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Even with the widespread clinical use of cannabinoid receptor (CBR) stimulating compounds, such as palmitoylethanolamine, the role of CBR agonists on inflammatory skin diseases is not yet fully understood. This study was performed to investigate the effects of CBR agonists on skin inflammation, using acute and chronic inflammation animal models.The effectiveness of the newly synthesized cannabinoid receptor 1 (CB1R) agonists was determined using in vitro assays. Markers for epidermal permeability barrier function and skin inflammation were measured, and histological assessments were performed for evaluation.Topical application of CB1R-specific agonist significantly accelerated the recovery of epidermal permeability barrier function and showed anti-inflammatory activity in both acute and chronic inflammation models. Histological assessments also confirmed the anti-inflammatory effects, which is consistent with previous reports.All of the results suggest that topical application of CB1R-specific agonist can be beneficial for alleviating the inflammatory symptoms in chronic skin diseases, including atopic dermatitis.