Category Archives: Colon Cancer

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

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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

 

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/

Expression of the cannabinoid type I receptor and prognosis following surgery in colorectal cancer.

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“The cannabinoid system has been considered to be a potential target of colorectal carcinoma therapy. The aim of this study was to address the correlation between cannabinoid type 1 (CB1) receptor expression and disease severity/outcomes in patients with colorectal cancer (CRC).”

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 “…The high immunoreactivity of the cannabinoid type 1 receptor is a significant prognostic factor following surgery in stage IV CRC…

The effect of cannabinoids in colorectal cancer (CRC) has been demonstrated in in vitro experiments and animal models, which indicate the antiproliferative, apoptotic and antimetastatic actions of cannabinoid agonists…

Antineoplastic effects are mediated by the activation of cannabinoid type I (CB1), type 2 (CB2) or a non-cannabinoid receptor-mediated mechanism…”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576207/

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

Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism

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“Pancreatic adenocarcinoma is one of the most aggressive and devastating human malignancies with a death-to-incidence ratio of 0.99. Although it represents only 2–3% of all cancers, pancreatic adenocarcinoma is the fourth cause of death by tumors…

In recent years, there has been increasing interest in cannabinoids as therapeutic drugs for their antineoplastic, anticachectic, and analgesic potential. Growth inhibitory activities of cannabinoids have been demonstrated for various malignancies, including brain, breast, prostate, colorectal, skin and, recently, pancreatic cancer…

In the present study, we have demonstrated that the combination between the standard chemotherapy agent GEM and cannabinoids synergistically inhibited pancreatic adenocarcinoma cell growth by a ROS-dependent autophagic cell death.

These findings support a key role of the ROS-dependent activation of an autophagic program in the synergistic growth inhibition induced by GEM/cannabinoid combination in human pancreatic cancer cells.

GEM and cannabinoids strongly inhibited growth of human pancreatic adenocarcinoma cells in vivo.”

Read more: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122066/

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

Cannabinoids As Cancer Hope

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NORML - Working to reform marijuana laws

by Paul Armentano
Senior Policy Analyst
NORML | NORML Foundation

““Cannabinoids possess … anticancer activity [and may] possibly represent a new class of anti-cancer drugs that retard cancer growth, inhibit angiogenesis (the formation of new blood vessels) and the metastatic spreading of cancer cells.” So concludes a comprehensive review published in the October 2005 issue of the scientific journal Mini-Reviews in Medicinal Chemistry.

Not familiar with the emerging body of research touting cannabis’ ability to stave the spread of certain types of cancers? You’re not alone.

For over 30 years, US politicians and bureaucrats have systematically turned a blind eye to scientific research indicating that marijuana may play a role in cancer prevention — a finding that was first documented in 1974. That year, a research team at the Medical College of Virginia (acting at the behest of the federal government) discovered that cannabis inhibited malignant tumor cell growth in culture and in mice. According to the study’s results, reported nationally in an Aug. 18, 1974, Washington Post newspaper feature, administration of marijuana’s primary cannabinoid THC, “slowed the growth of lung cancers, breast cancers and a virus-induced leukemia in laboratory mice, and prolonged their lives by as much as 36 percent.”

Despite these favorable preclinical findings, US government officials dismissed the study (which was eventually published in the Journal of the National Cancer Institute in 1975), and refused to fund any follow-up research until conducting a similar — though secret — clinical trial in the mid-1990s. That study, conducted by the US National Toxicology Program to the tune of $2 million concluded that mice and rats administered high doses of THC over long periods experienced greater protection against malignant tumors than untreated controls.

Rather than publicize their findings, government researchers once again shelved the results, which only came to light after a draft copy of its findings were leaked in 1997 to a medical journal, which in turn forwarded the story to the national media.

Nevertheless, in the decade since the completion of the National Toxicology trial, the U.S. government has yet to encourage or fund additional, follow up studies examining the cannabinoids’ potential to protect against the spread cancerous tumors.

