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The potential role of cannabinoids in dermatology
Journal of Dermatological Treatment
Abstract
Cannabis is increasingly being used world-wide to treat a variety of dermatological conditions. Medicinal cannabis is currently legalized in Canada, 31 states in America and 19 countries in Europe. The authors reviewed the literature on the pharmacology and use of cannabinoids in treating a variety of skin conditions including acne, atopic dermatitis, psoriasis, skin cancer, pruritus, and pain. Cannabinoids have demonstrated anti-inflammatory, antipruritic, anti-ageing, and antimalignancy properties by various mechanisms including interacting with the newly found endocannabinoid system of the skin thereby providing a promising alternative to traditional treatments.
... Numerous cannabinoid-containing products have potential uses in a variety of dermatological conditions, such as acne vulgaris, allergic dermatitis, psoriasis, and pruritus. [9][10][11] One particularly interesting effect is the antipruritic effect, which has been infrequently studied, especially in patients with uremic pruritus. These effects are mediated by neuronal activation and mast cell modulation. ...
... Cannabinoid binding to CB1 and CB2 receptors inhibits mast cell differentiation, aggregation, and histamine release, whereas cannabinoid binding to TRP-iron receptors reduces peripheral nerve activation. 9,12,13 Thus, cannabinoids seem to be effective in relieving pruritus through various mechanisms. ...
... [12][13][14] Abundant research has demonstrated several effects of CBD and THC, such as anti-pruritic properties; however, most of these studies were performed in nondialysis patients. 9 Szepietowski et al demonstrated the efficacy of an endocannabinoid cream in treating uremic pruritus in hemodialysis patients. 8 Cannabis sativa L, belonging to the Cannabaceae family, contains significant amounts of CBD and a small quantity of THC. ...
Rationale & Objective
This study aims to compare the efficacy of a cannabis cream and a placebo in the treatment of chronic kidney disease (CKD)-associated pruritus.
Study Design
A double-blind randomized controlled study.
Setting & Participants
Sixty hemodialysis patients with the worst itching intensity numerical rating scale (WI-NRS) ≥3.
Exposure
Patients received cannabis cream or placebo.
Outcomes
The primary endpoint was the WI-NRS score at week 4. The secondary endpoints included the WI-NRS at week 2, the Skindex-10 score at weeks 2 and 4, and the mean difference score between baseline and week 4 for the WI-NRS and the Skindex-10 score.
Analytical Approach
We used unpaired t tests or Mann Whitney U tests, along with χ² or Fisher exact tests as appropriate. The adjusted mean differences were determined using ANCOVA, adjusting for baseline scores.
Results
Among 60 participants, the mean age was 61.6 ± 14.4 years and the mean baseline WI-NRS was 6.7 ± 1.7. The placebo and cannabis cream groups were similar at baseline, although more individuals in the placebo group had diabetes. At 4 weeks, the WI-NRS dropped to 2.6 in the cannabis group and 3.6 in the placebo group (the mean difference after adjustment for baseline scores:−1.1, 95% CI, −2.1 to −0.2; P = 0.02). Skindex-10 scores at week 4 were also lower in the cannabis group, but after adjustment for baseline scores, statistical significance was not maintained. No side effects were observed in either group.
Limitations
A single study with a small sample size restricts its generalizability. Variances in participants’ diabetes statuses might have affected the itch outcomes. The absence of cannabinoid level assessment in blood prevents conclusive determination of the potential systemic impacts. A 4-week follow-up period inadequately captures long-term effect.
Conclusions
In CKD-associated pruritus, the topical cream containing cannabis significantly reduced the severity of itching symptoms compared to the placebo.
Trial Registration
clinicaltrials.gov Identifier: NCT06159686
... Psoriasis, which emphasizes two clinical manifestations, psoriasis vulgaris and psoriatic arthritis, is the most common autoimmune skin disease that currently affects about 4% of the population [51]. pCBs are known as candidate drugs in the treatment of psoriasis due to their effects of inhibiting the proliferation of keratinocytes and modulating the associated inflammatory response [57]. Acne vulgaris (acne) affects 9.4% of the world's population and 85% of adolescents [58]. ...
... The pathogenesis of psoriasis is complex and involves an association between genetic and environmental factors (trauma, infections, psychological stress, and drugs) [110]. The condition develops due to pathological interactions between skin immune cells and epidermal keratinocytes, leading to increased inflammation (due to the production of cytokines such as IL-17, IL-22, and TNF-α) and the excessive proliferation of keratinocytes, causing the characteristic alteration of skin called psoriatic plaque [7,57,105,110]. Cutaneous ECS inhibits cell growth and angiogenesis, leading to skin cell apoptosis, so CNBs have shown promising results in helping to treat psoriasis [7]. Clinically, psoriasis is characterized by erythematous, well-defined, raised plaques that are covered by pluristratified pearly white scales that are easily removable. ...
... Painful fissures may occur. After the remission of psoriasis plaques, post-inflammatory hypopigmentation or hyperpigmentation can be observed, and it is expected that these will fade in a few months [7,57,110]. ...
The chemical constituents of the Cannabis plant known as cannabinoids have been extensively researched for their potential therapeutic benefits. The use of cannabinoids applied to the skin as a potential method for both skin-related benefits and systemic administration has attracted increasing interest in recent years. This review aims to present an overview of the most recent scientific research on cannabinoids used topically, including their potential advantages for treating a number of skin conditions like psoriasis, atopic dermatitis, and acne. Additionally, with a focus on the pharmacokinetics and security of this route of administration, we investigate the potential of the transdermal delivery of cannabinoids as a method of systemic administration. The review also discusses the restrictions and difficulties related to the application of cannabinoids on the skin, emphasizing the potential of topical cannabinoids as a promising route for both localized and systemic administration. More studies are required to fully comprehend the efficacy and safety of cannabinoids in various settings.
... As the endocannabinoid system is present in the skin, the understanding of the mechanisms and receptors involved in the skin ECS have been researched [5][6][7]. As a consequence, new skin treatments may be developed [4,[8][9][10][11][12][13][14][15]. Therefore, this report aims to highlight the potential of CBD to formulations designed to skin diseases treatment or cosmetic therapy. ...
... TRPV channels, PPARγ as well as TRPA-1 and TRPM-8 are secundary targets of cannabinoids [17]. Cannabinoids may be used to improve skin health either in the treatment of skin disorders [15,18] or as cosmeceutical [15]. Regarding skin disorders, they may be useful in the treatment of inflammatory diseases such as psoriasis and acne [18]. ...
... TRPV channels, PPARγ as well as TRPA-1 and TRPM-8 are secundary targets of cannabinoids [17]. Cannabinoids may be used to improve skin health either in the treatment of skin disorders [15,18] or as cosmeceutical [15]. Regarding skin disorders, they may be useful in the treatment of inflammatory diseases such as psoriasis and acne [18]. ...
Cannabinoids display potential therapeutic applications. Regarding cannabidiol (CBD) to skin application, it shows an anti-inflammatory and antioxidant effect. Therefore, it has potential application in the treatment of acne, dermatitis, psoriasis, and on aged skin. CBD modulates several receptors of the endocannabinoid system of the skin (ECS) which are found all over skin components such as fibroblasts, keratinocytes, and sebaceous glands. In this review, CBD applications to skin treatments as well as the proposed mechanisms of action of CBD were described. The reports evaluated CBD effects alone or associated with other ingredient, in vitro or in vivo assays. The clinical trials, although incipient, showed the potential applications of CBD. Moreover, modulation of transient receptors potential channels family is believed to be related to its anti-acne, anti-atopic dermatitis and anti-aging properties. On the other hand, the anti-psoriasis activity is probably related to modulation of G protein-coupled receptor 55 and peroxisome proliferator-Abstract CIENT PERIODIQUE
... Cada día, es más abundante la evidencia científica que respalda el uso de ingredientes derivados de C. sativa para el manejo de afecciones cutáneas, como el acné, la dermatitis atópica, psoriasis, cáncer de piel, prurito y/o dolor (Izzo et al., 2009;Sheriff et al., 2020). Su uso en dermocosmética genera serias inquietudes en los consumidores, por una parte, porque son pocos los estudios clínicos que respaldan las bondades dermocosméticas de los fitocannabinoides; y por otra, porque tanto dermatólogos como usuarios están poco informados sobre las diferencias entre los derivados de la cannabis (Nickles y Lio, 2020). ...
... Mientras que a los cosméticos que incluyen extractos enriquecidos con fitocannabinoides se les atribuyen mayores propiedades terapéuticas (p.ej. antiinflamatorias, antipruriginosas, antienvejecimiento y antineoplásicas) debido a su interacción con el sistema endocannabinoide cutáneo (Sheriff et al., 2020). ...
... Las afirmaciones más comunes son "con CBD" (48%), "libre de THC" (32%), "de cannabis" (25%) y "con cannabis" (21%). Es de destacar, que ninguno de los cosméticos cannábicos revisados incluye otros fitocannabinoides como el Cannabigerol (CBG) o Cannabicromeno (CBC) que son de interés en dermocosmética (Citti et al., 2018;Sheriff et al., 2020). ...
A los ingredientes provenientes de la Cannabis sativa se les atribuyen numerosos beneficios para la piel, lo que ha dado lugar
al aumento vertiginoso de cosméticos que la incluyen en su formulación. El objetivo de este artículo es evaluar los cosméticos cannábicos de venta libre en Colombia, con especial interés en responder a la pregunta, si estos son recomendables
para su uso dermocosmético. Para cumplir con este objetivo se llevó a cabo una revisión sistemática de los ingredientes y las
características de 98 productos cosméticos para el cuidado de la piel con Notificación Sanitaria Obligatoria-NSO vigente en
el país. A grandes rasgos, está revisión arrojó que la mayoría (90%) de los cosméticos cannábicos disponibles en Colombia
son fabricados en el país. El 44% incluye en su formulación CBD, el 35% utiliza extractos de semilla de cannabis, mientras
que el 11% combina estos dos ingredientes. El análisis de los ingredientes reveló varias debilidades en la composición de
estos productos que limitan su uso dermocosmético. En algunos otros casos, se observaron ingredientes que incluso podrían
representar riesgos para la salud de la piel. Los hallazgos de esta revisión llevan a concluir que los cosméticos cannábicos
comercializados en el país no cuentan con estudios de aceptabilidad y eficacia que respalden su uso dermocosmético, ni
tampoco con pruebas que justifiquen muchas de las acciones cosméticas que indican en sus etiquetas. Dado la gran cantidad
de opciones de cosméticos cannábicos de venta libre, es recomendable que los consumidores verifiquen si estos cosméticos
cuentan con evidencia clínica que justifique su uso dermocosmético.
... Phytocannabinoids convey various biologically beneficial effects and properties; thus, they have been used as therapeutics since antiquity [54]. Further, they are linked to the modulation of the endocannabinoid mechanism and the class of receptors CB1 and CB2 distributed in various cells [55]. Additionally, some studies have reported that several phytocannabinoids exhibit potent antimicrobial activity against bacterial and fungal systems, and thus they can be used as antibiotics [55]. ...
... Further, they are linked to the modulation of the endocannabinoid mechanism and the class of receptors CB1 and CB2 distributed in various cells [55]. Additionally, some studies have reported that several phytocannabinoids exhibit potent antimicrobial activity against bacterial and fungal systems, and thus they can be used as antibiotics [55]. Moreover, phytocannabinoids might have therapeutic potential have antifungal properties, such as Phompsis ganjae [4], Stachybotrys bisbyi, Fusarium oxysporum [36], and Saccharomyces cerevisiae [37]. ...
... Phytocannabinoids convey various biologically beneficial effects and properties; thus, they have been used as therapeutics since antiquity [54]. Further, they are linked to the modulation of the endocannabinoid mechanism and the class of receptors CB 1 and CB 2 distributed in various cells [55]. Additionally, some studies have reported that several phytocannabinoids exhibit potent antimicrobial activity against bacterial and fungal systems, and thus they can be used as antibiotics [55]. ...
