Cannabinoids inhibit fibrogenesis in diffuse systemic sclerosis fibroblasts.

Posted on May 28, 2016 by David

Rheumatology

“Recently, it has also been demonstrated that the pleiotropic cannabinoid system is involved in both liver and pancreatic fibrosis. Furthermore, cannabinoids may play a pro- or anti-fibrogenic role depending on their interaction with CB1r or CB2r.

This raises the possibility that pharmacologic modulation of the endocannabinoid system could be a target to limit tissue damage in pathologic fibrosis.

It has been demonstrated that the endocannabinoid system is up-regulated in pathologic fibrosis and that modulation of the cannabinoid receptors might limit the progression of uncontrolled fibrogenesis.

Both CB1 and CB2 receptors were over-expressed in dcSSc fibroblasts compared with healthy controls.

Our preliminary findings suggest that cannabinoids are provided with an anti-fibrotic activity, thereby possibly representing a new class of agents targeting fibrosis diseases.”

http://rheumatology.oxfordjournals.org/content/48/9/1050.long

Can Cannabinoids Modulate Fibrotic Progression in Systemic Sclerosis?

Posted on May 28, 2016 by David

“Since ancient times, plants have been used for therapeutic purposes.

Cannabis sativa has been widely used as a medicinal herb by Ayurveda and traditional Chinese medicine for centuries.

According to our in vitro and in vivo experimental models, cannabinoids are able to modulate fibrosis.

The exact mechanism underlying this effect requires further investigation, but it seems to go beyond their anti-inflammatory and immunomodulatory properties.

Based on the above observations, we aimed to investigate the role of cannabinoids in systemic sclerosis (SSc), an autoimmune disease characterized by diffuse fibrosis.

Since preclinical data on cannabinoids show their capability to modulate fibrosis, inflammation and vasodilatation, these molecules could be ideal drugs for targeting SSc.”

http://www.ima.org.il/FilesUpload/IMAJ/0/193/96907.pdf

[MEDICAL CANNABIS – A SOURCE FOR A NEW TREATMENT FOR AUTOIMMUNE DISEASE?].

Posted on May 25, 2016 by David

“Medical uses of Cannabis sativa have been known for over 6,000 years. Nowadays, cannabis is mostly known for its psychotropic effects and its ability to relieve pain, even though there is evidence of cannabis use for autoimmune diseases like rheumatoid arthritis centuries ago. The pharmacological therapy in autoimmune diseases is mainly based on immunosuppression of different axes of the immune system while many of the drugs have major side effects. In this review we set out to examine the rule of Cannabis sativa as an immunomodulator and its potential as a new treatment option. In order to examine this subject we will focus on some major autoimmune diseases such as diabetes type I and rheumatoid arthritis.”

http://www.ncbi.nlm.nih.gov/pubmed/27215114

Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis

Posted on May 20, 2016 by David

“Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive.

One of the receptors, CB receptor 1 (CB₁), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB₂) is expressed primarily by immune cells.

Theoretically, selective CB₂ agonists should be devoid of psychoactive effects.

In this study, we investigated therapeutic effects of a selective CB₂ agonist on arthritis.

The present study suggests that a selective CB₂ agonist could be a new therapy for RA that inhibits production of inflammatory mediators from FLS, and osteoclastogenesis.

This is the first report of therapeutic effect of a selective CB₂ agonist on CIA.

Although the effect was mild, optimization of dosage and/or treatment protocol might enhance the effect.

Perhaps, more potent selective CB₂agonists might solve this problem.

Cannabinoids are pharmacologically active components of Cannabis sativa.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243420/

The synthetic cannabinoid WIN55,212-2 mesylate decreases the production of inflammatory mediators in rheumatoid arthritis synovial fibroblasts by activating CB2, TRPV1, TRPA1 and yet unidentified receptor targets

Posted on May 20, 2016 by David

“Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint inflammation and cartilage destruction.

In this study we assessed the ability of WIN to modulate cytokine and MMP-3 production in SFs over a wide concentration range and identified specific receptor targets that mediate the effects of this synthetic cannabinoid.

The synthetic cannabinoid WIN in low concentrations exhibits anti-inflammatory effects in synovial fibroblasts independent of CB₁ and CB₂ while CB₂ and yet unidentified receptor targets are responsible for WIN effects in micromolar concentrations.

