Cannabinoid receptor systems: therapeutic targets for tumour intervention.

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“The past decade has witnessed a rapid expansion of our understanding of the biological roles of cannabinoids and their cognate receptors. It is now certain that Delta9-tetrahydrocannabinol, the principle psychoactive component of the Cannabis sativa plant, binds and activates membrane receptors of the 7-transmembrane domain, G-protein-coupled superfamily.

Several putative endocannabinoids have since been identified, including anandamide, 2-arachidonyl glycerol and noladin ether. Synthesis of numerous cannabinomimetics has also greatly expanded the repertoire of cannabinoid receptor ligands with the pharmacodynamic properties of agonists, antagonists and inverse agonists.

Collectively, these ligands have proven to be powerful tools both for the molecular characterisation of cannabinoid receptors and the delineation of their intrinsic signalling pathways. Much of our understanding of the signalling mechanisms activated by cannabinoids is derived from studies of receptors expressed by tumour cells; hence, this review provides a succinct summary of the molecular pharmacology of cannabinoid receptors and their roles in tumour cell biology.

Moreover, there is now a genuine expectation that the manipulation of cannabinoid receptor systems may have therapeutic potential for a diverse range of human diseases. Thus, this review also summarises the demonstrated antitumour actions of cannabinoids and indicates possible avenues for the future development of cannabinoids as antitumour agents.” http://www.ncbi.nlm.nih.gov/pubmed/14640910

http://www.tandfonline.com/doi/abs/10.1517/14728222.7.6.749

The endocannabinoid system and its therapeutic exploitation.

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“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

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

Active Component Of Marijuana Has Anti-Cancer Effects, Study Suggests

“Guillermo Velasco and colleagues, at Complutense University, Spain, have provided evidence that suggests that cannabinoids such as the main active component of marijuana (THC) have anticancer effects on human brain cancer cells.

In the study, THC was found to induce the death of various human brain cancer cell lines and primary cultured human brain cancer cells by a process known as autophagy.

Consistent with the in vitro data, administration of THC to mice with human tumors decreased tumor growth and induced the tumor cells to undergo autophagy. As analysis of tumors from two patients with recurrent glioblastoma multiforme (a highly aggressive brain tumor) receiving intracranial THC administration showed signs of autophagy, the authors suggest that cannabinoid administration may provide a new approach to targeting human cancers.”  http://www.sciencedaily.com/releases/2009/04/090401181217.htm

“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells” https://www.jci.org/articles/view/37948

 

Federal Government Reports Marijuana Effective in Combatting Certain Cancers Reports ADSI – NBC News

“LOS ANGELES, March 12, 2013 (GLOBE NEWSWIRE) — The following is a statement by Advocates for the Disabled and Seriously Ill:

In a recent report, the National Cancer Institute (NCI), part of the Federal government’s National Institutes of Health (NIH), stated that marijuana “inhibited the survival of both estrogen receptor–positive and estrogen receptor–negative breast cancer cell lines.” The same report showed marijuana slows or stops the growth of certain lung cancer cells and suggested that marijuana may provide “risk reduction and treatment of colorectal cancer.”

Referring to the NCI report, Patient Rights attorney Matthew Pappas said, “The Federal government’s continuing attack on people prescribed medical cannabis by their doctors is hypocritical considering the benefits reported by its own National Cancer Institute.” Pappas represents patients in defending their right to reasonably obtain medical marijuana. The patients contend the Federal government and various municipalities are trying to prevent them from obtaining cannabis for medical purposes in direct contravention of state laws. “Cities that ban dispensaries are denying patients the ability to obtain a medicine the Federal government’s National Institutes of Health says fights cancer and they’re doing it with the Obama Administration’s help.” Recently, the City of Los Angeles repealed its ban of medical marijuana collectives after Bill Rosendahl, a member of its city council diagnosed with cancer and prescribed medical marijuana said to fellow council members about the ban, “You want to kill me? You want to throw me under the bus?”

