Exploring the Biological Activity of Phytocannabinoid Formulations for Skin Health Care: A Special Focus on Molecular Pathways

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“Recent advancements have highlighted the potential of cannabis and its phytocannabinoids (pCBs) in skin health applications.

These compounds, through their interaction with the endocannabinoid system (ECS), show promise for skin health products. Their ability to regulate inflammation, oxidative stress and cell proliferation makes them useful in addressing skin problems such as inflammation, scarring, healing, acne and aging, positioning them as valuable tools for innovative skincare solutions.

In the present work, the cellular and molecular effects of proprietary pCB-based formulations on ECS modulation, inflammation and skin regeneration were investigated.

Using human dermal fibroblasts (HDF) and keratinocytes (HaCaT), the effect of formulations in both pre-treatment and treatment scenarios following exposure to stress-inducing agents was assessed. Key molecular markers were analyzed to tackle their efficacy in mitigating inflammation and promoting structural integrity and regeneration.

In vitro results showed that these formulations significantly reduced inflammation, promoted skin regeneration and improved structural functions. In vivo studies confirmed that the formulations were well-tolerated and led to noticeable improvements in skin health, including enhanced barrier function.

This study demonstrates the safety and efficacy of pCB-based formulations for cosmeceutical applications. By combining molecular analysis with in vivo testing, this research provides new insights into the therapeutic potential of pCBs for managing various skin conditions.”

https://pubmed.ncbi.nlm.nih.gov/39684852/

“This study confirms the safety and efficacy of pCB-based formulations for skin applications, highlighting their potential to enhance regeneration and structural processes. The findings underscore the promise of cannabis-based products in cosmetics and dermatology, meeting the rising demand for natural, effective skincare solutions and shaping the future of modern skincare and therapeutic approaches.”

https://www.mdpi.com/1422-0067/25/23/13142

Cannabis-Based Phytocannabinoids: Overview, Mechanism of Action, Therapeutic Application, Production, and Affecting Environmental Factors

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“This review provides an overview of cannabis-based phytocannabinoids, focusing on their mechanisms of action, therapeutic applications, and production processes, along with the environmental factors that affect their quality and efficacy.

Phytocannabinoids such as THC (∆9-tetrahydrocannabinol), CBD (cannabidiol), CBG (cannabigerol), CBN (cannabinol), and CBC (cannabichromene) exhibit significant therapeutic potential in treating various physical and mental health conditions, including chronic pain, epilepsy, neurodegenerative diseases, skin disorders, and anxiety.

The cultivation of cannabis plays a crucial role in determining cannabinoid profiles, with indoor cultivation offering more control and consistency than outdoor methods. Environmental factors such as light, water, temperature, humidity, nutrient management, CO2, and the drying method used are key to optimizing cannabinoid content in inflorescences.

This review outlines the need for broader data transfer between the health industry and technological production, especially in terms of what concentration and cannabinoid ratios are effective in treatment. Such data transfer would provide cultivators with information on what environmental parameters should be manipulated to obtain the required final product.”

https://pubmed.ncbi.nlm.nih.gov/39457041/

“Phytocannabinoids, including THC, CBD, CBG, CBN, and CBC, present broad therapeutic potential in a wide range of physical and mental conditions. They have shown efficacy in treating chronic pain, reducing seizure activity, slowing neurodegenerative processes, psoriasis, acne, loss of appetite, sleep disorders, and psychosis. Dose dependence was notable in most cases, and thus, this requires careful management.”

https://www.mdpi.com/1422-0067/25/20/11258

The Potential Role of Cannabidiol in Cosmetic Dermatology: A Literature Review

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“Cannabidiol (CBD) is a non-psychotropic cannabinoid with multiple pharmacological properties. Cannabidiol has attracted growing attention in the cosmetic industry, with an increasing number of CBD-containing skincare products on the market in recent years.

The aim of this review is to evaluate the current evidence on the use of CBD for cosmetic purposes. Following an overview of CBD and the endocannabinoid system in the skin, we summarize pre-clinical and clinical studies that address the potential of CBD in cosmetic dermatology.

