There is quite a bit of buzz going on in the brain cancer world about the possibility that marijuana derivatives could be helpful for patients with glioblastoma. http://www.huffingtonpost.com/2014/11/18/marijuana-brain-cancer_n_6181060.html?ir=Healthy+Living . I would like to try to shine some light on this issue since it is extraordinarily fuzzy and confusing. I would like to describe the different categories of marijuana derivatives and discuss some of the evidence that might indicate that they could be beneficial for patients.
First off, marijuana is called cannabis, and molecules derived from cannabis are called cannabinoids. These are a diverse group of compounds that can act on receptors in the body called cannabinoid receptors. Cannabinoids can be produced not only by marijuana but also endogenously in the human body and animals, or they can be produced synthetically. The most notable cannabinoid is THC, which is the primary psychoactive compound and marijuana. Another type of constituent of the plant marijuana is called Cannabidiol (CBD). There are dozens of different CBD molecules that can be isolated from marijuana and they all have different effects. It should be noted that CBD is not psychoactive and is not thought to affect the psychoactivity of THC. CBD and its molecular derivatives have been shown to have potential against cancer. Numerous reports have shown that CBD molecules can inhibit glioma cells both in vitro an in vivo by inducing a apoptosis, or programmed cell death, and they may also affect angiogenesis. Researchers at California Pacific Medical Center in San Francisco, with whom I used to work, including Dr. Sean McAllister, have determined some of the molecular mechanisms by which CBD can inhibit glioblastoma cell growth. Researchers at California Pacific Medical Center discovered CBD’s ability to “turn off” the activity of ID1, the gene responsible for metastasis in breast and other types of cancers, including the particularly aggressive triple negative breast cancer. The researchers hope to start human trials soon.
It appears that one general theme related to CBD molecules is that they increase the production of reactive oxygen species in tumor cells. Reactive oxygen species are molecules like superoxide that can cause destruction of other molecules in the cellular environment and promote injury to cellular DNA. Thus, if CBD molecules induce DNA injury in a cell, and that cell is also being injured by another chemotherapeutic drug such as temozolomide, this combined injury may promote a generalized increase in sensitivity of the tumor cell to the chemotherapeutic drug. In other words, CBD may increase the sensitivity of tumor cells to standard chemotherapeutic agents.
It should be noted, there is no clear evidence that the other marijuana derivative THC has been found to be beneficial for patients in terms of blocking tumor growth. It is likely that smoking marijuana or consuming marijuana products will have little if any effect on glioblastoma growth, since it is unknown in any given source of marijuana whether or not the appropriate CBD may even be contained within the specimen being smoked or consumed. In order to capitalize on the effects of CBD in glioblastoma and other malignancies, there are efforts underway by some biotech companies such as Stella therapeutics in Seattle, and GW Pharmaceuticals in the UK, to develop drugs to treat patients that target these pathways. At this point, there is only one clinical trial ongoing which is being performed by GW pharmaceuticals in 15 countries. http://www.gwpharm.com/oncology.aspx . Hopefully further research in this area will lead to other CBD derivatives that will be potent as stand-alone therapeutics or in combination with currently available anti-neoplastic agents.
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