The skin is the largest organ in the human anatomy. One of its major functions is to guard the body against external agents and it is the first resistive barrier of the innate immune system. Other prominent functions of the skin include regulating body temperature, sustaining the hydro-electrolytic balance and grasping painful or pleasurable stimuli. Any alteration in the functioning or appearance of the skin can have important outcomes for our physical and mental health. Many of the problems present in the skin are defined to it. Meanwhile in some cases, however, the skin can reveal a dysfunction affecting the entire body.
Development of Pharmaceuticals in Dermatology
Nearly 37% of primitive health care patients have some acute or chronic skin disease and it is unusual how few new pharmaceuticals are being produced to treat these infirmities – especially those most regularly treated by dermatologists and non-dermatologists when associated to other diseases and conditions. According to Eaglstein and Corcoran, 2011, one important reason why few pharmaceutical associations are producing drugs for skin diseases is that the economic interest on such drugs (especially topical skin products) is proportionately small compared to the demand for pharmaceuticals for other conditions (e.g. cardiovascular diseases).
Another factor restricting the development of pharmaceuticals based on natural commodities – including developments of Cannabis Sativa – is the fact that in most circumstances it is not possible to establish sufficient protection for cerebral property of the drug, an imperative inventive to investment in the advancement of new pharmaceuticals for any utilisation. It is therefore hardly surprising that the great majority of skin diseases, particularly inflammatory diseases, are handled with over-the-counter health care merchandises, where the effectiveness, in most cases, is not justified.
Cannabinoids in Dermatology
The topical use of Cannabis Sativa L dates back to ancient China, where cannabis establishments were used externally to manage skin rashes, wounds and hair loss. There is also archaeological proof suggesting that topical cannabis preparations were used by the antiquated Egyptians to treat eye conditions and also in bandages for treating wounds. Cannabis stalks were used in medieval Arab medicine to treat skin diseases such as pityriasis and lichen planus. Most lately, in the initial twentieth century, before prescription, tinctures of cannabis were generally sold in pharmacies. Among other utilisation, they were used to treat calluses, irritable bladder, menstrual pains and as an aid for quitting opium addiction.
The skin controls all the elements of the endocannabinoid system, i.e., endocannabinoid composites (AEA and 2-AG), metabotropic (CB1R and CB2R) and ionotropic (TRPV-1) receptors of key cannabinoids and the enzymes included in the synthesis and metabolism of endocannabinoids (e.g. FAAH and MAGL). The various components in the endocannabinoid system are implicated in key mechanisms of skin regulation, such as control of growth of the epidermis and skin annexes, cell survival, immune and inflammatory responses, the transmission of sensory stimuli to the central nervous system (pain, itching) and the synthesis of lipids, among other activities.
Despite this long chronicle of topical use of cannabis and progress in our understanding of the endocannabinoid system of the skin, analysis into the use of cannabinoids for skin pathologies is one of the youngest fields of experimentation in this area and clinical data on the use of cannabis in dermatological practice remain remarkably limited. Nevertheless, there is progressing evidence of the potential of cannabinoids for the treatment of inflammatory skin diseases, including psoriasis and atopic dermatitis and for the treatment of auto-immune diseases such as scleroderma, characterized by inflammation and fibrosis.
Psoriasis is one of the several common chronic inflammatory skin diseases. It is distinguished by hyperproliferation and shedding of keratinocytes, emerging from infiltration of T-cells and neutrophils and activation of dendritic cells and macrophages. However
the pathogenesis of psoriasis is not fully understood, there is solid evidence that deregulation of the immune cells in the skin, indistinct, Th1 and Th17 cells, performs a critical role in the development of psoriasis.
Although there is at present only anecdotal evidence on the use of Cannabis Sativa L preparations for topical use in psoriasis, a 2016 research shows the therapeutic potentialities of cannabinoids acting through CB2R and through mechanisms that are independent of classical cannabinoid receptors are very comprehensive, given their role in the organisation of Th1 and Th17 lymphocytes. A different study, done in 2006, showed that some phytocannabinoids hinder the proliferation of keratinocytes through non-CB1R and CB2R paths.
