Marijuana May Fight Lung Tumors WebMD

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“Cannabis Compound Slows Cancer Spread in Mice, Researchers Say.
 
… the active ingredient in marijuana may help combat lung cancer, new research suggests. In lab and mouse studies, the compound, known as THC, cut lung tumor growth in half and helped prevent the cancer from spreading, says Anju Preet, PhD, a Harvard University researcher in Boston who tested the chemical.While a lot more work needs to be done, “the results suggest THC has therapeutic potential,” she tells WebMD.Moreover, other early research suggests the cannabis compound could help fight brain, prostate, and skin cancers as well, Preet says.

The findings were presented at the annual meeting of the American Association for Cancer Research.

The finding builds on the recent discovery of the body’s own cannabinoid system, Preet says. Known as endocannabinoids, the natural cannabinoids stimulate appetite and control pain and inflammation.

THC seeks out, attaches to, and activates two specific endocannabinoids that are present in high amounts on lung cancer cells, Preet says. This revs up their natural anti-inflammatory properties. Inflammation can promote the growth and spread of cancer.

In the new study, the researchers first demonstrated that THC inhibited the growth and spread of cells from two different lung cancer cell lines and from patient lung tumors. Then, they injected THC into mice that had been implanted with human lung cancer cells. After three weeks, tumors shrank by about 50%, compared with tumors in untreated mice.

Paul B. Fisher, PhD, a professor of clinical pathology at Columbia University, says that though the work is “interesting,” it’s still very early.

“The issue with using a drug of this type becomes the window of concentration that will be effective. Can you physiologically achieve what you want without causing unwanted effects?” he tells WebMD.”

More:http://www.webmd.com/lung-cancer/news/20070417/marijuana-may-fight-lung-tumors

{Delta}-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer.”  http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2007/1_Annual_Meeting/4749%20?maxtoshow&hits=80&RESULTFORMAT&fulltext=cannabinoid&searchid=1&FIRSTINDEX=1760&resourcetype=HWCIT

“Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo.” http://www.ncbi.nlm.nih.gov/pubmed/17621270

Marijuana Chemical May Fight Brain Cancer – WebMD

“Active Component In Marijuana Targets Aggressive Brain Cancer Cells, Study Says
 
The active chemical in marijuana promotes the death of brain cancer cells by essentially helping them feed upon themselves, researchers in Spain report.Guillermo Velasco and colleagues at Complutense University in Spain have found that the active ingredient in marijuana, THC, causes brain cancer cells to undergo a process called autophagy. Autophagy is the breakdown of a cell that occurs when the cell essentially self-digests.The team discovered that cannabinoids such as THC had anticancer effects in mice with human brain cancer cells and people with brain tumors. When mice with the human brain cancer cells received the THC, the tumor growth shrank.Two patients enrolled in a clinical trial received THC directly to the brain as an experimental treatment for recurrent glioblastoma multiforme, a highly aggressive brain tumor.  Biopsies taken before and after treatment helped track their progress.  After receiving the THC, there was evidence of increased autophagy activity.

The findings appear in the April 1 issue of the Journal of Clinical Investigation.

The patients did not have any toxic effects from the treatment. Previous studies of THC for the treatment of cancer have also found the therapy to be well tolerated, according to background information in journal article.

Study authors say their findings could lead to new strategies for preventing tumor growth.”

http://www.webmd.com/cancer/brain-cancer/news/20090401/marijuana-chemical-may-fight-brain-cancer

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

Marijuana Compounds Could Beat Back Brain Cancer – ABCNews

“Preliminary research suggests that a combination of compounds in marijuana could help fight off a particularly deadly form of brain cancer.

But the findings shouldn’t send patients rushing to buy pot: the levels used in the research appear to be too high to obtain through smoking. And there’s no sign yet that the approach works in laboratory animals, let alone people.

Still, the finding does suggest that more than one compound in marijuana might boost cancer treatment, said study author Sean McAllister, an associate scientist at California Pacific Medical Center Research Institute in San Francisco. “Combination therapies might be more appropriate,” McAllister said.

Researchers have long studied the compounds in marijuana known as cannabinoids, which are thought to hold possible health benefits. One, known as THC, is well known for its role in making people high when they smoke or eat pot. Researchers have been testing it as a treatment for the brain tumors known as glioblastomas.

In the new study, researchers tested THC and cannabidiol, another compound from marijuana, on brain cancer cells. The findings appear in the January issue of Molecular Cancer Therapeutics.

The study authors found that the combination treatment seemed to work better at killing the cancerous cells and preventing them from growing back.

About 9,000 people in the United States develop glioblastomas each year, said Dr. Paul Graham Fisher, chief of the Division of Child Neurology at Stanford University and Lucile Packard Children’s Hospital. The most famous patient was the late U.S. Senator Ted Kennedy.

The prognosis for people with the condition is grim because tumors spread throughout the brain. It can be impossible for treatments to remove the entire tumor, Fisher said.

“No matter what you do, this tumor has a larger border than you ever think,” he said. “We know there are microscopic satellites all throughout one side of the brain and pretty soon in the other side of the brain. The only thing that will fix this disease is something that provides a more blanket approach.”