The NCI report also examined whether patients who smoke marijuana rather than ingesting it orally are exposed to a higher risk of lung and certain digestive system cancers. According to the government, 19 studies “failed to demonstrate statistically significant associations between marijuana inhalation and lung cancer.” The report also identified a separate study of 611 lung cancer patients that showed marijuana was “not associated with an increased risk of lung cancer or other upper aerodigestive tract cancers and found no positive associations with any cancer type.” In the area of prostate cancer, the NCI report was inconclusive and suggested further research was necessary. In its report, the National Cancer Institute also identified a “study of intratumoral injection of delta-9-THC in patients with recurrent glioblastoma” that showed tumor reduction in the test participants.

Despite the Federal government sanctioned and authorized NCI report, Pappas said Congress and the Obama Administration have continued to thwart marijuana research. In an announced effort to displace state medical marijuana laws, the Office of National Drug Control Policy described “medical” marijuana as a “myth” fueling “troubling misconceptions” in documents found on its website. The Federal government appears to be focused on creating more chemical drugs, many of which are the subject of various attorney television commercials seeking out those adversely impacted by those drugs. Pappas said both the Drug Enforcement Administration and the Office of National Drug Control Policy continue to assert marijuana lacks any medicinal value despite the research showing cannabis reduces certain cancer risks and inhibits the growth of tumor cells. He also commented that the Federal government’s anti-marijuana position contributes to and encourages prejudice and public misconception about the legitimate use of medical cannabis as treatment for seriously ill patients.

In addition to anti-cancer properties, separate research reported marijuana appears to have “profound nerve-protective and brain-enhancing properties that could potentially treat many neurodegenerative disorders.” In its report, the National Cancer Institute stated cannabis effectively treats insomnia and referenced a placebo-controlled study in cancer patients showing increased quality of sleep and relaxation in those treated with tetrahydrocannabinol, an active component in marijuana.

Responding to a White House statement that only a small percentage of patients prescribed medical cannabis under state laws use it to treat cancer, Pappas said “marijuana isn’t just for cancer or AIDS patients – it can also treat, for example, sleeplessness.” Although generally not a life threatening condition, Pappas referred to insomnia as a health issue regularly treated with prescription drugs zolpidem (brand name Ambien) and eszopiclone (brand name Lunesta). According to their manufacturers’ websites, zolpidem and eszopiclone have been shown to cause severe side effects including aggressiveness, hallucinations, confusion, or suicidal thoughts. Pappas noted that, unlike those drugs, studies on insomnia similar to those reported by the National Cancer Institute show medical marijuana effectively treats insomnia at a far lower cost and with fewer side effects. Marijuana has also been prescribed for glaucoma, multiple sclerosis, chronic pain, and a variety of other physical and mental conditions.

Addressing the White House website statement that medical marijuana should remain criminally illegal under federal law, Pappas said that “with every drug, the doctor must consider the benefits versus any possible side effects. In its 3000-plus year history of medicinal use, there has never been a known, confirmed death caused by overdose of marijuana. To suggest that prescription drugs known to have severe negative side effects are alright and that marijuana can only be used for cancer or AIDS is nonsensical. It demonstrates how the Federal government’s decision to usurp state sovereignty is harming people because burdening citizens with federal criminal records based on medical marijuana provided for under state law is simply wrong. To continue outlawing the use of a drug shown to have life-saving, anti-cancer benefits that has been used safely as a medication for thousands of years is irresponsible.”

Jan., 2013 National Cancer Institute PDQ® report on cannabis:

www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page2

July, 2009 NIH report on cannabis reducing neck and head squamous cell carcinoma:

www.ncbi.nlm.nih.gov/pubmed/19638490

Nov., 2012 NIH report on cannabis breast cancer treatment:

www.ncbi.nlm.nih.gov/pubmed/22776349

Report on study showing smoked marijuana does not cause cancer:

www.washingtonpost.com/wp-dyn/content/article/2006/05/25/AR2006052501729.html

Report on neuroprotective benefits of marijuana:

www.foxnews.com/health/2012/03/20/researchers-study-neuroprotective-properties-in-cannabis/

White House “Fact Sheet” on Marijuana Legalization:

http://www.whitehouse.gov/sites/default/files/ondcp/Fact_Sheets/marijuana_legalization_fact_sheet_3-3-11.pdf

Office of National Drug Control Policy documents:

www.whitehouse.gov/sites/default/files/page/files/marijuana_fact_sheet_3-28-12.pdf and

www.whitehouse.gov/sites/default/files/ondcp/issues-content/medical_marijuana_information_packet.pdf

For more information, contact Advocates for the Disabled and Seriously Ill at (213) 531-1788.”

http://www.nbcnews.com/id/51148243/ns/business-press_releases/t/federal-government-reports-marijuana-effective-combatting-certain-cancers-reports-adsi/

Cannabinoids may be therapeutic in breast cancer.