Atopic dermatitis (D) is the most persistent chronic inflammatory disease of the skin. Preliminaries and progression of the disease are induced by interactions of genetic, environmental and immunological factors. The clinical features of AD include dryness of the skin through loss of the epidermal barrier, erythema, exudation, scabs, and lichenification. Furthermore, AD is discriminated by intense itching which leads to repeated scratching and infection by Staphylococcus. There is no remedy for AD and the main goal of treatment is to overcome the symptoms (itching and dermatitis), prevent exacerbations and minimize the risk of skin epidemic. Conventional forms of treatment for managing AD centres on the use of anti-inflammatory topical preparations with corticoids and hydration of the skin, but in severe cases, people may need systemic treatment with persuasive immune-suppressants and antibiotics to inhibit infection by staphylococcus-type bacteria.
Numerous para-pharmaceutical qualifications are now available based on oil from the cannabis plant, for the treatment of AD. However, despite the misleading advertisement often used to market such commodities, hemp seed oil does not contain cannabinoids or distinct bioactive phenolic composites, and its therapeutic effect goes no besides any other preparation containing polyunsaturated fatty acids and favouring skin hydration.
Though, to judge form pre-clinical studies, cannabinoids also have a great potential for therapeutic supervision of AD. In this interest, selective CB1R agonists restrain the activation of mastocytes and the discharge of histamine. Besides, topical application of anandamide analogues has been shown to lessen skin inflammation in animal models of AD. Recently authors have suggested that CB1R appearance in keratinocytes plays a consistent role in maintaining the epidermal barrier. Lastly, in a study done in 2006, it has also been specified that the discharge of histamine from CB2R inhibits the inflammatory skin reaction encountered with AD.
According to a different study, the anti-bacterial action of cannabis preparations and phytocannabinoids has been well-known for decades, although only more lately has the anti-bacterial motion of cannabinoids THC, CBD, CBG and their precursors (acid forms) against methicillin-resistant Staphylococcus been illustrated.
Approximately 100 cannabinoids have been distinguished in the cannabis plant, collectively with a large number of bioactive composites, such as phenolics and terpenes, which also have important antioxidant and anti-inflammatory activities. The cannabinoids and other types of compounds are estimated to have interacting synergic outcomes. This would describe why in some in vitro studies, better results have been achieved with extracts from the plant that with pure, confined compounds. Although the content of cannabinoids and other types of compounds alternate depending on the variety of plant, cannabinoids can be said to have an enormous potential for treating AD, given their anti-inflammatory and anti-bacterial properties.
Cannabinoids and Fibrotic Skin Diseases
Systemic scleroderma (or sclerosis) SSc) is a rare auto-immune disease that has three main characters: dysfunction of fibroblasts, leading to an increase in the deposition of proteins from the extracellular matrix, vasculopathy of small vessels resulting in tissue hypoxia and immune response with the generation of pro-inflammatory cytokines and auto-antibodies. SSc is identified by progressive thickening fibrosis of the skin, inconsiderable to excessive accumulation of collagen, which can be confined to the skin (localized – or limited – cutaneous SSc) or extends to internal bodies (diffuse SSc). SSc drives with microvascular injury and inflammation. This is accompanied by fibroblast activation, a key event in the development of fibrosis.
Current evidence clarifies that genetic and pharmacological manipulation of the endocannabinoid system modulated the fibrotic response. CB1 and CB2 receptors, too, have manifested different patterns in experimental models of dermal fibrosis. Blockage of CB1R inhibits activation of fibroblasts and has a powerful antifibrotic effect. The role of CB1R as a profibrotic receptor has also been verified in mice, in which high levels of endocannabinoids can persuade fibrosis through a CB1R-dependent path. On the other hand, activation of CB2R limits cutaneous fibrosis and the infiltration of tissue leukocytes in models of experimental dermal fibrosis. It has also been illustrated that dual agonists of CB2R show a powerful anti-inflammatory and anti-fibrotic activity in experimental models of SSc.
However the clinical analysis remains in the early stages, studies have shown that full extract cannabis topicals show enormous promise for the treatment of inflammatory skin diseases, even more so than some conventional over-the-counter treatments.
Disclaimer: the principles contained here is not designed nor meant to be a substitute for professional medical advice, it is only achieved for educational confidences only. You should recognise full responsibility for the way you decide on to use this information.
Tags: Skin Conditions, Topicals