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Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

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Abstract

The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.

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... A dysregulation of the SGs may cause hypersecretion of sebum, leading to hyperproliferation of keratinocytes and sebocytes, and to the concomitant colonization by bacteria, mainly Cutibacterium acnes, in the obstructed pilosebaceous unit, causing acne vulgaris. C. acnes has been shown to trigger inflammatory reactions in the skin by inducing the expression of pro-inflammatory cytokines [62,87]. ...
... Cannabidiol has been suggested as a promising therapeutic agent for the treatment of acne vulgaris since it normalizes the lipogenesis of sebocyte cells (lipostatic effect, without compromising cell viability), decreases the proliferation of these cells (antiproliferative effect, without inducing sebocyte apoptosis) and decreases the levels of pro-inflammatory cytokines (anti-inflammatory effect) [62]. It is interesting that CBD has an opposite effect to that of ECBs. ...
... It is interesting that CBD has an opposite effect to that of ECBs. While ECBs stimulate the lipid synthesis in SGs via the 'classical' signaling pathway involving CB2R, CBD exerts a sebostatic (lipostatic and antiproliferative) action by activating TRPV4 receptors [42,62]. ...
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The use of natural products in dermatology is increasingly being pursued due to sustainability and ecological issues, and as a possible way to improve the therapeutic outcome of chronic skin diseases, relieving the burden for both patients and healthcare systems. The legalization of cannabis by a growing number of countries has opened the way for researching the use of cannabinoids in therapeutic topical formulations. Cannabinoids are a diverse class of pharmacologically active compounds produced by Cannabis sativa (phytocannabinoids) and similar molecules (endocannabinoids, synthetic cannabinoids). Humans possess an endocannabinoid system involved in the regulation of several physiological processes, which includes naturally-produced endocannabinoids, and proteins involved in their transport, synthesis and degradation. The modulation of the endocannabinoid system is a promising therapeutic target for multiple diseases, including vascular, mental and neurodegenerative disorders. However, due to the complex nature of this system and its crosstalk with other biological systems, the development of novel target drugs is an ongoing challenging task. The discovery of a skin endocannabinoid system and its role in maintaining skin homeostasis, alongside the anti-inflammatory actions of cannabinoids, has raised interest in their use for the treatment of skin inflammatory diseases, which is the focus of this review. Oral treatments are only effective at high doses, having considerable adverse effects; thus, research into plant-based or synthetic cannabinoids that can be incorporated into high-quality, safe topical products for the treatment of inflammatory skin conditions is timely. Previous studies revealed that such products are usually well tolerated and showed promising results for example in the treatment of atopic dermatitis, psoriasis, and contact dermatitis. However, further controlled human clinical trials are needed to fully unravel the potential of these compounds, and the possible side effects associated with their topical use.
... The latter is dispersed in a chilled surfactant solution and homogenized at high-pressure at or below room temperature. The nanoparticles obtained generally have larger size and broader size distribution compared to those prepared by hot homogenization [30]. ...
... The use of proper amount and type of surfactant will allow the formation of lipid nanoparticles using a simple ultrasonication or high-shear homogenization method [31]. However, metal contamination has to be considered when an ultrasonic probe sonicator is used [30]. ...
... Typically, the ratio of microemulsion to cold water lies in the range of 1:25 to 1:50. Due to the dilution, the nanoparticles obtained will have lower lipid content than those prepared by the homogenization method [30]. Furthermore, this method is useful for encapsulating drugs which are sensitive to mechanical stress [19,32]. ...
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Acne vulgaris (acne) is one of the most common dermatological problems affecting adolescents and young adults. Although acne may not lead to serious medical complications, its psychosocial effects are tremendous and scientifically proven. The first-line treatment for acne is topical medications composed of synthetic compounds, which usually cause skin irritation, dryness and itch. Therefore, naturally occurring constituents from plants (phytochemicals), which are generally regarded as safe, have received much attention as an alternative source of treatment. However, the degradation of phytochemicals under high temperature, light and oxygen, and their poor penetration across the skin barrier limit their application in dermatology. Encapsulation in lipid nanoparticles is one of the strategies commonly used to deliver drugs and phytochemicals because it allows appropriate concentrations of these substances to be delivered to the site of action with minimal side effects. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are promising delivery systems developed from the combination of lipid and emulsifier. They have numerous advantages that include biocompatibility and biodegradability of lipid materials, enhancement of drug solubility and stability, ease of modulation of drug release, ease of scale-up, feasibility of incorporation of both hydrophilic and lipophilic drugs and occlusive moisturization, which make them very attractive carriers for delivery of bioactive compounds for treating skin ailments such as acne. In this review, the concepts of SLNs and NLCs, methods of preparation, characterization, and their application in the encapsulation of anti-acne phytochemicals will be discussed.
... Main processing steps to convert hemp biomass into high purity distillate covers trim and flowers collection, extraction with crude oil, removing of fats by winterization, activation with decarboxylation, and purification by distillation, the chain is schematically showed in Figure 5. Many researchers have studied CBD's effect on human health, several research papers report the benefits of CBD for the skin, including combating inflammation [4][5][6], pain [7], and melanoma; acting as an analgesic to promote wound healing [8]. Many researchers have studied CBD's effect on human health, several research papers report the benefits of CBD for the skin, including combating inflammation [4][5][6], pain [7], and melanoma; acting as an analgesic to promote wound healing [8]. ...
... Many researchers have studied CBD's effect on human health, several research papers report the benefits of CBD for the skin, including combating inflammation [4][5][6], pain [7], and melanoma; acting as an analgesic to promote wound healing [8]. Many researchers have studied CBD's effect on human health, several research papers report the benefits of CBD for the skin, including combating inflammation [4][5][6], pain [7], and melanoma; acting as an analgesic to promote wound healing [8]. ...
... The topical administration of CBD ointment, without any THC, is a safe and effective non-invasive alternative for improving the quality of life in patients with some skin disorders, especially on inflammatory backgrounds [9]. Results of research conducted by A. Olah et al. proved that CBD had universal sebostatic activity, which was accompanied by substantial anti-inflammatory effects on human skin and would be very much desired in the clinical treatment of acne vulgaris [5]. CBD normalized the pathologically elevated lipogenesis induced by "pro-acne" agents, both quantitatively and qualitatively, suppressed cell proliferation, and prevented the actions of TLR activation or "pro-acne" agents to elevate proinflammatory cytokine levels (universal anti-inflammatory effect). ...
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Hemp fiber variety, Bialobrzeskie, contains phenolic acids in its chemical composition giving it inherent antioxidant and antibacterial activity. The use of this raw material in fabric manufacture allows the creation of functional clothing with a positive effect on human skin. The aim of the study was to develop biologically active functional clothing made of pure industrial hemp raw materials, where cannabidiol (CBD) extract applied on the fabric surface strengthened the fiber bioactivity. The design of the clothing technology was focused on keeping the hemp inherent properties on a steady level and avoiding the use of chemicals in each stage of the value chain from plant cultivation up to garment manufacture. The research covered the evaluation of phenolic acids content and The Ferric Ion Reducing Antioxidant Power FRAP antioxidant activity of the hemp fabric. The hemp fabric enriched with CBD was used for clothing preparation. The human trials covered wearing of the clothing by 15 volunteers for six weeks and evaluation of hemp garment effect on human skin. The skin parameters were tested twice, before and after six weeks of clothing wearing, according to the own methodology that included measurements of skin biophysical properties including tests of skin moisture, transepidermal water loss, and sebum. Also, the effect of the active substances present on the fabrics on the in vitro culture of human keratinocytes was evaluated. Results of the research proved, that the wearing of developed functional hemp clothing with CBD extracts applied on the fabric surface was safe and caused improvement of skin condition, which can have an influence on slowing down of skin aging. The invention covering the pure hemp functional clothing with hybrid bioactivity resulting from the joined activity of fiber and cannabidiol was applied for a patent, Patent Application No: P.438388, 2021.
... Pesquisas relacionadas ao tema acne estão à procura de ativos dermatológicos que possam atuar nas múltiplas etapas que envolvem a sua patogenesia, tais como superprodução de sebo, proliferação de sebócitos e inflamação, sem que tenha qualquer efeito colateral no tratamento. (Oláh et al., 2014). ...
... Além disso, muitos países já desenvolveram protocolos para a prática clínica sem quaisquer efeitos colaterais significativos, para outras patologias, o que pode ser promissor para abertura de pesquisas em inúmeras áreas. (Oláh et al., 2014). ...
