Category Archives: Psoriasis.

Cannabinoids in the Pathophysiology of Skin Inflammation.

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molecules-logo“Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component.

This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer.

In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances.

Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.”

https://www.ncbi.nlm.nih.gov/pubmed/32033005

https://www.mdpi.com/1420-3049/25/3/652

“Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429381/

Cannabinoids for the Treatment of Chronic Pruritus: A Review.

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Journal of the American Academy of Dermatology Home“Medical marijuana is becoming widely available to patients in the U.S. and with recreational marijuana now legalized in many states, patient interest is on the rise.

The endocannabinoid system plays an important role in skin homeostasis in addition to broader effects on neurogenic responses such as pruritus and nociception, inflammation, and immune reactions. There are numerous studies of in vitro and animal models that provide insight into the possible mechanisms of cannabinoid modulation on pruritus, with the most evidence behind neuronal modulation of both peripheral itch fibers and centrally-acting cannabinoid receptors.

In addition, human studies, while limited due to differences in cannabinoids used, disease models, and delivery method, have consistently shown significant reductions in both scratching and symptomatology in chronic pruritus. Clinical studies that have shown reduction in pruritus in several dermatologic (atopic dermatitis, psoriasis, asteatotic eczema, prurigo nodularis, allergic contact dermatitis) and systemic (uremic pruritus, cholestatic pruritus) diseases.

These preliminary human studies warrant controlled trials to confirm the benefit of cannabinoids for treatment of pruritus and to standardize treatment regimens and indications. In patients who have refractory chronic pruritus after standard therapies, cannabinoid formulations may be considered as an adjuvant therapy where it is legal.”

https://www.ncbi.nlm.nih.gov/pubmed/31987788

https://www.jaad.org/article/S0190-9622(20)30120-1/pdf

The potential role of cannabinoids in dermatology.

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 Publication Cover“Cannabis is increasingly being used world-wide to treat a variety of dermatological conditions. Medicinal cannabis is currently legalized in Canada, 31 states in America and 19 countries in Europe. The authors reviewed the literature on the pharmacology and use of cannabinoids in treating a variety of skin conditions including acne, atopic dermatitis, psoriasis, skin cancer, pruritus, and pain. Cannabinoids have demonstrated anti-inflammatory, antipruritic, anti-ageing, and antimalignancy properties by various mechanisms including interacting with the newly found endocannabinoid system of the skin thereby providing a promising alternative to traditional treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/31599175

https://www.tandfonline.com/doi/abs/10.1080/09546634.2019.1675854?journalCode=ijdt20

Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation.

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cells-logo “Cannabidiol (CBD), a natural phytocannabinoid without psychoactive effect, is a well-known anti-inflammatory and antioxidant compound.

The possibility of its use in cytoprotection of cells from harmful factors, including ultraviolet (UV) radiation, is an area of ongoing investigation. Therefore, the aim of this study was to evaluate the effect of CBD on the regulatory mechanisms associated with the redox balance and inflammation in keratinocytes irradiated with UVA [30 J/cm2] and UVB [60 mJ/cm2].

Spectrophotometric results show that CBD significantly enhances the activity of antioxidant enzymes such as superoxide dismutase and thioredoxin reductase in UV irradiated keratinocytes. Furthermore, despite decreased glutathione peroxidase and reductase activities, CBD prevents lipid peroxidation, which was observed as a decreased level of 4-HNE and 15d-PGJ2 (measured using GC/MS and LC/MS). Moreover, Western blot analysis of protein levels shows that, under stress conditions, CBD influences interactions of transcription factors Nrf2- NFκB by inhibiting the NFκB pathway, increasing the expression of Nrf2 activators and stimulating the transcription activity of Nrf2.

In conclusion, the antioxidant activity of CBD through Nrf2 activation as well as its anti-inflammatory properties as an inhibitor of NFκB should be considered during design of new protective treatments for the skin.”

https://www.ncbi.nlm.nih.gov/pubmed/31382646

https://www.mdpi.com/2073-4409/8/8/827

Modulators of the endocannabinoid system influence skin barrier repair, epidermal proliferation, differentiation and inflammation in a mouse model.

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Experimental Dermatology banner“Endocannabinoids (ECs) are important regulators of cell signaling.

Cannabinoid receptors are involved in keratinocyte proliferation/differentiation.

