Cannabis has been used for several millennia medicinally, recreationally, and to manufacture paper, clothing and rope.
The cannabis plant has three species: Cannabis sativa, Cannabis indica, and Cannabis ruderalis, all with slightly different chemical properties. These plants contain 3 major classes of bioactive molecules: flavonoids, terpenoids, and more than 60 types of cannabinoids. Cannabinoids are a group of 21-carbon–containing terpenophenolic compounds produced uniquely by the cannabis species. These plant-derived compounds may be referred to as phytocannabinoids. The main active antitumor cannabinoid in cannabis is delta-9-THC. Another important active anti-tumor cannabinoid is cannabidiol (CBD), which also relieves pain, reduces inflammation, treats seizures, and decreases anxiety without causing the "high" of delta-9-THC.1,2,3 These cannabinoids selectively target cancer cells for programmed cell death, while sparing normal cells, which are left unaffected. Cannabis Cancer Research
To date, more than 15,000 modern peer-reviewed scientific articles on the chemistry and pharmacology of cannabis and cannabinoids have been published, as well as more than 2,000 articles on the body's natural endocannabinoids. The basic science of cannabis cancer research involves studying cancer cells in cultures by treating them with mainly THC and CBD and other agents, after which the cancer cells are studied to determine the effect. A second method is the in-vivo animal study usually done with mice injected with cancer cells (called a xenograft), and then treated with cannabis agents. The mice are observed, later sacrificed, and their organs studied to determine effect. Cannabinoids show potential as therapeutic agents across a wide range of cancers, both in vitro and in vivo. Numerous studies showing positive anticancer effects have now been conducted in several cell lines, including breast4, 5, 6, 7, 8, 9, glioma10, 11, 12, 13, prostate14, 15, 16, 17, pancreas18, melanoma19, liver20, and lung21. In general, cannabinoids exert anti-proliferative, pro-apoptotic, anti-migratory, and anti-invasive actions in a wide spectrum of cancer cells in culture. Additionally, there is substantial evidence suggesting that cannabinoids inhibit cancer growth in animal models.22, 23, 24, 25, 26, 27 Researchers in Italy studied breast cancer in a xenograft animal model. They used subcutaneous injection of human breast cancer cells into mice. Their 2006 paper showed cannabidiol to be the most potent inhibitor of cancer cell growth, with cancer cells undergoing apoptosis.28 Research strongly suggests that cannabinoid-based medicines may be useful for the treatment of most breast tumor subtypes.29, 30, 31, 32 Cases of cancer patients going into remission continue to be reported in the media, but still human studies involving cannabis and cancer have been limited by governmental restrictions. Consequently, cannabinoids still are not yet approved for the treatment of tumor progression, although their antitumor effects have been known for over 30 years.33 Scientists at California Pacific Medical Center have established that cannabidiol, or CBD, can switch off the DNA that cause many types of cancer. CBD is the second-most abundant cannabinoid in medical cannabis (in most strains) - and does not cause the psychotropic (high) of its cousin molecule, THC. “We started by researching breast cancer, but now we've found that cannabidiol (CBD) works with many kinds of aggressive cancers - brain, prostate - any kind in which these high levels of ID-1 are present." - Dr. Pierre Despre Cannabinoids inhibit tumor growth by causing cell death, slowing cell growth, and suffocating the blood vessels that feed tumors, while protecting normal cells. Cannabinoids reduce inflammation of the colon and other body tissues which reduces the risk of acquiring colon and other cancers. Cannabinoids can also play an important role in the treatment of pain, nausea, vomiting, and appetite for cancer patients.34, 35 Years before any state had authorized the medical use of cannabis, a 1991 Harvard Medical School study revealed that nearly half (44%) of U.S. oncologists were recommending cannabis to their patients as a way of mitigating the side effects of cytotoxic chemotherapy and radiation cancer treatments.36 Medical Cannabis Legalities
The political interference with cannabis research and its use as a medicine in the U.S. originated with the Marihuana Tax Act of 1937. This Tax Act imposed a levy of one dollar per ounce for medical use of cannabis and 100 dollars per ounce for recreational use. The AMA believed that evidence of cannabis’ harmful effects was limited and the Act would prevent further research into its medicinal worth. Many industries that competed with hemp, however, wanted cannabis, particularly hemp, eliminated from the marketplace. The Act greatly restricted access to cannabis, even for medical and research purposes. In that same year, Du Pont filed its patent on Nylon, a synthetic fiber that took over many of the textile markets that would have gone to hemp. At that time, more than half of American cars were built by GM, which guaranteed Du Pont a captive market for paints, varnishes, plastics, and rubber, all of which could have been made, in part, from hemp. With the Marijuana Tax Law all competition from hemp had been outlawed. Du Pont and the timber companies that made paper, the alcohol and tobacco industries, the pharmaceutical drug companies, and today, the urine testing, property seizure, police and prison industries, have all benefited from the illegality of cannabis. In 1942, cannabis was removed from the U.S. Pharmacopeia because of perceived harm. In 1951, Congress passed the Boggs Act, which included cannabis with narcotic drugs for the first time. In 1970, Congress passed the Controlled Substances Act (CSA), which created a federal law classifying all drugs. The law organized drugs into schedules based on their potential for abuse, status in international treaties, and medical benefits. Cannabis was temporarily designated as Schedule 1, but President Richard Nixon created a commission to do a review of the drug to determine if it should keep the most restrictive scheduling. Nixon appointed Pennsylvania Governor Raymond Shafer to chair the National Commission on Marihuana and Drug Abuse. In 1972, the commission presented its report to Congress, “Marihuana: A Signal of Misunderstanding.” The Shafer report concluded that, "Neither the marihuana user nor the drug itself can be said to constitute a danger to public safety. Therefore, the Commission