**6. Cannabinoids and Inflammatory Skin Disorders**

Phytochemicals have been increasingly employed in skin disorders as emerging data demonstrate their utility. Cannabinoids and their receptors are regarded with increasing interest for their implications in skin pathology, especially in the field of inflammatory skin disorders. While some action mechanisms are still unclear, encouraging data is becoming available as a result of a multitude of in vivo and in vitro studies investigating this topic [151]. Based on the reported anti-inflammatory properties, the application of cannabinoids has been attempted for various conditions such as acne, psoriasis, atopic dermatitis and even cancer [152]. Among the most common tested substances, CBD is preferred due to its lack of psychoactive effects, and there is evidence that it is effective in various skin inflammations, despite the incomplete understanding of its effects and interactions in molecular signaling pathways [153].

The simple and effective topical administration of cannabinoids on skin lesions is helpful not only in ensuring substance delivery to the inflammation site but also in observing local adverse effects [154]. The additional anti-aging, anti-oxidative and antitumoral effects provide supplementary benefits in the use of cannabinoids in other diseases that are associated with inflammation, including cancer [155,156]. However, many of the studies are preclinical, and there are very few trials free of bias with a large enough number of participants to be considered high-quality [157]. Nevertheless, the in vitro and animal models

support further research due to the uncovered effects of cannabinoids on inflammatory cells, cytokines and signaling pathways, which are mediated to various degrees by CB receptors, depending on the affinity and effectiveness of the tested substance [156].

The cannabinoid receptors are widely dispersed in the skin. CB1 and CB2 receptors have been identified on nerve fibers, keratinocytes and mast cells [158]. CB1 was isolated in the hair follicles, while CB2 was found in sebocytes [159,160]. The intensely studied TRP channels have been identified in the sensory nerve endings, keratinocytes, endothelial cells, mast cells and dendritic cells [161,162].