Instead of targeting the tumors itself, he explained, treatments need to do something like disrupt the pathways that cancer cells use to communicate.

In the big picture, “you’re seeing a lot more thinking outside the box about trying to treat glioblastoma,” he said. “I think in the next 10 to 15 years we’re going to start seeing progress forward.”

For now, he said, there’s no evidence that marijuana is good or bad for glioblastoma tumors.

Back in the laboratory, McAllister said the next step is to test the combination treatment on laboratory animals and then on people. The treatment may be given to people directly through the brain, which could be expensive. But the compounds themselves may not be expensive, McAllister said.

As for the idea of getting the same effect through a couple of marijuana joints, he had this to say: “It’s unlikely that you could reach effective concentrations by smoking the plant.””

http://abcnews.go.com/Health/Healthday/marijuana-compounds-beat-back-brain-cancer/story?id=9534388

“Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells.”
http://www.ncbi.nlm.nih.gov/pubmed/16078104

The Endocannabinoid System and the Brain.

Abstract

“The psychoactive constituent in cannabis, Δ(9)-tetrahydrocannabinol (THC), was isolated in the mid-1960s, but the cannabinoid receptors, CB1 and CB2, and the major endogenous cannabinoids (anandamide and 2-arachidonoyl glycerol) were identified only 20 to 25 years later. The cannabinoid system affects both central nervous system (CNS) and peripheral processes. In this review, we have tried to summarize research-with an emphasis on recent publications-on the actions of the endocannabinoid system on anxiety, depression, neurogenesis, reward, cognition, learning, and memory. The effects are at times biphasic-lower doses causing effects opposite to those seen at high doses. Recently, numerous endocannabinoid-like compounds have been identified in the brain. Only a few have been investigated for their CNS activity, and future investigations on their action may throw light on a wide spectrum of brain functions. Expected final online publication date for the Annual Review of Psychology Volume 64 is November 30, 2012. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.”

http://www.ncbi.nlm.nih.gov/pubmed/22804774

[The endocannabinoid system as a target for the development of new drugs for cancer therapy].

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“Studies on the main bioactive components of Cannabis sativa, the cannabinoids, and particularly delta 9-tetrahydrocannabinol (THC), led to the discovery of a new endogenous signalling system that controls several physiological and pathological conditions: the endocannabinoid system. This comprises the cannabinoid receptors, their endogenous agonists–the endocannabinoids–and proteins for endocannabinoid biosynthesis and inactivation.

Recently, evidence has accumulated indicating that stimulation of cannabinoid receptors by either THC or the endocannabinoids influence the intracellular events controlling the proliferation and apoptosis of numerous types of cancer cells, thereby leading to anti-tumour effects both in vitro and in vivo.

This evidence is reviewed here and suggests that future anti-cancer therapy might be developed from our knowledge of how the endocannabinoid system controls the growth and metastasis of malignant cells.”

http://www.ncbi.nlm.nih.gov/pubmed/12723496

Endocannabinoid system modulation in cancer biology and therapy.

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“The discovery of the endocannabinoid system and the recognition of its potential impact in a plethora of pathological conditions, led to the development of therapeutic agents related to either the stimulation or antagonism of CB1 and CB2 cannabinoid receptors, the majority of which are actually tested in preclinical studies for the pharmacotherapy of several diseases. Endocannabinoid-related agents have been reported to affect multiple signaling pathways and biological processes involved in the development of cancer, displaying an interesting anti-proliferative, pro-apoptotic, anti-angiogenic and anti-metastatic activity both in vitro and in vivo in several models of cancer. Emerging evidence suggests that agonists of cannabinoid receptors, which share the useful property to discern between tumor cells and their non-transformed counterparts, could represent novel tumor-selective tools to treat cancer in addition to their already exploited use as palliative drugs to treat chemotherapy-induced nausea, pain and anorexia/weight loss in cancer patients. The aim of this review is to evidence and update the recent emerging knowledge about the role of the endocannabinoid system in cancer biology and the potentiality of its modulation in cancer therapy.”  http://www.ncbi.nlm.nih.gov/pubmed/19559362

http://www.sciencedirect.com/science/article/pii/S1043661809000863

Changes in the Endocannabinoid System May Give Insight into new and Effective Treatments for Cancer

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“The endocannabinoid system comprises specific cannabinoid receptors such as Cb1 and Cb2, the endogenous ligands (anandamide and 2-arachidonyl glycerol among others) and the proteins responsible for their synthesis and degradation. This system has become the focus of research in recent years because of its potential therapeutic value several disease states. The following review describes our current knowledge of the changes that occur in the endocannabinoid system during carcinogenesis and then focuses on the effects of anandamide on various aspects of the carcinogenic process such as growth, migration, and angiogenesis in tumors from various origins.

