Over the last decade there have been numerous publications demonstrating the anti-cancer effects of plant and synthetic cannabinoids. Notably, the main ingredient of Cannabis, THC (tetrahydrocannabinol), has demonstrated the ability to kill multiple types of cancers in a variety of cancer research models. CBD (cannabidiol), another common plant component, has also shown the ability to kill cancer cells, recently it has been used to successfully treat breast cancer in a mouse research model of the disease.

Certain types of brain cancer appear to be vulnerable to cannabinoids such as THC and CBD. Scientific research has demonstrated that THC and other cannabinoids can kill extremely aggressive brain cancers known as glioblastoma multiforme (GBM) or grade IV astrocytomas. Researchers have also experimented with combining different cananbinoids for the treatment of aggressive brain cancers. So far, the results have been extremely promising. There is a need for new treatments for GBMs, as current  treatments for these cancers can extend life for up to 15 months, if you’re lucky.

Last year, the journal of Molecular Cancer Therapeutics published research demonstrating that combination’s of THC and CBD, the two most abundant cannabinoids on the plant, can lead to a greater-than-additive or synergistic inhibition of cancer growth. Now, nearly a year to the date, the journal has published another article studying the anti-cancer effects of THC and CBD. The new article takes the next steps towards getting this therapy in to the clinic by testing THC and CBD in animals along side a common brain tumor drug TMZ (temozolomide).

The study was conducted in Spain, and the experiments analyzing the effects of cannabinoids were conducted with tumors or brain cancer cells from human samples and a tumor xenograft mouse model. A tumor xenograft model is basically a cancer that is induced into an animal that has a compromised immune system. This allows researchers to give a mouse a tumor consisting of human cells, thus a promising anti-cancer treatment can be tested on a human tumor in a more natural environment, than a petri dish.

The plant cannabinoids used for this study were “kindly provided by GW pharmaceuticals.”  THC and CBD were also provided as plant extracts or “botanical drug substances,” meaning they contained small amounts of other cannabinoids. Allowing these researchers to construct a custom anti-cancer, Sativex-like substance.  Other synthetic cannabinoids such as SR141716A and SR144528 were donated by Sonafi-Aventis.

The figure below shows that THC and TMZ can drastically inhibit the size of tumor.

In the following figure, the authors also examined combinations of THC,CBD, TMZ , and SAT-L (a “botonical drug substance” or extract containing a 1:1 ratio of THC and CBD, 7.5mg each). Interestingly their results also showed that TMZ resistant cells, can be killed by cannabinoids or in combination with cannabinoids.

The researchers conclude that:

“Taken together, our observations support that the administration of cannabinoids, and in particular of Sativex, which is currently used for palliative applications in patients with cancer and multiple sclerosis, alone or in combination with TMZ, could be of potential interest for the management of GBM.”

Cannabis-based medicines are most often prescribed to increase quality of life or treat symptoms of disease. As research continues on this ancient medicine, scientific data suggests that cannabinoids are not only promising treatments but represent potential cures.

Links to Cannabinoid & Cancer Studies:

Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

Cannabidiol enhances the inhibitory effects of Delta⁹-tetrahydrocannabinol on human glioblastoma cell proliferation and survival

Cannabinoids for Cancer Treatments: Progress and Promise

Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum stress-related genes

Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines

Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma

Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation

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Last month, Dr. Sean McAllister traveled from California to talk in Philadelphia on a potential new breast cancer treatment. Dr. McAllister has been studying the anti-cancer effects of cannabinoids for years and he has discovered that the cannabinoid, CBD (Cannabidiol) is a very potent inhibitor of breast cancer. Usually, his research draws a lot of media interest and then some.  His research sparks an interest in the general public, as CBD is also the second most abundant compound on the Cannabis plant.

Dr.McAllister shared his results of his recently published study on CBD and breast cancer. This is not the first paper on the anti-cancer activity of CBD, the McAllister lab also published other articles on cannabinoids and cancer: CBD and Breast Cancer and THC&CBD kill brain cancer cells.  The current study is an in depth look at how CBD kills breast cancer cells in an animal model. Specifically, CBD affects a protein called ID-1. ID-1 appears to be a major conductor of cancer cells and thus is an excellent target for a cancer treatment.

There are a variety of ways for a scientist to measure how effective an anticancer drug is. For instance in the image below is an experiment testing how CBD can stop the invasion of cancer cells. When cancer spreads it can eat through tissue, and CBD appears to be able to inhibit this aspect of breast cancer cells. The cancer cells are placed on a gel which contain small holes. The cells are dosed with a drug and after a few days you can count the number of cells that have made it through. This simulates what a tumor does as it eats its way through human tissues. The little black triangles are the cells, you can see that only a half-dozen or so made it through the gel when dosed with CBD (on the right). Without CBD, the control on the left, the cancer cells easily move through the gel.

Invasion assay pic control vs CBD

Dr.McAllister has previously demonstrated  that cannabinoids may have the unique ability to selectively kill cancer cells. The lab has also posted a youtube video showing this effect.