... dos na faixa fentomolar em queratinócitos e células de fibroblastos.(Baswan et al., 2020;Tallima & El Ridi, 2018).Com administração de CBD na de pele humana, houve a inibição das ações lipogênicas de alguns compostos, sendo eles o ácido araquidônico e uma combinação de ácido linoléico e testosterona, e com isso suprimiu a proliferação de sebócitos.(Oláh et al., 2014). ...
Article
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O canabidiol é um canabinóide não psicoativo isolado da Cannabis sativa que, devido às suas alegadas propriedades benéficas e seu potencial terapêutico, está sendo cada vez mais discutido na comunidade científica, à medida que a descriminalização e a legalização desses produtos continuam a se expandir. Tendo em vista o crescente interesse, ainda que a legislação sobre este tema no Brasil seja limitada, o objetivo principal deste estudo foi investigar a aplicação do canabidiol (CBD) na influência dos aspectos relacionados às propriedades anti-inflamatórias e antimicrobiana sobre a acne. Internacionalmente, protocolos para o uso do produto já foram estabelecidos. Nesse contexto, foi realizada uma revisão da literatura atual para evidenciar as aplicações de canabidiol para a pele, a partir de estudos químicos e farmacológicos, com diversos alvos moleculares, incluindo receptores de canabinoides e do sistema endocanabinoide, com os quais eles interagem. Foi identificado que os produtos canabinoides apresentam potencial para tratar uma variedade de doenças de pele, incluindo acne. No entanto, a maioria dos dados disponíveis sobre esses compostos são estudos pré-clínicos, que necessitam de estudos controlados de alta qualidade para avaliar seus efeitos de forma complementar. Este artigo fornece uma atualização sobre os avanços na pesquisa de CBD e as áreas potenciais de exploração futura.
... Although research on CBD oil as a topical agent is still emerging, supplementary use has been shown to decrease inflammation and improve therapeutic outcomes for severe inflammatory skin diseases, supporting this potential role. [16][17][18] Anecdotally, the improvements observed for the combination of retinol and water-soluble CBD are better than for either product alone, suggesting an additive, or potentially synergistic benefit. Larger controlled studies will need to be carried out in order to understand the relative effects of CR-Topical and retinol and to define any synergistic activity for the 2 ingredients. ...
... 19 Because retinol suppresses the expression of Nrf2-target antioxidative genes, the addition of CBD oil can potentially restore antioxidative effects inhibited by retinol while allowing for retention of skin-strengthening properties. 8,10,18 This activity of CBD is in addition to independent mechanisms, including modulation of the human endocannabinoid system, which is linked to anti-aging effects through its role in maintaining skin homeostasis and barrier function, antioxidant and anti-inflammatory activity, as well optimal sebum production. [18][19][20] For Retinol, independent effects are manifested through promoting keratinocyte proliferation, strengthening of the epidermis, and increasing collagen (through the protection of existing collagen and stimulation of neocollagenesis) in the skin. ...
... 8,10,18 This activity of CBD is in addition to independent mechanisms, including modulation of the human endocannabinoid system, which is linked to anti-aging effects through its role in maintaining skin homeostasis and barrier function, antioxidant and anti-inflammatory activity, as well optimal sebum production. [18][19][20] For Retinol, independent effects are manifested through promoting keratinocyte proliferation, strengthening of the epidermis, and increasing collagen (through the protection of existing collagen and stimulation of neocollagenesis) in the skin. 8,9 Importantly, the combination of CBD and retinol appears to reduce skin irritation often observed with retinol alone. ...
Article
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Background While retinol is known to reduce the appearance of fine lines and wrinkles, it is associated with irritating effects. When combined with water-soluble cannabidiol (CBD; CR-Topical) however, CBD acts to reduce oxidative stress and inflammation, mitigating irritation from retinol and further improving the skin’s appearance through independent anti-aging mechanisms. Objective To assess efficacy and tolerability of CR-Topical for improving facial skin. Methods In this prospective, single-center pilot study, 10 female subjects and one male subject aged 20-53 years who presented with facial skin imperfections (visible pores, dehydration, roughness, and/or static/dynamic wrinkles), applied CR-Topical to the entire face once daily for 42 days. Outcomes were measured at days 1, 21, and 42 using the Global Ranking Scale (GRS) with Comprehensive Skin Analysis by the subject and senior investigator, as well as by a blinded reviewer (board certified plastic surgeon). Dynamic videos and static imagery were taken before and after treatment and subject satisfaction surveys were completed. Results Global improvement across all 13 domains was observed, with the greatest mean differences for visible pores (2.0; 95% CI, 1.5-2.5), dehydration (2.0; 95% CI, 1.4-2.6), surface roughness (1.8; 95% CI, 1.2-2.4), static wrinkles (1.8; 95% CI, 1.1-2.5), and dynamic wrinkles (1.6; 95% CI, 0.8-2.3). Subject satisfaction (100%) and willingness to recommend the product to others (90%) was high and tolerability of CR-Topical was excellent. Conclusions CR-Topical is effective at improving global skin quality, including static and dynamic wrinkles. This study also used 4D analysis in the evaluation, a novel and developing method.
... In recent years, the investigation and use of CBD for its anti-inflammatory and immunomodulatory effects has become extensive amongst the scientific community. 20 The therapeutic potential of CBD has been extensively supported in various immunological, neurodegenerative, cancer, cardiovascular, and dermatological diseases, as conditions with an inflammatory component. 21 To date, Epidiolex remains the first and sole FDA-approved prescription CBD drug used to treat seizures. ...
... In a study evaluating the effects of CBD on human sebaceous glands, CBD was evaluated in the context of immortalized human sebocytes under "acne-like" conditions. 20 In this study, CBD was shown to dose-dependently inhibit excessive lipid synthesis (lipogenesis) in sebocyte cultures that were pre-treated with "pro-acne" inducing inflammatory compounds such as arachidonic acid, linoleic acid, and testosterone. 20 The anti-inflammatory effects of CBD were also observed in the reduction of inflammatory cytokine TNF-α. ...
... 20 In this study, CBD was shown to dose-dependently inhibit excessive lipid synthesis (lipogenesis) in sebocyte cultures that were pre-treated with "pro-acne" inducing inflammatory compounds such as arachidonic acid, linoleic acid, and testosterone. 20 The anti-inflammatory effects of CBD were also observed in the reduction of inflammatory cytokine TNF-α. Lipopolysaccharides 36 were used to pre-treat sebocytes to induce "pro-acne" inflammatory conditions. ...
Article
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Acne is the most common skin condition in the United States and affects approximately 85% of people ages 12-24. As a multifactorial disease, the pathogenesis of acne involves overproduction of sebum, irregular shedding of the cutaneous cells, accretion of Cutibacterium acnes at the pilosebaceous unit, and inflammation. To date, conventional therapies for acne include topical retinoids, over-the-counter bactericidal agents, and systematic treatments, such as oral antibiotics and isotretinoin. However, the potential for significant side effects and risk of antibiotic resistance remain limitations in these therapies, in turn reducing patient compliance and adherence to acne treatment regimens. Therefore, the use of natural plant-derived treatments or phytotherapeutics as an alternative or adjuvant to conventional treatments is attractive to patients due to their safety and minimal risk for side effects. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid of the Cannabis sativa (hemp) plant. The therapeutic use of CBD has been implicated in many diseases with an inflammatory aspect, including cancers, neurodegeneration, immunological disorders, and dermatological diseases. However, the use of CBD for acne treatment remains a novel window of opportunity. Herein, we summarize the available and relevant data, highlighting the potential use of CBD in acne for its anti-inflammatory properties. To that extent, CBD and other cannabis constituents such as cannabis seeds were found to reduce inflammation and expression of inflammatory cytokines including TNF-α and IL-1β when evaluated in acne-like conditions. Treatment with these cannabis extracts was also found to be safe and well tolerated, further strengthening the prospect of CBD as an anti-inflammatory therapeutic for acne.
... The most common skincare products are vitamins (thiamine, ascorbic acid, and tocopherol), retinol, retinoic acid, niacinamide, salicylic acid, glycolic acid, lactic acid, azelaic acid, hyaluronic acid, ceramides, and omega-3 fatty acids (Draelos 2010). Since cannabidiol possesses sebostatic, antioxidant, and anti-inflammatory action (Oláh et al. 2014), several cannabis-based dermal (skin) care products have been developed (Eagleston et al. 2018). The sebostatic activity of CBD is attributed to inhibition of lipogenic actions of compounds such as arachidonic acid and a combination of linoleic acid and testosterone and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels (Oláh et al. 2014). ...
... Since cannabidiol possesses sebostatic, antioxidant, and anti-inflammatory action (Oláh et al. 2014), several cannabis-based dermal (skin) care products have been developed (Eagleston et al. 2018). The sebostatic activity of CBD is attributed to inhibition of lipogenic actions of compounds such as arachidonic acid and a combination of linoleic acid and testosterone and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels (Oláh et al. 2014). The CBD-laced lotion or cream is used on sore joints or muscles for quick relief . ...
