“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
“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.”
“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 (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
“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.”
“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.
Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.
The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.
Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.
Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.
Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.
One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.
Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.
In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”
“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.”
“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.”
“This study was performed to investigate the effects of CBR agonists on skin inflammation, using acute and chronic inflammation animal models.
All of the results suggest that topical application of CB1R-specific agonist can be beneficial for alleviating the inflammatory symptoms in chronic skin diseases, including atopic dermatitis.”
… preclinical data encourage one to systematically explore whether ECS-modulating drugs can be exploited in the management of common skin disorders…
… we review preliminary data and discuss the possible applications of ECS-targeted therapies…ECS-targeted approaches in skin diseases. Modulations of the fine-tuned tone of the cutaneous endocannabinoid system (ECS) could have therapeutic values in the management of a large variety of human skin diseases…
… it is envisaged (this is also strongly supported by pilot studies) that the targeted manipulation of the ECS might be beneficial in a multitude of human skin diseases. However, to predict the real therapeutic potential and translate the exciting preclinical observations discussed earlier into clinical practice, numerous important questions should carefully be addressed. Nevertheless, targeting the cutaneous ECS for therapeutic gain remains an intriguing and provocative possibility warranting future studies.”
Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757311/