The bioactive effects of cannabinoids on skin
: from daily care to disease management applications

Student thesis: Doctoral Thesis

Abstract

Cannabinoids were first isolated in the 1960s from the Cannabis sativa L. plant. The study into the pharmacological and therapeutic potential of cannabinoids has gained traction in the past decades. This comes as a result of their recognized bioactivity, including antimicrobial, anti-inflammatory, and immunomodulatory activity, and due to the decriminalization of Cannabis-derived products continuing to expand worldwide. Cannabidiol (CBD) is one of the most researched cannabinoids. In particular, its anti-inflammatory activity has been vastly investigated, with a consequent unravelling of direct and indirect interactions with a myriad of receptors, broadening the potential therapeutic applications of CBD. More recently, cannabigerol (CBG), the main precursor of all phytocannabinoids, has also been in focus, although reports on this cannabinoid are still scarce in comparison with its counterpart CBD. Studies concerning the use of CBD and CBG for different therapies have increased, although the current role of cannabinoids in treating dermatological conditions has yet to be defined. Therefore, this thesis aims to explore the use of CBD and CBG for topical applications and to enlighten their potential as promotors of skin health and skin care. To this end, we first assessed their safety through a range of chemical and biological assays, including sensitization and mutagenicity tests. Although CBD extracted from the plant has solidified its use for topical applications, the CBG used in this work is produced through fermentation technology, and its safety profile has yet to be elucidated. After concluding both molecules were safe for topical application, we evaluated their potential as cosmetic ingredients. Several assays were performed to determine if CBD and CBG could be used for skin care and hair care, with both compounds demonstrating their ability to prevent inflammation in keratinocytes after exposure to pollution, and CBG presenting the capacity to induce hair growth in an ex vivo hair follicle model. Next, and considering the antimicrobial activity reported for cannabinoids, we focused on evaluating the antimicrobial and antibiofilm activity of CBD and CBG against bacteria and fungi belonging to the skin microbiota or associated with skin disorders and assessed their anti-adhesion effect against Staphylococci in keratinocytes. For the first time, we reported the MIC and MBC for Cutibacterium acnes, Pseudomonas aeruginosa and Escherichia coli. Thus, this study cemented the use of cannabinoids as antimicrobial agents, besides reporting on their potential as preservative ingredients and their positive lack of impact on the normal skin microbiota. We then evaluated the capacity of CBD and CBG to ameliorate the profile of inflammatory skin conditions, including psoriasis, irritant contact dermatitis (ICD) and atopic dermatitis (AD). Firstly, we developed, optimized, and validated ex vivo skin models with these conditions, and then assessed the impact of cannabinoids on them. Regarding the psoriatic model, CBD and CBG significantly reduced the inflammation and the hyperproliferation of keratinocytes, two of the main characteristics of this disease. Finally, the treatment of CBD and CBG for ICD and AD was also successful, with a reestablishment of the epidermal barrier and a reduction in inflammatory markers. These results are important as inflammatory skin conditions are associated with a low quality of life, and although corticosteroids are the go-to medications to alleviate symptoms, it has been demonstrated these medicines lose efficiency over time and have several side effects. We also attested that neither CBD nor CBG have a side effect common to betamethasone, hypertrichosis. Overall, the works herein reported provide valuable contributions in the field of dermatology, providing a step towards developing new applications for cannabinoids and potentially uncovering new topical treatments for skin disorders.
Date of Award26 Jan 2024
Original languageEnglish
Awarding Institution
  • Universidade Católica Portuguesa
SupervisorJoão C. Fernandes (Supervisor), João Azevedo Silva (Co-Supervisor) & Sara Silva (Co-Supervisor)

Keywords

  • Cannabidiol
  • Cannabigerol
  • Inflammatory skin conditions
  • Skin microbiota
  • Ex vivo models

Designation

  • Doutoramento em Biotecnologia

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