies; mixed populations including healthy individuals and those with psychiatric disorders; demographics varied by study |
| Intervention | Cannabis use (smoked, inhaled, or oral) or isolated cannabidiol; specific doses and durations not specified in abstract |
| Primary Outcome | Peripheral inflammatory biomarkers (pro-inflammatory and anti-inflammatory markers) compared between users and non-users |
| Key Result | Observational studies: cannabis use associated with higher anti-inflammatory biomarkers (SMD 0.298) AND pro-inflammatory biomarkers (SMD 0.166); RCTs of CBD showed small increase in pro-inflammatory markers (SMD 0.15); prospective studies inconsistent |
Where This Paper Deserves Skepticism
The abstract does not specify doses, frequency definitions, or duration of use, making it impossible to know if ‘regular use’ means daily consumption or weekly. The pooling of 178 cross-sectional and case-control studies creates significant risk of reverse causality and unmeasured confounding (people with inflammatory conditions may use cannabis for symptom relief). The small number of prospective studies (n=2) and RCTs (n=10) limits causal inference, and the abstract does not report effect sizes or confidence intervals for these critical subgroups. Publication bias screening was mentioned as absent, but the methodology and heterogeneity across biomarkers and populations is substantial and incompletely summarized here.
Dr. Caplan’s Take
This meta-analysis captures something real: cannabinoids appear to have immunomodulatory properties that don’t fit neatly into ‘pro’ or ‘anti-inflammatory’ buckets. The observational data are voluminous but plagued by confounding; the RCT evidence on CBD is nascent and shows only modest effects. What I find clinically useful here is the reminder to stop selling cannabis as a blanket anti-inflammatory and to acknowledge we still don’t understand which patients, at which doses, might benefit or be harmed immunologically. The concurrent elevation of both marker types suggests cannabinoids may shift immune tone in ways we can’t yet predict from a single biomarker readout.
Clinical Bottom Line
Cannabis appears to modulate inflammatory pathways in complex, non-uniform ways based on observational data, but RCT and prospective evidence remains too sparse to guide therapeutic dosing or patient selection. Clinicians should resist claims of clear anti-inflammatory benefit and counsel patients that the immunological effects of cannabis remain incompletely understood.
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