Phytocannabinoids and gingival inflammation: Preclinical findings and a placebo-controlled double-blind randomized clinical trial with cannabidiol

J Periodontal Res. 2024 Jun;59(3):468-479. doi: 10.1111/jre.13234. Epub 2024 Feb 5.

Abstract

Objective: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis.

Background: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease.

Materials and methods: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD.

Results: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 μg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days.

Conclusions: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.

Keywords: cannabidiol; inflammation; microbiota; oral hygiene; periodontium; phytocannabinoid.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cannabidiol* / pharmacology
  • Cannabidiol* / therapeutic use
  • Cells, Cultured
  • Chlorhexidine / analogs & derivatives
  • Chlorhexidine / pharmacology
  • Chlorhexidine / therapeutic use
  • Double-Blind Method
  • Female
  • Fibroblasts* / drug effects
  • Gingiva* / drug effects
  • Gingivitis* / drug therapy
  • Heme Oxygenase-1
  • Humans
  • Interleukin-6 / analysis
  • Interleukin-8 / drug effects
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2
  • Periodontitis / drug therapy

Substances

  • Cannabidiol
  • NF-E2-Related Factor 2
  • Anti-Inflammatory Agents
  • NFE2L2 protein, human
  • Chlorhexidine
  • chlorhexidine gluconate
  • Interleukin-6
  • Interleukin-8
  • Heme Oxygenase-1