Study uncovers marijuana’s potential to treat autoimmune diseases

“A team of University of South Carolina researchers led by Mitzi Nagarkatti, Prakash Nagarkatti and Xiaoming Yang have discovered a novel pathway through which marijuana can suppress the body’s immune functions. Their research has been published online in the Journal of Biological Chemistry.

The university study has uncovered yet another potential application for marijuana, in the suppression of immune response to treat autoimmune diseases.”

http://www.news-medical.net/news/20140603/Study-uncovers-marijuanas-potential-to-treat-autoimmune-diseases.aspx

http://www.thctotalhealthcare.com/category/autoimmune-disease/

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/

 

Tumor Necrosis Factor activation of vagal afferent terminal calcium is blocked by cannabinoids

Figure 4

“The early proinflammatory cytokine tumor necrosis factor (TNF) is released in significant quantities by the activated immune system in response to infection, leukemia, autoimmune disorders, and radiation sickness. Nausea, emesis, and anorexia are common features of these disorders. TNF action on vagal afferent terminals in the brainstem is a likely cause of the malaise associated with these disorders.

For millennia, cannabinoids(CB) have been used to combat the visceral malaise associated with chronic disease…

These results help to explain the effectiveness of cannabinoids in blocking the malaise generated by TNF-releasing disease processes by opposing effects on ryanodine channels.

We believe that this is the first demonstration of the likely intracellular mechanism used by CB1 analogs to block the effects of TNF on neurotransmitter mechanisms that cause pain and visceral malaise.

These results may explain how cannabinoids can be effective in the treatment of the allodynia and visceral malaise of chronic disease.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342927/

Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells.

Fig. 1

“Immune-mediated liver diseases including autoimmune and viral hepatitis are a major health problem worldwide. Natural cannabinoids such as Delta(9)-tetrahydrocannabinol (THC) effectively modulate immune cell function, and they have shown therapeutic potential in treating inflammatory diseases.

We investigated the effects of THC in a murine model of concanavalin A (ConA)-induced hepatitis…

Our data demonstrate that targeting cannabinoid receptors using exogenous or endogenous cannabinoids and use of FAAH inhibitors may constitute novel therapeutic modalities to treat immune-mediated liver inflammation.

δ-9-Tetrahydrocannabinol (THC), the major psychoactive component of marijuana (Cannabis sativa), has wide-ranging pharmacological properties. The cannabinoid compounds possess significant immunosuppressive and anti-inflammatory properties. THC and cannabinoid receptor agonists have shown promise in several models of inflammation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828293/

Role of Myeloid-Derived Suppressor Cells in Amelioration of Experimental Autoimmune Hepatitis Following Activation of TRPV1 Receptors by Cannabidiol

Figure 1

“Myeloid-derived suppressor cells (MDSCs) are getting increased attention as one of the main regulatory cells of the immune system. They are induced at sites of inflammation and can potently suppress T cell functions. In the current study, we demonstrate how activation of TRPV1 vanilloid receptors can trigger MDSCs, which in turn, can inhibit inflammation and hepatitis…

This study demonstrates for the first time that MDSCs play a critical role in attenuating acute inflammation in the liver, and that agents such as CBD, which trigger MDSCs through activation of TRPV1 vanilloid receptors may constitute a novel therapeutic modality to treat inflammatory diseases.

Cannabidiol (CBD) is a major non-psychoactive cannabinoid component of marijuana.

Together, these studies not only demonstrate that CBD can protect the host from acute liver injury but also provide evidence for the first time that MDSCs may play a critical role in protecting the liver from acute inflammation.

Non-psychoactive cannabinoids such as CBD possess great therapeutic potential in treating various inflammatory liver diseases, including autoimmune hepatitis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069975/

Targeting the cannabinoid pathway limits the development of fibrosis and autoimmunity in a mouse model of systemic sclerosis.

Figure 1

“Our aim was to evaluate the roles of the cannabinoid pathway in the induction and propagation of systemic sclerosis (SSc) in a mouse model…

Experiments performed in CB2-deficient mice confirmed the influence of CB2 in the development of systemic fibrosis and autoimmunity. Therefore, we demonstrate that the CB2 receptor is a potential target for the treatment of SSc because it controls both skin fibroblast proliferation and the autoimmune reaction.

In this report, we demonstrate for the first time the highly protective role of cannabinoid agonists in SSc. Because these agonists are available and well-tolerated under clinical conditions, our data offer a new therapeutic opportunity in this life-threatening disease.

In conclusion, modulation of the endocannabinoid system is a novel approach for the treatment of various inflammatory diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893662/