Cannabis belongs to the family Cannabaceae, and phytocannabinoids are produced by the Cannabis sativa L. plant. A long-standing debate regarding the plant is whether it contains one or more species. Phytocannabinoids are bioactive natural products found in flowers, seeds, and fruits. They can be beneficial for treating human diseases (such as multiple sclerosis, neurodegenerative diseases, epilepsy, and pain), the cellular metabolic process, and regulating biological function systems. In addition, several phytocannabinoids are used in various therapeutic and pharmaceutical applications. This study provides an overview of the different sources of phytocannabinoids; further, the biosynthesis of bioactive compounds involving various pathways is elucidated. The structural classification of phytocannabinoids is based on their decorated resorcinol core and the bioactivities of naturally occurring cannabinoids. Furthermore, phytocannabinoids have been studied in terms of their role in animal models and antimicrobial activity against bacteria and fungi; further, they show potential for therapeutic applications and are used in treating various human diseases. Overall, this review can help deepen the current understanding of the role of biotechnological approaches and the importance of phytocannabinoids in different industrial applications.
... According to Sheriff et al. (2020), the skin possesses a functional ECS with cannabinoid receptors in keratinocytes, glands that produce sebum, hair follicle cells, perspiration gland cells, neurons for sensation, immune system cells, mast cells, and fibroblasts. Skin problems including acne, psoriasis, seborrheic dermatitis, allergic contact dermatitis and even skin cancer may be related to disruption of the epidermal growth layer. ...
... Certain skin problems have been suggested to be treated by specialized agonists as well as inhibitors of the receptors for cannabinoids (CB1 and CB2). These drugs work by activating or inactivating these receptors [7]. ...
Biotechnology, as an interdisciplinary scientific field, is crucial in identifying the valuable active ingredients of plants. Their application extends beyond medical and pharmaceutical formulations to encompass cosmetics, in which these natural substances play a significant role. This article aimed to investigate the potential advantages of integrating cannabis-derived compounds into skincare cosmetic formulations. Their therapeutic efficacy on diverse dermatoses was emphasised. The diverse applications of cannabinoids and terpenes in cosmetic formulations were also examined. Scientific report analysis confirms the beneficial effects of cannabis-derived compounds, including cannabidiol and seed oil, in enhancing skin health and addressing inflammation and dermatological issues. The potential of cannabis-derived compounds in creating novel and effective cosmeceutical products was emphasised.
... Research into cannabinoids has unveiled their complex interplay with the pathogenesis of psoriasis through various skin receptors, such as CB1, CB2, GPCR55, TRPV1, and PPAR γ receptors [24][25][26][27][28][29]37]. CBD, a nonpsychoactive compound from Cannabis sativa, has demonstrated significant potential psoriasis management. ...
... Its efficacy, coupled with minimal addictive properties, positions CBD as a promising therapeutic agent. CBD achieves its effects by several mechanisms: inhibiting keratinocyte proliferation, reducing inflammation through the suppression of NF-kB and TNF-α activities, balancing Th1-Th2 immune responses, and modulating cytokine levels by inhibiting IL-17 and IFN-γ [24,27,28,30,[37][38][39][40][41][42]. ...
Introduction
Current topical treatments for psoriasis offer limited efficacy and are associated with long-term adverse effects in a subset of patients, highlighting the need for new therapeutic options. Cannabidiol (CBD), a non-psychoactive cannabinoid derived from Cannabis sativa L., has shown potential in reversing psoriasis pathology through its action on skin receptors in preclinical studies. Given the promising properties of CBD, transdermal patches containing this compound represent a novel approach to psoriasis treatment. However, comprehensive data on their efficacy and safety remain scarce.
Methods
We outline a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of CBD transdermal patches with minimal tetrahydrocannabinol (THC) in 60 patients with mild to moderate plaque-type psoriasis at a university hospital in Thailand (n = 60). This study aims to evaluate the changes in the local psoriasis severity index (LPSI), itch score via a visual analog scale, and occurrence of adverse events on day 0, 30, 60, and 90 of the study. Additionally, we will examine the alteration in the skin, gut, and oral microbiome in a subset of participants to explore potential correlations with treatment outcomes. The primary outcome will focus on the difference in LPSI scores at the end of the study period, employing an intention-to-treat analysis. Multivariate logistic regression will be used to identify baseline clinical and microbiological predictors of treatment response.
Conclusion
This study aims to investigate the efficacy and safety of CBD transdermal patches in alleviating the symptoms of psoriasis. The results of this study may highlight a novel topical treatment option that reduces suffering in patients with psoriasis. We also designed to provide a holistic evaluation by considering both clinical outcomes and the underlying biological mechanisms, including the interaction with the human microbiome. Through this trial, we aim to contribute valuable insights into personalized psoriasis management strategies.
... Specifically, CBD exhibits sebostatic properties, effectively inhibiting the lipogenic actions of compounds like arachidonic acid and a combination of linoleic acid and testosterone. It also suppresses sebocyte proliferation through the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels [301][302][303][304][305]. Given these properties, CBD is a promising candidate for the treatment of acne. ...
... [ [299][300][301][302][303][304][305] Biologic treatments (e.g., TNF-α inhibitors like adalimumab; IL-17 and IL-23 inhibitors like secukinumab) ...
Acne vulgaris is a common dermatological condition that can present across different ages but predominantly affects adolescents and young adults. Characterized by various lesion types, the pathogenesis of acne is complex, involving genetic, hormonal, microbial, and inflammatory factors. This review comprehensively addresses current and emerging acne management strategies, emphasizing both topical and systemic treatments, procedural therapies, and dietary modifications. Key topical agents include retinoids, benzoyl peroxide, antibiotics, and other specialized compounds. Systemic options like antibiotics, hormonal therapies, and retinoids offer significant therapeutic benefits, particularly for moderate to severe cases. Procedural treatments such as laser devices, photodynamic therapy, chemical peels, and intralesional injections present viable alternatives for reducing acne symptoms and scarring. Emerging therapies focus on novel biologics, bacteriophages, probiotics, and peptides, providing promising future options. This review underscores the importance of personalized approaches to treatment due to the multifaceted nature of acne, highlighting the potential of innovative therapies for improving patient outcomes.
... Isomerization of CBD to tetrahydrocannabinol under aqueous acidic conditions has also been reported (Gaoni and Mechoulam, 1966;Golombek et al., 2020). For these reasons, there remains ongoing interest in developing new compounds to target the cutaneous eCB system (Sheriff et al., 2020). ...
... The importance of the eCB system in epidermal homeostasis has become clear (Maccarrone et al., 2003), suggesting directions for the development of topical therapies on the basis of cutaneous eCB regulation (Angelina et al., 2020;Sheriff et al., 2020). This study showed that CBD activates a stress response and MTF-1metallothionein axis but only weakly inhibits eCB degradation mediators and cytokine pathways. ...
The endocannabinoid (eCB) system plays an active role in epidermal homeostasis. Phytocannabinoids such as CBD modulate this system but also act through eCB-independent mechanisms. This study evaluated effects of CBD, bakuchiol (BAK) and ethyl (linoleate/oleate) (ELN) in keratinocytes (KCs) and reconstituted human epidermis (RHE). Molecular docking simulations showed that each compound binds the active site of the eCB carrier fatty-acid-binding protein 5 (FABP5). However, BAK and ethyl linoleate bound this site with highest affinity when combined 1:1 (w/w) and in vitro assays showed that BAK+ELN most effectively inhibited FABP5 and fatty acid amide hydrolase (FAAH). In TNF-stimulated KCs, BAK+ELN reversed TNF-induced expression shifts and uniquely down-regulated type I interferon genes and PTGS2 (COX-2). BAK+ELN also repressed expression of genes linked to KC differentiation but up-regulated those associated with proliferation. Finally, BAK+ELN inhibited cortisol secretion in RHE skin (not observed with CBD). These results support a model in which BAK and ELN synergistically interact to inhibit eCB degradation, favoring eCB mobilization and inhibition of downstream inflammatory mediators (e.g., TNF, COX-2, type I interferon). Topical combination of these ingredients may thus enhance cutaneous eCB tone or potentiate other modulators, suggesting new ways to modulate the eCB system for innovative skincare product development. [200 words]
... In recent years, the importance of the endocannabinoid system for skin homeostasis has been demonstrated (Sheriff et al. 2020) as well as its involvement in some pathological processes (specifically, the CB1r seems to be involved in the processes of skin fibrosis), which justifies the possibility that its medicinal influence can be used for therapeutic purposes (Bíró et al. 2009;Correia-Sá et al. 2020). ...
Atopic dermatitis (AD) is a chronic inflammatory skin condition of significant health and social importance, which justifies the search for new means of treatment. Since the endogenous cannabinoid system appears to be involved in the pathogenesis of AD, the proposed article summarizes the clinical impact on skin inflammation in a rat model of 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis-like condition after exogenous systemic administration of the cannabinoid receptor type 1 (CB1r) agonist anandamide, as well as after local treatment with a newly synthesized pyrrole moiety containing bioconjugate of FELL tetrapeptide with CB1r-dependent analgesic activity. The changes in skin lesions and ear thickness were estimated along with the CB1r expression immunohistochemically determined on skin punch biopsies. The results showed attenuation of skin lesions by anandamide and lack of positive effect after introduction of CB1r antagonist, accompanied by a change in CB1r expression, suggesting the involvement of the cannabinoid system in the defensive functions of the skin. The topically applied newly synthesized bioconjugate also favorably affected skin manifestations of inflammation, but without a change in CB1r expression, suggesting the involvement of other mechanisms in the reported effects.
... In Canada, atopic dermatitis is one of the most common dermatologic conditions being treated with topical cannabis [60]. Dietary hempseed oil and CBD may have a beneficial effect on the symptoms and immune pathways of AD, respectively [61]. ...
Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic and recreational use of cannabis-based products. Sensitization possibly leading to allergy symptoms can occur not only through the smoking of cannabis, but also through ingestion, the inhalation of pollen, or direct contact. The severity of symptoms varies from benign pruritus to anaphylaxis. There is scant information available to support clinicians throughout the entire therapeutic process, starting from diagnosis and ending in treatment. In this review, we present six cases of patients in whom molecular in vitro testing revealed sensitization to cannabis extract and/or cannabis-derived nsLTP molecules (Can s 3). Based on these cases, we raise important questions regarding this topic. The article discusses current proposals and highlights the importance of further research not only on cannabis allergy but also on asymptomatic sensitization to cannabis allergens, which may be ascertained in some percentage of the population.
... . This is mainly the case with the activation of cannabinoid receptors (CB1/2) that are involved in the regulation of inflammation by modifying the level of TNFα and redox balance as well as the level of ROS [6]. The levels of the above parameters also change as a result of cell exposure to UV radiation [7]. Both phytocannabinoids and their 2-3-component systems were tested for their potential therapeutic use in lymphoma, glioblastoma multiform, and leukaemia [8][9][10]. ...
UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such consequences without causing undesirable side effects. The aim of this study was to analyse in vitro the effects of the phytocannabinoids cannabigerol (CBG) and cannabidiol (CBD), which differ in terms of biological effects. Furthermore, the combined use of both compounds (CBG+CBD) has been analysed in order to increase their effectiveness in human skin fibroblasts and keratinocytes protection against UVA-induced alternation. The results obtained indicate that the effects of CBG and CBD on the redox balance might indeed be enhanced when both phytocannabinoids are applied concurrently. Those effects include a reduction in NOX activity, ROS levels, and a modification of thioredoxin-dependent antioxidant systems. The reduction in the UVA-induced lipid peroxidation and protein modification has been confirmed through lower levels of 4-HNE-protein adducts and protein carbonyl groups as well as through the recovery of collagen expression. Modification of antioxidant signalling (Nrf2/HO-1) through the administration of CBG+CBD has been proven to be associated with reduced proinflammatory signalling (NFκB/TNFα). Differential metabolic responses of keratinocytes and fibroblasts to the effects of the UVA and phytocannabinoids have indicated possible beneficial protective and regenerative effects of the phytocannabinoids, suggesting their possible application for the purpose of limiting the harmful impact of the UVA on skin cells.
