Dose-Related Effects of Cannabidiol on Inflammatory and Redox Responses, Bacterial Dissemination, and Multiorgan Injury in CLP-Induced Septic Rats

Background: Sepsis couples dysregulated inflammation, oxidative imbalance, microbial dissemination, and multiorgan injury. Cannabidiol (CBD) has anti-inflammatory and redox-modulating properties, but its dose-related effects in polymicrobial sepsis, particularly alongside culture-recoverable bacterial burden, remain incompletely characterized. Methods: Forty-eight male Wistar rats were randomized to Control, Sham, Untreated CLP, or CLP plus CBD at 2.5, 5, or 25 mg/kg (n = 8/group). CBD or vehicle was administered intraperitoneally after cecal ligation and puncture (CLP). Inflammatory, immunometabolic, neurotrophic, oxidative, biochemical, microbiological, and histopathological outcomes were evaluated at 10 h. Results: Untreated CLP increased pro-inflammatory cytokines, asprosin, resistin, oxidative-stress indices, organ-injury biomarkers, and reported culture-recoverable bacterial burdens, while decreasing IL-10, apelin, BDNF, TAS, and immunoreactive SOD, CAT, and GPx concentrations (all omnibus p < 0.001). CBD was associated with progressive improvement across most systemic outcomes, and 25 mg/kg produced the most consistent overall response. Histopathological lesion scores were greatest in Untreated CLP animals and generally lower in CBD-treated groups; however, tissue-level changes were not uniformly dose-ordered across every organ and lesion domain. Conclusions: Within this acute exploratory model, CBD exposure was associated with coordinated improvements across host-response, redox, biochemical, and morphological domains. The microbial summaries suggested lower recoverable burdens, but require animal-level verification of non-detect handling. These findings support pharmacokinetic, safety, mechanistic, survival, and prospectively powered confirmatory studies; they do not establish direct antibacterial activity or a clinically applicable dose.