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Cannabis & Cancer
One of the most exciting advances in tumor biology is the fact that laboratory animal, preclinical studies and phase 1 human clinical trials have all demonstrated that cannabinoids cause reproducible and in some cases extraordinary antitumor effects by various mechanisms. These include the induction of cell death, inhibition of cell growth and the inhibition of tumor angiogenesis invasion and metastasis. If all of these findings can be confirmed in additional human trials, they would demonstrate an obvious need for the legalization of cannabinoids and their introduction into the routine practice of medicine. These results will represent a windfall for the entire industry.
What is interesting is that the mechanism of action for the killing of tumor cells varies among each of the different cannabinoids. The plant Cannabis sativa for yields more than 60 different compounds. For example Cannabidiol [CBD] is able to decrease survival of both estrogen receptor positive and estrogen receptor negative breast cancer cell lines. This cell kill has nothing to do with binding to endocannabinoid receptors. Additionally, this agent causes programmed cell death in breast cancer cell lines. Cannabidiol is able to cause programmed cell death [APOPTOSIS] in a concentration dependent fashion.
CBD has been shown to have other wonderful properties in the treatment of cancer. Mouse models have been used which mimic the disease in humans. In a mouse model of colon cancer, it was demonstrated that a chemopreventive benefit was substantiated. An additional extraordinary benefit was demonstrated in lung cancer cell lines. There was an up regulation of a modulating molecule known as ICAM—1 or intracellular adhesion molecule, leading to a decrease in cancer invasiveness. These benefits are extraordinary. In colon cell lines CBD demonstrated an ability to retard the oxidative metabolism of DNA, increased the level of endocannabinoids and reduced cell proliferation.
The cannabinoids not only appear to cause cell death to tumor cells but they also appear to provide protection to normal cells. Such therapeutic benefits are without precedent. In the mouse and rat model, the cannabinoids cause cell mediated death of glioma tumors while protecting normal connective tissue in the brain. This effect occurs through the stimulation of an endoplasmic reticulum stress pathway. The mechanism of action has been elegantly demonstrated.
THC mediates its benefits through modulation of the CB 2 receptor. This compound is able to dramatically reduce the incidence of hepatocellular carcinoma in an animal model system. For example, nodules of hepatocellular carcinoma have been implanted under the skin of mice lacking an immune system [nude mice.] Those models which are exposed to THC have a dramatic decrease in the incidence of a malignant process.
One experiment demonstrated the power of THC to provide antiangiogenic and antiproliferative properties. Human non-small lung cancer lines were placed under the skin of immunodeficient mice. As compared to control specimens those mice exposed to THC had a 60% decrease in the incidence of cancer.
Based upon these in vitro and animal model studies Guzmán and colleagues performed a phase 1 clinical trial in patients with recurrent glioblastoma multiforme , which is the most aggressive form of brain cancer. A total of nine patients were studied. Median survival in this group of patients was 24 weeks. All patients had failed previous treatment with surgery as well as radiation therapy. Two patients had received previous chemotherapy with temozolomide. All patients had been shown to have a progression of disease by MRI. All patients demonstrated clinical benefit when THC was administered. There was a shrinkage of tumor associated with the administration of a solution of THC directly into the tumor bed. In this preliminary clinical trial THC proved at least as good if not superior to the use of both surgery and radiation therapy.
Currently, all cannabinoids are regulated as schedule 1 drugs by the Drug Enforcement Administration. When one takes into account the demonstrable benefits in the patient with cancer who suffers from nausea and vomiting, this degree of regulation appears inappropriate. Indeed, it appears immoral that this drug not be more widely available, at least to patients with malignant disease.
It is the recommendation of Dr. Greenleaf that cannabinoid compounds be made freely available to the following patients:
Patients with hepatocellular carcinoma.
Patients with adenocarcinoma of the breast.
Patients with non-small cell lung cancer.
Patients with refractory gliomas of the brain.
In all of these patients and in preclinical models, there are documented measurable improvements in the malignant process. The drug THC should be made available either as a synthetic compound, a bio similar or the natural agent as found in cannabis. It should be made available off guidelines for those patients who suffer from intractable nausea and vomiting.