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Introduction: Cannabidiol (CBD) exhibits neuroprotective, anti-inflammatory, and immunomodulatory properties, making it a promising candidate for addressing inflammatory skin disorders like atopic dermatitis. Aim: This study aimed to (i) investigate CBD's impact on lymphocyte proliferation and lymphocyte viability; (ii) assess in vitro cytotoxicity U937 cells (a human promonocytic cell line) of CBD/cytotoxicity of CBD on U937 cells; (iii) provide insights into CBD immunomodulatory potential, and (iv) evaluate suitability of CBD for treating inflammatory skin conditions. Material and methods: To this aim PBMCs from healthy donors were cultured with mitogen and two different CBD doses (0.1 and 1 mg/ml), assessing B and T cell proliferation through flow cytometry. CBD inhibited mitogen-induced lymphocyte proliferation, reducing the percentage of proliferating T and B cells. Notably, both CBD doses did not exhibit cytotoxicity on lymphocytes as revealed by viability assessment. We also analysed the effect of CBD on U937 cells using an optical microscopy approach. Interestingly, the higher dose of CBD exerted a cytotoxic effect on U937 cells, while the lower dose was well tolerated. Results: We analysed the effect of an adjuvant treatment for atopic dermatitis with a CBD-containing cleansing cream in reducing itch. Notably, the treatment with the CBD-containing cleansing cream significantly reduced itch in patients suffering from atopic dermatitis. Conclusions: These findings affirm CBD's immunomodulatory characteristics, emphasizing its potential therapeutic application in inflammatory skin disorders. [ABSTRACT FROM AUTHOR]