Our results indicate a TRPV1/TRPA1 dependent mechanism of SF regulation that might be coupled to cellular energy status and calcium content.

In this report we demonstrated anti-inflammatory effects of the synthetic cannabinoid WIN in low and high concentrations.

Furthermore, this study demonstrated anti-inflammatory effects via modulation of TRP channels by WIN. Together, inactivation of TRPs and activation of cannabinoid receptors might also reduce the sensation of pain, which further underlines the potential of WIN in the treatment of chronic inflammation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858820/

Phytocannabinoids and cannabimimetic drugs: recent patents in central nervous system disorders.

Posted on May 19, 2016 by David

“Starting from the chemical structure of phytocannabinoids, isolated from Cannabis sativa plant, research groups designed numerous cannabimimetic drugs.

These compounds according to their activities can be partial, full agonists and antagonists of cannabinoid receptors.

Anecdotal reports and scientific studies described beneficial properties of cannabinoids and their derivatives in several pathological conditions like neurological and neuropsychiatric disorders, and in many other diseases ranging from cancer, atherosclerosis, stroke, hypertension, inflammatory related disorders, and autoimmune diseases.

The cannabinoid CB1 receptor was considered particularly interesting for therapeutic approaches in neurological diseases, because primarily expressed by neurons of the central nervous system. In many experimental models, these drugs act via this receptor, however, CB1 receptor independent mechanisms have been also described. Furthermore, endogenous ligands of cannabinoid receptors, the endocannabinoids, are potent modulators of the synaptic function in the brain. In neurological diseases, numerous studies reported modulation of the levels of endocannabinoids according to the phase of the disease and its progression.

CONCLUSIONS:

Finally, although the study of the mechanisms of action of these compounds is still unsolved, many reports and patents strongly suggest therapeutic potential of these compounds in neurological diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27184693

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Posted on April 19, 2016 by David

Image result for Curr Clin Pharmacol.

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

Cannabinoids and autoimmune diseases: A systematic review.

Posted on February 17, 2016 by David

“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/

Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

Posted on January 17, 2016 by David

“Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen.

Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis.

Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors.

Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease.

CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme.

Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD…

CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/26772776

The disease-modifying effects of a Sativex-like combination of phytocannabinoids in mice with experimental autoimmune encephalomyelitis are preferentially due to Δ9-tetrahydrocannabinol acting through CB1 receptors.

Posted on November 23, 2015 by David

“Sativex®, an equimolecular combination of Δ9-tetrahydrocannabinol-botanical drug substance (Δ9-THC-BDS) and cannabidiol-botanical drug substance (CBD-BDS), is a licensed medicine that may be prescribed for alleviating specific symptoms of multiple sclerosis (MS) such as spasticity and pain.

However, further evidence suggest that it could be also active as disease-modifying therapy given the immunomodulatory, anti-inflammatory and cytoprotective properties of their two major components.

In this study, we investigated this potential in the experimental autoimmune encephalitis (EAE) model of MS in mice.

We compared the effect of a Sativex-like combination of Δ9-THC-BDS (10mg/kg) and CBD-BDS (10mg/kg) with Δ9-THC-BDS (20mg/kg) or CBD-BDS (20mg/kg) administered separately by intraperitoneal administration to EAE mice.

Treatments were initiated at the time that symptoms appear and continued up to the first relapse of the disease.

The results show that the treatment with a Sativex-like combination significantly improved the neurological deficits typical of EAE mice, in parallel with a reduction in the number and extent of cell aggregates present in the spinal cord which derived from cell infiltration to the CNS.

These effects were completely reproduced by the treatment with Δ9-THC-BDS alone, but not by CBD-BDS alone which only delayed the onset of the disease without improving disease progression and reducing the cell infiltrates in the spinal cord.

Next, we investigated the potential targets involved in the effects of Δ9-THC-BDS by selectively blocking CB1 or PPAR-γ receptors, and we found a complete reversion of neurological benefits and the reduction in cell aggregates only with rimonabant, a selective CB1 receptor antagonist.

Collectively, our data support the therapeutic potential of Sativex as a phytocannabinoid formulation capable of attenuating EAE progression, and that the active compound was Δ9-THC-BDS acting through CB1 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/26590655