Category Archives: Gliomas

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

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“Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy…We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo.”

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“These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.

Δ9-Tetrahydrocannabinol (THC), the main active component of marijuana, exerts a wide variety of biological effects by mimicking endogenous substances — the endocannabinoids — that bind to and activate specific cannabinoid receptors. One of the most exciting areas of research in the cannabinoid field is the study of the potential application of cannabinoids as antitumoral agents.

Cannabinoid administration has been found to curb the growth of several types of tumor xenografts in rats and mice…

 Considering that no signs of toxicity were observed in the clinical trial patients or in tumor-bearing animals treated intracranially, peritumorally, or intraperitoneally with THC, and that no overt toxic effects have been reported in other clinical trials of cannabinoid use in cancer patients for various applications (e.g., inhibition of nausea, vomiting, and pain) and using different routes of administration (e.g., oral, oro-mucosal) our findings support that safe, therapeutically efficacious doses of THC may be reached in cancer patients.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/

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

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“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

 

Antitumor Effects of THC.

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“1-Trans-[delta.sup.9]-tetrahydrocannabinol (THC) the main active component of marijuana, has been shown to exhibit anticancer activity.

Galve-Roperh et al. reported that intratumoral administration of THC induces apoptosis of transformed neural cells in culture, and also induces a considerable regression of malignant gliomas in Wistar rats and in mice… These authors suggest that their “results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.”

Thus, in our studies, rats and mice that received THC for 2 years exhibited body weight reductions, enhanced survival rates, and decreased tumor incidences in several sites, mainly organs under hormonal control.

These earlier experimental carcinogenesis results on THC clearly lend further validity to the notion that cannabinoids may indeed be anticarcinogenic.”

http://www.thefreelibrary.com/Antitumor+Effects+of+THC.-a068148345

“Antitumor effects of THC.” http://www.ncbi.nlm.nih.gov/pubmed/11097557

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

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“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/

Cannabis Oil Cures Skin Cancer

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“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

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“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/

Local Delivery of Cannabinoid-Loaded Microparticles Inhibits Tumor Growth in a Murine Xenograft Model of Glioblastoma Multiforme

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“Treatment with cannabinoid-loaded microparticles activates apoptosis and inhibits tumor angiogensis. The aim of the present study was therefore to evaluate the antitumor efficacy of biodegradable polymeric microparticles allowing the controlled release of the phytocannabinoids THC and CBD. Our findings show that administration of cannabinoid-loaded microparticles reduces the growth of glioma xenografts supporting that this method of administration could be exploited for the design of cannabinoid-based anticancer treatments.

Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) – the two major ingredients of marijuana – have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w) of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

Δ9-Tetrahydrocannabinol (THC), the main active component of the hemp plant Cannabis sativa, exerts a wide variety of biological effects by mimicking endogenous substances – the endocannabinoids – that bind to and activate specific cannabinoid receptors. So far, two G protein–coupled cannabinoid-specific receptors have been cloned and characterized from mammalian tissues: CB1, abundantly expressed in the brain and at many peripheral sites, and CB2, expressed in the immune system and also present in some neuron subpopulations and glioma cells. One of the most active areas of research in the cannabinoid field is the study of the potential application of cannabinoids in the treatment of different pathologies. Among these therapeutic applications, cannabinoids are being investigated as anti-tumoral agents. Thus, cannabinoid administration curbs the growth of several types of tumor xenografts in rats and mice including gliomas. Based on this preclinical evidence, a pilot clinical trial has been recently run to investigate the anti-tumor action of THC on recurrent gliomas. The mechanism of THC anti-tumoral action relies on the ability of this compound to: (i) promote the apoptotic death of cancer cells (ii) to inhibit tumour angiogenesis and (iii) to reduce the migration of cancer cells.

Conclusions

Data presented in this manuscript show for the first time that in vivo administration of microencapsulated cannabinoids efficiently reduces tumor growth thus providing a proof of concept for the utilization of this formulation in cannabinoid-based anti-cancer therapies.”

Full text: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054795. 

Cannabinoids for Cancer Treatment: Progress and Promise

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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

Cannabinoids Halt Pancreatic Cancer, Breast Cancer Growth, Studies Say

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“Compounds in cannabis inhibit cancer cell growth in human breast cancer cell lines and in pancreatic tumor cell lines, according to a pair of preclinical trials published in the July issue of the journal of the American Association for Cancer Research.

In one trial, investigators at Complutense University in Spain and the Institut National de la Sante et de la Recherche Medicale (INSERM) in France assessed the anti-cancer activity of cannabinoids in pancreatic cancer cell lines and in animals. Cannabinoid administration selectively increased apoptosis (programmed cell death) in pancreatic tumor cells while ignoring healthy cells, researchers found. In addition, “cannabinoid treatment inhibited the spreading of pancreatic tumor cells … and reduced the growth of tumor cells” in animals.

“These findings may contribute to … a new therapeutic approach for the treatment of pancreatic cancer,” authors concluded.

In the second trial, investigators at Spain’s Complutense University reported that THC administration “reduces human breast cancer cell proliferation [in vitro] by blocking the progression of the cell cycle and by inducing apoptosis.” Authors concluded that their findings “may set the bases for a cannabinoid therapy for the management of breast cancer.”

Previous preclinical data published in May in the Journal of Pharmacological and Experimental Therapeutics reported that non-psychoactive cannabinoids, particularly cannabidiol (CBD), dramatically halt the spread of breast cancer cells and recommended their use in cancer therapy.

Separate trials have also shown cannabinoids to reduce the size and halt the spread of glioma (brain tumor) cells in animals and humans in a dose dependent manner. Additional preclinical studies have demonstrated cannabinoids to inhibit cancer cell growth and selectively trigger malignant cell death in skin cancer cells, leukemic cells, lung cancer cells, and prostate carcinoma cells, among other cancerous cell lines.”

http://norml.org/news/2006/07/06/cannabinoids-halt-pancreatic-cancer-breast-cancer-growth-studies-say

US Investigators Praise Cannabinoids As Chemo Treatment

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“Cannabinoids inhibit cancer cell proliferation and should be clinically tested as chemotherapeutic agents, according to a review published in the January issue of the journal Cancer Research.

Investigators at the University of Wisconsin School of Medicine and Public Health reported that the administration of cannabinoids halts the spread of a wide range of cancers, including brain cancer, prostate cancer, breast cancer, lung cancer, skin cancer, pancreatic cancer, and lymphoma.

Researchers suggested that cannabinoids may offer significant advantages over standard chemotherapy treatments because the compounds are both non-toxic and can uniquely target malignant cells while ignoring healthy ones.

“Cannabinoids … offer potential applications as anti-tumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival,” authors concluded. “[T]here is overwhelming evidence to suggest that cannabinoids can be explored as chemotherapeutic agents for the treatment of cancer.””

Read more: http://norml.org/news/2008/01/31/us-investigators-praise-cannabinoids-as-chemo-treatment