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/

The endocannabinoid system in cancer-potential therapeutic target?

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“Endogenous arachidonic acid metabolites with properties similar to compounds of Cannabis sativa Linnaeus, the so-called endocannabinoids, have effects on various types of cancer. Although endocannabinoids and synthetic cannabinoids may have pro-proliferative effects, predominantly inhibitory effects on tumor growth, angiogenesis, migration and metastasis have been described. Remarkably, these effects may be selective for the cancer cells, while normal cells and tissues are spared. Such apparent tumor cell selectivity makes the endocannabinoid system an attractive potential target for cancer therapy. In this review we discuss various means by which the endocannabinoid system may be targeted in cancer and the current knowledge considering the regulation of the endocannabinoid system in malignancy.”  http://www.ncbi.nlm.nih.gov/pubmed/18249558

http://www.sciencedirect.com/science/article/pii/S1044579X07001058

Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (review).

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“The medicinal properties of extracts from the hemp plant Cannabis sativa have been known for centuries but only in the 90s membrane receptors for the Cannabis major principle were discovered in mammalian cells. Later on the endogenous ligands for the cannabinoid receptors were identified and the term ‘endocannabinoid system’ was coined to indicate the complex signaling system of cannabinoid receptors, endogenous ligands and the enzymes responsible for their biosynthesis and inactivation.

The ‘endocannabinoid system’ is involved in a broad range of functions and in a growing number of pathological conditions.

There is increasing evidence that endocannabinoids are able to inhibit cancer cell growth in culture as well as in animal models.

Most work has focused on the role of endocannabinoids in regulating tumor cell growth and apoptosis and ongoing research is addressed to further dissect the precise mechanisms of cannabinoid antitumor action. However, endocannabinoids are now emerging as suppressors of angiogenesis and tumor spreading since they have been reported to inhibit angiogenesis, cell migration and metastasis in different types of cancer, pointing to a potential role of the endocannabinoid system as a target for a therapeutic approach of such malignant diseases.

The potential use of cannabinoids to retard tumor growth and spreading is even more appealing considering that they show a good safety profile, regarding toxicity, and are already used in cancer patients as palliatives to stimulate appetite and to prevent devastating effects such as nausea, vomiting and pain.”  http://www.ncbi.nlm.nih.gov/pubmed/17342320

https://www.spandidos-publications.com/or/17/4/813

The endocannabinoid system in the cancer therapy: an overview.

“The endocannabinoid system comprises the cannabinoid receptors type 1 (CB1) and type 2 (CB2), their endogenous ligands (endocannabinoids), and the proteins responsible for their biosynthesis and degradation. This ubiquitous signalling system, that has attracted a great deal of scientist interest in the past 15 years, regulates several physiological and pathological functions. In mammals, among other functions, the endocannabinoid is involved in nervous, cardiovascular, metabolic, reproductive and immune functions. Finally, yet importantly, endocannabinoids are known to exert important antiproliferative actions in a great number of tumor cells including breast, brain, skin, thyroid, prostate and colorectal. The following review describes our current knowledge on the effects of two of the most studied endocannabinoids (AEA and 2-AG) on various types of tumor and summarizes the possible mechanism of observed antitumor effects.”  http://www.ncbi.nlm.nih.gov/pubmed/21428888

http://www.eurekaselect.com/73874/article

The endocannabinoid system and cancer: therapeutic implication

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“The endocannabinoid system is implicated in a variety of physiological and pathological conditions (inflammation, immunomodulation, analgesia, cancer and others).

The main active ingredient of cannabis, Δ(9) -tetrahydrocannabinol (Δ(9) -THC), produces its effects through activation of CB(1) and CB(2) receptors. CB(1) receptors are expressed at high levels in the central nervous system (CNS), whereas CB(2) receptors are concentrated predominantly, although not exclusively, in cells of the immune system.

Endocannabinoids are endogenous lipid-signalling molecules that are generated in the cell membrane from phospholipid precursors. The two best characterized endocannabinoids identified to date are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Here we review the relationship between the endocannabinoid system and anti-tumour actions (inhibition of cell proliferation and migration, induction of apoptosis, reduction of tumour growth) of the cannabinoids in different types of cancer.

This review will focus on examining how activation of the endocannabinoid system impacts breast, prostate and bone cancers in both in vitro and in vivo systems. The therapeutic potential of cannabinoids for cancer, as identified in clinical trials, is also discussed.

Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis-like compounds offer therapeutic potential for the treatment of breast, prostate and bone cancer in patients.

