ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

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“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

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Ligands for cannabinoid receptors, promising anticancer agents.

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“Cannabinoids compounds are unique to cannabis and provide some interesting biological properties.

These compounds along with endocannabinoids, a group of neuromodulator compounds in the body especially in brain, express their effects by activation of G-protein-coupled cannabinoid receptors, CB1 and CB2.

There are several physiological properties attributed to the endocannabinoids including pain relief, enhancement of appetite, blood pressure lowering during shock, embryonic development, and blocking of working memory.

On the other hand, activation of endocannabinoid system may be suppresses evolution and progression of several types of cancer.

According to the results of recent studies, CB receptors are over-expressed in cancer cell lines and application of multiple cannabinoid or cannabis-derived compounds reduce tumor size through decrease of cell proliferation or induction of cell cycle arrest and apoptosis along with desirable effect on decrease of tumor-evoked pain.

Therefore, modulation of endocannabinoid system by inhibition of fatty acid amide hydrolase (FAAH), the enzyme, which metabolized endocannabinoids, or application of multiple cannabinoid or cannabis-derived compounds, may be appropriate for the treatment of several cancer subtypes. This review focuses on how cannabinoid affect different types of cancers.”

http://www.ncbi.nlm.nih.gov/pubmed/26764235

http://www.thctotalhealthcare.com/category/cancer/

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Cannabis May Help Combat Cancer-causing Herpes Viruses

ScienceDaily: Your source for the latest research news

“The compound in marijuana that produces a high, delta-9 tetrahydrocannbinol or THC, may block the spread of several forms of cancer causing herpes viruses, University of South Florida College of Medicine scientists report.

The findings, published Sept. 15 in the online journal BMC Medicine, could lead to the creation of antiviral drugs based on nonpsychoactive derivatives of THC.

The gamma herpes viruses include Kaposi’s Sarcoma Associated Herpes virus, which is associated with an increased risk of cancer that is particularly prevalent in AIDS sufferers. Another is Epstein-Barr virus, which predisposes infected individuals to cancers such as Burkitt’s lymphoma and Hodgkin’s disease.

Once a person is infected, these viruses can remain dormant for long periods within white blood cells before they burst out and begin replicating. This reactivation of the virus boosts the number of cells infected thereby increasing the chances that the cells will become cancerous.

The USF team, led by virologist Peter Medveczky, MD, found that this sudden reactivation was prevented if infected cells were grown in the presence of THC. While cells infected with a mouse gamma herpes virus normally died when the virus was reactivated, these same cells survived when cultured in the laboratory along with the cannabinoid compound – further evidence that THC prevents viral reactivation.

Furthermore, the researchers showed that THC acts specifically on gamma herpes viruses. The chemical had no effect on another related virus, herpes simplex-1, which causes cold sores and genital herpes.

Small concentrations of THC were more potent and selective against gamma herpes viruses than the commonly used antiviral drugs acyclovir, gancicyclovir and foscamet, said Dr. Medveczky, a professor in the Department of Medical Microbiology and Immunology.

The USF researchers suggest that THC selectively inhibits the spread of gamma herpes viruses by targeting a gene these viruses all share called ORF50.”

http://www.sciencedaily.com/releases/2004/09/040923092627.htm

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Endocannabinoid system in cancer cachexia.

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“More than 60% of advanced cancer patients suffer from anorexia and cachexia.

This review focuses on the possible mechanisms by which the endocannabinoid system antagonizes cachexia-anorexia processes in cancer patients and how it can be tapped for therapeutic applications.

Cannabinoids stimulate appetite and food intake…

Cannabinoid type 1 receptor activation stimulates appetite and promotes lipogenesis and energy storage.

Further study of cancer-cachexia pathophysiology and the role of endocannabinoids will help us to develop cannabinoids without psychotropic properties, which will help cancer patients suffering from cachexia and improve outcomes of clinical antitumor therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17563462

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The endocannabinoid signaling system in cancer.

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“The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancerpathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/23602129

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Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“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

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Cannabis Extracts for Treating Cancer

“Cannabis Extract Medicine and Disease. Cannabis extract medicine, also known as “hemp oil” when referring to the type pioneered by Rick Simpson, is a concentrated formulation of cannabis that is ingested orally. By eating large quantities of the oil over a three to six month period, nearly any disease you can imagine can either be cured or completely controlled. This is possible because cannabis medicine works fundamentally through the endocannabinoid system, the superregulatory system of our bodies that maintains homeostasis in the other systems.

