“Psoriasis is a common skin disorder characterized by hyper proliferation of keratinocytes. Although the exact pathophysiology of psoriasis is not entirely understood, immune system and its interaction with nervous system has been postulated and investigated as the underlying mechanism. The interaction between these two systems through cholinergic anti-inflammatory pathway and also endocannabinoid system, may suggest cannabinoids as potential addition to anti-psoriatic armamentarium.”
Category Archives: Psoriasis.
ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.
“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.”
Cannabinoids and autoimmune diseases: A systematic review.
“Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release.
Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines.
In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus.
They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma.
Studies in human models are scarce and not conclusive and more research is required in this field.
Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders.”
http://www.ncbi.nlm.nih.gov/pubmed/26876387
http://www.thctotalhealthcare.com/category/autoimmune-disease/
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.”
TRP Channel Cannabinoid Receptors in Skin Sensation, Homeostasis, and Inflammation.
“In the skin, cannabinoid lipids, whether of endogenous or exogenous origin, are capable of regulating numerous sensory, homeostatic and inflammatory events.
Although many of these effects are mediated by metabotropic CB receptors, a growing body of evidence has revealed that multiple members of the transient receptor potential (TRP) ion channel family can act as “ionotropic cannabinoid receptors”.
Furthermore, many of these same TRP channels are intimately involved in cutaneous processes that include the initiation of pain, temperature, and itch perception, the maintenance of epidermal homeostasis, the regulation of hair follicles and sebaceous glands, and the modulation of dermatitis.
Ionotropic cannabinoid receptors therefore represent potentially attractive targets for the therapeutic use of cannabinoids to treat sensory and dermatological diseases.
Furthermore, the interactions between neurons and other cell types that are mediated by cutaneous ionotropic cannabinoid receptors are likely to be recapitulated during physiological and pathophysiological processes in the central nervous system and elsewhere, making the skin an ideal setting in which to dissect general complexities of cannabinoid signaling.”
More Evidence Pot Treats Auto-Immune Diseases
“Researchers at the University of South Carolina have another clue as to why patients with auto-immune diseases like multiple sclerosis, psoriasis, rheumatoid arthritis, Crohn’s and celiac disease sometimes respond to medical marijuana therapies, according to Science World Reports.
The main active ingredient in pot, THC, regulates gene expression in immune cells, effectively switching off runaway inflammation at the DNA level.
The researchers used mice cells in vivo and the results suggest that “THC activates the expression of a subset of genes while suppressing the expression of another subset of genes.” The net result is less inflammatory response, which can severely damage and kill cells.
Autoimmune diseases involve an abnormal immune response of the body, causing immune cells to attack healthy cells instead of pathogens. Autoimmune diseases — a collection of about 80 diseases — are the 10th leading cause of death of women in all age groups up to 65 years old.
Despite the safety and efficacy of medical cannabis, providers remain under attack across America. California senators Barbara Boxer and Dianne Feinstein currently support the war on pot patients and providers. The Drug Policy Alliance has started a new campaign today to help citizens lobby Senators to defund the war on medical marijuana.”
Therapeutic potential of cannabinoid medicines.
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“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.
The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.
In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”
http://www.ncbi.nlm.nih.gov/pubmed/24006213
http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract
Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.
“Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors.
Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation.
Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation.
OBJECTIVE:
We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors.
CONCLUSION:
The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process.
Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.”
Epigenetic Control of Skin Differentiation Genes by Phytocannabinoids.
“A role for endocannabinoid signaling has been reported in the control of epidermal physiology, whereby anandamide is able to regulate the expression of skin differentiation genes through DNA methylation. Here, we have investigated the possible epigenetic regulation of these genes by selected phytocannabinoids, plant-derived cannabinoids holding potential as novel therapeutics for various human diseases.
CONCLUSIONS AND IMPLICATIONS:
These findings identify the phytocannabinoids cannabidiol and cannabigerol as transcriptional repressors that can control cell proliferation and differentiation, suggesting (especially for cannabidiol) a possible exploitation as lead compounds to be used in the development of novel therapeutics for skin diseases.”
The endocannabinoid system and its therapeutic exploitation.
“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.” http://www.ncbi.nlm.nih.gov/pubmed/15340387