Cancer
Tuesday, July 1, 2008 at 11:48PM
Cancer is a broad term that refers to a wide range of cellular diseases typified by the abnormal development of a group of cells. Abnormal cells can eventually disable the host organ leading to severe health problems. Cancerous cells are continually created in the body, but natural regulatory defenses usually counteract the disorganized cellular development in its incipient stages. Some cancers are thought to be hereditary in origin, but specific irritants, called carcinogens, can antagonize the body's natural defenses, leading to the continued development of renegade cells. Unchecked, these outlaw cells frequently spread to surrounding tissue and may enter the lymphatic and circulatory systems, thereby spreading to other parts of the body. Removal of cancerous issue by surgery and destruction of cancerous tissue by powerful chemotherapy and radiation therapy are the most common medical treatments.
Radiation and chemotherapy often include violent, gut-wrenching nausea. Delta-9 THC is legally prescribed for counteracting the severe side effects of these cancer therapies, and is prescribed by doctors under its trade name, Marinol. Marinol pills, which are taken orally to control vomiting, were shown to be a superior anti-emetic (anti-nausea drug) in six out of seven well-controlled studies reported in the Journal of the American Medical Association as early as 1981.[1] In earlier scientific studies, Marinol was also proven superior to other anti-emetics.[2], [3] However, Marinol falls short of perfection because of its super high potency, which often leads to intoxication and sedation.[4], [5] Also, oral administration is the least preferable method in this circumstance.
The paradox of swallowing a pill to eliminate vomiting has been noted by many physicians and patients, as well as the American Medical Association.[6] Ralph Seeley, an attorney who petitioned the State of Washington for access to medical cannabis and later died of bone cancer, was quick to point out, “I don’t know how many times I’ve taken one of those $12 pills and had it come right back up.”[7] Marijuana is commonly smoked, which is a quicker and more effective method than oral administration. In the words of the National Cancer Institute, “Marijuana cigarettes have been used to treat chemotherapy-induced nausea and vomiting, and research has shown that THC is more quickly absorbed from marijuana smoke than from an oral preparation.”[8]
A careful study determining that marijuana is more effective than Marinol was published in 1988, [9] but only one other research group, the Tennessee Board of Pharmacy, has been bold enough to confirm those findings.[10] The National Institutes of Health is officially knowledgeable that smoked marijuana is more effective than Marinol tablets; panelists of the NIH Workshop on the Medical Utility of Marijuana in 1997 made very strong statements about marijuana’s safety and medical value.[11] However, the National Institute on Drug Abuse, sole source of federal cannabis for legal research, does not support scientific investigations that might lead to rescheduling marijuana as medicine. As Donald Abrams, the one researcher allowed to study smoked cannabis, has discovered, clinical trials on marijuana as medicine may be approved as tests for medical safety only, not as tests for medical effectiveness. [12]
Marinol, the anti-emetic “rescue drug,” is directed for prescription when other medications fail, but research indicates that delta-9 THC is not the only cannabis constituent worthy of medical administration to relieve vomiting. A report from the Brettler Center for Medical Research at Hebrew University in Jerusalem administered delta-8 THC, a non-psychoactive cannabinoid not found in the Marinol tablet,, to eight children receiving chemotherapy treatments. Reportedly, “Vomiting was completely prevented.” [13] It is clear that the Marinol pill does not contain the complete range of medicinal cannabinoids shown to be effective in treating severe nausea.
