Cannabinoids in dermatology: a scoping review.

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“The therapeutic applications of cannabis and cannabinoids are an increasingly conspicuous topic as de-criminalization and legalization of these products continues to expand.

A limited number of cannabinoid compounds have been approved for a specific set of conditions. However, the current role of cannabinoids for the treatment of dermatologic conditions remains to be defined.

We conducted a review of the current literature to determine the applications of cannabinoids for the therapy of various skin diseases.

After conducting our analysis, we found that cannabinoid products have the potential to treat a variety of skin conditions, including acne vulgaris, allergic contact dermatitis, asteatotic dermatitis, atopic dermatitis, hidradenitis suppurativa, Kaposi sarcoma, pruritus, psoriasis, skin cancer, and the cutaneous manifestations of systemic sclerosis. However, the majority of available data on these compounds are pre-clinical and there is a corresponding lack of high-quality randomized, controlled trials that evaluate their effects.

Cannabinoids have shown some initial promise as therapy for a variety of skin diseases. However, there is a requirement for thorough pre-clinical research and large-scale, randomized, controlled trials before cannabinoids can be considered safe and effective treatments for these conditions.”

“The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders”  https://www.sciencedirect.com/science/article/abs/pii/S0006295218303484

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The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders.

Biochemical Pharmacology

“The skin is the largest organ of the body and has a complex and very active structure that contributes to homeostasis and provides the first line defense against injury and infection.

In the past few years it has become evident that the endocannabinoid system (ECS) plays a relevant role in healthy and diseased skin.

Specifically, we review how the dysregulation of ECS has been associated to dermatological disorders such as atopic dermatitis, psoriasis, scleroderma and skin cancer. Therefore, the druggability of the ECS could open new research avenues for the treatment of the pathologies mentioned.

Numerous studies have reported that phytocannabinoids and their biological analogues modulate a complex network pharmacology involved in the modulation of ECS, focusing on classical cannabinoid receptors, transient receptor potential channels (TRPs), and peroxisome proliferator-activated receptors (PPARs).

The combined targeting of several end-points seems critical to provide better chances of therapeutically success, in sharp contrast to the one-disease-one-target dogma that permeates current drug discovery campaigns.”

https://www.ncbi.nlm.nih.gov/pubmed/30138623

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303484

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Can marijuana help eczema?

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“A medical doctor and researchers in the cannabis industry explain the science behind cannabis as a potential treatment for atopic dermatitis.

Weed cream. THC lotion. CBD salve. They go by many names, and there is a lot of interest and hope in the dermatological community that marijuana—or cannabis—may provide an alternate treatment pathway for a variety of skin diseases, especially atopic dermatitis (AD).

Cannabinoids represent an exciting prospect for the future of AD therapy. With measurable anti-itch, anti-pain, anti-microbial and anti-inflammatory properties, the effect of cannabinoids in patients with AD has already begun to be demonstrated.”  https://nationaleczema.org/can-marijuana-help/

Can marijuana help eczema?

“Cannabis could help cure eczema by controlling bacteria that causes skin condition. Research from the National Eczema Association indicates cannabis may help relieve some skin conditions. CANNABIS might be able to solve some eczema problems as research indicates it could take away the itch that comes with the skin condition.” https://www.thesun.co.uk/news/6432805/cannabis-help-treat-cure-eczema/

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Topical cannabinoids in dermatology.

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“Topical cannabinoids are increasingly utilized by dermatology patients for a range of disorders; however, the acceptance of these over-the-counter products has far outpaced scientific investigation into their safety and efficacy. Here, we review the studies of topical cannabinoids in skin conditions and assess their current place in dermatology practice.”

https://www.ncbi.nlm.nih.gov/pubmed/28873100

“The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757311/

“Cannabinoid system in the skin – a possible target for future therapies in dermatology.” https://www.ncbi.nlm.nih.gov/pubmed/19664006

“Anti-inflammatory cannabinoids for skin diseases”  https://www.endoca.com/blog/discovery/anti-inflammatory-cannabinoids-skin-diseases/

“Topical cannabinoids may help to treat skin diseases”  http://www.medicalnewstoday.com/articles/316968.php

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The Inhibitory Effect of S-777469, a Cannabinoid Type 2 Receptor Agonist, on Skin Inflammation in Mice.

