title: Effect of cannabidiol on human gingival fibroblast extracellular matrix metabolism: MMP production and activity, and production of fibronectin and transforming growth factor β.
abstract: OBJECTIVE
  Marijuana (Cannabis sativa) use may be associated with gingival enlargement, resembling that caused by phenytoin. Cannabidiol (CBD), a nonpsychotropic Cannabis derivative, is structurally similar to phenytoin. While there are many reports on effects of phenytoin on human gingival fibroblasts, there is no information on effects of Cannabis components on these cells. The objective of this study was to determine effects of CBD on human gingival fibroblast fibrogenic and matrix-degrading activities.
  
  
  METHODS
  Fibroblasts were incubated with CBD in serum-free medium for 1-6 d. The effect of CBD on cell viability was determined by measuring activity of a mitochondrial enzyme. The fibrogenic molecule transforming growth factor β and the extracellular matrix molecule fibronectin were measured by ELISA. Pro-MMP-1 and total MMP-2 were measured by ELISA. Activity of MMP-2 was determined via a colorimetric assay in which a detection enzyme is activated by active MMP-2. Data were analysed using ANOVA and Scheffe's F procedure for post hoc comparisons.
  
  
  RESULTS
  Cannabidiol had little or no significant effect on cell viability. Low CBD concentrations increased transforming growth factor β production by as much as 40% (p < 0.001), while higher concentrations decreased it by as much as 40% (p < 0.0001). Cannabidiol increased fibronectin production by as much as approximately 100% (p < 0.001). Lower CBD concentrations increased MMP production, but the highest concentrations decreased production of both MMPs (p < 0.05) and decreased MMP-2 activity (p < 0.02).
  
  
  CONCLUSIONS
  The data suggest that the CBD may promote fibrotic gingival enlargement by increasing gingival fibroblast production of transforming growth factor β and fibronectin, while decreasing MMP production and activity.
authors.affiliation: College of Dentistry, Department of Periodontology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Rawal
authors.forename: M Kh
authors.initials: MKh
authors.lastname: Dabbous
authors.forename: D A
authors.initials: DA
authors.lastname: Tipton
mesh_terms: D002185:Cannabidiol / Q000494:pharmacology* / Q000633:toxicity; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects* / Q000201:enzymology; D005347:Fibroblasts / Q000187:drug effects*; D005351:Fibromatosis, Gingival / Q000503:physiopathology; D005353:Fibronectins / Q000096:biosynthesis / Q000187:drug effects*; D018093:Gelatinases / Q000096:biosynthesis / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000187:drug effects*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000187:drug effects*
chemical_list: D016895:Culture Media, Serum-Free; D004792:Enzyme Precursors; D005353:Fibronectins; D016212:Transforming Growth Factor beta; D002185:Cannabidiol; D018093:Gelatinases; D020782:Matrix Metalloproteinases; C069860:progelatinase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1