Many patients agree that Marinol is less effective than whole marijuana, and mane cancer specialists concur. In 1991, 44% of oncologists surveyed said they had already recommended cannabis to their patients, and 56% said that marijuana should be legally prescribable.[14] As early as 1975 the New England Journal of Medicine had reported that “THC is an effective anti-emetic for patients receiving cancer chemotherapy.” [15] Since then, dozens of scientific studies recognized by the US Food and Drug Administration and the National Cancer Institute have shown that the use of natural cannabis is a preferable remedy for adverse effects of the cancer-killing poisons employed in oncology. [16] Relief from the side effects of cancer chemotherapy is a widely accepted medical use of marijuana in the United States. The American Cancer Society is one of dozens of national and international health organizations that have voiced support for further research on the medical use of cannabis in cancer chemotherapy treatments. [17]
In addition to its well known anti-nausea effects, marijuana often relieves physical pain associated with cancer,[18] a finding that is supported by published research studies, [19] the testimony of physicians,[20] and the reports of the Institute of Medicine. [21] Some cancer survivors even claim that continued use of cannabis helps keep their disease in remission— a possibility that cannot be discounted in light of research by the National Toxicology Program.
Independent studies in the mid-1970s suggested that cannabinoids inhibited tumor growth in lab mice. [22] In 1979, a study commissioned by the Australian government concluded that cannabis is effective in the treatment of glaucoma, and “of potentially greater significance is the recent finding that THC inhibits the growth of some types of cancer in tissue culture.” [23] Intriguing as they may be, those citations pale in light of investigations by the US government. Ironically, pursuing common prohibitionist rhetoric proved quite perplexing upon analyzing the carcinogenic properties of THC. In the mid-1990s, the US federal government funded a two-year and two-million-dollar study by the National Toxicology Program under the review of the Federal Drug Administration, the National Cancer Institute, and other federal agencies. The study was designed to determine the cancer rate induced by injecting high does of THC in the bodies of mice, then injecting them with cancerous cells. Ironically, the study found that the mice injected with THC had a far lower incidence of cancer than did the control group. Assessing the unpublished draft version, cannabis researcher Donald Abrams summarized, “THC caused fewer tumors and prolonged survival in these laboratory animals.” [24] The deputy director of the National Toxicology Program study concurred, “We found absolutely no evidence of cancer.” The profound implication that cannabis use might actually help prevent cancer has not been officially released to the American public, purportedly because of a lack of personnel.[25], [26] The executive secretary of the Toxicology Program has remarked, “I think it’s terrible the way the government is handling this marijuana issue. There’s no reason this shouldn’t have been published.” [27]
Even without the Toxicology Program study, some leading scientists were already aware of this remarkable potential. Marijuana researcher Leo Hollister has noted the apparent dichotomy of investigations on cannabis and cancer:
The clinical implication of some of these findings is obscure. On the one hand, exposure to smoke from cannabis may be carcinogenic. On the other, the changes in nucleic acid synthesis, were they to be specific for rapidly dividing cells, such as those of malignancies, might be useful therapeutically in their treatment. [28]
The Institute of Medicine report of 1999 failed to address this intriguing potential of cannabinoid medicines in the prevention and treatment of cancer because the National Toxicology Program study had not been officially published. Instead, the popular subject of respiratory cancer figured heavily in the million-dollar report commissioned by the White House Office of National Drug Control Policy. However, the IOM Executive Summary cautiously avoided drawing negative conclusions from the available data:
Although cellular, genetic, and human studies all suggest that marijuana smoke is an important risk factor for the development of respiratory cancer, proof that habitual marijuana smoking does or does not cause cancer awaits the results of well-designed studies. [29]
For generations, prohibitionists have argues that smoking cannabis causes cancer, yet the government’s own National Toxicology Program study indicated that cannabis might actually help prevent cancer. After reviewing sixteen years of government studies on cannabis and respiratory cancer, the IOM report cites a lack of proof and calls for even more research. In the words of Stanford researcher Leo Hollister, “If field studies fail to provide evidence of harm from prolonged use of cannabis, it is unlikely that experimental studies will do better, and such has been the case.” [30]
Further studies continue to confirm the profound revelation that cannabis compounds actually reduce tumor development. In contrast to the extensive research that has been conducted twith the intention of blaming cannabis for cancerous development, cannabis is actually shown to help cure cancer. As one researcher has written:
Cannabinoids, the active components of Cannabis sativa Linnaeus (marijuana) and their derivatives have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects and tumor regression.[31]
Another researcher offers a similar finding:
Furthermore, compounds found in cannabis have been shown to kill numerous cancer types including: lung cancer, breast and prostate, leukemia and lymphoma, glioma, skin cancer, and pheochromocytoma.[32]
In September 2008 a review of data from 0ver 64,000 subjects indicated that marijuana smokers actually have a lower risk of cancer than tobacco smokers.