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“We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4-fluorobenzyl]-5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl]amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The oral administration of S-777469 significantly suppressed DNFB-induced ear swelling in a dose-dependent manner. In addition, S-777469 significantly alleviated mite antigen-induced atopic dermatitis-like skin lesions in NC/Nga mice. A histological analysis revealed that S-777469 significantly reduced the epidermal thickness and the number of mast cells infiltrating skin lesions. We demonstrated that S-777469 inhibited mite antigen-induced eosinophil accumulation in skin lesions and an endogenous CB2 ligand, 2-arachidonoylglycerol (2-AG)-induced eosinophil migration in vitro. Moreover, we confirmed that 2-AG levels significantly increased in skin lesions of mite antigen-induced dermatitis model. Together, these results suggest that S-777469 inhibits skin inflammation in mice by blocking the activities of 2-AG.”

https://www.ncbi.nlm.nih.gov/pubmed/28214870

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The Endocannabinoid System and Its Role in Eczematous Dermatoses.

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“The skin serves as the foremost barrier between the internal body and the external world, providing crucial protection against pathogens and chemical, mechanical, and ultraviolet damages. The skin is a central player in the intricate network of immune, neurologic, and endocrine systems. The endocannabinoid system (ECS) includes an extensive network of bioactive lipid mediators and their receptors, functions to modulate appetite, pain, mood, and memory, and has recently been implicated in skin homeostasis. Disruption of ECS homeostasis is implicated in the pathogenesis of several prevalent skin conditions. In this review, we highlight the role of endocannabinoids in maintaining skin health and homeostasis and discuss evidence on the role of ECS in several eczematous dermatoses including atopic dermatitis, asteatotic eczema, irritant contact dermatitis, allergic contact dermatitis, and chronic pruritus. The compilation of evidence may spark directions for future investigations on how the ECS may be a therapeutic target for dermatologic conditions.” https://www.ncbi.nlm.nih.gov/pubmed/28098721

“The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757311/

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Targeting Cutaneous Cannabinoid Signaling in Inflammation – A “High”-way to Heal?

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“The endocannabinoid system (ECS) is a recently emerging complex regulator of multiple physiological processes. It comprises several endogenous ligands (e.g. N-arachidonoylethanolamine, a.k.a. anandamide [AEA], 2-arachidonoylglycerol [2-AG], palmitoylethanolamide [PEA], etc.), a number of endocannabinoid (eCB)-responsive receptors (e.g. CB1 and CB2, etc.), as well as enzymes and transporters involved in the synthesis and degradation of the eCBs.

Among many other tissues and organs, various members of the ECS were shown to be expressed in the skin as well. Indeed, AEA, 2-AG, CB1 and CB2 together with the major eCB-metabolizing enzymes (e.g. fatty acid amide hydrolase [FAAH], which cleaves AEA to ethanolamine and pro-inflammatory arachidonic acid) were found in various cutaneous cell types. Importantly, the eCB-tone and cannabinoid signaling in general appear to play a key role in regulating several fundamental aspects of cutaneous homeostasis, including proliferation and differentiation of epidermal keratinocytes, hair growth, sebaceous lipid production, melanogenesis, fibroblast activity, etc.

Moreover, appropriate eCB-signaling through CB1 and CB2 receptors was found to be crucially important in keeping cutaneous inflammatory processes under control.

Collectively, these findings (together with many other recently published data) implied keratinocytes to be “non-classical” immune competent cells, playing a central role in initiation and regulation of cutaneous immune processes, and the “c(ut)annabinoid” system is now proven to be one of their master regulators.

Another recently emerging, fascinating possibility to manage cutaneous inflammation through the cannabinoid signaling is the administration of phytocannabinoids (pCB). Cannabis sativa contains over 100 different pCBs, the vast majority of which have no psychotropic activity, and usually possess a “favorable” side-effect profile, which makes these substances particularly interesting drug candidates in treating several inflammation-accompanied diseases.