Fortunately, scientists overseas have generously picked up where US researchers so abruptly left off. In 1998, a research team at Madrid’s Complutense University discovered that THC can selectively induce apoptosis (program cell death) in brain tumor cells without negatively impacting the surrounding healthy cells. Then in 2000, they reported in the journal Nature Medicine that injections of synthetic THC eradicated malignant gliomas (brain tumors) in one-third of treated rats, and prolonged life in another third by six weeks.

In 2003, researchers at the University of Milan in Naples, Italy, reported that non-psychoactive compounds in marijuana inhibited the growth of glioma cells in a dose dependent manner and selectively targeted and killed malignant cancer cells.

The following year, researchers reported in the journal of the American Association for Cancer Research that marijuana’s constituents inhibited the spread of brain cancer in human tumor biopsies. In a related development, a research team from the University of South Florida further noted that THC can also selectively inhibit the activation and replication of gamma herpes viruses. The viruses, which can lie dormant for years within white blood cells before becoming active and spreading to other cells, are thought to increase one’s chances of developing cancers such as Karposis Sarcoma, Burkitts lymphoma, and Hodgkins disease.

More recently, investigators published pre-clinical findings demonstrating that cannabinoids may play a role in inhibiting cell growth of colectoral cancer, skin carcinoma, breast cancer, and prostate cancer, among other conditions. When investigators compared the efficacy of natural cannabinoids to that of a synthetic agonist, THC proved far more beneficial – selectively decreasing the proliferation of malignant cells and inducing apoptosis more rapidly than its synthetic alternative while simultaneously leaving healthy cells unscathed.

Nevertheless, US politicians have been little swayed by these results, and remain steadfastly opposed to the notion of sponsoring – or even acknowledging – this growing body clinical research, preferring instead to promote the unfounded notion that cannabis use causes cancer. Until this bias changes, expect the bulk of research investigating the use of cannabinoids as anticancer agents to remain overseas and, regrettably, overlooked in the public discourse.”

http://norml.org/component/zoo/category/cannabinoids-as-cancer-hope

Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators.

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“Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB(½), TRPV1) are central components of the system. Many disease-ameliorating effects of cannabinoids-endocannabinoids are receptor mediated, but many are not, indicating non-CBR signaling pathways.

Cannabinoids-endocannabinoids are anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic in most cancers, in vitro and in vivo in animals.

They signal through p38, MAPK, JUN, PI3, AKT, ceramide, caspases, MMPs, PPARs, VEGF, NF-κB, p8, CHOP, TRB3 and pro-apoptotic oncogenes (p53,p21 waf1/cip1) to induce cell cycle arrest, autophagy, apoptosis and tumour inhibition. Paradoxically they are pro-proliferative and anti-apoptotic in some cancers. Differences in receptor expression and concentrations of cannabinoids in cancer and immune cells can elicit anti- or pro-cancer effects through different signal cascades (p38MAPK or PI3/AKT).

Similarities between effects of cannabinoids-endocannabinoids, omega-3 LCPUFA and CLAs/CLnAs as anti-inflammatory, antiangiogenic, anti-invasive anti-cancer agents indicate common signaling pathways.

Evidence in vivo and in vitro shows EPA and DHA can form endocannabinoids that: (i) are ligands for CB(½) receptors and possibly TRPV-1, (ii) have non-receptor mediated bioactivity, (iii) induce cell cycle arrest, (iii) increase autophagy and apoptosis, and (iv) augment chemotherapeutic actions in vitro. They can also form bioactive, eicosanoid-like products that appear to be non-CBR ligands but have effects on PPARs and NF-kB transcription factors. The use of cannabinoids in cancer treatment is currently limited to chemo- and radio-therapy-associated nausea and cancer-associated pain apart from one trial on brain tumours in patients. Further clinical studies are urgently required to determine the true potential of these intriguing, low toxicity compounds in cancer therapy. Particularly in view of their synergistic effects with chemotherapeutic agents similar to that observed for n-3 LCPUFA.”  https://www.ncbi.nlm.nih.gov/pubmed/23103355

http://www.sciencedirect.com/science/article/pii/S0163782712000537