... The CBD-laced lotion or cream is used on sore joints or muscles for quick relief . Several dermal formulations with cannabis are effective for dry skin, wrinkly skin, eczema, soothing topical pain, and acne (Oláh et al. 2014). ...
Chapter
Bhanga (Cannabis) has been reported with numerous therapeutic, traditional, commercial, and sacred uses in India and across the globe. Its uses are deeply rooted in the cultural, social, and economic lives of the people. The inclusion of Cannabis under ‘Scheduled E1’ drugs in India restricts its use. However, being a crop of economic and medicinal importance, the pharmaceutical and various other sectors are showing much interest in the plant. The present review article delineates traditional, culinary, cosmetic, ritual, social, spiritual, recreational, economic, and therapeutic uses of Cannabis. The review illustrates various uses of Cannabis across the globe; noted from articles, publications, and books providing description of various parts, viz. leaves and seeds (Bhanga), flowering and fruiting tops (Ganja), resin (Charas), extract, tincture, and whole plant, stalks (Fibers). The review may be helpful to researchers, clinicians, and pharmaceutical companies to carry out further research for developing cost-effective healthcare options.
... The most common skincare products are vitamins (thiamine, ascorbic acid, and tocopherol), retinol, retinoic acid, niacinamide, salicylic acid, glycolic acid, lactic acid, azelaic acid, hyaluronic acid, ceramides, and omega-3 fatty acids (Draelos 2010). Since cannabidiol possesses sebostatic, antioxidant, and anti-inflammatory action (Oláh et al. 2014), several cannabis-based dermal (skin) care products have been developed (Eagleston et al. 2018). The sebostatic activity of CBD is attributed to inhibition of lipogenic actions of compounds such as arachidonic acid and a combination of linoleic acid and testosterone and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels (Oláh et al. 2014). ...
... Since cannabidiol possesses sebostatic, antioxidant, and anti-inflammatory action (Oláh et al. 2014), several cannabis-based dermal (skin) care products have been developed (Eagleston et al. 2018). The sebostatic activity of CBD is attributed to inhibition of lipogenic actions of compounds such as arachidonic acid and a combination of linoleic acid and testosterone and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels (Oláh et al. 2014). The CBD-laced lotion or cream is used on sore joints or muscles for quick relief . ...
... The CBD-laced lotion or cream is used on sore joints or muscles for quick relief . Several dermal formulations with cannabis are effective for dry skin, wrinkly skin, eczema, soothing topical pain, and acne (Oláh et al. 2014). ...
Chapter
Ayurveda has delineated a unique classification entitled ‘Upavisha varga’ comprising of certain semi-poisonous medicinal plants. Bhanga (Cannabis) is one amongst them in this category depicting its narcotic nature from Sanskrit synonyms. Bhanga has been in use since the Vedic age under the controversial plant of Soma that had special importance due to its mystical effects on the brain. All the texts of Ayurveda have described Bhanga in detail of its pharmacological properties, indications, various dosage forms, doses, pharmacovigilance aspects, and its extensive use in Indian Alchemy. The following review throws light on the occurrence and usage of Bhanga in excerpts from classical texts of Ayurveda from a pharmacological and pharmaceutical point of view thus, providing a rationale for its safe medical usage.KeywordsAyurveda Bhanga CannabisClassicalEvidenceReviewUpavishaVijaya
... A study on SZ95 human sebocyte cultures performed by Oláh et al. demonstrated that CBD can prevent the increase of TNF-α when sebocytes are stimulated with linoleic acid and testosterone in an in vitro acne model [174]. Furthermore, CBD also decreased the expression of IL-1β and IL-6 when the sebocytes were stimulated with lipopolysaccharides, a finding that suggests a potential positive effect of CBD in the treatment of acne vulgaris. ...
... CBD TNF-α, IL-1β, IL-6 (↓) A2a adenosine receptor-cAMP-TRIB3-NF-κB pathway SZ95 human sebocytes cultures Oláh et al. [174] (↓) = decrease in expression and/or concentration; (↑) = increase in expression and/or concentration; BPC = β-Caryophyllene; OEA = oleoylethanolamide; TRPV = transient receptor potential channel; GPR = G-coupled protein receptor. CBD IL-1 and total protein content (↓) 5-HT1A receptor Lung inflammation induced by brain ischemia in newborn piglets Arruza et al. [121] WIN55,212-2 MMP-9 (↓) ERK1/2 signaling pathway Lung inflammation in mice exposed to cigarette smoke Tauber et al. [122] [190] AJA Decreased IL-31, IFN-β and γ, and T-helper cell inflammation Dermatomyositis Phase 2 Chen et al. [192] AJA ...
Article
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Recent studies have identified great similarities and interferences between the epithelial layers of the digestive tract, the airways and the cutaneous layer. The relationship between these structures seems to implicate signaling pathways, cellular components and metabolic features, and has led to the definition of a gut-lung-skin barrier. Inflammation seems to involve common features in these tissues; therefore, analyzing the similarities and differences in the modulation of its bi-omarkers can yield significant data promoting a better understanding of the particularities of specific signaling pathways and cellular effects. Cannabinoids are well known for a wide array of beneficial effects, including anti-inflammatory properties. This paper aims to explore the effects of natural and synthetic cannabinoids, including the components of the endocannabinoid system, in relation to the inflammation of the gut-lung-skin barrier epithelia. Recent advancements in the use of cannabinoids as anti-inflammatory substances in various disorders of the gut, lungs and skin are detailed. Some studies have reported mixed or controversial results, and these have also been addressed in our paper.
... The cooperation is complemented by receptors and pro-and anti-inflammatory cytokines and chemokines [49]. Dysfunction of this system can be observed in many diseases, such as atopic dermatitis, psoriasis, scleroderma, acne, dermatomyositis, keratin and hair growth disorders, carcinogenesis, together with symptoms such as pruritus, which shows potential for the future use of cannabinoids in the therapy of these disorders [9,28,49,52,[56][57][58][59][60]. ...
... Despite the limited number, clinical trials presented a significant decrease in pruritus after cannabinoid treatment in some dermatological disorders, such as atopic dermatitis, psoriasis, contact eczema, allergic contact dermatitis, and systemic conditions like uremic or cholestatic pruritus [56][57][58]. ...
Article
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Significant growth of interest in cannabis (Cannabis sativa L.), especially its natural anti-inflammatory and antioxidative properties, has been observed recently. This narrative review aimed to present the state of the art of research concerning the anti-inflammatory activity of all classes of cannabinoids published in the last five years. Multimodal properties of cannabinoids include their involvement in immunological processes, anti-inflammatory, and antioxidative effects. Cannabinoids and non-cannabinoid compounds of cannabis proved their anti-inflammatory effects in numerous animal models. The research in humans is missing, and the results are unconvincing. Although preclinical evidence suggests cannabinoids are of value in treating chronic inflammatory diseases, the clinical evidence is scarce, and further well-designed clinical trials are essential to determine the prospects for using cannabinoids in inflammatory conditions.
... Clinical trials testing for anti-acne activity have previously been reported for CBD [6] and a C. sativa extract [5]. CBD has been shown to be an effective sebostatic agent with anti-inflammatory properties in studies utilizing sebocytes [41]. Additionally, both CBG and CBD have been shown to possess strong antibacterial activity against C. acnes and several other harmful skin bacteria such as Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) [42]. ...
... Olah et al. showed that sebocytes treated with CBD conferred anti-inflammatory activity through the A2a receptor-dependent upregulation of tribbles homolog 3 (TRIB3) leading to inhibition of the NF-κB signaling pathway. The authors hypothesized that the A2a receptor was likely the main target for the anti-inflammatory activity of CBD in human sebocytes [41]. Moreover, CBG has previously been reported to activate transient receptor potential ankyrin 1 (TRPA1), a key pain and inflammation target [56], and to confer anti-inflammatory effects via the modulation of transient receptor potential vanilloid-3 and 4 (TRPV-3 and TRPV-4) [57]. ...
