Combined Cannabidiol and Δ9-Tetrahydrocannabinol Modulate Inflammation and Nociceptive Signaling in Human Dental Pulp Cells.

Soe Z.; Nan D.; Wahyudi R.; Sriwattanapong K.; Porntaveetus T.; Chantarangsu S.; Kamolratanakul P.; Everts V.; Kornsuthisopon C.; Osathanon T. et al. · Journal of endodontics · 2026

**Background & Methods** This in vitro study investigated the combined effects of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) on human dental pulp cells stimulated with lipopolysaccharide (LPS) to model inflammatory conditions. Multiple cellular assays including qPCR, ELISA, Western blotting, and functional assays (viability, proliferation, migration, and mineralization) were performed to evaluate anti-inflammatory, anti-nociceptive, and regenerative effects. **Key Findings** • The CBD/THC combination more effectively reduced pro-inflammatory cytokines (IL-6, IL-12, IL-1β) and increased anti-inflammatory IL-10 expression compared to either cannabinoid alone, demonstrating synergistic anti-inflammatory effects in LPS-stimulated dental pulp cells. • Combined treatment enhanced expression of cannabinoid receptors (CNR1, CNR2), modulated the nociceptive marker TRPV1, and significantly improved cell proliferation, migration, and mineralized nodule formation—markers associated with tissue regeneration. • The combination upregulated odontogenic differentiation markers (DMP1) and angiogenic factors (VEGF and bFGF), suggesting potential to promote vital pulp healing and regenerative capacity while maintaining cellular viability at tested concentrations. **Dosage & Administration** CBD: 2.5 μg/mL; THC: 0.6 μg/mL. Route of administration: Not applicable (in vitro cell culture study). Clinical translation dosing and administration routes not established. **Safety & Adverse Effects** Cytotoxicity assays determined optimal non-cytotoxic concentrations for both cannabinoids; no adverse effects were reported at the tested doses. Specific toxicity data, off-target effects, or dose-limiting adverse events were not detailed. **Evidence Quality** This is an in vitro mechanistic study with significant limitations restricting clinical applicability. The research provides preliminary cellular evidence but lacks in vivo validation, animal models, and human clinical trials. Results are derived from isolated human dental pulp cells under artificial inflammatory conditions (LPS stimulation), which may not fully replicate clinical pulpal pathology. The study does not address pharmacokinetics, bioavailability, or tissue penetration in the pulpal environment. No comparison with established vital pulp therapies is provided. While findings are promising for basic science investigation of cannabinoid mechanisms in endodontics, substantial additional preclinical and clinical research is required before therapeutic recommendations can be made for treating dental pulp inflammation in patients.

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