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.”

http://www.ncbi.nlm.nih.gov/pubmed/24915599

Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoimmune Disease.

“The impact of the endogenous cannabinoids (AEA, 2-AG, PEA, and virodamine) on the immune cell expressed cannabinoid receptors (CB1, CB2, TRPV-1, and GPR55) and consequent regulation of immune function is an exciting area of research with potential implications in the prevention and treatment of inflammatory and autoimmune diseases.

Despite significant advances in understanding the mechanisms through which cannabinoids regulate immune functions, not much is known about the role of endocannabinoids in the pathogenesis or prevention of autoimmune diseases.

Inasmuch as CB2 expression on immune cells and its role has been widely reported, the importance of CB1 in immunological disorders has often been overlooked especially because it is not highly expressed on naive immune cells.

Therefore, the current review aims at delineating the effect of endocannabinoids on CB1 receptors in T cell driven autoimmune diseases. This review will also highlight some autoimmune diseases in which there is evidence indicating a role for endocannabinoids in the regulation of autoimmune pathogenesis.

Overall, based on the evidence presented using the endocannabinoids, specifically AEA, we propose that the peripheral CB1 receptor is involved in the regulation and amelioration of inflammation associated with autoimmune diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/24911431

Marijuana can treat autoimmune diseases, scientific study states

“Weed enthusiasts are getting their case for nationwide decriminalization of marijuana bolstered considerably by a new scientific study that promises the controversial plant can treat multiple medical maladies.

Scientists at the University of South Carolina have discovered marijuana’s potential to treat autoimmune diseases — such as arthritis, lupus, colitis and multiple sclerosis — in which chronic inflammation plays a pivotal role.

The Journal of Biological Chemistry published the researchers’ findings that state marijuana’s potential key role in fighting these diseases lies in its capacity to suppress certain immune functions, most particularly inflammation.

The study examined whether marijuana’s main active constituent, tetrahydrocannabinol (THC), could affect DNA through “epigenetic” pathways.

The group of molecules with the capacity to alter DNA and the functioning of genes it controls is collectively referred to as the epigenome. It includes a group of molecules called histones, which are responsible for inflammation, both beneficial and harmful.

The research team, led by Mitzi Nagarkatti, Prakash Nagarkatti and Xiaoming Yang, found that THC can, indeed, affect DNA expression through epigenetic pathways by altering histones.

As recreational and medical use of marijuana become more acceptable in developed countries, more research is being conducted and more potential health applications are being uncovered.

Marijuana already has a variety of medical uses including treatment of chronic pain, nausea, vomiting and the wasting syndrome experienced by some AIDS patients.”

http://atlantadailyworld.com/2014/06/05/marijuana-can-treat-autoimmune-diseases-scientific-study-states/

Marijuana could treat autoimmune diseases: study

“The drug has potential to work on chronic inflammation, found in disease like arthritis, lupus, colitis and MS. It may work by suppressing immune functions.

 New findings suggest marijuana’s potential key role in fighting autoimmune diseases lies in its capacity to suppress certain immune functions, notably inflammation.

Building the case for the most widely used illicit drug in developed countries, researchers from the University of South Carolina have discovered marijuana’s potential to treat autoimmune diseases in which chronic inflammation plays a pivotal role.”

http://www.nydailynews.com/life-style/health/marijuana-treat-autoimmune-diseases-study-article-1.1816609

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 arthritisCrohn’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.”

http://www.eastbayexpress.com/LegalizationNation/archives/2014/06/03/more-evidence-pot-treats-auto-immune-diseases

Marijuana Might be Effective in Treating Autoimmune Diseases: Study

 Marijuana

“University of South Carolina researchers say that marijuana can reduce inflammation and could be effective in treating autoimmune diseases such as arthritis, lupus and colitis.

