Objective The study objective was to evaluate the therapeutic effect of cannabidiol (CBD) on a combination of caecal slurry, lipopolysaccharide (LPS), and Escherichia coli (E. coli)-induced systemic inflammatory response syndrome (SIRS) in male Sprague Dawley rats. Methods The therapeutic activity was monitored in behavioral tests and inflammatory biomarkers by the enzyme-linked immune sorbent assay (ELISA) method. Results Behavioral tasks were significantly increased like a tail flick response by 73.84% (p ≤ 0.001), grip strength by 33.56% (p ≤ 0.028), locomotor activity by 20.71% (p = 0.034) in the CBD (60 mg/kg) group compared to disease control (DC) group. Levels of inflammatory serum biomarkers like interleukin-1β (IL-1β), matrix metallopeptidase-9 (MMP-9), IL-6, and tumor necrosis factor-alpha (TNF-α) were significantly decreased by 29.56 (p = 0.041), 71.20 (p ≤ 0.001), 35.05 (p ≤ 0.001), and 75.56% (p = 0.002), respectively, in the CBD-60 compared with DC. Inflammatory cytokines levels, viz. IL-1β, MMP-9, IL-6, and TNF-α, in the liver were significantly (p ≤ 0.001) decreased by 81.01, 40.41, 22.84, and 69.46%, respectively, in CBD-60 to DC. Similarly, levels of inflammatory cytokines such as IL-1β and MMP-9 in the kidney were significantly (p ≤ 0.001) decreased by 80.90 and 43.93%, respectively, in CBD-60 compared to DC. Conclusion Taken together, results suggest that CBD treatment significantly improved behavioral tasks and decreased the level of inflammatory cytokines under SIRS conditions that might provide an opportunity to manage acute and chronic inflammatory disorders.
