CANNABINOID USE MODULATE THE SECRETORY PROFILE OF ANTI-INFLAMMATORY CYTOKINES IN INDIVIDUALS WITH MULTIPLE SCLEROSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Multiple sclerosis remains an important chronic neuroinflammatory disease, marked by immune dysregulation and the production of inflammatory mediators that contribute to the progression of neurological damage. In this context, cannabinoids, derived from cannabis sativa, have attracted interest due to their immunomodulatory potential through alterations in cytokine secretion, which could contribute to controlling the inflammatory activity of the disease. Therefore, this article aims to understand the effects of cannabinoid use on the secretory profile of anti-inflammatory cytokines in patients with multiple sclerosis. This is a systematic review and meta-analysis conducted according to PRISMA, encompassing clinical trials, cohorts, and case-control studies published up to September 2025 in the PubMed, Cochrane, and SciELO databases. The selection and evaluation of articles were performed by independent researchers using tools for assessing risk of bias. The meta-analysis used RevMan 4.2.2 and the meta package. Differences were calculated using 95% CI, and heterogeneity was assessed using the I² test. The systematic review included seven articles. Of these, three were eligible for meta-analysis. In patients using cannabis sativa derivatives, there was a significant reduction in serum levels of IL-4 (-6.68; 95% CI -7.56 to -5.80) and IL-10 (-10.66; 95% CI -11.51 to -9.81). The use of cannabinoids modulated the cytokine secretory profile, promoting a reduction in the anti-inflammatory mediators IL-4 and IL-10 in patients with MS. Despite the described clinical benefit for pain and spasticity, these results should be interpreted with caution due to the high heterogeneity among studies and the lack of standardization of compounds and doses. Therefore, the immunomodulatory effects of medicinal cannabis on autoimmunity remain inconclusive.