Development of an Effective Acne Treatment Based on CBD and Herbal Extracts: Preliminary In Vitro, Ex Vivo, 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-1β and TNFα 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.

Bioactive Compounds from Natural Sources as Potential Adjuvants in the Treatment of Mild Acne Vulgaris

“…Moreover, in an ex vivo experimental model (human skin organ cultures) these three ingredients combined in a topical formulation showed efficacy in reducing proinflammatory cytokines IL-6 and IL-8 hypersecretion without hampering epidermal viability. The formulation turned out to be effective in a preliminary clinical study reducing significantly acne lesions and porphyrin levels [70]. Another study on miscellaneous natural products was carried out by Mias C. et al [71].…”

“…AE1 increased the expression level of TNF-α and suppressed the expression level of IL-1α and SRD5A1 (3-oxo-5α-steroid 4-dehydrogenase 1), whereas AE2 suppressed gene expression level of all those three [68]. Cohen G. et al (2023) investigated the anti-AV potential of different plant extracts and plant extract combinations with addition of cannabidiol, a phytocannabinoid from Cannabis sativa that exhibits promising spectrum of therapeutic actions for the treatment of acne [69]. The objective of this study that of exploring a possible synergistic effect between the plant extracts and the added active component by targeting different pathogenic factors of acne and minimizing side effects at the same time.…”

Treatment Advances for Acne Vulgaris: The Scientific Role of Cannabinoids

“…Although topical and systemic therapies are effective, as previously referred, they have some significant adverse effects that contribute to low patient compliance and adherence [88]. These side effects can result in patients discontinuing their treatment prematurely.…”

“…The potential side effects associated with conventional acne treatments can discourage patients from initiating or continuing their therapy, which reinforces the need for new and safer therapies [71]. Therefore, in the last years, there has been a growing interest in exploring natural and plant-derived ingredients, leading to the discovery and development of new products that offer efficiency while causing less irritation, resulting in improved outcomes and adherence [88].…”

In vitro acne disease model from inertial focusing effect for studying the interactions between sebocyte glands and macrophages

“…To further explore the applications of this model, we investigated the therapeutic mechanism of cannabidiol (CBD)-a clinically investigated drug, for treating acne, and revealed the roles of CBD in regulating lipid secretion, oxidative levels, and inflammation in acne. [25][26][27]…”