Article
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Cannabigerol (CBG) is a minor non-psychoactive cannabinoid present in Cannabis sativa L. (C. sativa) at low levels (<1% per dry weight) that serves as the direct precursor to both cannabidiol (CBD) and tetrahydrocannabinol (THC). Consequently, efforts to extract and purify CBG from C. sativa is both challenging and expensive. However, utilizing a novel yeast fermentation technology platform, minor cannabinoids such as CBG can be produced in a more sustainable, cost-effective, and timely process as compared to plant-based production. While CBD has been studied extensively, demonstrating several beneficial skin properties, there are a paucity of studies characterizing the activity of CBG in human skin. Therefore, our aim was to characterize and compare the in vitro activity profile of non-psychoactive CBG and CBD in skin and be the first group to test CBG clinically on human skin. Gene microarray analysis conducted using 3D human skin equivalents demonstrates that CBG regulates more genes than CBD, including several key skin targets. Human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (NHEKs) were exposed in culture to pro-inflammatory inducers to trigger cytokine production and oxidative stress. Results demonstrate that CBG and CBD reduce reactive oxygen species levels in HDFs better than vitamin C. Moreover, CBG inhibits pro-inflammatory cytokine (Interleukin-1β, -6, -8, tumor necrosis factor α) release from several inflammatory inducers, such as ultraviolet A (UVA), ultraviolet B (UVB), chemical, C. acnes, and in several instances does so more potently than CBD. A 20-subject vehicle-controlled clinical study was performed with 0.1% CBG serum and placebo applied topically for 2 weeks after sodium lauryl sulfate (SLS)-induced irritation. CBG serum showed statistically significant improvement above placebo for transepidermal water loss (TEWL) and reduction in the appearance of redness. Altogether, CBG’s broad range of in vitro and clinical skin health-promoting activities demonstrates its strong potential as a safe, effective ingredient for topical use and suggests there are areas where it may be more effective than CBD.
... However, the specific antagonist of TRPV4 significantly alleviated the toxicity of CBD. CBD has been reported to be an agonist for TRPV4 in sebocytes [23] but not in cancer. TRPV4 is a nonselective calcium permeant cation channel; many cellular processes are highly sensitive to the change of calcium ion homeostasis and the abnormal function of these channels have been associated with uncontrolled proliferation and resistance to cell death. ...
... Cells were washed with PBS (Hyclone, SH30256.01) and collected into RIPA buffer (Beyotime, P0013 C) containing protease (Thermo Scientific, 36,978) and phosphatase inhibitors (Beyotime, ST640). Protein was collected at 10,000 g and 4°C for 30 min, and the protein concentration was determined using a Pierce TM BCA Protein Assay Kit (Thermo Scientific, 23,225). Total cell lysates (20 μg protein) were separated by 8-10% SDS-PAGE. ...
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Glioma is the most common primary malignant brain tumor with poor survival and limited therapeutic options. The non-psychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against glioma; however, the molecular target and mechanism of action of CBD in glioma are poorly understood. Here we investigated the molecular mechanisms underlying the antitumor effect of CBD in preclinical models of human glioma. Our results showed that CBD induced autophagic rather than apoptotic cell death in glioma cells. We also showed that CBD induced mitochondrial dysfunction and lethal mitophagy arrest, leading to autophagic cell death. Mechanistically, calcium flux induced by CBD through TRPV4 (transient receptor potential cation channel subfamily V member 4) activation played a key role in mitophagy initiation. We further confirmed TRPV4 levels correlated with both tumor grade and poor survival in glioma patients. Transcriptome analysis and other results demonstrated that ER stress and the ATF4-DDIT3-TRIB3-AKT-MTOR axis downstream of TRPV4 were involved in CBD-induced mitophagy in glioma cells. Lastly, CBD and temozolomide combination therapy in patient-derived neurosphere cultures and mouse orthotopic models showed significant synergistic effect in both controlling tumor size and improving survival. Altogether, these findings showed for the first time that the antitumor effect of CBD in glioma is caused by lethal mitophagy and identified TRPV4 as a molecular target and potential biomarker of CBD in glioma. Given the low toxicity and high tolerability of CBD, we therefore propose CBD should be tested clinically for glioma, both alone and in combination with temozolomide.
... The decreased prevalence of acne among these cases can be attributed to sebostatic effects of cannabis. Oláh et al. [28] showed that cannabidiol (CBD) derived from Cannabis sativa might improve acne vulgaris through a sebostatic mechanism. CBD had antiproliferative effects on both keratinocytes and sebocytes, thus decreasing the formation of comedones and production of sebum as well as demonstrable antimicrobial activity. ...
... CBD had antiproliferative effects on both keratinocytes and sebocytes, thus decreasing the formation of comedones and production of sebum as well as demonstrable antimicrobial activity. [28,29] Larkin et al. [30] in a systemic review of hospital-based studies found thirteen studies reporting a positive association between hesitation cuts/repetition of self-harm and drug abuse/dependence. In the current study as well, 16.3% cases had the presence of hesitation cuts, most commonly over forearms. ...
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Background: Substance use has turned out to be one of the growing social problems of the present society cutting across all sorts of boundaries of the world with Kashmir Valley being no exception to this growing pathological phenomenon. Aims and objectives: To find the prevalence and pattern of dermatological manifestations among substance users across Kashmir Valley. Materials and methods: Cross-sectional study where patients of all age-groups, irrespective of gender, were enrolled in the three largest districts of Kashmir Valley over a span of 18 months. Results: Sample size was 710 with a male/female ratio of 12.4:1. The mean age of the cases was 25.2 ± 7.05 years. Heroin, one of the opioids, was the most common substance used (n = 515), followed by cannabis (n = 334). Pruritus was found to be the most common dermatological manifestation overall and statistically significant among heroin users. Stigmata of injection drug use (IDU) with the presence of track marks and sooting tattoos (93.1%), atrophic scars secondary to skin popping (30.7%), active skin ulcers (18.8%), and puffy hand syndrome (8.7%) were specifically seen among injection drug users. Oral involvement was seen in 48.5%, including periodontal disease, oral thrush, and stomatitis nicotinica. Hyperhidrosis was present in 30%, and hesitation cuts over arms in 16.3% of all substance users. Conclusion: Dermatological manifestations are quite prevalent among substance users in the population of Kashmir. Pruritus with temporal relation to substance use, stigmata of injectable drug use including track marks and sooting tattoos, atrophic scars at injection sites, active skin ulcers, and skin and soft tissue infections, and hyperhidrosis are among important dermatological clues for detecting substance use. Recognition of such cutaneous signs is important in these cases for more effective diagnosis and treatment.
... In the first study, researchers administered CBD to cultured human sebocytes and human skin organ culture, which inhibited the lipogenic actions of various compounds (arachidonic acid, linoleic acid, and testosterone) and suppressed sebocyte proliferation and lipogenesis through TRPV4 activation. [59][60][61] In a second study, male volunteers applied a 3% cannabis seed extract in a vehicle to one cheek or vehicle alone to the other cheek for 12 weeks. Using a sebumeter, the researchers found a significant reduction in sebum production with cannabis extract versus vehicle alone (p < 0.05). ...
... Other CBs have potential anti-acne potential with similar effects on human sebocytes, so whether CBD alone or the CB mixture in hemp extract is more effective is unknown. [59][60][61] Theoretically, CBD could impact inflammatory skin conditions. However, human data on CBD's impact on rosacea, eczema, or psoriasis is nonexistent in the biomedical literature. ...
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After completing the activity, learners will be able to ● Discuss cannabidiol's known pharmacologic profile ● Identify FDA-approved indications for prescription cannabidiol and other indications in which research is promising ● Distinguish the FDA-approved cannabidiol from various nonprescription products in terms of quality and risk/benefit profile ● Maximize the pharmacist's role in helping patients who are good candidates for prescription cannabidiol or use nonprescription cannabidiol products either with or without other prescription drug therapies After completing the continuing education activity, pharmacy technicians will be able to ● Discuss the basic facts about cannabidiol products ● Acquire reputable sources for patients who have an interest in cannabidiol to find information ● Distinguish between nonprescription and prescription cannabidiols ● Infer when to refer patients to the pharmacist for recommendations or referral
... Sugere através de estudos já realizados por Oláh et al. que o Canabidiol é um potente ativo para cosméticos que visam tratar acne, prurido crônico e dermatite atópica. Porém demonstra a necessidade de estudos mais aprofundados para colocar em evidência a segurança e eficácia da substância, além de suas doses, concentrações e vias de administração.Oláh A. et al., 2014. "Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes."O ...
