Development of an Effective Acne Treatment Based on CBD and Herbal Extracts: Preliminary <i>In Vitro</i>, <i>Ex Vivo,</i> and Clinical Evaluation

Abstract

Acne vulgaris, the most common form of acne, is characterized by a mixed eruption of inflammatory and noninflammatory skin lesions primarily affecting the face, upper arms, and trunk. The pathogenesis of acne is multifactorial and includes abnormal keratinization and plugging of the hair follicles, increased sebum production, proliferation and activation of Cutibacterium acnes ( C. acnes ; formerly Propionibacterium acnes , P. acnes ), and finally inflammation. Recent studies have found that cannabidiol (CBD) may be beneficial in the treatment of acne. The aim of this study was to explore natural plant extracts that, when combined with CBD, act synergistically to treat acne by targeting different pathogenic factors while minimizing side effects. The first stage of the study investigated the capacity of different plant extracts and plant extract combinations to reduce C. acnes growth and decrease IL‐1 β and TNF α secretion from U937 cells. The results found that Centella asiatica triterpene (CAT) extract as well as silymarin (from Silybum marianum fruit extract) had significantly superior anti‐inflammatory activity when combined with CBD compared to either ingredient alone. In addition, the CAT extract helped potentiate CBD‐induced C. acnes growth inhibition. The three ingredients were integrated into a topical formulation and evaluated in ex vivo human skin organ cultures. The formulation was found to be safe and effective, reducing both IL‐6 and IL‐8 hypersecretion without hampering epidermal viability. Finally, a preliminary clinical study of this formulation conducted on 30 human subjects showed a statistically significant reduction in acne lesions (mainly inflammatory lesions) and porphyrin levels, thereby establishing a tight correlation between in vitro , ex vivo , and clinical results. Further studies must be conducted to verify the results, including placebo‐controlled clinical assessment, to exclude any action of the formulation itself.