Archive for January, 2010

“Published Study Shows How Cannabis Inhibits Brain Cancer”-ASA Blog

Tuesday, January 12th, 2010

I was invited to write a blog for American’s for Safe Access. Here is a link to the ASA blog.

As a member of ASA’s Medical & Scientific Advisory Board, I’ve been actively engaged in pursuing further evidence of the medical efficacy of cannabis based medicine. Some of this work occurred while I was working at the California Pacific Medical Center Research Institute (CPMCRI), and yesterday the findings of that work were published by the peer-reviewed journal Molecular Cancer Therapeutics. With this study, we have shown that cannabis compounds can work together to inhibit glioblastoma (GBM), one of the nastiest and most aggressive of all brain cancers. GBM is the type of brain cancer that caused the recent death of Senator Ted Kennedy.
 
Tetrahydrocannabinol (THC) is the most prevalent compound found in the cannabis (marijuana) plant. Many studies have focused on THC and its therapeutic qualities, however other compounds in the plant should not be overlooked from a medical and scientific standpoint. In fact, the recently published study illustrates how THC and other compounds (known as Cannabinoids) found in the cannabis plant work synergistically to kill cancer cells and reduce tumor size. The anti-cancer effect, which is mediated through the activation of cannabinoid receptors on cancer cells, has been shown through both in vitro and in vivo experimentation.
 
The other most abundant compound in the cannabis plant is Cannabidiol (CBD). One of the main findings of our research was how THC and CBD act synergistically to inhibit GBM brain cancer cell proliferation and induce cell death. The research team at CPMCRI, lead by Dr. Sean McAllister, discovered that a ratio of about 4:1 of THC to CBD resulted in a synergistic or enhanced killing effect.  We determined that CBD was the most active of 4 other natural cannabinoids, therefore, we tried it in combination with THC.
 
Interestingly, the individual doses of THC and CBD had little effect on the cancer cells or other proteins in the cells. However, when these two compounds were combined, the amount of cell death, or apoptosis, dramatically increased. And, as if this wasn’t enough, our research team discovered another potential breakthrough from the combined use of THC and CBD — a decrease in the protein known as ERK (extracellular signal-regulated kinase). The levels of ERK, often associated with cancer found in the body, were only affected by the combination of THC and CBD, suggesting that these compounds either converge on a shared pathway or together they activate a specific response in cancer cells.
 
Since these cannabinoids are relatively non-toxic and selectively kill cancer cells, large doses can be provided for in vivo studies. Hence, a direct injection to the site of the tumor or cancer, versus the more widely used methods of smoke or vapor inhalation, may be the most efficient for killing cancer cells. With more targeted applications, a much higher concentration of the active ingredients can be used without toxic side effects. We also speculate that other, non-cannabinoid components of the plant may also improve anti-cancer activity.
 
An improvement in the life expectancy of people with GBM has not occurred in 50 years, and because GBM is so aggressive and effective treatments have not yet been found, this study may represent a major breakthrough in the field. The next obvious step is further testing of how this combination of cannabinoids affects brain cancer and finding ways to put this important discovery to use.

Acetaminophen Synergizes Through the CB1 Receptor

Sunday, January 3rd, 2010

Acetaminophen and cannabinoid receptor interactions were the focus of a research article published in the journal of Neuropharmacology in late December 2009. The research demonstrates that the effects of Acetaminophen on pain are mediated through the CB1 receptor. Acetaminophen has previously been shown to elevate the levels of endocannabinoids in the body. Thus increasing the amount of activated cannabinoid receptors, leading to pain relief and anti-inflammatory effects.

Most prescription narcotics such as percocet and vicodin are cut with acetaminophen by pharmaceutical companies. This gives the pain killers more of a “kick.” Without acetaminophen, some pain killers are not nearly as effective. Researchers have been investigating the molecular mechanism for this interaction and the Endocannabinoid System appears to be a big player. Previous research has also shown that there is some “cross talk” between opiate receptors and cannabinoid receptors.

The study investigated the effects of acetaminophen in combination with different pain killers. The authors found that a combination of acetaminophen with gabapentin or morphine produced synergistic pain killing effects in rats.  The results may have clinical significance because the effect was observed in rats that are a model of spinal cord injury. Interestingly, this synergistic pain relief disappeared when the rats were given AM251. AM251 blocks the Cannabinoid Type 1 Receptor (CB1R) thus inhibiting CB1R activation.

Given the notable toxicity of acetaminophen,  cannabinoids might be a reasonable supplement to accompany current treatments for pain.

Chronic Low Doses of a Cannabinoid Causes New Brain Cell Formation

Saturday, January 2nd, 2010

The Journal of Molecular Psychiatry recently published an LTE from a group of researchers who demonstrated that chronic low doses of the cannabinoid WIN55212, resulted in new brain cells or neurons in the hippocampus of old rats. As we age, our ability to make new cells decreases, this may be the cause of many age related disorders. A class of drugs that can restore neurons may be a potential cure for diseases such as Parkinson’s, depression, etc.

The data was simply amazing–3 weeks of treatment resulted in noticeable effects! So this blog includes the figures from the publication, see below.  On the left hand side, Figure A shows brain cells stained with red and green. Green, spindle like, staining indicates neuron growth. Pictures A and B show the typical neuron growth in developing brains. As you can see in pictures E and F, chronic administration of a non-psychotropic dose of WIN55212 restores neuron production in older rats, indicated by the green wisps. Note that this green stain is very low in old rats that did not receive the cannabinoid, pictures C and D.

The authors speculate, “Cannabinoid receptor stimulation therapy may thus provide clinical benefit for humans with age-associated memory impairment.”

Lots of molecules can activate cannabinoid receptors, so take your pick. More research is needed to determine which cannabinoids are the best option. None of the plant cannabinoids have not been explored for this effect. This not the first time cannabinoids have been linked to neurogenesis; HU-210 has also demonstrated similar effects.

The cannabinoid WIN55212 causes new brain cell formation in old rats