... Anti-inflammatory activity. The basis of CBD application in products intended for treating dermatological conditions such as acne, atopic dermatitis, or psoriasis is its ability to modulate the skin's inflammatory response [15]. CBD inhibits nuclear factor kappa B (NF-κB) and its inflammatory signaling pathway via stimulation of the kinase IKK (IκB kinase) [12]. ...
Known for its natural bio-compounds and therapeutic properties, hemp is being utilized in the development of skin products. These products offer a wide range of applications and benefits in the fields of natural bio-compounds, pharmaceutical technology, topical delivery systems, and cosmeceuticals. This manuscript deals with hemp actives, such as cannabinoids, terpenes, and flavonoids, and their diverse biological properties relative to topical application, including anti-inflammatory, antimicrobial, and antioxidant effects. Also, the paper reviews strategies to overcome poor penetration of hemp actives, as well as the integration of hemp actives in cosmeceuticals that provide natural and sustainable alternatives to traditional skincare products offering a range of benefits, including anti-aging, moisturizing, and soothing properties. The review aims to provide a comprehensive understanding of the development and manufacturing processes of skin products containing hemp actives. By delving into the science behind hemp-based products, the paper provides valuable insights into the potential of hemp as a versatile ingredient in the pharmaceutical and cosmetic industries. The utilization of hemp in these innovative products not only offers therapeutic benefits but also promotes natural and sustainable approaches to skincare.
... This work shows the possibility of inhibiting these two matrix metalloproteinases by CBD-loaded hydrogel and carriers containing both CBD and TER. Since the endocannabinoid system (ECS) receptors, CB1 and CB2, have endogenous ligands located in the skin, cannabinoid compounds, including CBD, can act as a stimulant or an inhibitory agent for the ECS, responsible for maintaining homeostasis, regulating sebum production, inhibiting or promoting the proliferation of keratinocytes, or inhibiting inflammatory promoters [73][74][75]. Thus, the regenerating and protective effects of cannabinoids and their positive effect on the skin aging processes may result from both the influence on the ECS and the inhibition of the activity of collagenase and elastase. ...
Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result , research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.
... The physicochemical characteristics of CBD condition its therapeutic efficacy by different routes of administration, which has made it necessary to find strategies to protect or/and encapsulate this active substance with the aim of improving its pharmacological activity and minimizing side effects. Many attempts have been made to design an optimal CBD formulation for topical administration due to its lipophilicity and the inherent potential of therapeutic use of phytocannabinoids for the treatment of skin disorders [29,30]. A CBD solution using propylene glycol as a vehicle showed interesting transdermal absorption in vitro, with the formulation including some essential oils and oleic acid as penetration enhancers [31]. ...
Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with potential anti-inflammatory and antioxidant activity for the topical treatment of inflammatory skin disorders. The microemulsion system was composed of a 20% CBD oil, which served as the hydrophobic phase; Labrasol/Plurol Oleique (1:1), which served as surfactant and cosurfactant (S/CoS), respectively; and an aqueous vegetal extract obtained from Sambucus ebulus L. (S. ebulus) ripe fruits, which has potential anti-oxidant and anti-inflammatory activity and which served as the aqueous phase. A pseudo-ternary phase diagram was generated, leading to the selection of an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after its reproducibility was tested, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size (by laser scattering), compatibility of components (by differential scanning calorimetry) and rheological properties (using a rotational rheometer). The designed microemulsion showed good stability and slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the aqueous phase of the microemulsion were studied via in vitro diffusion experiments using flow-through diffusion cells and were compared to those of a CBD oil and a microemulsion containing only CBD as an active substance. It was found that the inclusion of the original oil in microemulsions did not result in a significant modification of the release of CBD, suggesting the possibility of including hydrophilic active compounds in the formulation and establishing an interesting strategy for the development of future formulations.
... The physicochemical characteristics of CBD conditions its therapeutic efficacy by different routes of administration, which has made it necessary to find some strategies to protect or/and encapsulate this active substance with the aim to improve its pharmacological activity showing little side-effects. Many attempts have been made to design an optimal formulation with CBD for topical administration, due to its lipophilicity, and the inherent potential of therapeutic use of phytocannabinoids for the treatment of skin disorders [29,30]. A CBD solution using propylene glycol as a vehicle showed interesting transdermal absorption in vitro, including some essential oils and oleic acid as penetration enhancers [31]. ...
Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic antiinflamatory and antioxidant activity. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with a potential anti-inflammatory and antioxidant action for topical treatment of inflammatory skin disorders. The micro-emulsion system was obtained from a 20% CBD oil as hydrophobic phase, Labrasol/Plurol Oleique (1:1) as surfactant and cosurfactant (S/CoS) respectively and an aqueous vegetal extract obtained from S. ebulus L. ripe fruits, with a potential anti-oxidant and anti-inflammatory activity, as water phase. A pseudo-ternary phase diagram was elaborated, selecting an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after testing its reproducibility, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size by laser scattering, compatibility of components by differential scanning calorimetry and rheological properties using a rotational rheometer. The designed microemulsion showed good stability and a slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the water phase of the microemulsion were studied by in vitro diffusion experiments using flow-through diffusion cells in comparison to a CBD oil and a microemulsion only with CBD as active substance. It was evidenced that the inclusion of the original oil in microemulsions did not provoke a significant modification of the release of CBD, incorporating the possibility of including hydrophilic active compounds in the formulation, stablishing an interesting strategy for the development of future formulations.
... Clinical trials have reported that a combination of Lactobacillus plantarum and Bifidobacterium lactis significantly improves skin barrier function in atopic dermatitis patients [67,68]. Interestingly, cannabinoids, including tetrahydrocannabinol (THC) and cannabidiol (CBD) [69], have been shown to modulate macrophage polarization and reduce inflammation in skin disorders such as psoriasis and atopic dermatitis [70][71][72]. A recent study reported that topical application of a CBD-enriched ointment significantly improved skin barrier function in atopic dermatitis patients [73]. ...
Macrophages are critical components of the immune system and play vital roles in pathogen defense, immune regulation, and tissue repair. These cells exhibit different polarization states depending on environmental signals, and the M1/M2 paradigm is a useful tool for comprehending these states. This review article comprehensively presents the underlying mechanisms of M1 and M2 macrophage polarization and examines their polarization in various skin diseases. Additionally, this paper discusses therapeutic strategies that target M1 and M2 macrophage polarization in skin diseases. A more profound understanding of macrophage polarization in skin diseases could provide valuable insights for the development of innovative therapeutic strategies.
... Recent studies have reported the presence of a unique ECS within the skin. This discovery is supported by the identification of endogenous ligands for CB1R and CB2R receptors in the skin [47]. The epidermal ECS actively contributes to skin homeostasis and skin barrier integrity, with endocannabinoids intricately involved in regulating various neuro-immunoendocrine functions of the skin [1,48]. ...
Acne vulgaris is a prevalent dermatological disorder that impacts the quality of life for millions of people around the world. The multifactorial nature of this disorder requires innovative and effective treatment strategies. Over time, there has been a growing interest regarding the use of natural topical therapies, with cannabinoids emerging as a promising group of compounds for investiga-tion. In the context of acne treatment, cannabinoids are of particular interest due to their anti-acne properties, namely, lipostatic, anti-inflammatory, antiproliferative, and antimicrobial activities. Among these bioactive compounds, cannabidiol stands out as a notable derivative, exhibiting a promising spectrum of therapeutic actions. Pre-clinical and clinical studies have proven its ability to modulate sebum production, reduce inflammation, and inhibit bacterial proliferation - all of which are critical components in the pathogenesis of this dermatosis. This review provides a comprehen-sive overview of cannabinoids' potential as a novel and holistic approach to acne vulgaris treatment and summarizes recent developments in this area.
... The Cannabis sativa L. plant contains over a hundred different compounds, including terpenes, carbohydrates, esters, amides, and specific molecules named cannabinoids. Although more than 150 cannabinoids have been isolated from cannabis, the attention has been focused mainly on the "major cannabinoids": ∆9-tetrahydrocannabinol, cannabinol, cannabidiol (CBD), cannabigerol (CBG), and cannabichromene [1][2][3][4][5][6]. ...
Cannabigerol (CBG), a cannabinoid from Cannabis sativa L., recently attracted noteworthy attention for its dermatological applications, mainly due to its anti-inflammatory, antioxidant, and antimicrobial effectiveness similar to those of cannabidiol (CBD). In this work, based on results from studies of in vitro permeation through biomimetic membranes performed with CBG and CBD in the presence and in the absence of a randomly substituted methyl-β-cyclodextrin (MβCD), a new CBG extemporaneous emulgel (oil-in-gel emulsion) formulation was developed by spray-drying. The powder (SDE) can be easily reconstituted with purified water, leading to a product with chemical-physical and technological characteristics that are comparable to those of the starting emulgels (E). Thermogravimetric analysis (TGA), attenuated total reflection-Fourier transformed infrared spectroscopy (ATR-FTIR), x-ray powder diffraction (XRPD), and high-performance liquid chromatography (HPLC) analyses demonstrated that the spray-drying treatment did not alter the chemical properties of CBG. This product can represent a metered-dosage form for the localized treatment of cutaneous afflictions such as acne and psoriasis.
... Interestingly, human skin also participates in the ECS, and there are endogenous ligands in the skin that interact with two primary cannabinoid receptors [75]. However, these receptors exist in many skin structures, including epidermal keratinocytes, melanocytes, dermal cells, mast cells, sweat glands, hair follicles, and cutaneous nerve fibers [76,77]. ...
Cannabis plants have been used in medicine since ancient times. They are well known for their anti-diabetic, anti-inflammatory, neuroprotective, anti-cancer, anti-oxidative, anti-microbial, anti-viral, and anti-fungal activities. A growing body of evidence indicates that targeting the endocannabinoid system and various other receptors with cannabinoid compounds holds great promise for addressing multiple medical conditions. There are two distinct avenues in the development of cannabinoid-based drugs. The first involves creating treatments directly based on the components of the cannabis plant. The second involves a singular molecule strategy, in which specific phytocannabinoids or newly discovered cannabinoids with therapeutic promise are pinpointed and synthesized for future pharmaceutical development and validation. Although the therapeutic potential of cannabis is enormous, few cannabis-related approved drugs exist, and this avenue warrants further investigation. With this in mind, we review here the medicinal properties of cannabis, its phytochemicals, approved drugs of natural and synthetic origin, pitfalls on the way to the widespread clinical use of cannabis, and additional applications of cannabis-related products.
... Cannabinoids are a significant group of biologically active substances similar to the primary psychoactive compound derived from Cannabis sativa [2,3]. They are divided into three classes based on their site of production (Table 1). ...
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.
... O sistema endocanabinoide (SECB) é um sistema fisiológico que existe naturalmente no corpo humano recentemente descoberto. É composto por um conjunto de receptores específicos, enzimas destinadas a degradação e produção de endocanabinoides e moléculas sinalizadoras19 . Este sistema é responsável por regular diversas funções corporais e está envolvido na manutenção da homeostasia da pele por influenciar crescimento, diferenciação e sobrevivência celulares assim como nas respostas imunológica e inflamatória 20,21,22 . ...