Marijuana and its derivatives have been used in medicine for centuries, however, it was not until the isolation of the psychoactive component of Cannabis sativa (Δ9-tetrahydrocannabinol; Δ9-THC) and the subsequent discovery of the endogenous cannabinoid signaling system that research into the therapeutic value of this system reemerged. Ongoing research is determining that regulation of the endocannabinoid system may be effective in the treatment of pain (Calignano et al., 1998; Manzanares et al., 1999), glaucoma (Voth and Schwartz, 1997), and neurodegenerative disorders such as Parkinson’s disease (Piomelli et al., 2000) and multiple sclerosis (Baker et al., 2000). In addition, cannabinoids might be effective anti-tumoral agents because of their ability to inhibit the growth of various types of cancer cell lines in culture (De Petrocellis et al., 1998; Ruiz et al., 1999; Sanchez et al., 1998, 2001) and in laboratory animals (Galve-Roperh et al., 2000).

In conclusion, the endocannabinoid system exerts a myriad of effects on tumor cell growth, progression, angiogenesis, and migration. With a notable few exceptions, targeting the endocannabinoid system with agents that activate cannabinoid receptors or increase the endogenous levels of AEA may prove to have therapeutic benefit in the treatment of various cancers. Further studies into the downstream consequences of AEA treatment are required and may illuminate other potential therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791688/

Receptor-dependent and Receptor-independent Endocannabinoid Signaling: A Therapeutic Target for Regulation of Cancer Growth.

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“The endocannabinoid system comprises the G-protein coupled CB1 cannabinoid receptor (CB1R) and CB2 cannabinoid receptor (CB2R), their endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and catabolism. Recent works have revealed several important interactions between the endocannabinoid system and cancer. Moreover, it is now well established that synthetic small molecule cannabinoid receptor agonist acting on either CB1R or CB2R or both exert anti-cancer effects on a variety of tumor cells. Recent results from many laboratories reported that the expression of CB1R and CB2R in prostate cancer, breast cancer, and many other cancer cells are higher than corresponding non-malignant tissues. The mechanisms by which cannabinoids acting on CB1R or CB2R exert their effects on cancer cells are quite diverse and complex. Further, several studies demonstrated that some of the anti-proliferative and apoptotic effects of cannabinoids are mediated by receptor-independent mechanisms. In this minreview we provide an overview of the major findings on the effects of endogenous and/or synthetic cannabinoids on breast and prostate cancer. We also provide insight into receptor independent mechanisms of the anti-cancer effects of cannabinoids under in vitro and in vivo conditions.” http://www.ncbi.nlm.nih.gov/pubmed/23069587

http://www.sciencedirect.com/science/article/pii/S0024320512005930

Targeting the endocannabinoid system for the treatment of cancer– a practical view.

“In recent years, considerable interest has been generated by findings that cannabinoids not only have useful palliative effects, but also can affect the viability and invasivity of a variety of different cancer cells. In the present review, the potential of targeting the cannabinoid system for the treatment of cancer is considered from a practical, rather than a mechanistic viewpoint, addressing questions such as whether human tumour cells express CB receptors; whether the potencies of action of cannabinoids in vitro match the potencies expected on the base of receptor theory; what is known about the in vivo effects of cannabinoids and cancer, and how relevant the experiments undertaken are to the clinical situation; and finally, what approaches can be taken to minimise unwanted effects of cannabinoid treatment. It is concluded that cannabinoids (or agents modulating the endogenous cannabinoid system) are an attractive target for drug development in the cancer area, but that more in vivo studies, particularly those investigating the potential of cannabinoids as an addition to current treatment strategies, are needed.”  http://www.ncbi.nlm.nih.gov/pubmed/20370711

http://www.eurekaselect.com/85470/article

Cannabinoids, Endocannabinoids and Cancer

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“The endocannabinoid system consists of an array of endogenously produced bioactive lipids that activate cannabinoid receptors. Although the primary focus of endocannabinoid biology has been on neurological and psychiatric effects, recent work has revealed several important interactions between the endocannabinoid system and cancer. Several different types of cancer have abnormal regulation of the endocannabinoid system that contributes to cancer progression and correlates to clinical outcomes.

Modulation of the endocannabinoid system by pharmacological agents in various cancer types reveals that it can mediate antiproliferative and apoptotic effects by both cannabinoid receptor-dependent and -independent pathways. Selective agonists and antagonists of the cannabinoid receptors, inhibitors of endocannabinoid hydrolysis, and cannabinoid analogs have been utilized to probe the pathways involved in the effects of the endocannabinoid system on cancer cell apoptosis, proliferation, migration, adhesion, and invasion. The antiproliferative and apoptotic effects produced by some of these pharmacological probes reveal that the endocannabinoid system is a promising new target for the development of novel chemotherapeutics to treat cancer.”

Although there is a strong set of data in vitro, in cellular model systems, and in mouse model systems, there is a dearth of clinical data on the effects of cannabinoids in the treatment of cancer in humans. This fact is quite surprising considering the large library of compounds that have been developed and used to study the effects of cannabinoids on cancer in model systems.

Despite the lack of preclinical and clinical data, there is a strong agreement that pharmacological targeting of the endocannabinoid system is emerging as one of the most promising new methods for reducing the progression of cancer. In particular, combination therapy utilizing both traditional chemotherapeutics and molecules targeting the endocannabinoid system may be an excellent next generation treatment for cancer.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366283/