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

Ülker U.; Bayraktar B.; Karan T.; Sinmez &.; Tüfekçi E.; Bilici E.; Alpman U.; Kotan G.; Yeni M. · Pharmaceuticals (Basel, Switzerland) · 2026

**Background & Methods** This randomized controlled trial evaluated dose-related effects of cannabidiol (CBD) in 48 male Wistar rats subjected to cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Animals were randomized to control, sham, untreated CLP, or CLP plus CBD at 2.5, 5, or 25 mg/kg administered intraperitoneally, with comprehensive inflammatory, oxidative, microbiological, and histopathological assessments conducted at 10 hours post-intervention. **Key Findings** - Untreated CLP significantly elevated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), asprosin, and resistin while decreasing anti-inflammatory IL-10, apelin, and BDNF (p < 0.001); CBD treatment produced progressive dose-dependent improvements across these systemic markers, with 25 mg/kg demonstrating the most consistent beneficial effects. - CBD exposure reduced oxidative stress indices and increased antioxidant enzyme concentrations (SOD, CAT, GPx) and total antioxidant status (TAS) in a dose-dependent manner; organ-injury biomarkers were lower in CBD-treated animals compared to untreated septic controls. - Histopathological lesion scores were greatest in untreated CLP animals and generally reduced in CBD-treated groups; however, improvements were not uniformly dose-ordered across all organs and lesion domains, suggesting variable tissue-level responses. **Dosage & Administration** Cannabidiol was administered intraperitoneally at doses of 2.5, 5, or 25 mg/kg following cecal ligation and puncture induction. The 25 mg/kg dose produced the most consistent overall systemic response. **Safety & Adverse Effects** Not reported. **Evidence Quality** This is an early exploratory study with significant limitations. The model uses acute 10-hour timepoint assessment in rodents, which does not capture longer-term clinical outcomes or survival benefit. The authors acknowledge incomplete characterization of dose-response relationships for bacterial burden and note that microbial data require animal-level verification of non-detect handling. The study does not establish direct antibacterial activity, does not report safety data, and lacks power calculations for confirmatory conclusions. Findings support mechanistic investigation and pharmacokinetic studies but do not translate to clinical applicability or identify optimal dosing for human use.

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