A dermatite atópica e a psoríase são doenças inflamatórias crônicas da pele com manifestações características. A dermatite atópica, associada à predisposição genética, apresenta eczemas devido a uma tríade de causas: desregulação imunológica, alteração do microbioma cutâneo e disfunção da barreira cutânea. Há teorias que debatem a sequência dessas causas, com alguns alegando que a disfunção da barreira desencadeia a resposta imunológica e outros acreditando no contrário. A psoríase é marcada pelo surgimento de lesões papuloescamosas e pode estar associada à artrite psoriática. Sua fisiopatologia está relacionada a desequilíbrios no sistema imunológico, particularmente envolvendo células CD4+, Th1 e Th17. Uma planta, a Cannabis sativa, tem ganhado destaque no tratamento dessas condições devido à presença de canabinóides, especialmente o CBD. O sistema endocanabinoide, presente no corpo humano, interage com esses canabinóides, proporcionando efeitos anti-inflamatórios e antioxidantes, que são benéficos para o tratamento da dermatite atópica e da psoríase. Estudos apontam para a eficácia dos canabinóides na inibição da proliferação de queratinócitos e modulação de componentes inflamatórios. No entanto, ainda é necessário maior investigação para a padronização das doses e formulações, bem como para determinar a segurança e a eficácia do uso medicinal do CBD em condições dermatológicas.
... The cannabinoid receptors CB 1 and CB 2 have been identified in various cells of skin and hair follicles. Numerous skin disorders, such as atopic dermatitis, psoriasis, scleroderma, acne, hair growth disorders, skin pigmentation, allergic contact dermatitis and diseases related to keratin formation, are associated with dysregulation of the endocannabinoid system (Río et al., 2018;Sheriff et al., 2020;Peč et al., 2022). In a recent study, CBD showed a favorable response in the topical treatment of psoriasis (Puaratanaarunkon et al., 2022). ...
Although medical cannabis was legalized in Czechia in 2013 and its use in topical treatments of skin disorders is now allowed, galenic formulations prepared from medical cannabis have not been widely implemented in the Czech healthcare system. One of the main reasons is the lack of a straightforward standardized protocol for their preparation. Cannabinoids, e.g., cannabidiol (CBD) and tetrahydrocannabinol (THC), have been shown to have therapeutic effects on various skin conditions, such as atopic dermatitis, psoriasis, scleroderma, acne and skin pigmentation. Recognizing the potential of dermatological treatment with medical cannabis, the present study aimed to evaluate the extraction capacity of various pharmaceutical bases for cannabinoids and the stability of prepared galenic formulations for dermatological applications with respect to cannabinoid content. The results showed that the stability of cannabinoids in formulations depended on the bases’ physical and chemical properties. The highest THC decomposition was observed in cream bases and Vaseline, with estimated percentage loss of total content of up to 5.4% and 5.6% per week, respectively. In contrast, CBD was more stable than THC. Overall, the tested bases were comparably effective in extracting cannabinoids from plant material. However, olive oil and Synderman bases exhibited the highest cannabinoid extraction efficiencies (approximately 70%) and the best storage stabilities in terms of the content of monitored compounds. The proposed preparation protocol is fast and easily implementable in pharmacies and medical facilities.
... On the other hand, the CB2R located in the basal layer of epidermal keratinocytes, once activated, intensifies the body's anti-inflammatory response via reduction in the generation of ROS and TNFα. Hence, targeting CB2R may prove to be beneficial in the treatment of AD [166]. Improved epidermal barrier function, decreased Th2 inflammatory response, and suppressed mast cell production were observed after activating CB1R in various experimental mouse models of AD [167][168][169]. ...
Atopic dermatitis represents a complex and multidimensional interaction that represents potential fields of preventive and therapeutic management. In addition to the treatment armamentarium available for atopic dermatitis, novel drugs targeting significant molecular pathways in atopic dermatitis biologics and small molecules are also being developed given the condition’s complex pathophysiology. While most of the patients are expecting better efficacy and long-term control, the response to these drugs would still depend on numerous factors such as complex genotype, diverse environmental triggers and microbiome-derived signals, and, most importantly, dynamic immune responses. This review article highlights the challenges and the recently developed pharmacological agents in atopic dermatitis based on the molecular pathogenesis of this condition, creating a specific therapeutic approach toward a more personalized medicine.
... Hemp contains fatty acids that serve to maintain our skin supple and healthy while also avoiding indications of ageing and sun damage. In addition, hemp oil-based moisturisers and serums can be reported to regenerate healthy skin cells, such as keratinocytes, melanocytes, and Langerhans cells (Sheriff et al., 2020). The phenolic acid, phloroglucinol glucoside found in hemp seed oil is said to fight skin ageing (Hammond & Mahlberg, 1994). ...
Cannabis sativa L. is a flowering plant in the family Cannabaceae, and has been cultivated since ancient times for its fibres, oils, resins, dried inflorescences, and leaves. It can be used for a variety of industrial purposes. Over the years, the therapeutic and pharmacological efficacy of its phytoconstituents is shown in a variety of human diseases and health. The use and exploitation of the plant have sparked controversy; however, there are recent legalizations of its use for medical and other purposes in many countries within the corresponding legislative framework. In addition to this legalization, C. sativa is encouraging the very rapid growth of the cannabis oriented pharmaceutical industry. This chapter summarized recent developments in the science of C. sativa and its products about their industrial application, while also addressing gaps in the existing knowledge and future research directions for this high-value multi-use, and potential industrial plant with universal benefits.
... Several skin benefits have been reported for Cannabis extracts, including antiinflammatory, antioxidant, antiaging, and cytoprotective properties without psychoactive effects [1,2]. CBD has been used to treat numerous skin conditions, including urticaria, persistent psoriasis, acne, and epidermolysis bullosa [3][4][5]. As an antioxidant, CBD regulates the redox states of cells by reducing the formation of reactive oxygen species (ROS) and raising the level and activity of both nonenzymatic and enzymatic endogenous antioxidants at the transcriptional level. ...
The aim of this study was to encapsulate cannabidiol (CBD) extract in nanostructured lipid carriers (NLCs) to improve the chemical stability and anti-inflammatory activity of CBD for dermal delivery. CBD-loaded NLCs (CBD-NLCs) were prepared using cetyl palmitate (CP) as a solid lipid and stabilized with Tego® Care 450 (TG450) or poloxamer 188 (P188) by high-pressure homogenization (HPH). The CBD extract was loaded at 1% w/w. Three different oils were employed to produce CBD-NLCs, including Transcutol® P, medium-chain triglycerides (MCT), and oleic acid (OA). CBD-NLCs were successfully prepared with an entrapment efficiency (E.E.) of 100%. All formulations showed particle sizes between 160 and 200 nm with PDIs less than 0.10. The type of surfactant and oil used affected the particle sizes, zeta potential, and crystallinity of the CBD-NLCs. CBD-NLCs stabilized with TG450 showed higher crystallinity after production and storage at 30 °C for 30 days as compared to those with P188. Encapsulation of the CBD extract in NLCs enhanced its chemical stability after exposure to simulated sunlight (1000 kJ/m2) compared to that of the CBD extract in ethanolic solution. The CBD-NLCs prepared from MCT and OA showed slower CBD release compared with that from Transcutol® P, and the kinetic data for release of CBD from CBD-NLCs followed Higuchi’s release model with a high coefficient of determination (>0.95). The extent of CBD permeation through Strat-M® depended on the oil type. The cytotoxicity of the CBD extract on HaCaT and HDF cells was reduced by encapsulation in the NLCs. The anti-inflammatory activity of the CBD extract in RAW264.7 cell macrophages was enhanced by encapsulation in CBD-NLCs prepared from MCT and OA.
... Cannabinoids are a large group of compounds belonging to lipid mediators interacting with cannabinoid receptors (CB1 and CB2), which includes endocannabinoid, phytocannabinoids, and synthetic cannabinoids [1]. Endocannabinoids are lipid mediators, which are derivatives of polyunsaturated fatty acids, such as amides or esters (including anandamide, AEA and 2-arachidonoylglycerol, 2-AG), which are synthesized in the human organism through various metabolic pathways [2]. ...
Phytocannabinoids are naturally occurring compounds, the main source of which is Cannabis sativa L. Through direct action or interaction with G protein-coupled receptors, they affect ROS and pro-inflammatory cytokines levels and modify the effectiveness of transcription factor responsible for the biosynthesis of antioxidants which lead to oxidative stress and its consequences. Due to the modification of the redox balance and inflammation, phytocannabinoids are used in the treatment of various diseases, including autoimmune dermatoses, such as atopic dermatitis and psoriasis. Psoriasis is one of the most common dermatoses, and one of unknown etiology. A disturbed redox balance with a shift towards the oxidation leads to oxidative stress, resulting in oxidative modifications, mainly of lipids and proteins, and prolonged activation of immune cells and increased generation of pro-inflammatory cytokines, resulting in chronic inflammation. Given the biological activity of phytocannabinoids, they have become the focus of research as components of pharmacotherapy for psoriasis. Beneficial effects were shown by various representatives of phytocannabinoids, but the effect of cannabidiol (CBD) on skin cells (in vitro and ex vivo) and on blood cells from patients with psoriasis vulgaris and psoriatic arthritis has been most often evaluated in recent years.
... Phytocannabinoids have been described as promising agents in the treatment of psoriasis due to their capacity to inhibit keratinocytes hyperproliferation, while also ameliorating the associated inflammatory component [196]. Indeed, cannabinoid receptors are widely expressed throughout the skin epithelium, where CB1 activation has been associated with a decrease in the proliferation of epidermal keratinocytes. ...
The phytocannabinoid cannabidiol (CBD) is receiving increasing attention due to its pharmacological properties. Although CBD is extracted from Cannabis sativa, it lacks the psychoactive effects of Δ9-tetrahydrocannabinol (THC) and has become an attractive compound for pharmacological uses due to its anti-inflammatory, antioxidant, anticonvulsant, and anxiolytic potential. The molecular mechanisms involved in CBD’s biological effects are not limited to its interaction with classical cannabinoid receptors, exerting anti-inflammatory or pain-relief effects. Several pieces of evidence demonstrate that CBD interacts with other receptors and cellular signaling cascades, which further support CBD’s therapeutic potential beyond pain management. In this review, we take a closer look at the molecular mechanisms of CBD and its potential therapeutic application in the context of cancer, neurodegeneration, and autoimmune diseases.
... The results demonstrated that CBD, CBG and CBD/THC combination consistently reduced proinflammatory cytokines, such as TNF-α, IL-1β, IL-6 and INF-γ 136]. Other preclinical and clinical studies suggest that cannabinoids can attenuate symptoms of many chronic inflammatory and autoimmune disorders, such as MS, rheumatoid arthritis, colitis, Parkinson's disease, hepatitis, and other [7,133,134,[137][138][139][140][141][142], as well as neuropathic and inflammatory pain [143][144][145]. Considering that the SARS-CoV-2 infection is associated with a cytokine storm and overproduction of IL-6, IL-8 and TNF-α, cannabinoids have been preliminarily tested for alleviating the symptoms of the disease and reducing the ongoing inflammation [99]. ...
Cannabidiol (CBD) has been reported to have a plethora of therapeutic opportunities in many diseases. Current CBD delivery systems include suspension, emulsion, or nanoparticles, which enable the rapid release of CBD. However, in some cases, long-term exposure to drugs is preferred, such as in controlling inflammation. This study aimed to prepare a CBD-rich hydrogel that exhibits controlled and sustained release of CBD while maintaining CBD bioactivity. Herein, PVA mixed with propylene glycol (PG) or vegetable glycerine (VG) in the presence of CBD were used to fabricate hydrogels through a cyclic freeze–thaw process. The successful loading of CBD inside the PVA gel was macroscopically demonstrated by the uniform pink color of the gel and chemically identified by the characteristic absorptions of CBD at 1630 and 1585 cm⁻¹ in Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) revealed small, fine pores dispersed throughout the gels when PG or VG was added. Differential scanning calorimeter (DSC) curves showed that the gels containing VG were more amorphous than those without VG. Thermogravimetric analyzer (TGA) results showed that the CBD-containing gels were stable up to 100 °C when they started to lose water and up to about 200 °C when they started to lose other molecules such as PG, indicating a good shelf-life. A compression test showed that the hydrogel was soft and could tolerate more than 60% deformation and 45 kPa pressure. CBD in vitro release assessment through ultraviolet-visible (UV-vis) spectrophotometer and UPLC-MS/MS analysis demonstrated that the hydrogel can continually release CBD for at least 24 h. Adding VG could significantly reduce PVA crystallinity and promote the release of CBD from the hydrogel into an aqueous solution; adding PG and VG together can regulate the release rate of CBD. Finally, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay proved that the CBD released from the hydrogels through 24 h had good antioxidant activity. Considering the biocompatible nature of PVA, the CBD-enriched PVA hydrogels developed in this study can be used to topically deliver CBD to tissues or the body to treat inflammation and promote wound healing.