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A planta Cannabis sativa ficou conhecida por ser utilizada para obter as sensações de excitação e relaxamento que as substâncias provenientes de suas flores são capazes de proporcionar. Uma delas é o Canabidiol, um composto não psicoativo que possui diversas propriedades terapêuticas. Objetivo: Analisar os estudos que elucidam o Sistema Endocanabinoide Epidérmico (EES) e a propriedade anti-inflamatória do Canabidiol na pele, identificando assim, os benefícios do uso do Canabidiol em tratamentos terapêuticos menos invasivos para acne vulgar causada por Cutibacterium acnes. Metodologia: Para que isso fosse possível, foi realizada uma revisão de literatura integrativa, nos seguintes bancos de dados: Scientific Electronic Library Online (SciELO), Google Acadêmico e PubMed, utilizando os descritores Cannabis sativa, Canabidiol, Acne vulgar, Cosméticos e Terapia farmacológica. Resultados: Estudos e pesquisas in vitro e in vivo apontam que o Canabidiol possui atividade anti-inflamatória na pele e tem potencial para ser manipulado em forma de cosmético de uso tópico para prevenir e combater a acne causada por bactéria, sem ocasionar danos ao paciente. Conclusão: Apesar de sua atividade terapêutica ter sido constatada, mais estudos em relação ao ativo precisam acontecer. Enquanto isso, o seu uso segue sendo apenas uma esperança para futuros tratamentos alternativos da acne vulgar, tendo em vista que a substância faz parte de uma planta que ainda é criminalizada.
... 38 These key features create an attractive natural compound that lends itself to an array of therapeutic applications in the medical field, such as the topical application of CBD in treating certain skin disorders, including atopic dermatitis, 39 epidermolysis bullosa, 40 and acne/seborrhea. 41 Cannabidiol is a 21-carbon terpenophenolic compound. 42 Phenolic compounds consist of one or more aromatic rings that contain at least one hydroxyl group. ...
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This study investigated a unique one-pot microwave-assisted green synthesis method of gold (Au) and silver (Ag) nanoparticles (NPs) using cannabidiol (CBD) as a capping and reducing agent. Furthermore, Au and Ag NPs were also chemically synthesized using poly(vinyl pyrrolidone), which functioned as reference materials when comparing the size, shape, and cytotoxicity of NPs. Synthesis parameters such as reaction time, temperature, and precursor molar ratio were optimized to control the size and shape of the biosynthesized NPs. Various characterization techniques such as transmission electron microscopy, ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction were used to confirm the formation and properties of Au and Ag NPs. Both biosynthesized metal NPs were spherical and monodispersed, with average particle sizes of 8.4 nm (Au-CBD) and 4.8 nm (Ag-CBD). This study also explored the potential cytotoxicity of CBD-capped NPs in human keratinocyte cells, which was observed to be of minimal concern. The novel synthesis approach presented in this study is free from harsh chemical reagents; therefore, these NPs can be used in a wide array of applications, including the pharmaceutical and biomedical fields.
... 17 An in vitro study demonstrated the sebostatic and anti-inflammatory effects of CBD on sebocytes, while a subsequent clinical trial using BTX 1503 (a 5% CBD topical solution) preliminarily confirmed the therapeutic effect and safety of CBD in acne patients. 18,19 However, further clinical efficacy and related mechanisms of CBD in acne treatment still remain to be resolved. ...
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Background: Acne is a common inflammatory skin disease, while cannabidiol (CBD) is a representative non-psychoactive phytocannabinoid which has been proved to exert universal anti-inflammatory properties. This study aimed to explore the effect of CBD on acne inflammation induced by Cutibacterium acnes-derived extracellular vesicles (CEVs) in keratinocytes and reveal the underlying mechanisms. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated by CEVs in the presence of CBD or vehicle. Interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels were examined by RT-PCR and ELISA. The expression of cannabinoid type-2 (CB2) receptor and transient receptor potential vanilloid type-1 (TRPV1) was detected by Western blotting. TNF-α levels in the presence of CB2 receptor antagonist (AM630) or TRPV1 antagonist (Capsazepine) were detected by RT-PCR. The activation of MAPK and NF-κB signaling pathways and the nuclear translocation of NF-κB p65 upon CBD treatment were analyzed by Western blotting and immunofluorescence assay, respectively. Results: The expression of inflammatory cytokines (IL-6, IL-8 and TNF-α) in CEVs-stimulated NHEKs was suppressed by CBD. CB2 receptor expression was upregulated by CBD, whereas CEVs-promoted TRPV1 expression was downregulated by CBD. AM630 reversed TNF-α levels inhibited by CBD. Capsazepine exerted an inhibitory effect on CEVs-induced inflammation and had synergistic effect with CBD. The phosphorylation of ERK1/2 and NF-κB p65 and nuclear translocation of NF-κB p65 were induced by CEVs but reduced by CBD. Conclusion: The results indicated that CBD could inhibit inflammation induced by CEVs in NHEKs, which was mediated by activation of CB2 receptor and enhanced by the TRPV1 antagonist, through inactivation of the MAPK and NF-κB signaling pathways. CBD might be a potential novel strategy for acne treatment in the future.
... The application of CBD in the cosmetic industry has also grown rapidly [3]. Anti-inflammatory properties enhance the therapeutic effects of acne vulgaris, since it counteracts multiple pathogenic factors of acne: sebum over-production, and sebocyte over proliferation [4]. In addition, its antioxidation function is able to help counteract oxidative cell damage generated by free radicals, decreasing visible signs of skin aging [5]. ...
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Cannabidiol (CBD) hemp seed oil is a commercial raw material with antioxidant and anti-inflammatory benefits that has been formulated into body wash and skin care products. The biggest analytical challenge is how to simultaneously quantify CBD and hemp seed oil as they deposited on the skin surface. CBD is easily separated and quantified from skin surface extracts via a HPLC-mass spectrometry methodology. However, the structural skeleton of triacylglycerides (TAGs) in hemp seed oil is same as those from the skin surface sebum. The strong hydrophobicity with subtle structural difference challenges their separation. In this project, a new reverse phase HPLC-high resolution mass spectrometry methodology was developed with a strong mobile phase normal propanol. The separated hemp seed oil TAGs in the chromatogram were identified and characterized using data-dependent acquisition (DDA) technology. Based on the daughter ion characterization, the separated peak with an ammonium adduct at 890.7226 [M + NH4]+ was confirmed as the parent ion of glycerol with three omega-3 fatty acid chains. This is the first time TAG structure with direct HPLC-tandem mass spectrometry technology has been elucidated without a hydrolysis reaction. The confirmed TAG structure with an ammonium adduct at 890.7226 ± 0.0020 can be used as a representative chemical marker for the hemp seed oil quantification.
... Although CBD can cross the blood-brain barrier, it does not cause psychoactive effects that lack abuse potential. CBD has been shown to reduce the inflammation in cultured human sebocytes and human skin organ culture through coupling to A2A adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of NF-κB signaling (Oláh et al., 2014). Moreover, the intervention of CBD delayed the onset of type 1 diabetes in non-obese diabetic mice and alleviated pancreas inflammation (Lehmann et al., 2016). ...
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Alcohol abuse and high-fat diet–induced liver diseases have been the most prevalent chronic liver diseases and the leading reasons for liver transplantation around the world. Cannabidiol (CBD) is a botanical component extracted from marijuana plants without psychoactive impact. In our previous reports, we found that CBD can prevent fatty liver induced by Lieber–DeCarli ethanol diet or non-alcoholic fatty liver disease (NAFLD) induced by high-fat high-cholesterol diet. The current work is a further study on whether CBD can alleviate liver injuries induced by ethanol plus high-fat high-cholesterol diet (EHFD), which is a model simulating heavy alcohol drinkers in a Western diet. A mice liver injury model induced by EHFD for 8 weeks was applied to explore the protective properties of CBD and the underlying mechanisms. We found that CBD prevented liver steatosis and oxidative stress induced by EHFD. CBD treatment inhibited macrophage recruitment and suppressed activation of NFκB–NLRP3–pyroptosis pathway in mice livers. The hepatoprotective property of CBD in the current model might be a result of inhibition of inflammation via alleviating activation of the hepatic NFκB–NLRP3 inflammasome–pyroptosis pathway by CBD.
... In addition, researchers postulate that CBD can both quantitatively and qualitatively normalize the excessive and abnormal lipid production that often leads to the development of acne. Based on these reports, it is possible to conclude about the potential antiacne effect of cannabidiol [17]. ...
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Cannabidiol (CBD) is one of the main active ingredients in hemp. It shows a number of valuable biological properties, such as anti-cancer, anti-depressant or anti-inflammatory. The aim of the article was to present the most importantproperties of cannabidiol and its possible application in cosmetology and dermatology. The wide therapeutic potential of CBD makes it possible to use in the treatment of, not only cancer or mental disorders, but also many dermatoses.
... Phytocannabinoids can regulate lipogenesis in sebaceous glands and the proliferation of sebocytes [49]. Thus, THCV inhibited the proliferation of human SZ95 sebocytes with a TRPV4-dependent mechanism [50]. ...
