Cannabidiol (CBD) differentially shapes systemic cytokines and transcriptomic profiles in the liver and spleen: insights from a male mouse model.

Żurowski J.; Ocłoń E.; Jasielczuk I.; Szmatoła T.; Mizera-Szpilka K.; Semik-Gurgul E.; Sawicki S.; Gurgul A. · Molecular genetics and genomics : MGG · 2026

**Background & Methods** This study investigated dose- and time-dependent effects of cannabidiol (CBD) on systemic cytokine responses and transcriptomic profiles in male C57BL/6J mice. Animals received CBD intraperitoneally at 0.2, 10, or 20 mg/kg body weight for either 2 days (short-term) or 28 days (long-term), with vehicle-treated controls; serum cytokines were measured by ELISA and RNA-Seq was performed on liver and spleen tissue. **Key Findings** • CBD significantly reduced circulating pro-inflammatory cytokines (IL-1β and TNF-α) following short-term treatment across all doses tested, while IL-6 decreased primarily during long-term exposure with the strongest reduction observed at day 14 and partial persistence to day 28 at higher doses. • Hepatic transcriptome exhibited pronounced dose- and time-dependent remodeling with the largest number of differentially expressed genes at 20 mg/kg short-term exposure; pathway enrichment analyses revealed modulation of mitochondrial and translational pathways after short-term high-dose treatment, lipid and fatty acid metabolism during long-term exposure, and circadian-associated regulation at higher-dose long-term treatment. • Splenic transcriptional changes were comparatively modest, with limited differential expression during long-term treatment and clearer responses only after short-term exposure to the highest dose (20 mg/kg), demonstrating organ-specific and regimen-dependent transcriptomic responses. **Dosage & Administration** CBD administered intraperitoneally at 0.2, 10, or 20 mg/kg body weight for either 2 days (short-term) or 28 days (long-term). **Safety & Adverse Effects** Not reported. **Evidence Quality** This is a preclinical study using a single mouse strain (C57BL/6J) with male-only subjects, limiting generalizability to other populations and sexes. The intraperitoneal route of administration does not reflect typical human oral CBD consumption. While RNA-Seq provides comprehensive transcriptomic data, the mechanistic interpretation of gene expression changes without functional validation (e.g., protein level confirmation) represents a limitation. The study demonstrates CBD acts as an immunometabolic modulator rather than a simple immunosuppressant, but findings require translation to human studies before clinical application can be established.

More recent cannabis research