Clinical Efficacy of Endocannabinoid-Mimetic Fatty Acid Amide as a Skin-Soothing Ingredient 

The use of cannabidiol (CBD) in cosmetics has gained significant attention due to its potential skin benefits; however, regulatory issues and the instability of CBD in topical formulations have hindered its widespread application. These challenges have prompted the search for alternatives that can mimic the effects of CBD without the associated drawbacks. The endocannabinoid system (ECS), which mediates the activity of phytocannabinoids in cells, has emerged as a target for the development of alternative molecules. This study explores the use of endocannabinoid-mimetic fatty acid amides, synthesized from sunflower oil, as a potential skin-soothing ingredient. 

Methods  

Endocannabinoid-mimetic fatty acid amides were synthesized using a lipase-catalyzed process. The activation of cannabinoid receptors was measured using a cAMP assay. The anti-inflammatory activity was evaluated using cultured human monocytes and ex vivo human skin explants. A clinical study was conducted to assess skin hydration, barrier function, and redness. 

Key Findings 

● Cannabinoid Receptor Activation: The synthesized sunflower oil-derived endocannabimimetic fatty acid amides activated both cannabinoid receptor 1 (CB1R) and CB2R in in vitro assays, with a higher potency for CB1R. This suggests that these molecules can interact with the ECS similarly to endocannabinoids. 

●Anti-Inflammatory Effects: In vitro studies using human monocytes showed that the endocannabimimetic fatty acid amide reduced the production of inflammatory cytokines (TNF-α, IL-6, and IL-8) induced by lipopolysaccharide (LPS) treatment. This indicates an anti-inflammatory potential comparable to that of CBD and arachidonylethanolamine (AEA). In ex vivo human skin explant models, the endocannabimimetic reduced inflammatory responses induced by physical damage and UVB radiation. Further, the expression of CB1R in the epidermal layer was increased by physical stress, and topical application of endocannabimimetics further upregulated CB1R expression. 

●Improved Skin Hydration and Barrier Function: Clinical studies involving 20 female subjects with acne-prone skin demonstrated that the topical application of a cream containing 0.1% of the sunflower oil-derived endocannabimimetic fatty acid amides resulted in a significant reduction in trans-epidermal water loss (TEWL) and increased skin hydration after 4 weeks. 

●Reduced Skin Redness and Sensitivity: Clinical assessments also showed a decrease in skin redness and an improvement in skin sensitivity, as indicated by a reduction in the ratio of interleukin-1-receptor antagonist (IL-1RA) to IL-1α in corneocytes after 4 weeks of product use. These findings suggest the potential of the ingredient to reduce inflammation and improve skin sensitivity. 

Researchers in the study presented a novel approach to developing skin-soothing cosmetic ingredients by using endocannabinoid-mimetic fatty acid amides derived from sunflower oil. The research is significant because it offers an alternative to CBD that can overcome regulatory hurdles and stability issues, while also showing promising efficacy in improving skin hydration, barrier function, and reducing inflammation. The study suggests that this new ingredient can be a promising alternative in cosmetic and therapeutic applications, and future research should explore the long-term effects and potential combination with other bioactive ingredients. 

Link to the study: https://www.mdpi.com/2079-9284/11/6/225