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Despite the very large number of phytocannabinoids isolated from Cannabis (Cannabis sativa L.), bioactivity studies have long remained focused on the so called “Big Four” [Δ9-THC (1), CBD (2), CBG (3) and CBC (4)] because of their earlier characterization and relatively easy availability via isolation and/or synthesis. Bioactivity information on the chemical space associated with the remaining part of the cannabinome, a set of ca 150 compounds traditionally referred to as “minor phytocannabinoids”, is scarce and patchy, yet promising in terms of pharmacological potential. According to their advancement stage, we sorted the bioactivity data available on these compounds, better referred to as the “dark cannabinome”, into categories: discovery (in vitro phenotypical and biochemical assays), preclinical (animal models), and clinical. Strategies to overcome the availability issues associated with minor phytocannabinoids are discussed, as well as the still unmet challenges facing their development as mainstream drugs.
... CBD can be helpful to cure acne: a skin disease due to sebaceous glands inflammation and high sebum production, affecting more than 9% of population. CBD may be an efficient and safe way to treat acne (Oláh et al. 2014;Tan and Bhate 2015). CBD is also effective against Parkinson's disease and Alzheimer's disease (Chagas et al. 2014;Watt and Karl 2017). ...
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Rising human population has increased the utilization of available resources for food, clothes, medicine, and living space, thus menacing natural environment and mounting the gap between available resources, and the skills to meet human desires is necessary. Humans are satisfying their desires by depleting available natural resources. Therefore, multifunctional plants can contribute towards the livelihoods of people, to execute their life requirements without degrading natural resources. Thus, research on multipurpose industrial crops should be of high interest among scientists. Hemp, or industrial hemp, is gaining research interest because of its fastest growth and utilization in commercial products including textile, paper, medicine, food, animal feed, paint, biofuel, biodegradable plastic, and construction material. High biomass production and ability to grow under versatile conditions make hemp, a good candidate species for remediation of polluted soils also. Present review highlights the morphology, adaptability, nutritional constituents, textile use, and medicinal significance of industrial hemp. Moreover, its usage in environmental conservation, building material, and biofuel production has also been discussed.
... That is, CBD was shown to have lipostatic action and even decreased sebocyte proliferation. In this same study, CBD was able to inhibit pro-acne agents, such as arachidonic acid (AA), a combination of linoleic acid and testosterone (LA-T), AEA, 2-arachidonylglycerol, that induced excessive lipid synthesis in human sebocytes, leading to acne [266]. ...
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The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.
... CBD has anti-inflammatory, anti-oxidative, anti-epileptic, analgesic, anti-neoplastic, sedative, neuroprotective, and anti-anxiety activities [173][174][175][176][177][178][179][180][181][182][183][184][185][186][187][188]. Moreover, CBD inhibits sebocyte lipogenesis by activating the TRPV4 ion channel that interferes with the pro-lipogenic ERK1/2 MAPK pathway [189]. ...
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Antibiotic resistance has become an increasing challenge in the treatment of various infectious diseases, especially those associated with biofilm formation on biotic and abiotic materials. There is an urgent need for new treatment protocols that can also target biofilm-embedded bacteria. Many secondary metabolites of plants possess anti-bacterial activities, and especially the phytocannabinoids of the Cannabis sativa L. varieties have reached a renaissance and attracted much attention for their anti-microbial and anti-biofilm activities at concentrations below the cytotoxic threshold on normal mammalian cells. Accordingly, many synthetic cannabinoids have been designed with the intention to increase the specificity and selectivity of the compounds. The structurally unrelated endocannabinoids have also been found to have anti-microbial and anti-biofilm activities. Recent data suggest for a mutual communication between the endocannabinoid system and the gut microbiota. The present review focuses on the anti-microbial activities of phytocannabinoids and endocannabinoids integrated with some selected issues of their many physiological and pharmacological activities.
... In recent years, research has been conducted on the effects of cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa L., which does not have psychoactive properties [5] but exhibits antioxidant and anti-inflammatory properties on the skin and skin cells [6,7]. In various experimental models, ranging from a typical in vitro experiment using cell cultures to ex vivo experiments using cells isolated from the skin of patients, and animal studies, the effects of cannabidiol have been extensively evaluated [8][9][10][11][12][13]. ...
Article
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Chronic UV radiation causes oxidative stress and inflammation of skin and blood cells. Therefore, in this study, we assessed the effects of cannabidiol (CBD), a natural phytocannabinoid with antioxidant and anti-inflammatory properties, on the phospholipid (PL) and ceramide (CER) profiles in the plasma of nude rats irradiated with UVA/UVB and treated topically with CBD. The results obtained showed that UVA/UVB radiation increased the levels of phosphatidylcholines, lysophospholipids, and eicosanoids (PGE2, TxB2), while downregulation of sphingomyelins led to an increase in CER[NS] and CER[NDS]. Topical application of CBD to the skin of control rats significantly upregulated plasma ether-linked phosphatidylethanolamines (PEo) and ceramides. However, CBD administered to rats irradiated with UVA/UVB promoted further upregulation of CER and PEo and led to significant downregulation of lysophospholipids. This was accompanied by the anti-inflammatory effect of CBD, manifested by a reduction in the levels of proinflammatory PGE2 and TxB2 and a dramatic increase in the level of anti-inflammatory LPXA4. It can therefore be suggested that topical application of CBD to the skin of rats exposed to UVA/UVB radiation prevents changes in plasma phospholipid profile resulting in a reduction of inflammation by reducing the level of LPE and LPC species and increasing antioxidant capacity due to upregulation of PEo species.
... Compelling evidence has revealed the multifaced pharmacologic effects of CBD, such as reducing tumor growth, relieving pain, alleviating depression and anxiety, neuroprotectivity, and inhibiting inflammation (Pisanti et al. 2017;Friedman et al. 2019). CBD has been shown to exert anti-inflammation and immunosuppression effects in several inflammatory degenerative diseases, such as colitis and dermatitis (Olah et al. 2014;Sohn 2015;Casares et al. 2020). These effects are achieved partially by binding to canonical CB receptor and other various receptors, thus strongly inhibiting the production of inflammatory cytokines and chemokines (Sacerdote et al. 2005;Liou et al. 2008;De Filippis et al. 2011;Ribeiro et al. 2015). ...
Article
Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure. Notably, the enrichment of genes associated with the NOD, LRR, and NLRP3 pyrin domain–containing protein 3 (NLRP3) inflammasome pathway is downregulated after CBD treatment. The expression of cleaved-gasdermin D (GSDMD) and the percentage of pyroptotic cells are reduced as well. In addition, CBD decreases the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), which subsequently inhibits the generation of oxidized mitochondria DNA and suppresses inflammasome activation. These immunomodulating effects of CBD are mostly blocked by peroxisome proliferator activated receptor γ (PPARγ) antagonist and partially antagonized by CB 1 receptor antagonist. Our results demonstrate that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which are mediated mostly by PPARγ in the nucleus and partially by CB 1 in the plasma membrane.
... Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro models and have demonstrated the ability to ameliorate various inflammatory degenerative diseases [11,12]. However, the mechanisms of these effects are not completely understood but may be the result of interaction with the cannabinoid receptor 2 (CB2) resulting in decreased adenosine signaling [13][14][15]. The COVID-19 infection results in Severe Acute Respiratory Syndrome (SARS-CoV-2) in a small percentage of cases. ...
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Background: The coronavirus disease-19 (COVID-19) pandemic is attributable to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The pathogenesis of SARS-CoV-2 is attributed to the activation of multiple inflammatory pathways secondary to the interaction of virus and host immune responses. 15% of patients over the age of 60 with COVID-19 require hospitalization. In addition, ICU admissions are as high as 5% of COVID-19 patients in this same age group. Most with one or more underlying conditions, undergo the pathophysiologic process of hyper-inflammation and its accompanying Cytokine Storm Syndrome (CSS) which results in significant morbidity and mortality. Therapeutics, which reduce the release of inflammatory cytokines, have been sought to slow disease progression. A growing body of literature attests to the anti-inflammatory effects of the naturally occurring cannabinoids found in both cannabis and hemp plants. The major cannabinoid, cannabidiol (CBD), results in decreased cytokine production via Cannabinoid receptor 2 (CB2). In addition, recent evidence indicates: (1) CBD may protect against infection by inducing anti-viral cellular activity; and (2) two specific cannabinoids exhibit binding to the spike protein thereby preventing infection in vitro. Therefore, examination of the activity of a CBD-rich oil on cellular inflammatory markers, as a potential natural intervention and as an adjuvant to recognized therapeutic interventions, is considered here. Materials and methods: COVID-19 has influenced all sectors of the world’s economic, scientific and commercial communities. This is true also of the investigative work within this report which adapted to the COVID-19 outbreak during the execution of the study. Part 1 of this report focuses on the initial study designed to evaluate the reported anti-inflammatory effects of a hemp-based full-spectrum CBD and cannabinoid-rich microcellular formulation (i.e. Hempzorb81™) on healthy volunteers comparing a treatment group of 100 with a placebo group of 50. Part 2 extends the report to the effects of the Hempzorb81™ formulation on a subset of 44 study subjects who tested positive for COVID-19 infection compared to a 39 subject COVID-19 negative test control group. Results: In Part 1, the treatment cohort found two cytokines associated with the development of SARS-CoV-2. Both TNFα and IL-6 showed statistically significant reductions compared to placebo in healthy patients. Two inflammatory markers, ESR and CRP, showed reductions of 19.4% and 12.5%, respectively, but the results were not statistically significant. In Part 2, TNFα, CRP, IL-1,6 and White Blood Cell count (WBC) all showed statistically significant p-values in the COVID-19 positive cohort. In the course of the study, no COVID-19 positive patients were hospitalized or died. A 2-fold reduction in white blood cell count at the time of diagnosis over the treatment course was an additional significant indicator for improved outcome post-infection.