Available in vitro and in vivo evidence suggests that CBD has anti-oxidant, anti-inflammatory, moisturizing, anti-acne, wound-healing, and anti-aging properties. However, only a few clinical studies have been conducted on the use of CBD in the skin. In addition, there is a critical need to develop an efficient drug-delivery system for topical/transdermal application of CBD. Further research, including clinical and pharmacokinetic studies, are needed to fully evaluate the role of CBD in cosmetic dermatology.”

https://pubmed.ncbi.nlm.nih.gov/39369127/

“Available evidence suggests that CBD has multiple beneficial properties in cosmetic dermatology, including anti-oxidant, anti-inflammatory, and anti-aging effects. Indeed, the skin is an ideal delivery route for CBD, enabling high local concentrations while minimizing systemic side effects. Given its highly lipophilic nature, delivering CBD through the stratum corneum into deeper skin layers requires specialized delivery systems, which are still under research and development.”

https://link.springer.com/article/10.1007/s40257-024-00891-y

Cannabinol modulates the endocannabinoid system and shows TRPV1-mediated anti-inflammatory properties in human keratinocytes

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“Cannabinol (CBN) is a secondary metabolite of cannabis whose beneficial activity on inflammatory diseases of human skin has attracted increasing attention. Here, we sought to investigate the possible modulation by CBN of the major elements of the endocannabinoid system (ECS), in both normal and lipopolysaccharide-inflamed human keratinocytes (HaCaT cells).

CBN was found to increase the expression of cannabinoid receptor 1 (CB1) at gene level and that of vanilloid receptor 1 (TRPV1) at protein level, as well as their functional activity. In addition, CBN modulated the metabolism of anandamide (AEA) and 2-arachidonoylglicerol (2-AG), by increasing the activities of N-acyl phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH)-the biosynthetic and degradative enzyme of AEA-and that of monoacylglycerol lipase (MAGL), the hydrolytic enzyme of 2-AG.

CBN also affected keratinocyte inflammation by reducing the release of pro-inflammatory interleukin (IL)-8, IL-12, and IL-31 and increasing the release of anti-inflammatory IL-10. Of note, the release of IL-31 was mediated by TRPV1. Finally, the mitogen-activated protein kinases (MAPK) signaling pathway was investigated in inflamed keratinocytes, demonstrating a specific modulation of glycogen synthase kinase 3β (GSK3β) upon treatment with CBN, in the presence or not of distinct ECS-directed drugs.

Overall, these results demonstrate that CBN modulates distinct ECS elements and exerts anti-inflammatory effects-remarkably via TRPV1-in human keratinocytes, thus holding potential for both therapeutic and cosmetic purposes.”

https://pubmed.ncbi.nlm.nih.gov/39275884/

“Taken together, our data suggest that CBN may hold true therapeutic potential to treat different human skin diseases. Such a biological activity of CBN occurs through engagement of selected elements of the endocannabinoid system—in particular TRPV1—a finding that paves the way to the development of distinct formulations of cannabis extracts for selected therapeutic applications.”

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.2122

Cheungsam Seed Husk Extract Reduces Skin Inflammation through Regulation of Inflammatory Mediator in TNF-α/IFN-γ-Induced HaCaT Cells

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“Cannabis contains numerous natural components and has several effects such as anticancer, anti-inflammatory and antioxidant.

Cheungsam is a variety of non-drug-type hemp, developed in Korea and is used for fiber (stem) and oil (seed). The efficacy of Cheungsam on skin is not yet known, and although there are previous studies on Cheungsam seed oil, there are no studies on Cheungsam seed husk.

In this study, we investigated the potential of Cheungsam seed husk ethanol extract (CSSH) to alleviate skin inflammation through evaluating the gene and protein expression levels of inflammatory mediators.

The results showed that CSSH reduced pro-inflammatory cytokines (IL-1β, IL-6, IL-8, MCP-1 and CXCL10) and atopic dermatitis-related cytokines (IL-4, CCL17, MDC and RANTES) in TNF-α/IFN-γ-induced HaCaT cells. Furthermore, ERK, JNK and p38 phosphorylation were decreased and p-p65, p-IκBα, NLRP3, caspase-1, p-JAK1 and p-STAT6 were suppressed after CSSH treatment. CSSH significantly increased the level of the skin barrier factors filaggrin and involucrin.

