Astrocytoma GBM And Cannabis

Astrocytoma GBM
Astrocytoma GBM
Dr Michelle Weiner
 By Dr. Michelle Weiner

Researchers across the world have discovered that medical marijuana and cannabis extracts have been able to decrease the size of brain tumors by stopping the growth of blood vessels that supply the tumor. Cannabis has chemicals called cannabinoids, which are the chemicals that could effectively starve tumors to death and increase a patient’s chance of survival. How is it possible that cannabinoid compounds can destroy cancer cells while leaving healthy cells untouched?  Cannabinoids including THC and CBD are both potent antioxidants, according to the U.S. government, which filed a patient on the antioxidant and neuroprotective properties of cannabinoids based on research from 1998. CBD has potent antitumoral properties and works synergistically with chemotherapy in promoting cancer cell death.

Many biological pathways that involve mitochondria such as energy homeostasis, neurotransmitter release and oxidative stress are modulated by endogenous and exogenous cannabinoids.  By effectively neutralizing free radicals and mitigating oxidative stress, antioxidants provide a broad range of therapeutic benefits from slowing down the aging process to reducing the risk of DNA damage linked to cancer.  The creation of oxidative stress is necessary for obtaining energy and sustaining cellular function.  Cell survival is dependent on this ongoing regenerative mechanism called autophagy. Too much oxidative stress is a signal for the cell to destroy itself, a process called apoptosis. The fate of the cell is contingent on the kind of stress and its duration.  Chemotherapy regimens typically involve generating excessive oxidative stress to precipitate apoptosis.

Cannabinoids interestingly enough exert opposite effects in different situations. At low stress conditions, cannabinoids increase mitochondrial activity and trigger autophagic repair. They will buffer high stress conditions and protect cells by decreasing mitochondrial activity. Endocannabinoids can increase stress to the point where the cell undergoes apoptosis.  The death of cancer cells promotes homeostasis and the survival or the person as a whole.

Senator John McCain has been diagnosed with a brain tumor called a Glioblastoma. The diagnosis was based on a biopsy of the tissue removed from his brain at the Mayo Clinic Hospital in Phoenix. Symptoms generally include headaches, blurred vision, seizures.  Glioblastoma multiforme (GBM)is the most common and the most aggressive form of a malignant primary brain tumor. It is difficult to treat with a reported survival rate of less than 10% in the first five years. Interestingly, while GBM and gliomas have been highly resistant to traditional treatment, much of what is known about the demonstrated ability of cannabis to fight cancer comes from research conducted on GBM and glioma tumor cells.

Scientists hypothesize that because brain cells have the highest concentration of cannabinoid-binding receptors in the body, brain tumors also rich in these receptors may respond best to cannabinoids. Pre-clinical studies and one pilot clinical trial have been performed on the anti-tumor effects of cannabinoids on gliomas alone.  UK scientists have found that a combination of THC and CBD used with radiation treatment was most effective in dramatically shrinking high-grade glioma masses in mice.

As reported in the British Journal of Cancer in 2006, a study on terminal patients with recurrent brain cancer, specifically glioblastoma multiforme; In view of the fair safety profile of THC, together with its possible antiproliferative action on tumor cells (Guzmán, 2003), it would be desirable that additional trials were run to determine whether cannabinoids, as single drugs or in combination with established antitumoral drugs could be used, other than for their palliative effects, to inhibit tumor growth.  In 2004, Guzman and colleagues reported that cannabinoids inhibited glioma tumor growth in animals and in human GBM tumor samples by altering blood vessel morphology. In the issue of Cancer Research, investigators concluded, “The present laboratory and clinical findings provide a novel pharmacological target for cannabinoid-based therapies.”

Several additional investigators have also recently called for further exploration of cannabis-based therapies for the treatment of glioma. A separate case report, published in 2011 in the journal of the International Society for Pediatric Neurosurgery, also documents the spontaneous regression of residual brain tumors in two children coinciding with the subjects use of cannabis.

On September 29th, 2014, Insys Therapeutics announced that the United States Food and Drug Administration had granted orphan drug designation to its proprietary cannabidiol product for the treatment of glioma. The scientific and anecdotal evidence supporting glioma treatment with cannabis is quite strong. Investigators at the California Pacific Medical Center Research Institute reported that the administration of THC on human glioblastoma multiforme cell lines decreased the proliferation of malignant cells and induced cell death more rapidly than did the administration of the synthetic cannabinoid agonist WIN 55,212-2. Researchers also noted that THC selectively targeted malignant cells while ignoring healthy ones in a more profound manner than the synthetic alternative. A separate preclinical trial reported that the combined administration of THC and the pharmaceutical agent temozolomide (TMZ) “enhanced autophagy”   in brain tumors resistant to conventional anti-cancer treatments.

A 2013 study found that “activation of the transient receptor potential vanilloid type 2 (TRPV2) has been found to inhibit human GBM cell proliferation and overcome BCNU [an anti-cancer drug] resistance of GBM cells,” and that the administration of CBD helped trigger this TRPV2 activation, making otherwise limited treatments like temozolomide and BCNU more effective and toxic to tumor cells. “CBD by triggering TRPV2-dependent Ca(2+) influx increases drug uptake and synergizes with cytotoxic agents to induce apoptosis of glioma cells, whereas no effects were observed in normal human astrocytes.”

An FDA-approved clinical trial of a cannabis treatment produced by GW Pharmaceuticals also found the administration of THC and CBD helped improve the condition of patients already taking temozolomide for glioblastomas. GW noted that “The study showed that patients with documented recurrent GBM treated with THC:CBD had an 83% one year survival rate compared with 53% for patients in the placebo cohort” and that “Median survival for the THC:CBD group was greater than 550 days compared with 369 days in the placebo group.”

According to the government’s own cancer website, “One study showed that coadministration of THC and CBD over single-agent usage had greater antiproliferative activity in an in vitro study with multiple human glioblastoma multiforme cell lines,” meaning adding CBD to THC helped stop tumor growth. Overall, as Dr. Manuel Guzman from Spain has shown, THC induces programmed cell death in glioma cells. CBD has also been shown to kill multiple types of glioma cell lines, in addition to inhibiting migration, proliferation, growth, invasion, and angiogenesis. There is an enormous potential for the role of Cannabis in Cancer and specifically with GBM..

Dr. Michelle Weiner, is an Interventional Pain Management Physician board certified in Physical Medicine and Rehabilitation. She completed her residency and fellowship training at the University of Miami. Her specialty is focused on prevention, treatment, reversal of health deterioration, increasing function and managing pain. Dr. Weiner focuses on diagnosing and treating spine and musculoskeletal pain as well as chronic migraines.

Spine and Wellness Centers of America