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Review

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

by
Bruno Moreira Candeloro
1,
Camila M. de Oliveira
2,
Fabiana Veronez Martelato Gimenez
1,3,
Marianne P. C. N. Barbosa
1,
Beatriz Paiva Soares
1,
Ana C. F. Ruiz
1,
Derfel R. M. A. Folegatti
1,
Sandra Maria Barbalho
2,4,5,6,*,
Nancy S. Oliveira
1,
Andrey A. Porto
1,
David Matthew Garner
7,
Fernando H. Sousa
1 and
Vitor E. Valenti
1,*
1
Systematic Reviews Center for Cardiovascular and Metabolic Health, School of Philosophy and Sciences, São Paulo State University, Marília 17525-900, São Paulo, Brazil
2
Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
3
The Academic Graduate Program in Health and Aging, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
4
Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
5
UNIMAR Charity Hospital, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
6
Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Marília 17500-000, São Paulo, Brazil
7
Cardiorespiratory Research Group, School of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Headington Campus, Gipsy Lane, Oxford OX3 0BP, Oxfordshire, UK
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(23), 11618; https://doi.org/10.3390/ijms262311618 (registering DOI)
Submission received: 5 November 2025 / Revised: 27 November 2025 / Accepted: 27 November 2025 / Published: 30 November 2025
(This article belongs to the Special Issue Advancements in Inflammatory and Oxidative Disease Research)
Versions Notes

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.
Keywords: cannabidiol (CBD); Δ9-tetrahydrocannabinol (THC); inflammatory biomarkers; systemic inflammation; systematic review and meta-analysis cannabidiol (CBD); Δ9-tetrahydrocannabinol (THC); inflammatory biomarkers; systemic inflammation; systematic review and meta-analysis

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MDPI and ACS Style

Candeloro, B.M.; de Oliveira, C.M.; Gimenez, F.V.M.; Barbosa, M.P.C.N.; Soares, B.P.; Ruiz, A.C.F.; Folegatti, D.R.M.A.; Barbalho, S.M.; Oliveira, N.S.; Porto, A.A.; et al. The Pleiotropic Influence of Cannabidiol and Tetrahydrocannabinol on Inflammatory Biomarkers: A Systematic Review and Meta-Analytical Synthesis. Int. J. Mol. Sci. 2025, 26, 11618. https://doi.org/10.3390/ijms262311618

AMA Style

Candeloro BM, de Oliveira CM, Gimenez FVM, Barbosa MPCN, Soares BP, Ruiz ACF, Folegatti DRMA, Barbalho SM, Oliveira NS, Porto AA, et al. The Pleiotropic Influence of Cannabidiol and Tetrahydrocannabinol on Inflammatory Biomarkers: A Systematic Review and Meta-Analytical Synthesis. International Journal of Molecular Sciences. 2025; 26(23):11618. https://doi.org/10.3390/ijms262311618

Chicago/Turabian Style

Candeloro, Bruno Moreira, Camila M. de Oliveira, Fabiana Veronez Martelato Gimenez, Marianne P. C. N. Barbosa, Beatriz Paiva Soares, Ana C. F. Ruiz, Derfel R. M. A. Folegatti, Sandra Maria Barbalho, Nancy S. Oliveira, Andrey A. Porto, and et al. 2025. "The Pleiotropic Influence of Cannabidiol and Tetrahydrocannabinol on Inflammatory Biomarkers: A Systematic Review and Meta-Analytical Synthesis" International Journal of Molecular Sciences 26, no. 23: 11618. https://doi.org/10.3390/ijms262311618

APA Style

Candeloro, B. M., de Oliveira, C. M., Gimenez, F. V. M., Barbosa, M. P. C. N., Soares, B. P., Ruiz, A. C. F., Folegatti, D. R. M. A., Barbalho, S. M., Oliveira, N. S., Porto, A. A., Garner, D. M., Sousa, F. H., & Valenti, V. E. (2025). The Pleiotropic Influence of Cannabidiol and Tetrahydrocannabinol on Inflammatory Biomarkers: A Systematic Review and Meta-Analytical Synthesis. International Journal of Molecular Sciences, 26(23), 11618. https://doi.org/10.3390/ijms262311618

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