The authors analyzed existing evidence on the carcinogenicity of marijuana smoke. Although it has long been hypothesized that marijuana smoke might cause cancer because it contains tars with known carcinogenic properties, like tobacco smoke, the authors note that epidemiological studies have so far failed to show a convincing causal relation between marijuana and smoking-related cancers.
While the authors noted there is some evidence to suggest that the cannabinoids in marijuana may actually suppress cancer, they concluded that more studies are needed to settle the question one way or another. In the meantime, says Dr. Sidney, the conclusions of his original study stand: "marijuana use and cancer were not associated" ("Marijuana use and cancer incidence (California, United States)," Cancer Causes and Control, Vol. 8, 1997).
--Special thanks to Paul Armentano, Policy Director of NORML, www.NORML.org
Related sections: AIDS, Anorexia, Analgesia, Marinol, Respiratory Disease. Smoking Hazards
[1] Poster, Penta, Bruno, and Macdonald, “Delta-9-tetrahydrocannabinol in clinical oncology, “ Journal of the American Medical Association, Vol. 245, No. 20, pp. 2047-2051, May 22, 1988
[2] Orr, Mckernan, and Bloome, “Anti-emetic effect of tetrahydrocannabinol compared with placebo and prochlorperazine in chemotherapy-associated nausea and emisis.” Archive of Internal Medicine, Vol. 140, No. 11, pp. 1431-1433, November 1980
[3] Williams, Boulton, de Pemberton, and Whitehouse, “Antiemetics for patients treated with antitumor chemotherapy.” Cancer Clinical Trials, Vol. 3, No. 4, pp. 363-367, 1980
[4] Ekert, Waters, Jurk, Mobilia, and Loughnan, “Amelioration of cancer chemotherapy-induced nausea and vomiting by Delta-9-tetrahydrocannabinol.” Medical Journal of Australia, Vol. 2, No. 12, pp. 657-659, December 15, 1979
[5] Williams, Boulton, de Pemberton, and Whitehouse, op. cit.
[6] “American Medical Association House of Delegates Report.” December 9, 1997
[7] Seeley, Town Meeting. KOMO TV 4 in Seattle, March 9, 1997
[8] National Cancer Institute, Marijuana Use in Supportive Care for Cancer Patients. Cancer Information Service, September 1997, Source: http://www.cancernet.nci/
[9] Vinciguerra, Moore, and Brennen, “Inhalation of marijuana as an anti-emetic for chemotherapy.” New York State Journal of Medicine, Vol. 88, pp. 525-527, 1988
[10] NORML News. February 13, 1998, http:/www.norml.org/
[11] “NIH panelists agree: Marijuana is safe and effective medicine.” MPP News, Marijuana Policy Project. August 4, 1997, http://www.mpp.org/
[12] Abrams, Lindesmith Center Lecture, San Francisco, May 17, 1999
[13] Abramamov, Abrahamov, and Mechoulam, “An efficient new cannabinoid antiemetic in pediatric oncology.” The Brettler Center for Medical Research, Hebrew University, Jerusalem, 1995
[14] Doblin and Kleiman, “Marijuana as antiemetic medicine: A survey of oncologists experiences and attitudes.” Journal of Clinical Oncology, Vol. 9, pp. 1314-1319, 1991
[15] Sallen, Zinberg, and Frei, :Antiemetic effects of Delta-9 THC in patients receiving cancer chemotherapy.” New England Journal of Medicine, Vol. 296, No. 16, 1975
[16] Gieringer, “Review of Human Studies on Medical Use of Marijuana.” 1994, CANORML, http://www.norml.org/canorml/
[17] Letter from American Cancer Society to CA Senator Vasconcellos, July 25, 1997
[18] Conversations with Ralph Seeley and others, 1997-1998
[19] Noyes, Brunk, Baram, and Canter, “Analgesic effect of delta-9 tetrahydrocannabinol.” Journal of Clinical Pharmacology, Vol. 2, No. 3, pp. 139-143, February 15, 1975
[20] Statement of Dr. Richard Cohen, Consulting Medical Oncologist, California Pacific Medical Center, San Francisco. Source: Californians for Medical Rights
[21] Institute of Medicine, Marijuana and Medicine: Assessing the Science Base. Washington DC: National Academy Press, 1999
[22] Grinspoon and Bakalar, Medical Uses of Illicit Drugs, 1997
[23] Bertrand, Affidavit before Ontario Court (Canada) in the case of Christopher Clay, Source: http://www.hempnation.com/challenge/bertrand.html/
[24] Abrams, op. cit.