These results suggest that Cheungsam seed husk ethanol extract regulates the mechanism of skin inflammation and can be used as a new treatment for skin inflammatory diseases.”

https://pubmed.ncbi.nlm.nih.gov/38931136/

“The extract exerted anti-inflammatory and anti-atopic effects through mechanism regulation and skin barrier recovery. Therefore, Cheungsam seed husk extract may be useful for treating atopic dermatitis as well as other skin inflammatory diseases.”

https://www.mdpi.com/2223-7747/13/12/1704

Potential of cannabidiol as acne and acne scar treatment: novel insights into molecular pathways of pathophysiological factors

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“Cannabidiol (CBD), which is derived from hemp, is gaining recognition because of its anti-inflammatory and lipid-modulating properties that could be utilized to treat acne.

We conducted experiments to quantitatively assess the effects of CBD on acne-related cellular pathways. SEB-1 sebocytes and HaCaT keratinocytes were exposed to various CBD concentrations.

CBD exhibited a concentration-dependent impact on cell viability and notably reduced SEB-1 viability; furthermore, it induced apoptosis and a significant increase in the apoptotic area at higher concentrations. Additionally, CBD remarkably reduced pro-inflammatory cytokines, including CXCL8, IL-1α, and IL-1β. Additionally, it inhibited lipid synthesis by modulating the AMPK-SREBP-1 pathway and effectively reduced hyperkeratinization-related protein keratin 16. Simultaneously, CBD stimulated the synthesis of elastin, collagen 1, and collagen 3.

These findings emphasize the potential of CBD for the management of acne because of its anti-inflammatory, apoptotic, and lipid-inhibitory effects. Notably, the modulation of the Akt/AMPK-SREBP-1 pathway revealed a novel and promising mechanism that could address the pathogenesis of acne.”

https://pubmed.ncbi.nlm.nih.gov/38904694/

“In conclusion, this study highlights CBD’s potential to address multiple facets of acne pathophysiology through its anti-inflammatory, apoptotic, lipid-inhibitory effects, and modulation of the Akt/AMPK-SREBP-1 pathway. Additionally, it suggests the potential for CBD to contribute to the improvement of acne scarring through the synthesis of collagen and elastin. These findings offer a fresh perspective on acne management, suggesting that CBD-based treatments could provide a more comprehensive approach for individuals prone to inflammation and scarring. While further research is warranted, CBD’s unique mechanism of action presents a promising avenue for advancing acne therapeutics and improving patients’ quality of life.”

https://link.springer.com/article/10.1007/s00403-024-03131-9

Minor Cannabinoids as Inhibitors of Skin Inflammation: Chemical Synthesis and Biological Evaluation

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“Despite millennia of therapeutic plant use, deliberate exploitation of Cannabis‘s diverse biomedical potential has only recently gained attention. Bioactivity studies focus mainly on cannabidiol (CBD) and tetrahydrocannabinol (THC) with limited information about the broader cannabinome’s “minor phytocannabinoids”. In this context, our research targeted the synthesis of minor cannabinoids containing a lateral chain with 3 or 4 carbon atoms, focusing on cannabigerol (CBG) and cannabichromene (CBC) analogues. Using known and innovative strategies, we achieved the synthesis of 11 C3 and C4 analogues, five of which were inhibitors of skin inflammation, with the CBG-C4 ester derivative emerging as the most potent compound.”

https://pubmed.ncbi.nlm.nih.gov/38889235/

https://pubs.acs.org/doi/10.1021/acs.jnatprod.4c00212

Cannabinoids and Their Receptors in Skin Diseases

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“The therapeutic application of cannabinoids has gained traction in recent years. Cannabinoids interact with the human endocannabinoid system in the skin. A large body of research indicates that cannabinoids could hold promise for the treatment of eczema, psoriasis, acne, pruritus, hair disorders, and skin cancer. However, most of the available data are at the preclinical stage. Comprehensive, large-scale, randomized, controlled clinical trials have not yet been fully conducted. In this article, we describe new findings in cannabinoid research and point out promising future research areas.”

