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Cannabis has been found to help cancer patients with the symptoms that usually accompany cancer such as pain, nausea, wasting, and loss of appetite. Notably, in a meta-analysis of 30 clinical studies on the therapeutic use of cannabis for chemotherapy-induced nausea and vomiting, Delta9-THC (dronabinol AKA marinol) proved superior to modern anti-emetics. Additionally, patients showed a clear preference for cannabinoids as anti-emetic medication over conventional drugs, when receiving chemotherapy.
Only one clinical trial has ever been published on the effects of Delta9-THC on cancer growth in humans. Doctors administered oral Delta 9-THC to nine patients who experienced tumor progression despite surgical therapy and radiation treatments. The major finding of the study was that Delta 9-THC was safe and did not cause any obvious psychoactive effects in a clinical setting. Furthermore, current research clearly indicates that cannabinoids can have tumor-reducing and anti-cancer properties.
Research on cannabis and chemotherapy
One of the most widely studied therapeutic applications for cannabis and the pharmaceutical drugs derived from cannabinoids is in the treatment of nausea and vomiting associated with cancer chemotherapy.. Numerous clinical studies have reported that the use of cannabis reduces pain, nausea, vomiting, and stimulates appetite, thereby reducing the severity of cachexia, or wasting syndrome, in patients receiving chemotherapy treatment.
The 1999 Institutes of Medicine report suggested: “In patients already experiencing severe nausea or vomiting, pills are generally ineffective, because of the difficulty in swallowing or keeping a pill down, and slow onset of the drug effect. Thus an inhalation (but, preferably not smoking) cannabinoid drug delivery system would be advantageous for treating chemotherapy-induced nausea.” For certain individuals unresponsive to conventional anti-emetic drugs, the use of smoked or vaporized cannabis can provide relief more effectively than oral THC (Marinol) which may be difficult to swallow or be vomited before taking effect. The IOM report concluded, “nausea, appetite loss, pain and anxiety … all can be mitigated by marijuana.”
A 1997 inquiry by the British Medical Association found cannabis more effective than Marinol, and a 1998 review by the House of Lords Science & Technology Select Committee concluded that “Cannabinoids are undoubtedly effective as anti-emetic agents in vomiting induced by anti-cancer drugs. Some users of both find cannabis itself more effective.”[17-18]
In 2009, a clinical trial involving 177 patients, with intractable cancer pain and experienced inadequate relief from opiates, showed remarkable reductions in pain scores from using a cannabis extract which contained THC and CBD. This THC:CBD extract was more effective than an extract containing only THC.
The effects of cannabis may also provide an improvement in mood. In addition to THC, other cannabinoids on the plant such as CBD, can inhibit the side effects of THC, as well provide relief from anxiety and depression. By contrast, several conventional medications commonly prescribed for cancer patients, e.g. phenothiazines such as haloperidol (known as “major tranquillizers”) may produce unwanted side effects such as excessive sedation, flattening of mood, and/or distressing physical “extrapyramidal” symptoms such as uncontrolled or compulsive movements.
Anti-cancer potential of cannabis and cannabinoids
Recent scientific advances in the study of cannabinoid receptors and endocannabinoids have produced exciting new leads in the search for anti-cancer treatments. Several-hundred research articles have been published on the effects of cannabinoids on cancer cells. We now know cannabinoids stop many kinds of cancers from growing and spreading, including brain, breast, leukemic, melanoma, phaeochromocytoma, liver and other kinds of cancer.[23-40] Cannabinoids have been repeatedly shown to promote apoptosis (programmed cell death of the tumor cells) and halt angiogenesis (blood vessel production to the tumor).[41-45]
The anti-cancer properties of cannabinoids are mediated through cannabinoid receptors. CB1 and CB2 cannabinoid receptors are abundantly expressed throughout the human body, making them an excellent target for disease treatment. Indeed, research on the complex interactions of endogenous cannabinoids and receptors is leading to greater scientific understanding of the basic mechanisms by which cancers develop. In multiple studies published between 2001 and 2003, cannabinoids inhibited tumor growth in laboratory animals.[47-50] In another study, injections of synthetic THC eradicated malignant brain tumors in one-third of treated rats, and prolonged life in another third by as much as six weeks.[51,52] And, research on pituitary cancers suggest that cannabinoids may be the key to regulating human pituitary hormone secretion.[53-56] A 2009 review of recent studies that have focused on the role of cannabinoids and cannabinoid receptors in the treatment of breast cancer notes that cannabinoids have been shown in laboratory models to be effective fighting many types of cancers.