[25] James, “Medical marijuana: Unpublished federal study found THC treated rats lived longer, had fewer cancers.” AIDS Treatment News, January 17, 1997
[26] Knox, “Study may undercut marijuana opponents: Report says THC did not cause cancer.” Boston Globe, January 30, 1997
[ [27] Abrams, op. cit.
[28] Hollister, “Health Aspects of Marijuana.” Pharmacological Review, Vol. 38, No. 1, 1986
[29] Institute of Medicine, op. cit.
[30] Hollister, op. cit.
[31] Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer, Sami Sarfaraz, Farrukh Afaq, Vaqar M. Adhami and Hasan Mukhtar, Department of Dermatology, University of Wisconsin, Madison, Wisconsin
[32] “ Cannabis and tobacco smoke are not equally carcinogenic”, Robert Melamede, Harm Reduction Journal, 18 Oct., 2005 (see Abstract and Studies section of this website)
Cancer Links
http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional
http://watch.montanapbs.org/video/1825223761
CannabisMedicalDictionary.com
Laboratory/Animal/Preclinical Studies
Antitumor Effects
Appetite Stimulation
Analgesia
Cannabinoids are a group of 21-carbon–containing terpenophenolic compounds produced uniquely byCannabis sativa and Cannabis indica species.[1,2] These plant-derived compounds may be referred to as phytocannabinoids. Although delta-9-tetrahydrocannabinol (THC) is the primary psychoactive ingredient, other known compounds with biologic activity are cannabinol, cannabidiol (CBD), cannabichromene, cannabigerol, tetrahydrocannabivarin, and delta-8-THC. CBD, in particular, is thought to have significant analgesic and anti-inflammatory activity without the psychoactive effect (high) of delta-9-THC.
One study in mice and rats suggested that cannabinoids may have a protective effect against the development of certain types of tumors.[3] During this 2-year study, groups of mice and rats were given various doses of THC by gavage. A dose-related decrease in the incidence of hepatic adenoma tumors and hepatocellular carcinoma was observed in the mice. Decreased incidences of benign tumors(polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo .[4] In addition, other tumors have been shown to be sensitive to cannabinoid-induced growth inhibition.[5-8]
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.[9-12] One review summarizes the molecular mechanisms of action of cannabinoids as antitumor agents.[13] Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death. These compounds have been shown to induce apoptosis in gliomacells in culture and induce regression of glioma tumors in mice and rats. Cannabinoids protect normal glial cells of astroglial and oligodendroglial lineages from apoptosis mediated by the CB1 receptor.[14]
The effects of delta-9-THC and a synthetic agonist of the CB2 receptor were investigated in hepatocellular carcinoma (HCC).[15] Both agents reduced the viability of hepatocellular carcinoma cellsin vitro and demonstrated antitumor effects in hepatocellular carcinoma subcutaneous xenografts in nude mice. The investigations documented that the anti-HCC effects are mediated by way of the CB2 receptor. Similar to findings in glioma cells, the cannabinoids were shown to trigger cell death through stimulation of an endoplasmic reticulum stress pathway that activates autophagy and promotes apoptosis. Other investigations have confirmed that CB1 and CB2 receptors may be potential targets innon-small cell lung carcinoma [16] and breast cancer.[17]
An in vitro study of the effect of CBD on programmed cell death in breast cancer cell lines found that CBD induced programmed cell death, independent of the CB1, CB2, or vanilloid receptors. CBD inhibited the survival of both estrogen receptor–positive and estrogen receptor–negative breast cancercell lines, inducing apoptosis in a concentration-dependent manner while having little effect on nontumorigenic, mammary cells.[18]
CBD has also been demonstrated to exert a chemopreventive effect in a mouse model of colon cancer.[19] In the experimental system, azoxymethane increased premalignant and malignant lesions in the mouse colon. Animals treated with azoxymethane and CBD concurrently were protected from developing premalignant and malignant lesions. In in vitro experiments involving colorectal cancer cell lines, the investigators found that CBD protected DNA from oxidative damage, increased endocannabinoid levels, and reduced cell proliferation.