You can see the reality of cannabis medicine’s effectiveness in all the things that smoking it is good for. It is widely known and observable that people with cancer, chronic pain, inflammatory conditions, and other conditions smoke cannabis with remarkable efficacy. When you think about that, it’s pretty crazy that setting something on fire and inhaling the resulting smoke (thus getting the cannabinoids in a low-concentration form through the lungs, which are not meant to ingest things) works better than many expensive pharmaceuticals. But with cannabis extract oil, there are two primary differences. First, the cannabinoids are much more concentrated than with smoking, so it has a more powerful effect on your system. Second, the oil is ingested, not smoked, meaning it is digested through the system that is meant to absorb nutrients. Essentially, you are feeding your body the pure molecules that enable it to stay balanced, and since all disease is an imbalance of some kind, this medicine is effective against nearly anything. At least, that’s what the bulk of science and real experience show.

The prohibition of cannabis medicine is a crime against humanity, and as more human trials are conducted into the efficacy of cannabis extracts, the truth will be revealed.

The THC Molecule

Scientific Evidence

There are literally hundreds upon hundreds of scientific studies showing that cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as whole plant formulations, are effective against nearly any disease you can think of. LetFreedomGrow hosts an incredibly extensive list of peer-reviewed scientific studies and news reports about cannabis medicine. Here are just a few conditions that science has proven cannabinoids are therapeutically active against:

  • Arthritis
  • Cancer
  • Crohn’s
  • Diabetes
  • Fibromyalgia
  • Multiple sclerosis
  • Parkinson’s”

More: https://hubpages.com/health/Hemp-Oil-Cancer-Cure

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“Miracle” Cannabis Oil: May Treat Cancer, But Money and the Law Stand in the Way of Finding Out

“Cannabis oil, which cancer-sufferers credit with saving their lives, and which is supposedly useful in healing other ailments, from diabetes to skin rashes, is made by distilling raw bud down to its essential ingredients.”

 

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“First it was a cough. Then it was bronchitis. Then it was time to say goodbye to Michelle Aldrich.

The year 2011 was supposed to be a good one for the 66-year-old. That June, she and her husband, Michael, were feted with a lifetime achievement award by High Times magazine for their four decades of work on marijuana legalization. Yet something was off. She was smoking a lot, maybe more than ever.

And she couldn’t get high.

In the fall of that year — a bad time for the local marijuana movement, as the federal Justice Department began shutting down hundreds of California medical cannabis dispensaries — Aldrich went in to see a series of doctors for what she thought was a flu that just refused to go away.

After six weeks of progressively worse diagnoses — flu became bronchitis, which became pneumonia — a CT scan revealed the cause behind the “heat” she felt in the middle of her chest. A tumor, “poorly-differentiated non-small cell adenocarcinoma.” In other words, stage 3 lung cancer.

Lung cancer is a killer, with nearly 70 percent of new cases resulting in deaths, according to statistics published by the National Cancer Institute. “I thought I was going to die,” Aldrich says from her Marina District apartment. But she didn’t. And now, she is busy telling anyone who will listen that, along with diet and chemotherapy, a concoction of highly concentrated cannabis oil eliminated her cancer in less than four months.”

More: http://www.sfweekly.com/2013-04-24/news/key-words-cannabis-oil-cure-cancer-constance-finley/full/

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Fighting Cancer: Another Study Reveals the Cannabis and Cancer Prevention Link

“Does marijuana cause cancer? Revealing the link between cannabis and cancer yet again, researchers with the California Pacific Medical Center in San Francisco have released findings that further bolster cannabis as an anti-cancer solution.
The researchers have found a compound in the much-talked-about plant could “halt the spread” of many types of aggressive cancers, including breast cancer.

The Cannabis and Cancer Link

Cannabidiol is the compound, and while it fights cancer cells, it does not produce the high feelings commonly associated with cannabis. Instead, it seems to “switch off” the gene responsible for metastasizing breast cancer.

They reportedly found the compound doesn’t only stop the breast cancer cells from growing, but even causes them to return back to normal cells, cancer-free.”

More: http://naturalsociety.com/study-positive-cannabis-and-cancer-link/

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Smoking Marijuana Does Not Cause Lung Cancer

“New research shows here seems to be something in pot that actually undermines cancer, instead of causing it. — and the media are doing their best to ignore it.
 
There is a groundswell of attention in the news to marijuana’s role in causing and preventing various types of cancers. Last week, AlterNet published an article from the Marijuana Policy Project about a new study finding that pot smokers have a lower risk of head and neck cancers than people who don’t smoke pot…
 
Smoking pot doesn’t cause lung cancer. In fact, the study found that cigarette smokers who also smoked marijuana were at a lower risk of contracting lung cancer than tobacco-only smokers…
 

You’d think it would have been very big news in June 2005 when UCLA medical school professor Donald Tashkin reported that components of marijuana smoke somehow prevent them from becoming malignant.

 In other words, something in marijuana exerts an anti-cancer effect!”

More:http://www.alternet.org/story/142271/smoking_marijuana_does_not_cause_lung_cancer

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