Recent research published in 2009 has found that the non-psychoactive cannabinoid cannabidiol (CBD) inhibits the invasion of both human cervical cancer and human lung cancer cells. By manipulating cannabidiol’s up-regulation of a tissue inhibitor, researchers may have revealed the mechanism of CBD’s tumor-fighting effect. A further in vivo study demonstrated “a significant inhibition” of lung cancer metastasis in mice treated with CBD. The mechanism of the anti-cancer activity of CBD and othercannabinoids has also been repeatedly demonstrated with breast cancers.[59-63] Also in 2009, scientists reported on the anti-tumor effects of the cannabinoid THC on cholangiocarcinoma cells, an often-fatal type of cancer that attacks the liver’s bile ducts. They found that “THC inhibited cell proliferation, migration and invasion, and induced cell apoptosis.” At low levels, THC reduced the migration and invasion of cancer cells, while at high concentrations, THC triggered cell-death in tumors. In short, THC reduced the activity and number of cancer cells. This dose-dependent action of cannabinoids on tumors has also been demonstrated in animal studies.
Research on cannabinoids and gliomas, a type of aggressive brain cancer for which there is no cure, holds promise for future treatments. A study that examined both animal and human glioblastoma multiforme (GBM) tumors, the most common and aggressive form of brain cancer, describes how cannabinoids controlled glioma growth by regulating the blood vessels that supply the tumors. In another study, researchers demonstrated that the administration of the non-psychoactive cannabinoid cannabidiol (CBD) significantly inhibited the growth of subcutaneously implanted U87 human glioma cells in mice. The authors of the study noted that “… CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent. The targeted effects of cannabinoids on GBM were further demonstrated in 2005 by researchers who showed that the cannabinoid THC both selectively inhibited the proliferation of malignant cells and induced them to die off, while leaving healthy cells unaffected. While CBD and THC have each been demonstrated to have tumor-fighting properties, research published in 2010 shows that CBD enhances the inhibitory effects of THC on GBM cell proliferation and survival.
Similarly, researchers reported in 2010 that the way cannabinoid and cannabinoid-like receptors in brain cells “regulate these cells’ differentiation, functions and viability” suggests cannabinoids and other drugs that target cannabinoid receptors can “manage neuroinflammation and eradicate malignant astrocytomas,” a type of glial cancer. These recent studies confirm the findings of multiple studies that indicated the effectiveness of cannabinoids in fighting gliomas.[69-76]Indications of the remarkable potential of cannabinoids to fight cancer in humans have also been seen in three large-scale population studies done recently. The studies were designed to find correlations between smoking cannabis and cancers of the lung, throat, head and neck. Instead, the researchers discovered that the cancer rates of cannabis smokers were at worst no greater than those who smoked nothing at all or even better. One study found that 10-20 years of cannabis use significantly reduced the incidence of head, neck and throat cancers. Researchers suggest that cannabinoids may produce a prophylactic effect against cancer development, as seen in the anti-proliferation effect that has been demonstrated in vitro and in vivo.
While clinical research on using cannabis medicinally has been severely limited by federal restrictions, the accumulated data speaks strongly in favour of considering it as an option for most cancer patients, and many oncologists do. Survey data from a Harvard Medical School study in 1990, before any states had approved medical use, shows that 44% of oncologists had recommended cannabis to at least some of their patients, and more said they would do so if the laws were changed. According the American Cancer Society’s 2010 data, more than 1,529,000 Americans are diagnosed with cancer each year. At least 400,000 of them will undergo chemotherapy, meaning as many as 200,000 patients annually may have cannabis recommended to them to help fight the side effects of conventional treatments.
Authors of the Institute of Medicine report, Marijuana and Medicine: Assessing the Science Base, acknowledge that there are certain cancer patients for whom cannabis should be a valid medical option. A random-sample anonymous survey was conducted in the spring of 1990 measuring the attitudes and experiences of oncologists concerning the antiemetic use of cannabis in cancer chemotherapy patients. Of the respondents expressing an opinion, a majority (54%) thought cannabis should be available by prescription. Current research on cannabinoids has shown that activation of both cannabinoid receptors has a well known anti-proliferative effect on cancer cells and may also have anti-angiogenic, anti-adhesive, anti-invasive, and anti-metastatic properties. Since cannabinoids are generally well tolerated and patients do not develop toxic side effects of conventional treatments, more studies are warranted to develop a cannabis-based cancer treatment.