Further basic research on anti-cancer properties of cannabinoids as well as clinical trials of cannabinoid therapeutic efficacy in breast, prostate and bone cancer is therefore warranted.” http://www.ncbi.nlm.nih.gov/pubmed/21410463

“The available literature suggests that the endocannabinoid system may be targeted to suppress the evolution and progression of breast, prostate and bone cancer as well as the accompanying pain syndromes. Many in vitro and in vivo studies have shown that cannabinoids are efficacious in reducing cancer progression (i.e. inhibition of tumour growth and metastases as well as induction of apoptosis and other anti-cancer properties) in breast, prostate and bone cancer. Although this review focuses on these three types of cancer, activation of the endocannabinoid signalling system produces anti-cancer effects in other types of cancer.” http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01327.x/full

No medical benefit from marijuana? How about a cancer cure?

“It’s been known for a long time that THC and other cannabinoids can effectively treat symptoms of cancer sufferers and chemotherapy patients, such as nausea, pain, loss of appetite and fatigue. But what scientists have proven in laboratory experiments and testing on animals the last few years is that cannabinoids also can kill cancer cells and stop the spread of aggressive types of the disease — cancer of the breast, brain, prostate, colon or lungs.

The way cannabinoids work, simply put, is by blocking or deactivating a gene called ID-1 that spreads cancer. One compound that’s been found to be especially effective doing this is called cannabidiol, or CBD.

Also, CBD (which unlike THC is non-psychoactive) and other cannabinoids are non-toxic, which greatly reduces the risk of harmful effects from their use.”

http://kpbj.com/opinions/editors_view/2012-10-02/no_medical_benefit_from_marijuana_how_about_a_cancer_cure

THC From Cannabis Destroys Cancer Cells

“The study results strongly suggest that if taken regularly, cannabis oil may be able to induce remission in leukemia patients without the horrendous side effects typically associated with standard radio-chemical treatment options. Although this is only one such study, other similar studies have shown equally impressive results.

 Many of the active ingredients found in cannabis-derived drugs show exceptional promise in treating some of the greatest hurdles facing modern medical science. In addition to their aforementioned capacity for safely treating certain forms of deadly cancer, they also show great promise in alleviating autoimmune conditions such as rheumatoid arthritis, multiple sclerosis, and even inflammatory bowel disease. A growing number of experts also note their possible viability treating a range of neurological disorders including Alzheimer’s and Lou Gehrig’s disease.”

http://www.globalhealingcenter.com/natural-health/thc-from-cannabis-destroys-cancer-cells/

NBC News Reports that Cannabidiol (CBD) “Turns Off” the Cancer Gene Involved in Metastasis Findings by Scientists at California Pacific Medical Center gives Scientific Support for Cannabis Science Initiatives

“cannabidiol, (CBD), has the ability to “turn off” a gene that causes breast and other types of cancers to metastasize, according to the San Francisco Chronicle newspaper.

“What they found is that the cannabinoid turns off the overexpression of ID-1, which makes the cells lose their ability to travel to distant tissues. In other words, it keeps the cells more local and blocks their ability to metastasize. (spread to a new location) The researchers stressed cannabidiol works only on cancer cells that have these high levels of ID-1 and these do not include all cancerous tumors but, rather, aggressive, metastatic cells. But they’ve found such high levels in leukemia, colorectal, pancreatic, lung, ovarian, brain and other cancers.””

http://www.cnbc.com/id/49106127/NBC_News_Reports_that_Cannabidiol_CBD_Turns_Off_the_Cancer_Gene_Involved_in_Metastasis_Findings_by_Scientists_at_California_Pacific_Medical_Center_gives_Scientific_Support_for_Cannabis_Science_Initiatives

Marijuana Chemical Cannabidiol Halts Spread of Breast Cancer Tumors

“A non-psychoactive chemical that occurs naturally in the marijuana plant may prevent breast cancer from spreading, according to a study published in the journal Molecular Cancer Therapeutics.

Researchers found that a chemical called cannabidiol (CBD) affects the activity of a gene known as Id-1 in patients with hormone-independent breast cancer.

“Right now we have a limited range of options in treating aggressive forms of cancer,” co-author Sean D. McAllister said. “Those treatments, such as chemotherapy, can be effective but they can also be extremely toxic and difficult for patients. This compound offers the hope of a non-toxic therapy that could achieve the same results without any of the painful side effects.”

The researchers also expressed hope that CBD will also prove effective against other cancers that rely on Id-1, including brain, colon and prostate cancer.” 

http://www.naturalnews.com/023340_breast_cancer_Marijuana.html#ixzz29PViQxfy

Rimonabant inhibits human colon cancer cell growth and reduces the formation of precancerous lesions in the mouse colon

“Rimonabant inhibits human colon cancer cell growth and reduces the formation of precancerous lesions…” and “Cannabinoid receptor activation induces apoptosis… in colon cancer cells”

http://www.ncbi.nlm.nih.gov/pubmed/19479993