Given the growing interest in non-toxic materials with good anti-inflammatory and antimicrobial mechanical properties, this work focuses on preparing chitosan sponges with violacein and cannabis oil crosslinked with dialdehyde chitosan. The sponge was tested for its physicochemical and biological properties, presenting a high swelling rate, good thermal stability, and satisfactory mechanical properties. The obtained sponge's water vapor transmission rate was 2101 g/m²/day and is within the recommended values for ideal wound dressings. Notably, adding violacein favorably affected the material's porosity, which is essential for dressing materials. In addition, studies have shown that the designed material interacts with human serum albumin and exhibits good antioxidant and anti-inflammatory properties. The antibacterial properties of the prepared biomaterial were assessed using the Microtox test against A. fisherii (Gram-negative bacterium) and S. aureus (Gram-positive bacterium). The investigated material provides potential therapeutic benefits due to the synergistic action of chitosan, violacein, and cannabis oil so that it could be used as a dressing material. The natural origin of the substances could provide an attractive and sustainable alternative to traditional commercially available dressings.
Cannabinoids are compounds found in and derived from the Cannabis plants that have become increasingly recognised as significant modulating factors of physiological mechanisms and inflammatory reactions of the organism, thus inevitably affecting maintenance of homeostasis. Medical Cannabis popularity has surged since its legal regulation growing around the world. Numerous promising discoveries bring more data on cannabinoids’ pharmacological characteristics and therapeutic applications. Given the current surge in interest in the medical use of cannabinoids, there is an urgent need for an effective method of their administration. Surpassing low bioavailability, low water solubility, and instability became an important milestone in the advancement of cannabinoids in pharmaceutical applications. The numerous uses of cannabinoids in clinical practice remain restricted by limited administration alternatives, but there is hope when biodegradable polymers are taken into account. The primary objective of this review is to highlight the wide range of indications for which cannabinoids may be used, as well as the polymeric carriers that enhance their effectiveness. The current review described a wide range of therapeutic applications of cannabinoids, including pain management, neurological and sleep disorders, anxiety, and cancer treatment. The use of these compounds was further examined in the area of dermatology and cosmetology. Finally, with the use of biodegradable polymer-based drug delivery systems (DDSs), it was demonstrated that cannabinoids can be delivered specifically to the intended site while also improving the drug’s physicochemical properties, emphasizing their utility. Nevertheless, additional clinical trials on novel cannabinoids’ formulations are required, as their full spectrum therapeutical potential is yet to be unravelled.
Background
Atopic dermatitis (AD), psoriasis (PS), and inflammatory acne (IA) are well-known as inflammatory skin diseases. Studies of the transcriptome with altered expression levels have reported a large number of dysregulated genes and gene clusters, particularly those involved in inflammatory skin diseases.
Objective
To identify genes commonly shared in AD, PS, and IA that are potential therapeutic targets, we have identified consistently dysregulated genes and disease modules that overlap with AD, PS, and IA.
Methods
Microarray data from AD, PS, and IA patients were downloaded from Gene Expression Omnibus (GEO), and identification of differentially expressed genes from microarrays of AD, PS, and IA was conducted. Subsequently, gene ontology and gene set enrichment analysis, detection of disease modules with known disease-associated genes, construction of the protein-protein interaction (PPI) network, and PPI sub-mapping analysis of shared genes were performed. Finally, the computational docking simulations between the selected target gene and inhibitors were conducted.
Results
We identified 50 shared genes (36 up-regulated and 14 down-regulated) and disease modules for each disease. Among the shared genes, 20 common genes in PPI network were detected such as LCK, DLGAP5, SELL, CEP55, CDC20, RRM2, S100A7, S100A9, MCM10, AURKA, CCNB1, CHEK1, BTC, IL1F7, AGTR1, HABP4, SERPINB13, RPS6KA4, GZMB, and TRIP13. Finally, S100A9 was selected as the target gene for therapeutics. Docking simulations between S100A9 and known inhibitors indicated several key binding residues, and based on this result, we suggested several cannabinoids such as WIN-55212-2, JZL184, GP1a, Nabilone, Ajulemic acid, and JWH-122 could be potential candidates for a clinical study for AD, PS, and IA via inhibition of S100A9-related pathway.
Conclusion
Overall, our approach may become an effective strategy for discovering new disease candidate genes for inflammatory skin diseases with a reevaluation of clinical data.
In recent years, the medical use of cannabinoids has attracted growing attention worldwide. In particular, anti‐inflammatory properties of cannabinoids led to their emergence as potential therapeutic options for autoimmune and inflammatory disorders. Recent studies have also shown that cannabinoid receptors are widely expressed and have endogenous ligands in the skin, suggesting that the skin has its own endocannabinoid system. The aim of this review is to discuss the potential therapeutic effects of cannabinoids in autoimmune and inflammatory skin diseases. Following an overview of cannabinoids and the endocannabinoid system, we describe the cellular and molecular mechanisms of cannabinoids in skin health and disease. We then review the clinical studies of cannabinoids in autoimmune and inflammatory skin diseases including systemic sclerosis (SSc), dermatomyositis (DM), psoriasis (Pso) and atopic dermatitis (AD). A primary literature search was conducted in July 2023, using PubMed and Web of Science. A total of 15 articles were included after excluding reviews, non‐human studies and in vitro studies from 389 non‐duplicated articles. Available evidence suggests that cannabinoids may be beneficial for SSc, DM, Pso and AD. However, further studies, ideally randomized controlled trials, are needed to further evaluate the use of cannabinoids in autoimmune and inflammatory skin diseases.
Illicit or recreational drugs may lead to specific dermatological diseases, or may lead to exacerbation of chronic dermatological disease. Dermatology health care professionals are not yet routinely asking patients about the use of recreational drugs, although questioning about the use of alcohol and smoking history is routinely taught to medical students and other undergraduates. Recreational drugs may be prohibited in some cultures and societies, but this does not mean that they are not available or used. For many countries, it is important for dermatology health care professionals to be familiar with the use/type/consequences of illicit drug usage, and to be unafraid of asking patients directly and routinely about their use. Where there are socio‐legal implications of admitting to the use of recreational drugs (particularly if there is a risk of severe punishment for the use of illicit drugs), a careful but sympathetic approach may be necessary.
Acne vulgaris is a prevalent dermatological disorder that impacts the quality of life for millions of people around the world. The multifactorial nature of this disorder requires innovative and effective treatment strategies. Over time, there has been a growing interest regarding the use of natural topical therapies, with cannabinoids emerging as a promising group of compounds for investigation. In the context of acne treatment, cannabinoids are of particular interest due to their anti-acne properties, namely, lipostatic, anti-inflammatory, antiproliferative, and antimicrobial activities. Among these bioactive compounds, cannabidiol stands out as a notable derivative, exhibiting a promising spectrum of therapeutic actions. Pre-clinical and clinical studies have proven its ability to modulate sebum production, reduce inflammation, and inhibit bacterial proliferation—all of which are critical components in the pathogenesis of this dermatosis. This review provides a comprehensive overview of cannabinoids’ potential as a novel and holistic approach to acne vulgaris treatment and summarizes recent developments in this area.
Melanoma is one of the leading fatal forms of cancer, yet from a treatment perspective, we have minimal control over its reoccurrence and resistance to current pharmacotherapies. The endocannabinoid system (ECS) has recently been accepted as a multifaceted homeostatic regulator, influencing various physiological processes across different biological compartments, including the skin. This review presents an overview of the pathophysiology of melanoma, current pharmacotherapy used for treatment, and the challenges associated with the different pharmacological approaches. Furthermore, it highlights the utility of cannabinoids as an additive remedy for melanoma by restoring the balance between downregulated immunomodulatory pathways and elevated inflammatory cytokines during chronic skin conditions as one of the suggested critical approaches in treating this immunogenic tumor.
This article is categorized under: Cancer > Molecular and Cellular Physiology
Currently, there is an increased interest from both scientists and consumers in the application of cannabis/hemp/phytocannabinoids in skin-related disorders. However, most previous investigations assessed the pharmacological properties of hemp extracts, cannabidiol (CBD), or tetrahydro-cannabinol (THC), with very few studies focusing on minor phytocannabinoids from hemp. In this context, the current work explored the in vitro anti-melanoma, anti-melanogenic, and anti-tyrosinase effects of cannabidiol (CBD) and three minor phytocannabinoids, namely cannabigerol (CBG), cannabinol (CBN), and cannabichromene (CBC). Among the tested human malignant melanoma cells (A375, SH4, and G361), only A375 cells were highly susceptible to the 48 h treatment with the four phytocannabinoids (IC 50 values between 12.02 and 25.13 µg/mL). When melanogenesis was induced in murine melanoma B16F10 cells by α-melanocyte stimulating hormone (αMSH), CBD, CBG, and CBN significantly decreased the extracellular (29.76-45.14% of αMSH+ cells) and intracellular (60.59-67.87% of αMSH+ cells) melanin content at 5 µg/mL. Lastly, CBN (50-200 µg/mL) inhibited both mushroom and murine tyrosinase, whereas CBG (50-200 µg/mL) and CBC (100-200 µg/mL) down-regulated only the mushroom tyrosinase activity; in contrast, CBD was practically inactive. The current data show that tyrosinase inhibition might not be responsible for reducing the melanin biosynthesis in α-MSH-treated B16F10 cells. By evaluating for the first time the preliminary anti-melanoma, anti-melanogenic, and anti-tyrosinase properties of CBN and CBC and confirming similar effects for CBD and CBG, this study can expand the utilization of CBD and, in particular, of minor phytocannabinoids to novel cosmeceutical products for skin care.
Industrial Hemp, or Cannabis sativa L., belongs to Cannabiaceae family is an oleaginous, the oldest medicinal plant cultivated by humankind in India, China, Pakistan, Nepal, Bhutan, Afghanistan and Iran, Persians specifically for medicinal properties and non-edible fiber content. Initial uses of Cannabis date back to almost 5000 years in India which was well documented in Ayurveda. Cannabis sativa and Cannabis indica were native of Indian origin found as wild noxious weed in the Indian Himalayan Region. Since then, hemp consumption has been spurred on by its wide range of properties and uses from Indian Himalayan civilization to another through consecutive millennia. Cannabis research work remains years behind than other crops because of the long legacy of prohibition and stigmatization. Hemp has historically been attractive for its top-quality fiber and edible oil. Hemp fibers are used in paper, carpeting, home furnishing, construction materials, insulation materials, hempcrete, auto parts and composites. The female inflorescence is the main product of Medical Cannabis sativa (marijuana or drug type). Cannabis sativa has developed full of glandular type of trichomes. Phytocannabinoids are produced and stored in glandular trichomes, located all over the aerial part of the plant. Phytocannabinoids possess therapeutic, antibacterial, and antimicrobial properties. The nutritional value of hemp is attracting special attention since hemp seed protein and oil is used in treatment of several human diseases.