... Cannabis sativa with various pharmacological activities such as antiinflammatory, antipsychotic, anxiolytic, antiemetic, and antidiabetic actions (Ikarashi et al., 2021;Oláh et al., 2014). Cannabidiol has also been reported to affect atopic dermatitis, pruritus and acne (Baswan et al., 2020;Sheriff et al., 2019). ...
Article
Ethnopharmacological relevance Skin diseases are among the most common human health affections. A healthy skin promotes a healthy body that can be achieved through modern, allopathic and natural medicines. Therefore, medicinal plants can be a reliable therapy in treating skin diseases in humans through a diverse range of bioactive molecules they contain. Aim of the study This review aims to provide for the first-time scientific evidence related to the dermatological properties of Morocco's medicinal plants and it aims to provide a baseline for the discovery of new drugs having activities against skin issues. Methods This review involved an investigation with different search engines for Moroccan ethnobotanical surveys published between 1991 and 2021. The plants used to treat skin diseases have been determined. Information regarding pharmacological effects, phytochemical, and clinical trials related to the plants listed in this review was collected from different scientific databases like PubMed, Science Direct, Google Scholar, Web of Science and Scopus. The data were analyzed and summarized in the review. Results A total of 401 plants belonging to 86 families mainly represented by Asteraceae, Lamiaceae, Fabaceae, and Apiaceae which have been documented to be in common use by Moroccans for managing skin diseases. Among those plants recorded, the most commonly used are Allium cepa L, Chamaeleon gummifer (L.) Cass and Salvia rosmarinus Schleid. Mill. Leaves were the most commonly used plant part, while powder and decoction were the most common method of traditional drug preparation. 107 of the 401 plants (27%) have undergone pharmacological validation. A total of 44 compounds isolated from 27 plants were investigated to treat different types of skin diseases, and 25 plants have been clinically studied for their activities against skin diseases. Conclusion The beneficial effects of using Moroccan medicinal plants to treat skin diseases, according to traditional practices, have been proven in numerous scientific studies. Therefore, other studies should focus on isolating and identifying specific bioactive compounds from plant extracts, revealing more valuable therapeutic properties. Furthermore, additional reliable clinical trials are needed to confirm their beneficial effect on patients with skin diseases.
... cg00922748 is located on NRIP2, a member of the aspartic protease family [80]. Although there is no evidence on the association between NRIP2 and GDM, it was shown that decreased NRIP1 expression was able to affect the glucose metabolism [81]. However, the association of the corresponding genes of the left 4 CpG sites with GDM or glucose metabolism remains unclear, which still needs further investigation. ...
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Background: Gestational diabetes mellitus (GDM) is the most prevalent metabolic disease during pregnancy, but the diagnosis is controversial and lagging partly due to the lack of useful biomarkers. CpG methylation is involved in the development of GDM. However, the specific CpG methylation sites serving as diagnostic biomarkers of GDM remain unclear. Here, we aimed to explore CpG signatures and establish the predicting model for the GDM diagnosis. Methods: DNA methylation data of GSE88929 and GSE102177 were obtained from the GEO database, followed by the epigenome-wide association study (EWAS). GO and KEGG pathway analyses were performed by using the clusterProfiler package of R. The PPI network was constructed in the STRING database and Cytoscape software. The SVM model was established, in which the β-values of selected CpG sites were the predictor variable and the occurrence of GDM was the outcome variable. Results: We identified 62 significant CpG methylation sites in the GDM samples compared with the control samples. GO and KEGG analyses based on the 62 CpG sites demonstrated that several essential cellular processes and signaling pathways were enriched in the system. A total of 12 hub genes related to the identified CpG sites were found in the PPI network. The SVM model based on the selected CpGs within the promoter region, including cg00922748, cg05216211, cg05376185, cg06617468, cg17097119, and cg22385669, was established, and the AUC values of the training set and testing set in the model were 0.8138 and 0.7576. The AUC value of the independent validation set of GSE102177 was 0.6667. Conclusion: We identified potential diagnostic CpG signatures by EWAS integrated with the SVM model. The SVM model based on the identified 6 CpG sites reliably predicted the GDM occurrence, contributing to the diagnosis of GDM. Our finding provides new insights into the cross-application of EWAS and machine learning in GDM investigation.
... [8][9][10][11] There are other less confirmed effects still being studied against inflammation, anxiety, epilepsy, and cancer. [12][13][14] Although many other cannabinoids demonstrate biological activity, they have not been well studied due to their limited quantities and the difficulty of isolation. The total synthesis of the natural cannabinoids, chemical modifications and the synthesis of analogues would allow a greater understanding of these slight effects. ...
Article
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Cannabidiol‐C4 1 (CBD‐C4, cannabidibutol) is a natural product present in the extracts of Cannabis. Its isolation has not been reported to date. The aim of the proposed synthesis is to secure the availability of the pure compound, its spectroscopic characterization, and to confirm its presence in low amounts in the extracts. The enantioselective total synthesis is based on a) the use 3,5‐dimetoxybenzaldehyde as starting material, b) Corey‐Bakshi‐Shibata reduction, c) Claisen‐Ireland rearrangement, d) ring‐closing metathesis, and e) completely not‐trivial demethylation induced by sodium ethanethiolate.
... With its potential ability to regulate inflammation, scientists have researched whether CBD products may have a beneficial role in acute and chronic inflammatory diseases, including chronic inflammatory skin conditions, such as acne vulgaris, acne, eczema and dermatitis (Olah et al, 2014). ...
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Explores the effects of cannabis on wound healing
Chapter
Cannabis sativa L. was used for medicinal purposes for millennia, being useful for the treatment of several conditions such as pain, convulsions, insomnia, and lack of appetite, among others. However, due to its psychotropic side effects and the impossibility to prepare standardized formulations it was banned in the late 1930s and removed from therapeutics, being considered as a drug that was solely used for recreational purposes. In the last two decades, this situation has changed, and the therapeutic use of cannabis has resurged again, demonstrating that standardized cannabis preparations can be safe and useful for the treatment of a broad range of pathologies. In fact, several cannabis-based formulations have been approved with medicinal purposes. This chapter analyzes the medicinal use of cannabis, describing their benefits, risks, and current and future perspectives.
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Process approaches and intensification technological processes are integrated parts of available devices, which have a positive effect on the parameters of the obtained products. Nanoemulsions as delivery carriers are becoming more popular and there is a real need to increase the possibilities of formulation designing and engineering. Therefore, preparations of oil-in-water nanoemulsion with encapsulated cannabidiol (CBD) as oil phase were carried out in two ways: sonication method and two-stage high-pressure homogenization. The provided analysis showed spherical morphology and much larger sizes and polydispersity of nanoemulsions obtained by the sonication approach. The size of nanodroplets was from 216 nm up to 1418 nm for sonication, whereas for homogenization 128–880 nm. Additionally, it was observed that a proportionally higher percentage of surfactin resulted in a higher value of the Zeta potential. The formulations were found to be stable for at least 30 days. The in vitro experiments performed on human skin cell lines (HaCaT keratinocytes and normal dermal NHDF fibroblasts), and in vivo topical tests on probants established the biocompatibility of nanoemulsions with CBD. The last stage exhibits reduced discoloration and a higher degree of hydration by the selected systems with CBD and, thus indicating this nanoformulation as useful in cosmetics applications.
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Cannabis sativa L. plant is currently attracting increasing interest in cosmetics and dermatology. In this review, the biologically active compounds of hemp are discussed. Particularly the complex interactions of cannabinoids with the endocannabinoid system of the skin to treat various conditions (such as acne, allergic contact dermatitis, melanoma, and psoriasis) with clinical data. Moreover, the properties of some cannabinoids make them candidates as cosmetic actives for certain skin types. Hemp seed oil and its minor bioactive compounds such as terpenes, flavonoids, carotenoids, and phytosterols are also discussed for their added value in cosmetic formulation.