Marijuana is not an FDA-approved medication. The main ingredient in the drug – tetrahydrocannabinol (THC) – is approved to lower nausea and vomiting in people exposed to chemotherapy. The compound is also used to fight wasting syndrome in people with AIDS.”

http://www.natureworldnews.com/articles/7370/20140603/marijuana-effective-treating-autoimmune-diseases-researchers.htm

Marijuana Could Treat Autoimmune Disease: Study

marijuana autoimmune disease

“Building the case for the most widely used illicit drug in developed countries, researchers from the University of South Carolina have discovered marijuana’s potential to treat autoimmune diseases in which chronic inflammation plays a pivotal role.

These include arthritis, lupus, colitis and multiple sclerosis.

Published in the Journal of Biological Chemistry, the findings say marijuana’s potential key role in fighting these diseases lies in its capacity to suppress certain immune functions, notably inflammation.”

http://www.huffingtonpost.ca/2014/06/04/marijuana-autoimmune-disease_n_5445171.html

Do cannabinoids have a therapeutic role in transplantation?

Figure 1

“Cannabinoids are a group of terpenophenolic compounds structurally similar to delta-9-tetrahydrocannabinol (THC) from the plant Cannabis sativa.

Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties.

Significant clinical and experimental data on the use of cannabinoids as anti-inflammatory agents exist in many autoimmune disease settings, but virtually no studies have been undertaken on their potential role in transplant rejection. Here we suggest a theoretical role for the use of cannabinoids in preventing allograft rejection.

…manipulation of endocannabinoids in vivo by activating their biosynthesis and inhibiting cellular uptake and metabolism may offer another pathway to regulate immune response during allograft rejection.

…cannabinoids have emerged as novel anti-inflammatory agents because of their efficacy in the treatment of many immune-mediated disorders such as multiple sclerosis, rheumatoid arthritis and autoimmune hepatitis.

Transplantation is one critical area of medicine that requires the use of immunosuppressants.

 Inasmuch as, immune cells constitute an important resource of endocannabinoids, it may be easier to manipulate their levels during an immune response, which could have a direct and immediate impact on such cells that determine the fate of the allograft.

In summary, targeting cannabinoid receptors and understanding the role and use of exo-and endocannabinoids in experimental allograft rejection models may provide an exciting new beginning with significant translational impact.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923447/

Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression

“The cannabinoid system consists of cannabinoid receptors and their ligands, including endocannabinoids, synthetic cannabinoid receptor agonists and antagonists, and phytocannabinoids.

Administration of cannabinoid receptor 2 (CB2R) agonists in inflammatory and autoimmune disease and CNS injury models results in significant attenuation of clinical disease, and reduction of inflammatory mediators.

…cannabinoids contribute to resolve acute inflammation and to reestablish homeostasis.

Selective CB2R agonists might be valuable future therapeutic agents for the treatment of chronic inflammatory conditions by targeting activated immune cells, including DCs.

Because of their anti-inflammatory functions targeting various immune cells, CB2R agonists could represent valuable therapeutic agents for the treatment of chronic inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488886/

Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation.

Figure 2

“The cannabinoids are a group of terpenophenolic compounds present in the marijuana plant, Cannabis sativa. At present, three general types of cannabinoids have been identified: phytocannabinoids present uniquely in the cannabis plant, endogenous cannabinoids produced in humans and animals, and synthetic cannabinoids generated in a laboratory. It is worth noting that Cannabis sativa produces over 80 cannabinoids…

An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB(1), CB(2)) play a significant role in physiologic and pathologic processes, including cognitive and immune functions.

…there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer’sdisease to name a few), mainly mediated by CB(2) activation.

This review attempts to summarize recent advances in studies of CB(2) activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.

The full potential of CB2 agonists as therapeutic agents remains to be realized.

Despite some inadequacies of preclinical models to predict clinical efficacy in humans and differences between the signaling of human and rodent CB2 receptors, the development of selective CB2 agonists may open new avenues in therapeutic intervention.

Such interventions would aim at reducing the release of pro-inflammatory mediators particularly in chronic neuropathologic conditions such as HAND or MS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663904/