Cannabis sativa (Hemp) is an herbaceous species used in foods and beverages, cosmetics, pharmaceuticals, nutraceuticals, etc. It has two active constituents: Tetrahydrocannabinol and Cannabidiol. Cannabinoids suppress uncontrolled growth of cancerous cells, provide pain relief to HIV patients, and help with neurogenic symptoms. Cannabis extracts have exhibited more effectiveness against various bacteria and yeast. Improvement in skin hydration and skin elasticity was observed. Excessive sebum production and proliferation of sebocytes is normalized. Hemp extracts arrest the anagen phase of the hair cycle to cause reversal of the temporal and vertex thinning in Androgenetic alopecia. It has antioxidant potential as well as an anti-ageing effect. Owing to the variability in legislation in different countries, Cannabis sativa poses challenges in research. This chapter discusses the diverse applications of this double-edged herb.
Background: Marijuana extracts (cannabinoids) have been used for several millennia for pain treatment. Regarding the site of action, cannabinoids are highly promiscuous molecules, but only two cannabinoid receptors (CB1 and CB2) have been deeply studied and classified. Thus, therapeutic actions, side effects and pharmacological targets for cannabinoids have been explained based on the pharmacology of cannabinoid CB1/CB2 receptors. However, the accumulation of confusing and sometimes contradictory results suggests the existence of other cannabinoid receptors. Different orphan proteins (e.g., GPR18, GPR55, GPR119, etc.) have been proposed as putative cannabinoid receptors. According to their expression, GPR18 and GPR55 could be involved in sensory transmission and pain integration.
Methods: This article reviews select relevant information about the potential role of GPR18 and GPR55 in the pathophysiology of pain.
Results: This work summarized novel data supporting that, besides cannabinoid CB1 and CB2 receptors, GPR18 and GPR55 may be useful for pain treatment.
Conclusion: There is evidence to support an antinociceptive role for GPR18 and GPR55.
Background:
Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation.
Objective:
In order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation.
Methods:
The effects of selected compounds on FcεRI-induced histamine and β-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited.
Results:
We found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen-dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine.
Conclusion:
Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.
Rationale:
Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors. Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme.
Objectives:
Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD.
Results:
EAM was characterized by marked myocardial T cell-infiltration, profound inflammatory response, fibrosis (measured by qRT-PCR, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice.
Conclusion:
CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.
Escalated sebum fabrication is seen with an unattractive look and adds to the growth of acne. We aimed to investigate the efficacy and safety of 3% Cannabis seeds extract cream on human cheek skin sebum and erythema content. For this purpose, base plus 3% Cannabis seeds extract and base (control) were prepared for single blinded and comparative study. Healthy males were instructed to apply the base plus 3% Cannabis seeds extract and base twice a day to their cheeks for 12 weeks. Adverse events were observed to determine skin irritation. Measurements for sebum and erythema content were recorded at baseline, 2nd, 4th, 6th, 8th, 10th and 12th week in a control room with Sebumeter and Mexameter. Base plus 3% Cannabis seeds extract was found to be safe in volunteers. Measurements demonstrated that skin sebum and erythema content of base plus 3% Cannabis seeds extract treated side showed significant decrease (p<0.05) compared with base treated side. Base plus 3% Cannabis seeds extract showed safety. It was well tolerated for the reduction of skin sebum and erythema content. Its improved efficacy could be suggested for treatment of acne vulgaris, seborrhea, papules and pustules to get attractive facial appearance.
Cannabidiol (CBD), the main non-psychoactive cannabinoid, has been previously shown by us to ameliorate clinical symptoms and to decrease inflammation in myelin oligodendrocyte glycoprotein (MOG)35-55-induced mouse experimental autoimmune encephalomyelitis model of multiple sclerosis as well as to decrease MOG35-55-induced T cell proliferation and IL-17 secretion. However, the mechanisms of CBD anti-inflammatory activities are unclear.
Here we analyzed the effects of CBD on splenocytes (source of accessory T cells and antigen presenting cells (APC)) co-cultured with MOG35-55-specific T cells (TMOG) and stimulated with MOG35-55. Using flow cytometry, we evaluated the expression of surface activation markers and inhibitory molecules on T cells and B cells. TMOG cells were purified using CD4 positive microbead selection and submitted for quantitative PCR and microarray of mRNA transcript analyzes. Cell signaling studies in purified TMOG were carried out using immunoblotting.
We found that CBD leads to upregulation of CD69 and lymphocyte-activation gene 3 (LAG3) regulatory molecules on CD4(+)CD25(-) accessory T cells. This subtype of CD4(+)CD25(-)CD69(+)LAG3(+) T cells has been recognized as induced regulatory phenotype promoting anergy in activated T cells. Indeed, we observed that CBD treatment results in upregulation of EGR2 (a key T cell anergy inducer) mRNA transcription in stimulated TMOG cells. This was accompanied by elevated levels of anergy promoting genes such as IL-10 (anti-inflammatory cytokine), STAT5 (regulatory factor), and LAG3 mRNAs, as well as of several enhancers of cell cycle arrest (such as Nfatc1, Casp4, Cdkn1a, and Icos). Moreover, CBD exposure leads to a decrease in STAT3 and to an increase in STAT5 phosphorylation in TMOG cells, positive and negative regulators of Th17 activity, respectively. In parallel, we observed decreased levels of major histocompatibility complex class II (MHCII), CD25, and CD69 on CD19(+) B cells following CBD treatment, showing diminished antigen presenting capabilities of B cells and reduction in their pro-inflammatory functions.
Our data suggests that CBD exerts its immunoregulatory effects via induction of CD4(+)CD25(-)CD69(+)LAG3(+) cells in MOG35-55-activated APC/TMOG co-cultures. This is accompanied by EGR2-dependent anergy of stimulated TMOG cells as well as a switch in their intracellular STAT3/STAT5 activation balance leading to the previously observed decrease in Th17 activity.
While the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain less than 10%. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF/NRAS wildtype tumours. Targeting autophagy is a novel means to promote cancer cell death in chemotherapy-resistant tumours and the aim of the present study was to test the hypothesis that cannabinoids promote autophagy-dependent apoptosis in melanoma. Treatment with Δ(9)-Tetrahydrocannabinol (THC) resulted in the activation of autophagy, loss of cell viability and activation of apoptosis, while co-treatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wildtype melanoma xenografts substantially inhibited melanoma viability, proliferation and tumour growth paralleled by an increase in autophagy and apoptosis compared to standard single agent temozolomide. Collectively our findings suggest THC activates non-canonical autophagy-mediated apoptosis of melanoma cells, suggesting cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.Journal of Investigative Dermatology accepted article preview online, 10 February 2015. doi:10.1038/jid.2015.45.
Non-melanoma skin cancer and other epithelial tumors overexpress cyclooxygenase-2 (COX-2), differentiating them from normal cells. COX-2 metabolizes arachidonic acid to prostaglandins including, the J-series prostaglandins, which induce apoptosis by mechanisms including endoplasmic reticulum (ER) stress. Arachidonoyl-ethanolamide (AEA) is a cannabinoid that causes apoptosis in diverse tumor types. Previous studies from our group demonstrated that AEA was metabolized by COX-2 to J-series prostaglandins. Thus, the current study examines the role of COX-2, J-series prostaglandins, and ER stress in AEA-induced apoptosis. In tumorigenic keratinocytes that overexpress COX-2, AEA activated the PKR-like ER kinase (PERK), inositol requiring kinase-1 (IRE1), and activating transcription factor-6 (ATF6) ER stress pathways and the ER stress apoptosis-associated proteins, C/EBP homologous protein-10 (CHOP10), caspase-12, and caspase-3. Using an ER stress inhibitor, it was determined that ER stress was required for AEA-induced apoptosis. To evaluate the role of COX-2 in ER stress-apoptosis, HaCaT keratinocytes with low endogenous COX-2 expression were transfected with COX-2 cDNA or an empty vector and AEA-induced ER stress-apoptosis occurred only in the presence of COX-2. Moreover, LC-MS analysis showed that the novel prostaglandins, 15-deoxyΔ12,14PGJ2-EA and Δ12PGJ2/PGJ2-EA, were synthesized from AEA. These findings suggest that AEA will be selectively toxic in tumor cells that overexpress COX-2 due to the metabolism of AEA by COX-2 to J-series prostaglandin-ethanolamides (prostamides). Hence, AEA may be an ideal topical agent for the elimination of malignancies that overexpress COX-2. © 2015 Wiley Periodicals, Inc.
Ceramide (CER) with long-chain fatty acids (FAs) in human stratum corneum (SC) is important for the skin barrier functions. Changes in the CER profile have been associated with abnormal permeability of dermatoses such as atopic dermatitis (AD) and psoriasis. In addition, interferon-γ (IFN-γ) has been known to be abundant in both AD and psoriatic skin lesions. In this study, we aimed to identify the mechanism underlying the alteration of FA chain length of CERs in these diseases. Mass spectrometry analysis of CERs in the SC showed that proportion of CERs with long-chain FAs was significantly lower in AD and psoriasis patients than in healthy controls, and this reduction was more pronounced in psoriasis than in AD. Using cultured human keratinocytes and epidermal sheets, we found that only IFN-γ among various cytokines decreased the mRNA expression of elongase of long-chain fatty acid (ELOVL) and ceramide synthase (CerS), enzymes involved in FA chain elongation. Furthermore, quantitative analysis showed that IFN-γ decreased the levels of CERs with long-chain FAs. These results suggest that IFN-γ decreases CERs with long-chain FAs through the downregulation of ELOVL and CerS and that this mechanism may be involved in the CER profile alteration observed in psoriasis and AD.Journal of Investigative Dermatology accepted article preview online, 5 September 2013. doi:10.1038/jid.2013.364.
Cannabinoid receptors (CB) are expressed throughout human skin epithelium. CB1 activation inhibits human hair growth and decreases proliferation of epidermal keratinocytes. Since psoriasis is a chronic hyperproliferative, inflammatory skin disease, it is conceivable that the therapeutic modulation of CB signaling, which can inhibit both proliferation and inflammation, could win a place in future psoriasis management. Given that psoriasis is characterized by up-regulation of keratins K6 and K16, we have investigated whether CB1 stimulation modulates their expression in human epidermis. Treatment of organ-cultured human skin with the CB1-specific agonist, arachidonoyl-chloro-ethanolamide (ACEA), decreased K6 and K16 staining intensity in situ. At the gene and protein levels, ACEA also decreased K6 expression of cultured HaCaT keratinocytes, which show some similarities to psoriatic keratinocytes. These effects were partly antagonized by the CB1-specific antagonist, AM251. While CB1-mediated signaling also significantly inhibited human epidermal keratinocyte proliferation in situ, as shown by K6/Ki-67-double immunofluorescence, the inhibitory effect of ACEA on K6 expression in situ was independent of its anti-proliferative effect. Given recent appreciation of the role of K6 as a functionally important protein that regulates epithelial wound healing in mice, it is conceivable that the novel CB1-mediated regulation of keratin 6/16 revealed here also is relevant to wound healing. Taken together, our results suggest that cannabinoids and their receptors constitute a novel, clinically relevant control element of human K6 and K16 expression.
Cannabinoids modulate fibrogenesis in scleroderma. Ajulemic acid (AjA) is a non-psychoactive synthetic analogue of tetrahydrocannabinol that can bind the peroxisome proliferator-activated receptor-γ (PPAR-γ). Recent evidence suggests a key role for PPAR-γ in fibrogenesis.
To determine whether AjA can modulate fibrogenesis in murine models of scleroderma.
Bleomycin-induced experimental fibrosis was used to assess the antifibrotic effects of AjA in vivo. In addition, the efficacy of AjA in pre-established fibrosis was analysed in a modified model of bleomycin-induced dermal fibrosis and in mice overexpressing a constitutively active transforming growth factor β (TGFβ) receptor I. Skin fibrosis was evaluated by quantification of skin thickness and hydroxyproline content. As a marker of fibroblast activation, α-smooth muscle actin was examined. To study the direct effect of AjA in collagen neosynthesis, skin fibroblasts from patients with scleroderma were treated with increasing concentrations of AjA. Protein expression of PPAR-γ, and its endogenous ligand 15d-PGJ2, and TGFβ were assessed before and after AjA treatment.