With respect to the skin, we have recently shown that one of the best studied pCBs, (−)-cannabidiol (CBD), may have great potential in managing acne, an inflammation-accompanied, extremely prevalent cutaneous disease.

Collectively, in light of the above results, both increase/restoration of the homeostatic cutaneous eCB-tone by FAAH-inhibitors and topical administration of non-psychotropic pCBs hold out the promise to exert remarkable anti-inflammatory actions, making them very exciting drug candidates, deserving full clinical exploration as potent, yet safe novel class of anti-inflammatory agents.”

http://www.ebiomedicine.com/article/S2352-3964(17)30003-8/fulltext

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Cannabinoid system in the skin – a possible target for future therapies in dermatology.

“Cannabinoids and their derivatives are group of more than 60 biologically active chemical agents, which have been used in natural medicine for centuries.

The major agent of exogenous cannabinoids is Delta(9)-tetrahydrocannabinol (Delta(9)-THC), natural psychoactive ingredient of marijuana.

Recent discoveries of endogenous cannabinoids (e.g. arachidonoylethanolamide, 2-arachidonoylglycerol or palmithyloethanolamide) and their receptors initiated discussion on the role of cannabinoid system in physiological conditions as well as in various diseases.

Based on the current knowledge, it could be stated that cannabinoids are important mediators in the skin, however their role have not been well elucidated yet.

In our review, we summarized the current knowledge about the significant role of the cannabinoid system in the cutaneous physiology and pathology, pointing out possible future therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pubmed/19664006

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Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model.

“Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation.

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.

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.”

http://www.ncbi.nlm.nih.gov/pubmed/26848215

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“WILD CANNABIS”: A REVIEW OF THE TRADITIONAL USE AND PHYTOCHEMISTRY OF LEONOTIS LEONURUS.

“Leonotis leonurus, locally commonly known as “wilde dagga” (=wild cannabis), is traditionally used as a decoction, both topically and orally, in the treatment of a wide variety of conditions such as haemorrhoids, eczema, skin rashes, boils, itching, muscular cramps, headache, epilepsy, chest infections, constipation, spider and snake bites. The dried leaves and flowers are also smoked to relieve epilepsy. The leaves and flowers are reported to produce a mild euphoric effect when smoked and have been said to have a similar, although less potent, psychoactive effect to cannabis.

The phytochemistry of particularly the non-volatile constituents of Leonotis leonurus has been comprehensively investigated due to interest generated as a result of the wide variety of biological effects reported for this plant. More than 50 compounds have been isolated and characterised. Leonotis leonurus contains mainly terpenoids, particularly labdane diterpenes, the major diterpene reported is marrubiin. Various other compounds have been reported by some authors to have been isolated from the plant, including, in the popular literature only, the mildly psychoactive alkaloid, leonurine. Leonurine has however, never been reported by any scientific analysis of the extracts of L. leonurus.

Despite the publication of various papers on L. leonurus, there is still, however, the need for definitive research and clarification of other compounds, including alkaloids and essential oils from L. leonurus, as well as from other plant parts, such as the roots which are extensively used in traditional medicine. The traditional use by smoking also requires further investigation as to how the chemistry and activity are affected by this form of administration. Research has proven the psychoactive effects of the crude extract of L. leonurus, but confirmation of the presence of psychoactive compounds, as well as isolation and characterisation, is still required. Deliberate adulteration of L. leonurus with synthetic cannabinoids has been reported recently, in an attempt to facilitate the marketing of these illegal substances, highlighting the necessity for refinement of appropriate quality control processes to ensure safety and quality. Much work is therefore still required on the aspect of quality control to ensure safety, quality and efficacy of the product supplied to patients, as this plant is widely used in South Africa as a traditional medicine. Commercially available plant sources provide a viable option for phytochemical research, particularly with regard to the appropriate validation of the plant material (taxonomy) in order to identify and delimit closely related species such as L. leonurus and L. nepetifolia which are very similar in habit.”

http://www.ncbi.nlm.nih.gov/pubmed/26292023

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