How cannabis compares to other medications
The American Cancer Society lists more than 300 medications currently prescribed to treat cancer and its symptoms, and to treat the side effects of other cancer drugs. Some drugs are prescribed for pain caused by cancer, and cancer patients report pain relief with cannabis therapy. Many chemotherapy agents cause severe nausea and more than a dozen drugs are currently prescribed to treat nausea, including Marinol, a synthetic form of delta-9-THC, one of the active ingredients in cannabis. The newer antiemetics, Anzamet, Kytril and Zofran, are serotonin antagonists, blocking the neurotransmitter that sends a vomiting signal to the brain. Rare side effects of these drugs include fever, fatigue, bone pain, muscle aches, constipation, loss of appetite, inflammation of the pancreas, changes in electrical activity of heart, vivid dreams, sleep problems, confusion, anxiety and facial swelling.
Reglan, a substituted benzamide, increases emptying of the stomach, thus decreasing the chance of developing nausea and vomiting due to food remaining in the stomach. When given at high doses, it blocks the messages to the part of the brain responsible for nausea and vomiting resulting from chemotherapy. Side effects include sleepiness, restlessness, diarrhea and dry mouth. Rarer side effects are rash, hives and decreased blood pressure
Haldol and Inapsine are tranquilizers that block messages to the part of the brain responsible for nausea and vomiting. Possible side effects include decreased breathing rate, increased heart rate, decrease in blood pressure when changing position and, rarely, change in electrical activity of the heart.
Compazine and Torecan are phenothiazines, the first major anti-nausea drugs. Both have tranquilizing effects. Common side effects include dry mouth and constipation. Less common effects are blurred vision, restlessness, involuntary muscle movements, tremors, increased appetite, weight gain, increased heart rate and changes in electrical activity of heart. Rare side effects include jaundice, rash, hives and increased sensitivity to sunlight.
Benadryl, an antihistamine, is given along with Reglan, Haldol, Inapsine, Compazine and Torecan to counter side effects of restlessness, tongue protrusion, and involuntary movements. Its side effects include sedation, drowsiness, dry mouth, dizziness, confusion, excitability and decreased blood pressure.
Decadron (dexamethasone), a corticosteroid, is given with other chemotherapy drugs as an adjunct medication. Common side effects include increased appetite, irritation of stomach, euphoria, difficulty sleeping, mood changes, flushing, increased blood sugar, decreased blood potassium level. Possible side effects upon discontinuing the drug include adrenal insufficiency, weakness, aches, fever, dizziness, lowering of blood pressure when changing position, difficulty breathing, and low blood sugar.
Benzodiazepine drugs Ativan and Xanax are also prescribed to combat the effects of chemotherapy. Ativan causes amnesia. Abruptly stopping the drug can cause anxiety, dizziness, nausea and vomiting, and tiredness. It can cause drowsiness, confusion, weakness, and headache when first starting the drug. Nausea, vomiting, dry mouth, changes in heart rate and blood pressure, and palpitations are possible side effects.
In addition, in April 2003 the FDA approved the drug Emend (aprepitant) to help control delayed-onset nausea. It is given along with two other anti-nausea drugs. A regimen of three pills costs $250. The most common side effects with Emend are fatigue, nausea, loss of appetite, constipation, diarrhea.
Cannabis: By comparison, the side effects associated with cannabis are typically mild and are classified as “low risk.” Euphoric mood changes are among the most frequent side effects. Cannabinoids can exacerbate schizophrenic psychosis in predisposed persons. Cannabinoids impede cognitive and psychomotor performance, resulting in temporary impairment. Chronic use can lead to the development of tolerance. Tachycardia and hypotension are frequently documented as adverse events in the cardiovascular system. A few cases of myocardial ischemia have been reported in young and previously healthy patients. Inhaling the smoke of cannabis cigarettes induces side effects on the respiratory system. Cannabinoids are contraindicated for patients with a history of cardiac ischemias. In summary, a low risk profile is evident from the literature available. Serious complications are very rare and are not usually reported during the use of cannabinoids for medical indications.
Is cannabis safe to recommend?