AjA significantly prevented experimental bleomycin-induced dermal fibrosis and modestly reduced its progression when started 3 weeks into the disease. AjA strongly reduced collagen neosynthesis by scleroderma fibroblasts in vitro, an action which was reversed completely by co-treatment with a selective PPAR-γ antagonist.
AjA prevents progression of fibrosis in vivo and inhibits fibrogenesis in vitro by stimulating PPAR-γ signalling. Since therapeutic doses of AjA are well tolerated in humans, it is suggested that AjA as an interesting molecule targeting fibrosis in patients with scleroderma.
Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD) is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-α expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-γ, an increased glial cell activation and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.
To evaluate the available treatment options for pediatric atopic dermatitis.
A literature review was performed in MEDLINE (1950-February 2010) using the key word atopic dermatitis. The references identified were evaluated in comparative treatment. The references included in this review were limited to studies conducted in children less than 18 years of age and written in the English language.
All of the literature retrieved that was published within the last 5 years (2005-2010) was included in this review. Other pertinent articles published prior to 2005 were also included.
Atopic dermatitis is a chronic inflammatory skin disorder that usually begins during infancy. Potential causes include irritants such as soap and detergents, food allergens, contact allergens, and skin infections. Emollients, moisturizing agents that inhibit water loss and provide a protective coating, are recommended in all patients with atopic dermatitis. Additionally, emollients may reduce the need to use topical corticosteroids. Patients receiving desonide 0.05% plus an emollient achieved significant reductions in severity scores compared to those receiving desonide 0.05% as monotherapy (80% vs 70%; p < 0.01). Topical calcineurin inhibitors are not recommended as first-line therapy in pediatric patients with atopic dermatitis; however, their use in children above 2 years of age who fail to respond to topical corticosteroids may be considered.
Emollients are recommended in pediatric patients with a diagnosis of atopic dermatitis regardless of symptoms. Topical corticosteroids reduce the inflammation and pruritus associated with atopic dermatitis and are available in several formulations and strengths. Calcineurin inhibitors may be an alternative in children older than 2 years of age who do not respond to topical corticosteroids.
Nonmelanoma skin cancer is one of the most common malignancies in humans. Different therapeutic strategies for the treatment of these tumors are currently being investigated. Given the growth-inhibiting effects of cannabinoids on gliomas and the wide tissue distribution of the two subtypes of cannabinoid receptors (CB(1) and CB(2)), we studied the potential utility of these compounds in anti-skin tumor therapy. Here we show that the CB(1) and the CB(2) receptor are expressed in normal skin and skin tumors of mice and humans. In cell culture experiments pharmacological activation of cannabinoid receptors induced the apoptotic death of tumorigenic epidermal cells, whereas the viability of nontransformed epidermal cells remained unaffected. Local administration of the mixed CB(1)/CB(2) agonist WIN-55,212-2 or the selective CB(2) agonist JWH-133 induced a considerable growth inhibition of malignant tumors generated by inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors showed an increased number of apoptotic cells. This was accompanied by impairment of tumor vascularization, as determined by altered blood vessel morphology and decreased expression of proangiogenic factors (VEGF, placental growth factor, and angiopoietin 2). Abrogation of EGF-R function was also observed in cannabinoid-treated tumors. These results support a new therapeutic approach for the treatment of skin tumors.
Hempseed oil is a rich and balanced source of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). Anecdotal evidence indicated that dietary hempseed oil might be useful in treating symptoms of atopic dermatitis.
Dietary hempseed oil and olive oil were compared in a 20-week randomized, single-blind crossover study with atopic patients. Fatty acid profiles were measured in plasma triglyceride, cholesteryl and phospholipid fractions. A patient questionnaire provided additional information on skin dryness, itchiness and usage of dermal medications. Skin transepidermal water loss (TEWL) was also measured.
Levels of both essential fatty acids (EFAs), linoleic acid (18:2n6) and alpha-linolenic acid (18:3n3), and gamma-linolenic acid (GLA; 18:3n6) increased in all lipid fractions after hempseed oil, with no significant increases of arachidonic acid (20:4n6) in any lipid fractions after either oil. Intra-group TEWL values decreased (p=0.074), qualities of both skin dryness and itchiness improved (p=0.027) and dermal medication usage decreased (p=0.024) after hempseed oil intervention.
Dietary hempseed oil caused significant changes in plasma fatty acid profiles and improved clinical symptoms of atopic dermatitis. It is suggested that these improvements resulted from the balanced and abundant supply of PUFAs in this hempseed oil.
Melanoma causes the greatest number of skin cancer-related deaths worldwide. Despite intensive research, prevention and early detection are the only effective measures against melanoma, so new therapeutic strategies are necessary for the management of this devastating disease. Here, we evaluated the efficacy of cannabinoid receptor agonists, a new family of potential antitumoral compounds, at skin melanoma. Human melanomas and melanoma cell lines express CB1 and CB2 cannabinoid receptors. Activation of these receptors decreased growth, proliferation, angiogenesis and metastasis, and increased apoptosis, of melanomas in mice. Cannabinoid antimelanoma activity was independent of the immune status of the animal, could be achieved without overt psychoactive effects and was selective for melanoma cells vs. normal melanocytes. Cannabinoid antiproliferative action on melanoma cells was due, at least in part, to cell cycle arrest at the G1-S transition via inhibition of the prosurvival protein Akt and hypophosphorylation of the pRb retinoblastoma protein tumor suppressor. These findings may contribute to the design of new chemotherapeutic strategies for the management of melanoma.
Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading
causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity, we show that mice lacking both
known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase–deficient mice,
which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid
receptor antagonists exacerbated allergic inflammation, whereas receptor agonists attenuated inflammation. These results demonstrate
a protective role of the endocannabinoid system in contact allergy in the skin and suggest a target for therapeutic intervention.
Solar UV irradiation is an important carcinogen that leads to the development of skin cancer, which is the most common human cancer. However, the receptors that mediate UV-induced skin carcinogenesis have not yet been unequivocally identified. Here we showed that UV irradiation directly activates cannabinoid receptors 1 and 2 (CB1/2). Notably, our data indicated that the absence of the CB1/2 receptors in mice results in a dramatic resistance to UVB-induced inflammation and a marked decrease in UVB-induced skin carcinogenesis. A marked attenuation of UVB-induced activation of mitogen-activated protein kinases and nuclear factor- kappaB was associated with CB1/2 deficiency. These data provide direct evidence indicating that the CB1/2 receptors play a key role in UV-induced inflammation and skin cancer development.
We had previously shown that both locally produced endocannabinoids and exocannabinoids, via cannabinoid receptor-1 (CB1), are powerful inhibitors of human hair growth. To further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology, using human SZ95 sebocytes as cell culture model. Here, we provide the first evidence that SZ95 sebocytes express CB2 but not CB1. Also, prototypic endocannabinoids (arachidonoyl ethanolamide/anandamide, 2-arachidonoyl glycerol) are present in SZ95 sebocytes and dose-dependently induce lipid production and (chiefly apoptosis-driven) cell death. Endocannabinoids also up-regulate the expression of key genes involved in lipid synthesis (e.g., PPAR transcription factors and some of their target genes). These actions are selectively mediated by CB2-coupled signaling involving the MAPK pathway, as revealed by specific agonists/antagonists and by RNA interference. Because cells with "silenced" CB2 exhibited significantly suppressed basal lipid production, our results collectively suggest that human sebocytes utilize a paracrine-autocrine, endogenously active, CB2-mediated endocannabinoid signaling system for positively regulating lipid production and cell death. CB2 antagonists or agonists therefore deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions (e.g., acne vulgaris, seborrhea, dry skin).
Background
Lenabasum is a synthetic, non-immunosuppressive, selective cannabinoid receptor type 2 agonist that activates resolution of innate immune responses and limits fibrosis in animal models of SSc. Lenabasum had acceptable safety and tolerability, and improved efficacy outcomes in the 16-week, double-blinded, randomized, placebo-controlled Part A of Phase 2 trial JBT101-SSc-001 (NCT02465437) in dcSSc subjects.
Objectives
To provide long-term open-label safety and efficacy data in dcSSc subjects in study JBT101-SSc-001.
Methods
Subjects who completed Part A were eligible to receive oral lenabasum 20 mg BID in an open-label extension (OLE) that assessed safety and efficacy at 4 weeks, then every 8 weeks.
Results
36/38 (95%) eligible subjects enrolled in the OLE, with mean interval of 134 (range 33-392) days or 19.1 weeks from end of dosing in Part A to start of OLE when subjects received only standard-of care drugs. 34/36 (94%) subjects were on stable doses of immunosuppressive drugs. At safety data cut-off, 31 (86%) subjects finished 1 year, 30 (83%) finished 18 months, and 24 finished ≥ 2 years in the OLE. Thirty-five (97%) subjects experienced at least 1 AE; 239 AEs have occurred during the OLE to date. Seven (19%) subjects had ≥ 1 AE considered related to lenabasum in the OLE. Only fatigue (1 subject) was considered definitely-related, none of the related AEs were serious or severe. Most subjects experienced AEs that were mild (n = 6, 17%) to moderate (n = 24, 67%) in maximum severity. Four (11%) had severe AEs and 1 (3%) had a life-threating AE of renal crisis caused by high-dose steroids. AEs in ≥ 10% of subjects: upper respiratory tract infection (n = 11, 31%), skin ulcer and arthralgia (each n = 6, 17%), urinary tract infection (n = 5, 14%), and diarrhea, nasopharyngitis, and cough (each n = 4, 11%). Dizziness and fatigue occurred in 3 (8.3%) subjects each. At the time of efficacy data cut-off, 30/36 (83%) subjects had completed ≥ 18 months in the OLE. Improvement was seen in multiple physician- and patient-reported efficacy outcomes; selected outcomes are shown in Figure 1 Compared to Baseline at study start, the CRISS median score (primary efficacy outcome) was 0.99 (0.43 IQR) at Week 76 and mRSS declined by mean (SD) = -10.7 (7.2) points. HAQ-DI, Physician Global Assessment, Patient Global Assessment, skin symptoms, itch, and multiple PROMIS-29 domains also improved. FVC% predicted was relatively stable during the OLE; mean (SD) FVC% predicted decreased by 2.5% from study start.
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Figure 1 Change from Baseline in Selected Efficacy Outcomes in OLE of Phase 2 Trial JBT101-SSc-001
Conclusion
Lenabasum continues to have a favorable safety and tolerability profile in the OLE of Phase 2 trial JBT101-SSc-001 with no lenabasum-related serious AEs or study discontinuations. Only 7 (19%) subjects had an AE related to lenabasum in ≥ 18 months of OLE dosing. ACR CRISS score, mRSS, Physician Global Assessment, and multiple patient-reported outcomes show continued improvement, although background therapy, potential for spontaneous improvement, and open-label dosing limit what can be definitely attributed to lenabasum.
