The National Cancer Institute on Medical Cannabis
The U.S. Department of Health and Human Services has 11 operating divisions, including eight agencies in the U.S. Public Health Service and three human services agencies – one of which is the National Institutes of Health (NIH). The NIH is the nation’s medical research agency which is charged with overseeing 27 institutes and centers including the National Cancer Institute (NCI), which is the federal government’s principal agency for cancer research and training.
NCI is comprised of a team of nearly 4,000 people and is tasked with running the National Cancer Program. This wide-reaching program conducts and supports training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.
The program is also heavily involved in cancer research. It provides research grants and cooperative agreements to coordinate and support cancer research projects conducted by universities, hospitals, research foundations, and businesses throughout the U.S. and abroad. The agency also conducts cancer research in its own laboratories and clinics and encourages and coordinates cancer research by industrial concerns as well. The program also supports the Frederick National Laboratory for Cancer Research, which is the only federally funded research and development center dedicated exclusively to biomedical research.
Overall, NCI scientists and cancer researchers throughout the United States and the rest of the world have had an immense impact on the fight against cancer. In the U.S., the overall cancer death rate has declined since the early 1990s. NCI’s Surveillance, Epidemiology, and End Results (SEER) Statistics Review shows that cancer death rates decreased by:
1.8% per year among men from 2004 to 2013
1.4% per year among women from 2004 to 2013
1.4% per year among children ages 0–19 from 2009 to 2013
These trends reflect improvements in cancer treatment and advances in technology that have led to better tools for understanding, detecting, and diagnosing cancer. People with cancer are living longer and have a better quality of life than ever before.
However, although rates of smoking, a major cause of cancer, have declined, the U.S. population is aging and obesity is on the rise. These are risk factors for cancer that could cause rates to increase. More needs to be done in the fight against these diseases and NCI is backing research into a number of different avenues including causes, prevention, diagnosis, and treatment – including the potential for novel therapeutic approaches like cannabis.
CBD and Cancer
Between preclinical studies in the lab and preclinical studies on animals, preliminary research into the effects of cannabis-derived compounds as a treatment for cancer, cancer-related side effects, or treatment-related side effects has yielded some important discoveries.
The potential benefits of medicinal cannabis for people living with cancer include antiemetic effects (helps with nausea and vomiting), anxiolytic effects (reduces anxiety), appetite stimulation, pain relief, and improved sleep. Cannabidiol (CBD), in particular, is thought to have significant analgesic, anti-inflammatory, and anxiolytic activity without the psychoactive effect (high) of delta-9-THC. Generally, physicians recommend medicinal cannabis for symptom management for cancer patients. Pediatric patients are also seeking symptom relief with cannabis or cannabinoid treatment as well.
But what’s interesting is that cannabinoids and hemp oils have also shown antitumor effects.
In NCI’s cancer information summary, which provides an overview of the use of cannabis as a treatment for cancer-related symptoms (caused by the disease itself or its treatment), the agency laid out some of the research to date.
Antitumor effects in preclinical studies
Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis. They appear to kill tumor cells but do not affect their non-transformed counterparts and may even protect them from cell death.
In a review article published in the British Journal of Pharmacology in 2006, Italian researchers found that cannabinoids displayed anticancer effects on many different types of tumor cells including breast cancer cells, prostate cancer cells, rat glioma cells, human astrocitoma, human gioblastoma, thyroid cells, mouse skin carcinoma, and human umbilical vein endothelial cells.
Of course, most of the studies to date have focused on the anti-cancer properties of tetrahydrocannabinol (THC) which is the main psychoactive component of cannabis. In fact, the antitumorigenic effects of THC have been known since the 1970s.
For example, a study published in the Journal of the National Cancer Institute in 1975 found that Cannabinol and Δ8-THC inhibited tumor growth in a mouse model of Lewis lung adenocarcinoma after 20 days of treatment, whereas cannabidiol and Δ9-THC failed to show any effect. In another study by the National Toxicology Program which was published in 1996, researchers looked into the effects of THC on tumors using rodents. Groups of mice and rats were fed various doses of THC mixed with corn oil and the researchers were able to observe a dose-related decrease in the incidence of hepatic adenoma tumors and hepatocellular carcinoma in the mice. Adenoma is a type of non-cancerous (benign) tumor that may affect various organs while hepatocellular carcinoma is the most common type of liver cancer. The researchers also observed decreased incidences of benign tumors (polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis, and pancreas) in the rats.
But while THC has been extensively studied for its antitumor effects, researchers have begun looking into other cannabinoids as well, namely CBD.