“The smoking of cannabis, even long term, is not harmful to health…” So began a 1995 editorial statement of Great Britain’s leading medical journal, The Lancet. The long history of human use of cannabis also attests to its safety – nearly 5,000 years of documented use without a single death. In the same year as the Lancet editorial, Dr. Lester Grinspoon, a professor emeritus at Harvard Medical School who has published many influential books and articles on medical use of cannabis, had this to say in an article in the Journal of the American Medical Association (1995):
One of marihuana’s greatest advantages as a medicine is its remarkable safety. It has little effect on major physiological functions. There is no known case of a lethal overdose; on the basis of animal models, the ratio of lethal to effective dose is estimated as 40,000 to 1. By comparison, the ratio is between 3 and 50 to 1 for secobarbital and between 4 and 10 to 1 for ethanol. Marihuana is also far less addictive and far less subject to abuse than many drugs now used as muscle relaxants, hypnotics, and analgesics. The chief legitimate concern is the effect of smoking on the lungs. Cannabis smoke carries even more tars and other particulate matter than tobacco smoke. But the amount smoked is much less, especially in medical use, and once marihuana is an openly recognized medicine, solutions may be found; ultimately a technology for the inhalation of cannabinoid vapors could be developed. The technology Dr. Grinspoon imagined in 1995 now exists in the form of “vaporizers,” (which are widely available through stores and by mail-order) and recent research attests to their efficacy and safety. Additionally, pharmaceutical companies have developed sublingual sprays and tablet forms of the drug. Patients and doctors have found other ways to avoid the potential problems associated with smoking, though long-term studies of even the heaviest users in Jamaica, Turkey and the U.S. have not found increased incidence of lung cancer, lung disease, or other respiratory problems.
As Dr. Grinspoon notes, “the greatest danger in medical use of marihuana is its illegality, which imposes much anxiety and expense on suffering people, forces them to bargain with illicit drug dealers, and exposes them to the threat of criminal prosecution.” This was the same conclusion reached by the House of Lords, which recommended rescheduling and decriminalization.
Cannabis or Marinol?
Those committed to the prohibition on cannabis frequently cite Marinol, a Schedule III drug, as the legal means to obtain the benefits of cannabis. However, Marinol, which is a synthetic form of THC, does not deliver the same therapeutic benefits as the natural herb, which contains at least another 100 cannabinoids in addition to THC. Recent research conducted by GW Pharmaceuticals in Great Britain has shown that Marinol is simply not as effective for pain management as the whole plant; a balance of cannabinoids, specifically CBC and CBD with THC, is what helps patients most. In fact, Marinol is not labeled for pain, only appetite stimulation and nausea control. But studies have found that many severely nauseated patients experience difficulty in getting and keeping a pill down, a problem avoided by use of inhaled cannabis.
Clinical research on Marinol vs. cannabis has been limited by federal restrictions, but a 2001 review of clinical trials conducted in the 70’s and 80’s reports that “…the inhalation of THC appears to be more effective than the oral route.” Additionally, patients frequently have difficulty getting the right dose with Marinol, while inhaled cannabis allows for easier titration and avoids the negative side effects many report with Marinol. As the House of Lords observed, “Some users of both find cannabis itself more effective.”
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Sean D. McAllister, PhD, Scientist at California Pacific Medical Center Research Institute, et al., stated the following in their Aug. 2011 study titled “Pathways Mediating the Effects of Cannabidiol on the Reduction of Breast Cancer Cell Proliferation, Invasion, and Metastasis,” published in Breast Cancer Research and Treatment journal: “There is a general consensus in the field of cancer research that targeting multiple pathways that control tumor progression is the best strategy for the eradication of aggressive cancers. Since CBD has a low toxicity, it would be an ideal candidate for use in combination treatments with additional drugs already used in the clinic. Importantly, CBD appears to be interacting through a cellular system that regulates the expression of key transcriptional factors (e.g., Id-1) that control breast cancer cell proliferation, migration, and invasion. The experiments described in this manuscript not only define the pathways that CBD is working through to control breast cancer cell aggressiveness, but also demonstrate the efficacy of CBD in pre-clinical models. A greater understanding of this system may lead to future therapies for breast cancer patients, including the additional refinement of CBD analog synthesis.”
Aug. 2011 – Sean D. McAllister, PhD
[Editor’s Note: The CBD was acquired from the National Institute of Health through the National Institute of Drug Abuse. CBD was extracted from marijuana plants grown at the University of Mississippi.]
Manuel Guzman, PhD, Professor of Biochemistry and Molecular Biology at Madrid Complutense University, stated the following in his Oct. 2003 article titled “Cannabinoids: Potential Anticancer Agents,” published in the journal Nature Reviews – Cancer:
“Cannabinoids — the active components of Cannabis sativa and their derivatives — exert palliative effects in cancer patients by preventing nausea, vomiting and pain and by stimulating appetite.
In addition, these compounds have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell-signaling pathways.
Cannabinoids are usually well tolerated, and do not produce the generalized toxic effects of conventional chemotherapies.”
Oct. 2003 – Manuel Guzman, PhD
Jeremy R. Johnson, MBChB, former Medical Director at the Shropshire and Mid Wales Severn Hospice, et. al, wrote the following in a Nov. 6 2009 article titled “Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain,” published on the Journal of Pain and Symptom Management website: “The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo…
Conclusion: This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.” Nov. 6, 2009 – Jeremy R. Johnson, MBChB