“Cannabinoids are a group of compounds synthesized exclusively by the Cannabis sativa plant, commonly known as marijuana. In 1990, the first cannabinoid-specific membrane (CB1) was characterized and cloned (Matsuda, Lolait, Brownstein, Young, & Bonner, 1990), which catapulted biomedical research on these unique compounds.

 Cannabinoids refer to both marijuana-derived compounds with the active ingredient of 9-tetrahydrocannabinol (THC) and also the synthetic molecules that activate the same primary targets as THC.

Therapeutic properties of marijuana have been well established; however, the clinical use of either plant-sourced or pure cannabinoids remains limited.

The anticachexia properties of cannabinoids are found in tetrahydrocannabinol (oral capsules of synthetically generated THC) and are used to manage weight loss, wasting syndrome, and nausea and vomiting associated with cancer treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/23448745

Pot Fights Breast Cancer

“For years, cancer patients have used pot to combat the side effects of chemotherapy. But evidence has grown, both clinical and anecdotal, that cannabis has the potential to impede the spread of cancer itself. 

Now, researchers in Japan are reporting that CBDA keeps breast cancer cells from spreading. 

CBD, the miracle of component of cannabis that has been shown to have profound efficacy as a pain reliever, is obtained from its parent molecule, cannabidiolic acid or CBDA.

Until now, investigators have wondered whether CBDA is biologically active. But the study reports: “CBDA is an inhibitor of highly aggressive human breast cancer cell migration.””-

by Dan Skye

http://hightimes.com/news/dskye/7912

More: http://www.sciencedirect.com/science/article/pii/S0378427412012854

Role of cannabinoid and vanilloid receptors in invasion of human breast carcinoma cells.

“It is known that the diversified effects of cannabinoid on the fate of carcinoma cells are mediated predominantly through receptors. However, little is known about the effects of the individual activities of cannabinoid and noncannabinoid receptors. Here we investigate the role of cannabinoid receptor (CB) 1, CB2, and transient receptor potential vanilloid type 1 in cell proliferation and invasion patterns in the MDA-MB-231 cell line.

Our results showed that activation of CB1 and vanilloid receptors by methanandamide, a nonselective agonist, and arachidonyl-2′-choloroethylamide (ACEA) and N-oleoyldopamine, selective agonists, reduced invasion of MDA-MB-231 cells at pharmacological concentrations. Accordingly, CB1 activation resulted in decreased expression of matrix metalloproteinase (MMP) 2. On the other hand, administration of a CB2 agonist (CB65) increased cell invasion and expression of MMP2. The data obtained from MTT assay did not show any correlation between reduced invasion and cytotoxic effects of drugs. In addition, the level of vascular endothelial growth factor was significantly reduced in treatment with (R)-(+)-methanandamide, ACEA, CB65, and AM251 (a potent agonist for GPR55 and selective antagonist of CB1) compared with control. Elevated expression of cyclooxygenase-2 was observed in all of the MDA-MB-231 cells treated with agonists.

These results underline the influence of cannabinoid and vanilloid receptors on the invasiveness of MDA-MB-231 human breast carcinoma cells.”

http://www.ncbi.nlm.nih.gov/pubmed/23394450

Cannabis Oil Cures Skin Cancer

“After yesterday’s post about how cannabis oil helped a two-year old recover from a brain tumor, we thought we’d share another medical marijuana success story involving canna-oil. Cannabis Science, Inc., a pioneering U.S. biotech company developing pharmaceutical cannabis products, demonstrated yet another occurrence of medical marijuana’s important role in curing cancer. The firm issued a press release that shows cannabis extracts appeared to be effective against a patient’s third incidence of basal cell carcinoma—the most common form of cancer with over 800,000 cases occurring annually in the US. 