In a study published in Molecular Cancer Therapeutics in 2011, researchers from the Beth Israel Deaconess Medical Center in Boston, MA found that CBD induced programmed cell death in breast cancer cells without the activation of cannabinoid and vanilloid receptors in vitro. CBD induced both autophagy and apoptosis cell death in breast cancer cells and the researchers concluded that the interplay between apoptosis and autophagy in CBD-treated breast cancer cells warranted more research into the potential use of CBD as a cancer therapeutic.
To quickly review, autophagy is the natural, regulated, destructive mechanism of the cell that disassembles unnecessary or dysfunctional components. It allows the orderly degradation and recycling of cellular components. When a cell is damaged though oxidative stress, this function removes the faulty components and replaces them with new, better-working parts.
Apoptosis, on the other hand, is known as programmed cell death. If cells are no longer needed or if they’ve been damaged beyond repair, they commit suicide by activating an intracellular death program. This self destructive process is a necessary way to clear the system of cells that can’t be saved.
CBD has also been demonstrated to exert a chemopreventive effect in a mouse model of colon cancer. In a study published in Journal of molecular medicine in 2012, Italian researchers investigated CBD’s possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice (AOM is a potent carcinogen used to induce colon cancer in rodent models). They found that animals treated with azoxymethane and CBD concurrently were protected from developing premalignant and malignant lesions. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation. In a subsequent study conducted by researchers from Italy and the U.K. and published in Phytomedicine in 2014, researchers investigated the effect of a standardized Cannabis sativa extract with high content of CBD on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. They concluded that CBD attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation.
Another investigation into the antitumor effects of CBD examined the role of intercellular adhesion molecule-1 (ICAM-1). ICAM-1 plays a role in cell signaling by stabilizing cell-cell interactions. However, enhanced ICAM-1 levels on cancer cells may be involved in tumor suppression. In a study published in the FASEB Journal in 2012, researchers from Germany demonstrated for the first time that increased ICAM-1 levels elicited by CBD resulted in a decrease of tumor cell invasion and metastasis.
CBD may also enhance the effectiveness of cancer fighting drugs.
You see, the aggressive behavior of some cancers are mainly due to high invasiveness and proliferation rate as well as high resistance to standard chemotherapy. Several chemotherapeutic agents like temozolomide (TMZ), carmustine (BCNU) or doxorubicin (DOXO) are employed for treatment of some cancers, but they often display limited efficacy.
However, activation of the transient receptor potential vanilloid type 2 (TRPV2) has been found to inhibit human Glioblastoma multiforme (GBM) cell proliferation and overcome BCNU resistance of GBM cells. Glioblastoma is the most aggressive cancer that begins within the brain.
In a 2013 study published in Carcinogenesis, researchers evaluated the involvement of CBD-induced TRPV2 activation, in the modulation of glioma cell chemosensitivity to TMZ, BCNU and DOXO. They found that CBD increased TRPV2 expression and activity which increased drug uptake and synergized with cytotoxic agents to induce apoptosis (programmed cell death) of glioma cells without affecting normal human astrocytes (brain cells responsible for transmitting electrical impulses). Overall, the researchers demonstrated that co-administration of cytotoxic agents together with CBD increases drug uptake and potentiates cytotoxic activity in human glioma cells.
In a study published in Molecular Cancer Therapeutics in 2010, researchers from the California Pacific Medical Center Research Institute in San Francisco found that in the glioblastoma cell lines, Δ9-THC and cannabidiol acted synergistically to inhibit cell proliferation and survival. However, the mechanisms of action were not observed with either compound individually – indicating that combination treatment was more effective in the treatment of glioblastoma in cancer patients. In another study published in Molecular Cancer Therapeutics in 2011, researchers in Madrid, Spain also evaluated the effectiveness of the chemotherapeutic agent TMZ when combined with cannabinoids. Although they tried different combinations of drugs, they found that treatment with TMZ and submaximal doses of THC and CBD produced a strong antitumoral action in both TMZ-sensitive and TMZ-resistant tumors.
The need for human clinical trials
For people living with cancer, medical cannabis is making a real difference. With its effects on nausea, vomiting, anxiety, appetite, pain, sleep, and inflammation, cannabinoids are already proving to be effective alternatives to traditional pharmaceuticals.
However, although medical cannabis is being studied for a wide variety of cancer-related symptoms and side effects, it is still not widely studied for its potential antitumor effects on humans. Even through there is significant preliminary research supporting the potential therapeutic value of cannabinoids like THC and CBD, and even though many preclinical trials call for more investigation, barriers to research have slowed further exploration to a crawl.
If we are serious about winning the war against cancer, an all-of-the-above strategy needs to be employed. That includes researching novel therapeutic approaches like medical cannabis. By removing barriers to research, we can finally pave the way for rigorous clinical trials to determine whether or not cannabis can cure cancer.
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