Elevation of the endogenous cannabinoid tone leads to strong anti-inflammatory effects.

Here, we explored the influence of endocannabinoid system (ECS) modulators on skin permeability barrier repair, epidermal proliferation, differentiation and inflammation in hairless mice.

We used WOBE440, a selective fatty acid amide hydrolase (FAAH) inhibitor, WOL067-531, an inhibitor of endocannabinoid reuptake with no relevant FAAH activity, which both signal via cannabinoid receptor-1and 2 (CB-1R and CB-2R) and compared them to WOBE15 which signals via CB-2R.

We found that barrier repair was significantly delayed by WOL067-531.

In summary, we showed that WOL067-531 exhibits a significant effect on skin barrier repair, epidermal proliferation/differentiation and inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/31350927

https://onlinelibrary.wiley.com/doi/abs/10.1111/exd.14012

Cannabis sativa L. extract and cannabidiol inhibit in vitro mediators of skin inflammation and wound injury.

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Publication cover image“The present study investigates the potential effect of a Cannabis sativa L. ethanolic extract standardized in cannabidiol as antiinflammatory agent in the skin. The extract inhibited the release of mediators of inflammation involved in wound healing and inflammatory processes occurring in the skin. Cannabis extract and cannabidiol showed different effects on the release of interleukin-8 and vascular endothelial growth factor, which are both mediators whose genes are dependent on NF-κB. Our findings provide new insights into the potential effect of Cannabis extracts against inflammation-based skin diseases.” https://www.ncbi.nlm.nih.gov/pubmed/31250491

https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.6400

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

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

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

“Extracts of the hemp plant cannabis are traditionally used as a popular remedy against inflammation.” https://medicalxpress.com/news/2007-06-cannabinoids-human-body-anti-inflammatory-effect.html

Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System.

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molecules-logo

“The endocannabinoid system (ECS) has lately been proven to be an important, multifaceted homeostatic regulator, which influences a wide-variety of physiological processes all over the body. Its members, the endocannabinoids (eCBs; e.g., anandamide), the eCB-responsive receptors (e.g., CB₁, CB₂), as well as the complex enzyme and transporter apparatus involved in the metabolism of the ligands were shown to be expressed in several tissues, including the skin. Although the best studied functions over the ECS are related to the central nervous system and to immune processes, experimental efforts over the last two decades have unambiguously confirmed that cutaneous cannabinoid (“c[ut]annabinoid”) signaling is deeply involved in the maintenance of skin homeostasis, barrier formation and regeneration, and its dysregulation was implicated to contribute to several highly prevalent diseases and disorders, e.g., atopic dermatitis, psoriasis, scleroderma, acne, hair growth and pigmentation disorders, keratin diseases, various tumors, and itch. The current review aims to give an overview of the available skin-relevant endo- and phytocannabinoid literature with a special emphasis on the putative translational potential, and to highlight promising future research directions as well as existing challenges.”

https://www.ncbi.nlm.nih.gov/pubmed/30845666

https://www.mdpi.com/1420-3049/24/5/918

Knowledge, Attitudes, and Perceptions of Cannabinoids in the Dermatology Community

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“Recent research has identified potential uses of cannabinoids in dermatology, including psoriasis, atopic dermatitis, and wound healing.

This study examined dermatology providers’ knowledge, attitudes, and perceptions on therapeutic cannabinoids using a 20-question online survey.

The response rate was 21% (n=531). Most responders thought cannabinoids should be legal for medical treatment (86%). Nearly all (94%) believed it is worthwhile to research dermatologic uses of cannabinoids. 55% reported at least one patient-initiated discussion about cannabinoids in the last year. Yet, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most responders (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. 64% of respondents did not know that cannabidiol is not psychoactive and 29% did not know that tetrahydrocannabinol is psychoactive.

 

CONCLUSIONS:

Dermatology providers are interested in prescribing cannabinoids and patients are speaking about cannabinoids with their dermatologists. However, providers’ fund of knowledge on this subject is lacking. These results highlight the need for further education and research to detangle the dermatologic benefits and risks of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/30586258

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

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Cannabinoids in dermatology: a scoping review.

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Image result for dermatol online journal “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.”
https://www.ncbi.nlm.nih.gov/pubmed/30142706

“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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