The patient was an Australian woman from Queensland, the site of the highest rate of skin cancer in the world. She had numerous surgeries to remove previous lesions on her face including a basal cell carcinoma, but her lesions kept coming back. She then used cannabis oil topically as an alternative therapy – and it worked! Cannabis Science released a PDF that includes a series of photos that documents the disappearance of the lesion after ten days of self-administering topical cannabis extracts. They then received verbal confirmation from her physician that the sites of the former cancerous lesions are free of cancer cells. 

This is an amazing recovery from this patient, however the results aren’t atypical. Over 600 peer reviewed articles show that numerous cancer types (including lung, breast, prostate, glioma, thyroid, leukemia, lymphoma, basil cell carcinoma and melanoma) are killed by cannabinoids in tissue culture and animal studies. We know that medical marijuana  is effective against many diseases and ailments, including cancer—which is precisely why 15 states and Washington DC have passed medical marijuana laws allowing for the medical use of cannabis. It’s time that the rest of the country catches up. Let’s give patients the effective and safe medicine they need and deserve.”

https://www.marijuanadoctors.com/blog/marijuana-medical-conditions/Cannabis-Oil-Cures-Skin-Cancer

Cannabidiol Inhibits Growth and Induces Programmed Cell Death in Kaposi Sarcoma–Associated Herpesvirus-Infected Endothelium

“Kaposi sarcoma is the most common neoplasm caused by Kaposi sarcoma–associated herpesvirus (KSHV). Current treatments for Kaposi sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the host. When the host’s immune system weakens, KSHV begins to replicate again, and active tumor growth ensues. New therapeutic approaches are needed.

Cannabidiol (CBD), a plant-derived cannabinoid, exhibits promising antitumor effects without inducing psychoactive side effects. CBD is emerging as a novel therapeutic for various disorders, including cancer.

In this study, we investigated the effects of CBD both on the infection of endothelial cells (ECs) by KSHV and on the growth and apoptosis of KSHV-infected ECs, an in vitro model for the transformation of normal endothelium to Kaposi sarcoma….

Cannabidiol (CBD) was first isolated in 1940. It is a major component of the plant Cannabis sativa, which is also the source of Δ9-tetrahydrocannabinol (Δ9-THC). Due to its multiple biological activities, CBD has been identified as a potential clinical agent. Moreover, CBD affects these activities without the psychoactive side effects that typify Δ9-THC. Recent studies have documented the potential antitumorigenic properties of CBD in the treatment of various neoplasms, including breast cancer, lung cancer, bladder cancer, glioblastoma,and leukemia.CBD induces these effects through a variety of mechanisms and signaling pathways

CBD has been evaluated clinically for the treatment of various conditions, including anxiety, psychosis, and pain. In contrast to other members of the cannabinoid family, CBD has a strong safety profile and induces no psychotropic effects.Therefore, it has become an attractive agent in the search for new anticancer therapies.Our current study demonstrated that CBD preferentially enhanced apoptosis and inhibited the proliferation of KSHV-infected endothelial cells. This selective targeting of KSHV-induced neoplasia suggests that CBD may have a desirable therapeutic index when used to treat cancer. Moreover, a recent study demonstrated that CBD can be delivered effectively by nasal and transdermal routes, which may be particularly valuable for the treatment of Kaposi sarcoma oral or skin lesions.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527984/

Cannabinoids for Cancer Treatment: Progress and Promise

Cancer Research: 68 (2)

“Cannabinoid refers to a group of chemicals naturally found in the marijuana plant Cannabis sativa L. and includes compounds that are either structurally or pharmacologically similar to Δ(9)-tetrahydrocannabinol or those that bind to the cannabinoid receptors. Although anticancer effects of cannabinoids were shown as early as 1975 in Lewis lung carcinoma, renewed interest was generated little after the discovery of the cannabinoid system and cloning of the specific cannabinoid receptors.

Cannabinoids are a class of pharmacologic compounds that offer potential applications as antitumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival. In particular, emerging evidence suggests that agonists of cannabinoid receptors expressed by tumor cells may offer a novel strategy to treat cancer. Here, we review recent work that raises interest in the development and exploration of potent, nontoxic, and nonhabit forming cannabinoids for cancer therapy.”

Full Text: http://cancerres.aacrjournals.org/content/68/2/339.long