Objective: Periodontitis is an infectious disease leading to inflammation and destruction of tissue surrounding and supporting the tooth. The progress of the inflammatory response depends on the host’s immune system and risk factors such as stress. The aim of the present study was to investigate the role of the endocannabinoid anandamide (AEA) in experimental periodontitis with restraint stress, since the endocannabinoid system is known to modulate the hypothalamo-pituitary-adrenal axis as well as immune functions and has been found in human gingival tissues. Methods: Experimental periodontitis was induced by ligature around first inferior molars and immobilization stress for 2 h twice daily for 7 days in a rat model. Results: Corticosterone plasma levels, locomotor activity, adrenal gland weight and bone loss were increased in periodontitis and stress groups, and there was also less weight gain. The inflammatory parameters such as prostaglandin E₂ (radioimmunoassay), nitric oxide (radioconversion of ¹⁴C-arginine), tumor necrosis factor (TNF)-α (ELISA) and interleukin (IL)-1β (Western blot) measured in the gingival tissue were significantly increased in the periodontitis groups compared to the control group. Local injection of AEA (10^–8M, 30 µl) decreased corticosterone plasma levels and the content of the cytokines TNF-α and IL-1β in gingival tissue in periodontitis-stress groups. These AEA-induced inhibitions were mediated by CB₁ and CB₂ cannabinoid receptors since the injection of both antagonists together, AM251 (10^–6M) and AM630 (10^–6M) in 30 µl, prevented these effects. Conclusion: The endocannabinoid AEA diminishes the inflammatory response in periodontitis even during a stressful situation.

Periodontitis is a chronic inflammatory complex disease caused by microorganisms. It may be influenced by diverse systemic disorders, environmental, genetic and socio-psychological factors with the ability to alter the balance of the host neuro-immunoendocrine responses. It is characterized by the progressive destruction of the tooth supporting apparatus leading to tooth loss, with possible impact on general health. Starting with a brief description of the periodontium, etiopathogenesis, repair processes and several physiological mechanisms and their disarray on periodontium response to bacterial challenge. Following, the negative effects of stress on the disease and some remarks on the recently discovered effects of oxytocin that modulate stress response and its role in individual coping mechanisms to stress. We also focus on the participation of components and functions of endocannabinoid system with anti-inflammatory actions on gingiva. Finally, a discussion that may link between diabetes, cardiovascular diseases, stroke and metabolic syndrome associated with periodontal disease; all of them sharing a common denominator that is inflammation and oxidative stress.