https://pubmed.ncbi.nlm.nih.gov/38003712/

“In recent years, some components of cannabis, also known as marijuana, have been studied. Cannabis has been used for various purposes throughout history, including recreational, medicinal, and industrial uses. In recent years, cannabinoid components are emerging as therapeutic alternatives for patients with a variety of illnesses and conditions. In particular, their anti-inflammatory properties have piqued the interest of dermatologists [1]. Given the growing number of pre-clinical and clinical studies exploring the potential of cannabinoids to treat dermatologic conditions, we here summarize reports of cannabinoid use in dermatologic therapy.”

https://www.mdpi.com/1422-0067/24/22/16523

Analgesic and Anti-Inflammatory Effects of 1% Tropical Cannabidiol Gel in Animal Models

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“Introduction: Cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is an interesting candidate for studying its anti-inflammatory effects, especially in the pre-clinical and animal models. Its anti-inflammatory effects, such as reduction of edema and arthritis, have been demonstrated in animal models. However, topical CBD administration requires further evaluation of CBD dosage and efficacy in animal models and clinical settings. 

Methods: This in vivo study investigated the anti-inflammatory effects of topical CBD administration in an animal model. Scientific experiments, including the formalin test, writhing test, carrageenan-induced edema, histopathological examination, and detection of various proinflammatory mediators, were performed. 

Results: The anti-inflammatory effects in vivo after inflammation induction, represented by decreased times of paw licking, degree of paw edema, and decreased writhing response, showed that 1% of tropical CBD use had significantly comparable or better anti-inflammatory effects when compared with tropical diclofenac, an anti-inflammatory agent. Moreover, the anti-inflammatory effects were significant compared with the placebo. In addition, the histopathological examination showed that topical CBD drastically reduced leukocyte infiltration and the degree of inflammation. This study also showed that the levels of various proinflammatory mediators in the plasma of mice treated with topical CBD did not differ from those treated with diclofenac. 

Conclusions: The topical administration of 1% CBD gel is a potentially effective candidate for an anti-inflammatory agent. Candidate for an anti-inflammatory agent.”

https://pubmed.ncbi.nlm.nih.gov/37669453/

https://www.liebertpub.com/doi/10.1089/can.2023.0070

Therapeutic Potential of Minor Cannabinoids in Dermatological Diseases-A Synthetic Review

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“Dermatological diseases pose a significant burden on the quality of life of individuals and can be challenging to treat effectively. In this aspect, cannabinoids are gaining increasing importance due to their therapeutic potential in various disease entities including skin diseases. In this synthetic review, we comprehensively analyzed the existing literature in the field of potential dermatological applications of a lesser-known subgroup of cannabinoids, the so-called minor cannabinoids, such as cannabidivarin (CBDV), cannabidiforol (CBDP), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabielsoin (CBE), cannabimovone (CBM) or cannabinol (CBN), while drawing attention to their unique pharmacological properties. We systematically searched the available databases for relevant studies and analyzed the data to provide an overview of current thematic knowledge. We looked through the full-text, bibliographic and factographic databases, especially Scopus, Web of Science, PubMed, Polish Scientific Journals Database, and selected the most relevant papers. Our review highlights that minor cannabinoids exhibit diverse pharmacological activities, including anti-inflammatory, analgesic, antimicrobial, and anti-itch properties. Several studies have reported their efficacy in mitigating symptoms associated with dermatological diseases such as psoriasis, eczema, acne, and pruritus. Furthermore, minor cannabinoids have shown potential in regulating sebum production, a crucial factor in acne pathogenesis. The findings of this review suggest that minor cannabinoids hold therapeutic promise in the management of dermatological diseases. Further preclinical and clinical investigations are warranted to elucidate their mechanisms of action, determine optimal dosage regimens, and assess long-term safety profiles. Incorporating minor cannabinoids into dermatological therapies could potentially offer novel treatment options of patients and improve their overall well-being.”

https://pubmed.ncbi.nlm.nih.gov/37630401/

https://www.mdpi.com/1420-3049/28/16/6149