The therapeutic potential of CBD or a synthetic version thereof, is of interest to pharmaceutical companies. During his presentation, Dr. McAllister mentioned that work may soon start on a CBD and breast cancer clinical trial with STI pharmaceuticals.

However CBD is a scheduled drug in this country, but it doesn’t get you high and has virtually no toxicity! Furthermore, CBD also inhibits the negative effects of THC! Why is this safe and useful compound a scheduled drug of abuse!? Luckily, the government’s view on CBD hasn’t deterred researchers from developing this into a medicine.

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Articles like this and more are also available at www.examiner.com

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The original version of this article first appeared in the Lab Bench Science Column of the West Coast Leaf NewsPaper on June 4th 2010.

The Lab Bench

By Jahan Marcu

A research team from the School of Medicine at Temple University, Philadelphia, presented their preliminary cannabinoid and bone data at a scientific meeting in Anaheim, CA in April. Our results add to a growing body of scientific evidence, suggesting a prominent role for the endocannabinoid system in bone development.  For the last year, researchers have been trying to reproduce and build upon previous work on cannabinoids and bone, specifically, by characterizing the effects of removing the CB1 and CB2 receptors from mice.

Few labs have published new discoveries regarding cannabis and bone. However, those that have are surprising so far. Some findings are so profound that the upcoming International Cannabinoid Research Society (ICRS) meeting will have a special symposium to discuss the bone data produced by just a few laboratories.

Research shows that bone cells have cannabinoid receptors and produce endocannabinoids. Bone cells express a lot of CB2 receptors and nerves that traverse our bones produce CB1 receptors. The `anti-cannabinoid’ receptor, GPR55, is also expressed in bone.

These receptors appear to work together to regulate bone health. Some clinical evidence supports the role of cannabinoids in various diseases. The Clinical Endocannabinoid Deficiency (Russo 2004) is thought to underlie many treatment- resistant conditions such as irritable bowel syndrome, fibromyalgia, and chronic pain. Recently, CB1 receptor mutations were linked to migraines, bi-polar disorder, and major depression (Monteleone 2010).

Now CB2 receptor mutations may be linked to lower human bone density and hand-bone strength. Research from Japan and France shows that mutations correlate to osteoporosis in post-menopausal women. The two studies looked at 2,626 elderly adults with and without osteoporosis. A study out in Russia analyzed the hand-bone strength of 574 adults and found that those with CB2 receptor muta- tions had weaker hand-bone strength (Yamada 2007, Karsak 2005, 2009). These all suggest that a less functional receptor is related to poor bone health.

Researchers have been studying how the body responds to traumatic brain injuries (TBI). When TBI occurs in a mouse, endocannabinoids are made and new bone is formed. Thus, cannabinoids may enhance the healing of bones in some instances such as fractures.

Genetically modified mice without the cannabinoid receptors have a deregulated skeleton. Depending on genetic makeup, the animals make too much or too little bone. So, research has shown that cannabinoids can both increase and decrease bone mass. However, all mice without cannabinoid receptors eventually develop severe osteoporosis (Bab 2008).

Plant cannabinoids such as CBDV, CBG, CBN, THC, and THCV may increase the number of bone stem cells in rats (Scutt 2007). Conversely, Anandamide has been shown to increase bone turnover by acti- vating osteoclasts, the cells that remodel or dissolve bone. CBD can inhibit osteoclasts. The infamous diet drug Rimonabandt, or SR141716A, is thought to prevent bone loss in mice by activating GPR55, not the CB1 receptor. Additionally, derivatives like WIN55,212 and some JWH compounds appear to severely inhibit osteoclasts from remodeling bone. Researchers have already speculated that cannabinoids represent a new generation of drugs that could treat a variety of bone diseases. For more information check out this recent review of the scientific literature, which discusses the role of the endocannabinoid system in bone disease and pathology.

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Disclaimer: These views are strictly the views of the author and not those of Temple University or its units.
This blog is not intended to diagnose or treat any disease.

On August 20th 2009, researchers from Italy published an article in the Journal of Molecular Medicine on the benefits of cannabidiol (CBD) to treat Inflammatory bowel disease (IBD), in a mouse model of colitis. CBD dramatically reduced tissue damage and inflammation in vivo.

The research team showed, for the first time that CBD reduced radical oxygen species (ROS) and lipid peroxidation in intestinal cells of mice. ROS production is a hallmark of IBD, as oxidative stress is the leading tissue destructive force that contributes to the development of IBD. The article also features pictures of treated and untreated intestinal tissue.

Of additional interest is the pharmacology of CBD. CBD was most effective at 5mg/kg. However, there wasn’t much difference at higher doses, even a dose of 10mg/kg did not exert a further protective effect. Lower doses (1-2.5mg/kg) were not significantly effective.

Also, the researchers found that CBD inhibited Nitric Oxide Synthase, an enzyme with produces Nitric oxide (NO). High levels of NO correlate correlate well with IBD activity, and previous experiments have shown that other Nitric Oxide Synthase Inhibitors can also improve symptoms of IBD.

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Jahan