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Updated: May 22, 2026

Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
Long-term treatment with methanandamide attenuates LPS-induced periodontitis in rats
Cesar A Ossola1, Pablo N Surkin, Antonela Pugnaloni
1Laboratory of Oral Physiology, Department of Physiology, Dental School, University of Buenos Aires, Marcelo T. de Alvear 2142, 1122, Buenos Aires, Argentina.
Objective:
Evidence exists of the anti-inflammatory and immunological properties of endocannabinoids in various tissues; the aim of the present study was therefore to assess the effect of long-term treatment with the synthetic cannabinoid methanandamide (Meth-AEA) on the progression of periodontitis in rats.
Materials And Methods:
Periodontitis was induced by injecting LPS (1 mg/ml) into the gingiva around the neck of the first upper and lower molars, and into the inter-dental space between the first and second molars. This protocol was repeated for 6 weeks on days 1, 3, and 5 of each week.
Results:
Long-term treatment with topical Meth-AEA (500 ng/ml), applied daily to gingival tissue of rats induced with periodontitis, significantly diminished the alveolar bone loss, measured as the distance between the cemento-enamel junction and the alveolar crest, in both maxillary and mandibular first molars, compared to rats without treatment (P < 0.05). The treatment also reduced the production of some biological mediators of periodontal disease augmented by LPS, such as tumor necrosis factor alpha (from 119.4 ± 9.9 pg/mg protein to 75.1 ± 10.8, P < 0.05) and nitric oxide produced by inducible nitric oxide synthase (from 507.7 ± 107.1 pmol/min/mg protein to 163.1 ± 53.9, P < 0.01).
Conclusion:
These results demonstrate the beneficial effects of treatment with Meth-AEA on gingival tissue of rats with periodontitis.