Disclosure of Interests
Robert Spiera Grant/research support from: Roche-Genentech, GlaxoSmithKline, Bristol-Myers Squibb, Boehringer Ingelheim, Cytori, Chemocentryx, Corbux, Consultant for: Roche-Genentech, GlaxoSmithKline, CSL Behring, Sanofi Aventis, Laura Hummers Grant/research support from: Site PI for phase 2 and 3 clinical trials (Cumberland, Glaxo Smith Kline, Boerhinger Ingleheim, Corbus, Cytori), Consultant for: CSL Behring, Lorinda Chung Grant/research support from: United Therapeutics, Consultant for: Reata, Bristol Meyers Squibb, Boehringer Ingelheim, Mitsubishi Tanabe, Eicos, Tracy Frech: None declared, Robin Domsic Consultant for: Eicos Sciences Inc/Civi Biopharma and Boehringer-Ingelheim., Vivian Hsu: None declared, Daniel Furst Grant/research support from: F. Hoffmann-La Roche, Genentech, Jessica Gordon Grant/research support from: Corbus Pharmaceuticals Cumberland Pharmaceuticals, Maureen Mayes Grant/research support from: Maureen Mayes is a clinical trial investigator for Boehringer-Ingelheim; Galapagos, Reata, Sanofi, Merck-Serono, Consultant for: Maureen Mayes is a member of scientific advisory boards for Galapagos NV (Pharma), Boehringer-Ingelheim, Mitsubishi-Tanabe, Astellas: Grant Review Board for Actelion., Speakers bureau: Maureen Mayes received personal fees for being a conference speaker on the use of autoantibodies in connective tissue diseases for Medtelligence, Robert Simms: None declared, Elizabeth Lee Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc., Scott Constantine Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc., Nancy Dgetluck Employee of: Corbus Pharmaceuticals, Inc., Barbara White Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc.
Background:
Cannabinoid has long been used for medicinal purposes. Cannabinoid signaling has been considered the therapeutic target for treating pain, addiction, obesity, inflammation, and other diseases. Recent studies have suggested that in addition to CB1 and CB2, there are non-CB1 and non-CB2 cannabinoid-related orphan GPCRs including GPR18, GPR55, and GPR119. In addition, CB1 and CB2 display allosteric binding and biased signaling, revealing correlations between biased signaling and functional outcomes. Interestingly, new investigations have indicated that CB1 is functionally present within the mitochondria of striated and heart muscles directly regulating intramitochondrial signaling and respiration.
Conclusion:
In this review, we summarize the recent progress in cannabinoid-related orphan GPCRs, CB1/CB2 structure, Gi/Gs coupling, allosteric ligands and biased signaling, and mitochondria-localized CB1, and discuss the future promise of this research.
Background: Recent research has identified potential uses of cannabinoids in dermatology, including psoriasis, atopic dermatitis, and wound healing.
Objective: The extent of dermatologists’ familiarity with and interest in cannabinoids as therapeutics is unknown.
Methods: This study examined dermatology providers’ knowledge, attitudes, and perceptions on therapeutic cannabinoids using a 20-question online survey.
Results: The response rate was 21% (n=531). Most responders thought cannabinoids should be legal for medical treatment (86%). Nearly all (94%) believed it is worthwhile to research dermatologic uses of cannabinoids. 55% reported at least one patient-initiated discussion about cannabinoids in the last year. Yet, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most responders (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. 64% of respondents did not know that cannabidiol is not psychoactive and 29% did not know that tetrahydrocannabinol is psychoactive.
Limitations: Limited survey population.
Conclusions: Dermatology providers are interested in prescribing cannabinoids and patients are speaking about cannabinoids with their dermatologists. However, providers’ fund of knowledge on this subject is lacking. These results highlight the need for further education and research to detangle the dermatologic benefits and risks of cannabinoids.
J Drugs Dermatol. 2018;17(12):1273-1278.
Psoriasis is a chronic skin disease also affecting other sites such as joints. This disease highly depends on inflammation and angiogenesis as well as other pathways. At each step of the psoriasis molecular pathway, different inflammatory cytokines and angiogenic growth factors are involved such as hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), matrix metalo proteinases (MMPs), basic fibroblast growth factor (bFGF), Angiopoitin-2, interleukin-8 (IL-8), IL-17, and IL-2. Beside the mentioned growth factors and cytokines, cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which play roles in both angiogenesis and inflammation are also involved in the pathogenesis. Cannabinoids are active compounds of Cannabina Sativa inducing their effects through cannabinoid receptors (CBs). JWH-133 is a synthetic cannabinoid with strong anti-angiogenic and anti-inflammatory activities. This agent is able to inhibit HIF-1 α, VEGF, MMPs, bFGF, IL-8, IL-17, and other mentioned cytokines and adhesion molecules both in vivo and in vitro. Altogether, authors suggest using this cannabinoid for treatment of psoriasis due to its potential in suppressing the two main steps of psoriatic pathogenesis. Of course complementary animal studies and human trials are still required.
Psoriasis is a common skin disorder characterized by hyper proliferation of keratinocytes. Although the exact pathophysiology of psoriasis is not entirely understood, immune system and its interaction with nervous system has been postulated and investigated as the underlying mechanism. The interaction between these two systems through cholinergic anti-inflammatory pathway and also endocannabinoid system, may suggest cannabinoids as potential addition to anti-psoriatic armamentarium.
Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands. We have previously shown that a non-psychotropic phytocannabinoid ((–)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing ‘pro-acne agents’-induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes. Therefore, in this study we aimed to explore the putative anti-acne effects of further non-psychotropic phytocannabinoids ((–)-cannabichromene [CBC], (–)-cannabidivarin [CBDV], (–)-cannabigerol [CBG], (–)-cannabigerovarin [CBGV] and (–)-Δ9-tetrahydrocannabivarin [THCV]). Viability and proliferation of human SZ95 sebocytes were investigated by MTT and CyQUANT assays; cell death and lipid synthesis were monitored by DilC1(5)-SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT-qPCR, ELISA). Up to 10 μm, the phytocannabinoids only negligibly altered the viability of the sebocytes, whereas high doses (≥50 μm) induced apoptosis. Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, and CBDV had only minor effects, whereas CBG and CBGV increased it. Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)-induced ‘acne-like’ lipogenesis. Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti-inflammatory actions. Our data suggest that CBG and CBGV may have potential in the treatment of dry-skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti-acne agents. Moreover, based on their remarkable anti-inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations.
Cannabinoids compounds are unique to cannabis and provide some interesting biological properties. These compounds along with endocannabinoids, a group of neuromodulator compounds in the body especially in brain, express their effects by activation of G-protein-coupled cannabinoid receptors, CB1 and CB2. There are several physiological properties attributed to the endocannabinoids including pain relief, enhancement of appetite, blood pressure lowering during shock, embryonic development, and blocking of working memory. On the other hand, activation of endocannabinoid system may be suppresses evolution and progression of several types of cancer. According to the results of recent studies, CB receptors are over-expressed in cancer cell lines and application of multiple cannabinoid or cannabis-derived compounds reduce tumor size through decrease of cell proliferation or induction of cell cycle arrest and apoptosis along with desirable effect on decrease of tumor-evoked pain. Therefore, modulation of endocannabinoid system by inhibition of fatty acid amide hydrolase (FAAH), the enzyme, which metabolized endocannabinoids, or application of multiple cannabinoid or cannabis-derived compounds, may be appropriate for the treatment of several cancer subtypes. This review focuses on how cannabinoid affect different types of cancers.
Background:
UV, including UVA and UVB radiation, is one of the most ubiquitous environmental stress factors to human skin and leads to redox imbalance and, consequently, photoaging and cancer development. The aim of the study was to verify which skin cells, keratinocytes or fibroblasts, were more susceptible to UVA or UVB irradiation.
Objective:
Keratinocytes and fibroblasts were subjected to UVA and UVB irradiation.
Methods:
The redox potential (superoxide anion generation and antioxidant level/activity), electrophile level and endocannabinoid system were estimated.
Results:
The results presented in this paper demonstrate a strong relationship between UV-induced oxidative stress and changes in the endocannabinoid system. Simultaneously, in irradiated cells, the transcription factors Nrf1, Nrf2 and NFκB are activated to varying degrees. Fibroblasts have a greater susceptibility to ROS generation and transcription factor activation after both UVA and UVB irradiation than keratinocytes. Keratinocytes are more sensitive to changes in the electrophile levels connected with oxidative stress compared to fibroblasts.
Conclusion:
The differences demonstrated in the response of the tested cells to UV irradiation allow for a better understanding of the mechanisms occurring in the human skin, which may be exploited for future therapies in dermatology.
Endocannabinoids are neuromodulatory lipids that regulate central and peripheral physiological functions. Endocannabinoids have emerged as effective antitumor drugs due to their ability to induce apoptosis in various cancer studies. The G-protein coupled cannabinoid receptors (CB1 and CB2) and the TRPV1 ion channel were reported to mediate the antiproliferative activity of endocannabinoids. However, receptor-independent effects also account for their activity. Our previous studies showed that the antiproliferative activity of anandamide (AEA) was regulated by cyclooxygenase-2 (COX-2) via induction of endoplasmic reticulum (ER) stress. We also determined that AEA induced oxidative stress. However, the role of oxidative stress, the cannabinoid receptors, and TRPV1 in AEA-induced ER stress-apoptosis was unclear. Therefore, the current study examines the role of oxidative stress in ER stress-apoptosis and investigates whether this effect is modulated by CB1, CB2, or TRPV1. In non-melanoma skin cancer (NMSC) cells, AEA reduced the total intracellular level of glutathione and induced oxidative stress. To evaluate the importance of oxidative stress in AEA-induced cell death, the antioxidants, N-acetylcysteine (NAC) and Trolox, were utilized. Each antioxidant ameliorated the antiproliferative effect of AEA. Furthermore, Trolox inhibited AEA-induced CHOP10 expression and caspase 3 activity, indicating that oxidative stress was required for AEA-induced ER stress-apoptosis. On the other hand, selective blockade of CB1, CB2, and TRPV1 did not inhibit AEA-induced oxidative stress or ER stress-apoptosis. These findings suggest that AEA-induced ER stress-apoptosis in NMSC cells is mediated by oxidative stress through a receptor-independent mechanism. Hence, receptor-independent AEA signaling pathways may be targeted to eliminate NMSC. © 2015 Wiley Periodicals, Inc.
Even with the widespread clinical use of cannabinoid receptor (CBR) stimulating compounds, such as palmitoylethanolamine, the role of CBR agonists on inflammatory skin diseases is not yet fully understood. This study was performed to investigate the effects of CBR agonists on skin inflammation, using acute and chronic inflammation animal models.
The effectiveness of the newly synthesized cannabinoid receptor 1 (CB1R) agonists was determined using in vitro assays. Markers for epidermal permeability barrier function and skin inflammation were measured, and histological assessments were performed for evaluation.
Topical application of CB1R-specific agonist significantly accelerated the recovery of epidermal permeability barrier function and showed anti-inflammatory activity in both acute and chronic inflammation models. Histological assessments also confirmed the anti-inflammatory effects, which is consistent with previous reports.
All of the results suggest that topical application of CB1R-specific agonist can be beneficial for alleviating the inflammatory symptoms in chronic skin diseases, including atopic dermatitis.
© 2015 The International Society of Dermatology.
Bei chronischem, therapieresistenten Pruritus versagen häufig konventionelle Therapiemaßnahmen und neue Therapieansätze sind gefragt. Kürzlich wurde die Expression von Cannabinoidrezeptoren auf kutanen sensorischen Nervenfasern beschrieben, und der Einsatz von Cannabinoidagonisten zur Therapie von Pruritus scheint rational.In einer offenen Anwendungsbeobachtung erhielten 22 Patienten mit Prurigo, Lichen simplex und Pruritus eine N-Palmitoylethanolamin- (PEA-)haltige Pflegecreme.Bei 14/22 Patienten konnte ein guter bis sehr guter antipruritischer Effekt dokumentiert werden. Im Mittel war eine signifikante Juckreizreduktion um 86,4% zu verzeichnen. Die Therapie wurde von allen Patienten gut toleriert; es traten keine unangenehmen Sensationen wie Brennschmerz oder Kontaktekzeme auf.Die Ergebnisse zeigen, dass topische Cannabinoidagonisten eine effektive Therapie mit guter Verträglichkeit bei therapierefraktärem Juckreiz verschiedenster Ursache darstellen. Es darf spekuliert werden, dass Cremes mit einer höheren Konzentration an Wirkstoffen zu einem noch besseren Ansprechen des Pruritus mit breiterem Indikationsgebiet führen werden.