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The plant Cannabis sativa has been in use by humans for thousands of years, medicinally, for food and for various industrial uses. There are hundreds of different strains or cultivars of cannabis, and each has its own chemical profile which helps determine the therapeutic action. The key active constituents of cannabis, the phytocannabinoids and terpenes, are produced within glandular structures called trichomes which grow predominantly on the buds or flowers of the female plant. Two of the main phytocannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD); however, the plant has well over 500 chemical constituents. The ‘entourage effect’ describes the synergism between all active constituents which contributes to the overall therapeutic effect. When used medicinally, cannabis can take several forms including use as a raw or dried herb or in proprietary forms of medicines (e.g. oils or tinctures, oils in capsules and others). Proprietary forms of medicines include whole plant extracts as well as phytocannabinoid isolates, and there are also synthetic copies of THC which are clearly pharmaceuticals. This chapter presents an overview of medicinal cannabis, including its taxonomy, history of use, a little on regulations in the USA, different forms of medicinal cannabis, key active constituents and their therapeutic actions.KeywordsCannabisMarijuanaCannabidiolTetrahydrocannabinolTerpenesHistoryMental healthRegulations
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With the recent interest in medical marijuana, research into cannabinoids is regaining wider attention. Cannabinoids are collectively a group of active compounds that can be produced by animals (endocannabinoids), plants (phytocannabinoids), or synthetically. By acting on a number of different receptors like cannabinoids receptors and transient receptor potential ion channel family, cannabinoids are known to modulate cutaneous inflammation, pain, and itch. Rosacea is a highly prevalent disease and can be associated with a significant degree of morbidity associated with its symptom. Transient receptor potential ion channels are known to be triggered in rosacea and may underlie a portion of rosacea's pathophysiology. This article aims to detail the transient receptor potential channel pathways in rosacea and the known effects of cannabinoids on these pathways and further discussing the potential role of cannabinoids in treating rosacea.
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Topical therapy is a mainstay of dermatological treatment and holds many advantages, including ease of use, relative lack of systemic side effects, and patient-directed application. In hidradenitis suppurativa (HS), topical therapeutics are often used for early-stage lesions or as adjunct therapy to systemic or surgical treatments. The four categories of disease-modifying topical therapies for sHS include antibiotics, antiseptics, keratolytics, and bathing additives (each of which will be discussed in this chapter), while topical therapies aimed at symptom-control such as analgesics and antipruritics are reviewed in Chapter 19. Unfortunately, there is a lack of robust evidence supporting the use of most topical therapies in HS. Thus, in the absence of rigorous data, the decision regarding which topical treatment to use is often made at the clinician’s discretion as well as the patient’s preference. This chapter will provide an overview of topical therapies, including their dosing schedules, mechanisms of action, contraindications, and recommendations for use to better inform these decisions.
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Objective To evaluate patterns of cannabis use in patients with cutaneous lymphoma (CL), as well as the association between cannabis use and itch specifically. Design Cross-sectional survey created in partnership with the Cutaneous Lymphoma Foundation (CLF). Setting The online survey was distributed electronically via email to the CLF listserv and links posted to social media over a 2-week period. Main Outcome Measures Respondents were classified as current cannabis users, prior users, and never users. A visual analog scale (VAS) was used to assess itching severity, improvement of itch, and interest in learning about cannabis. Results A total of 119 patient responses (61% female, mean age 59 y) were included in analysis. The majority had mycosis fungoides or Sézary syndrome (74%; 88/119) and early stage (IA-IIA) disease (56%; 48/86). Mean VAS itch score was 3.2 + 2.8 for the cohort. Over half (55%; 60/110) reported ever having used cannabis, with 22% (24/110) endorsing current cannabis use. Common methods of cannabis use were smoking (54%) and vaporizing (46%). 25% (6/24) of current users reported using cannabis specifically to treat itch; these respondents noted that cannabis resulted in moderate improvement of itching (mean 6.6/10). There was strong interest in learning more about cannabis and cancer, and most desired this information from their CL doctor/nurse. Conclusions Cannabis use is common among patients with CL, and patients report improvement of itching as a result of using cannabis. Further studies are needed to elucidate the risks and benefits of cannabis use in this patient population.
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Le cannabidiol n’est pas un stupéfiant puisqu’il n’a pas de propriété addictogène. Les produits qui en contiennent sont de plus en plus disponibles, sous différentes formes, dans des magasins spécialisés et même en pharmacie. Cette substance, dont le profil de tolérance est acceptable, peut interagir avec certains traitements médicamenteux.
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The development of medications or cosmetics from botanicals such as the cannabis plant is the current major topic of interest in the pharmaceutical and cosmetic industry. Currently, several countries have legalized the use and dispensing of cannabis products. Cannabis is one of the most commonly abused or used addictive natural products after alcohol and tobacco. Concerning the cosmetic world, cannabis-based products are used extensively in various formulations. The most common personal care products are the skin, hair, eye, nails, or face formulations which are generally used to improve the appearance and prevent aging or risk of other diseases. This chapter deals with various cannabis-based cosmetic products and their uses.
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Many patients with hidradenitis suppurativa (HS) do not achieve adequate symptom coverage with conventional therapies and often resort to complementary and alternative medicine (CAM) in hopes of achieving relief. Current evidence suggests CAM use is popular among HS patients. This chapter discusses the various types of CAM as well as their demonstrated or potential utility for the treatment of HS in conjunction with current conventional therapies. While there has not been high quality level of evidence for CAM therapies in HS, the benefits and the favorable side effect profile of these modalities that have been seen in other inflammatory conditions can be considered in HS. Future investigations are needed to elucidate the mechanism, efficacy, and safety of CAM in HS.
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Summary The Gene Expression Omnibus (GEO) project was initiated at NCBI in 1999 in response to the growing demand for a public repository for data generated from high-throughput microarray experiments. GEO has a flexible and open design that allows the submission, storage, and retrieval of many types of data sets, such as those from high-throughput gene expression, genomic hybridization, and antibody array experiments. GEO was never intended to replace lab-specific gene expression databases or laboratory information management systems (LIMS), both of which usually cater to a particular type of data set and analytical method. Rather, GEO complements these resources by acting as a central, molecular abundance-data distribution hub. GEO is available on the World Wide Web at http://www.ncbi.nih.gov/geo (http://www.ncbi.nih.gov/geo).
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Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. However, the mechanisms of these effects are not completely understood. Using the BV-2 mouse microglial cell line and lipopolysaccharide (LPS) to induce an inflammatory response, we studied the signaling pathways engaged in the anti-inflammatory effects of cannabinoids as well as their influence on the expression of several genes known to be involved in inflammation. We found that the two major cannabinoids present in marijuana, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), decrease the production and release of proinflammatory cytokines, including interleukin-1beta, interleukin-6, and interferon (IFN)beta, from LPS-activated microglial cells. The cannabinoid anti-inflammatory action does not seem to involve the CB1 and CB2 cannabinoid receptors or the abn-CBD-sensitive receptors. In addition, we found that THC and CBD act through different, although partially overlapping, mechanisms. CBD, but not THC, reduces the activity of the NF-kappaB pathway, a primary pathway regulating the expression of proinflammatory genes. Moreover, CBD, but not THC, up-regulates the activation of the STAT3 transcription factor, an element of homeostatic mechanism(s) inducing anti-inflammatory events. Following CBD treatment, but less so with THC, we observed a decreased level of mRNA for the Socs3 gene, a main negative regulator of STATs and particularly of STAT3. However, both CBD and THC decreased the activation of the LPS-induced STAT1 transcription factor, a key player in IFNbeta-dependent proinflammatory processes. In summary, our observations show that CBD and THC vary in their effects on the anti-inflammatory pathways, including the NF-kappaB and IFNbeta-dependent pathways.
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This book is intended as a scientific resource for cannabinoid researchers carrying out animal and human experiments, and for those who are interested in learning about future directions in cannabinoid research. Additionally, this book may be of value to investigators currently working outside the field of cannabinoid research who have an interest in learning about these compounds and their atypical cannabinoid signalling. This book provides insight into the potential medical application of cannabinoids and their therapeutic development for the treatment of human disease. © Springer Science+Business Media New York 2013. All rights reserved.
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Structure and distribution Acne vulgaris Aetiology of acne Clinical features Treatment Uncommon associations with acne Severe acne variants Ectopic sebaceous glands Sebaceous gland hyperplasia, adenoma and carcinoma ‘Sebaceous’ (epidermoid) cysts and steatocystoma multiplex References
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