Another investigation into the antitumor effects of CBD examined the role of intercellular adhesion molecule-1 (ICAM-1).[12] ICAM-1 expression has been reported to be negatively correlated with cancermetastasis. In lung cancer cell lines, CBD upregulated ICAM-1, leading to decreased cancer cell invasiveness.
In an in vivo model using severe combined immunodeficient mice, subcutaneous tumors were generated by inoculating the animals with cells from human non-small cell lung carcinoma cell lines.[20] Tumor growth was inhibited by 60% in THC-treated mice compared with vehicle-treated control mice. Tumor specimens revealed that THC had antiangiogenic and antiproliferative effects. However, research with immunocompetent murine tumor models has demonstrated immunosuppression and enhanced tumor growth in mice treated with THC.[21,22]
In addition, both plant-derived and endogenous cannabinoids have been studied for anti-inflammatoryeffects. A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation.[23] As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.[24-27]
Many animal studies have previously demonstrated that delta-9-THC and other cannabinoids have a stimulatory effect on appetite and increase food intake. It is believed that the endogenous cannabinoid system may serve as a regulator of feeding behavior. The endogenous cannabinoid anandamide potently enhances appetite in mice.[28] Moreover, CB1 receptors in the hypothalamus may be involved in the motivational or reward aspects of eating.[29]
Understanding the mechanism of cannabinoid-induced analgesia has been increased through the study of cannabinoid receptors, endocannabinoids, and synthetic agonists and antagonists. The CB1 receptor is found in both the central nervous system (CNS) and in peripheral nerve terminals. Similar toopioid receptors, increased levels of the CB1 receptor are found in regions of the brain that regulate nociceptive processing.[30] CB2 receptors, located predominantly in peripheral tissue, exist at very low levels in the CNS. With the development of receptor-specific antagonists, additional information about the roles of the receptors and endogenous cannabinoids in the modulation of pain has been obtained.[31,32]
Cannabinoids may also contribute to pain modulation through an anti-inflammatory mechanism; a CB2 effect with cannabinoids acting on mast cell receptors to attenuate the release of inflammatory agents, such as histamine and serotonin, and on keratinocytes to enhance the release of analgesic opioids has been described.[33-35] One study reported that the efficacy of synthetic CB1- and CB2-receptor agonists were comparable with the efficacy of morphine in a murine model of tumor pain.[36]
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- Nasser MW, Qamri Z, Deol YS, et al.: Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion. PLoS One 6 (9): e23901, 2011. [PUBMED Abstract]
- Shrivastava A, Kuzontkoski PM, Groopman JE, et al.: Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol Cancer Ther 10 (7): 1161-72, 2011. [PUBMED Abstract]
- Aviello G, Romano B, Borrelli F, et al.: Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer. J Mol Med (Berl) 90 (8): 925-34, 2012. [PUBMED Abstract]
- Preet A, Ganju RK, Groopman JE: Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene 27 (3): 339-46, 2008. [PUBMED Abstract]
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