recommends the possession of marijuana for personal use no longer be an offense, [and that the] casual distribution of small amounts of marihuana for no remuneration, or insignificant remuneration no longer be an offense." It recommended the decriminalization of cannabis for personal use. President Nixon rejected the Shafer report and instead of accepting the findings of the Commission, scientists and doctors, Nixon declared a “War on Drugs.” and left cannabis as a Schedule 1 drug. The CSA defines Schedule 1 controlled substances, which also include heroin and lysergic acid diethylamide (LSD), as “those that have a potential for abuse, no current accepted medical use in treatment in the U.S., and lack of accepted safety for use under medical supervision.” Between 1972 and 2000, police arrested over 13 million Americans for marijuana offenses. According to statistics compiled by the FBI, most of those arrests were for simple possession. This Schedule 1 classification means that physicians cannot legally prescribe or administer any preparations of cannabis. In states that have legislated the authorization of cannabis for medical purposes, physicians can only “certify” or “recommend” that a patient has a qualifying medical condition and may use cannabis for that purpose. In 1996, California became the first state to legalize medical cannabis. Since then, numerous reviews by local, federal and international commissions have confirmed the relative safety and efficacy of cannabis as a medicine. Current research has further shown cannabis to have the potential to treat a variety of debilitating conditions for which conventional treatments are lacking. Yet, the use of cannabis remains completely prohibited by federal law, even for medical purposes. In spite of the obvious rule that natural substances cannot be patented, the U.S. government has a patent on medicinal use of “Cannabinoids as antioxidants and neuroprotectants” (US 6630507 B1). It would appear paradoxical that a U.S. government agency, the Dept. of Health and Human Services, would hold such a patent, and at the same time another U.S. government agency, the Drug Enforcement Administration (DEA), declares a ruling that Cannabis “has no accepted medical use.” The DEA still classifies cannabis as a dangerous drug with no medical value. That classification contradicts research showing cannabis to be both a safe and effective medicine. In 2014, the House of Representatives passed a bill prohibiting the DEA from using funds to arrest medical cannabis patients in states with medical cannabis laws. Twenty-nine states and Washington, DC, have authorized the medical use of cannabis. The FDA has not approved cannabis as a treatment for cancer, seizure disorders, or any other medical condition, but research shows that it is highly effective for numerous medical conditions and exhibits anticancer properties. Cannabis is often more effective, less expensive, and much safer than many drugs currently used in its place. If cannabis were to be reclassified as a Schedule 2 drug, which would mean it has a federally accepted medical use, researchers would no longer need clearance from the DEA to work with it. Congress could play a major role in speeding up the cannabis research process. Legislators have already written bills that would recategorize marijuana to Schedule 2, which would ease some steps of the research approval process. Cannabis Dosage in Cancer Treatment
There is a significant lack of information on cannabis dosage requirements to treat cancer. As with most treatments, dosage should be individualized, and monitored by a physician or experienced health care practitioner. Cancer patients are sometimes introduced to cannabis to reduce the side effects of chemotherapy and radiation, as it has been shown to reduce nausea, pain and aid sleep. However, cannabis as a cancer treatment is non-existent in conventional oncology, hence, standard dosages have not been established. Gathering information from patients who have had success in treating their cancer, this is what I have found. Generally, it is the cannabis oil that is consumed in the treatment of cancer. Which brings us to the question of what is the preferred type of cannabis oil, CBD or oil that contains THC. The preference usually is CBD for those who wish to avoid the “high” and THC oil for most everyone else. It is still undetermined which type of oil is more effective, as both have shown anticancer properties. Many physicians have discovered that for most people, it takes about 60 grams (or about 60 ml) of cannabis oil to be effective as an anticancer treatment. 1 gram of oil weighed out will be about the same as 1 ml of oil in an oral syringe. For the average person, it usually takes about 90 days to consume the full 60-gram treatment of cannabis oil. It is important to remember that the 60 gram/ml 90-day treatment protocol is just a recommendation and starting point. It may take some people a longer time to finish their treatment. Cancer patients who have used this protocol usually begin by orally ingesting three divided doses of cannabis oil per day. Generally, one half gram is divided into three doses for the first week and then the dose is doubled every four days until 1 gram or 1ml per day is ingested. Most people get to the point where they can ingest 1 gram per day in about 30-35 days. Once ingesting one gram of oil per day is achieved, dosage should continue at that rate until tests show that the cancer is resolved. However, some people report that they increased their daily doses to 2 grams or more. Most people use an oral syringe to fill empty pill capsules with oil. This allows for the dosing of the cannabis oil to be very consistent and precise. Oral syringes also make it very easy to store cannabis oil discreetly. Dosing the oil slowly over the first 30 days allows the body to build up a tolerance to it slowly. For people using THC oil who experience a "high" side effect or extreme tiredness during the day, the dosage may be reduced during the day hours and slightly increase before bed. This strategy may be promoting quality sleep, while building up a tolerance during sleep. At the end of their treatment, most people continue taking the oil, but at a much-reduced rate. About 1 to 2 grams a month is a good maintenance dose. That approximates to just a drop or two at night before bedtime. Cannabis oil (CBD or oil with THC) is an excellent addition to a cancer treatment regime, but unfortunately, many people who decide to start cannabis oil treatment have had their immunity and organs damaged by cytotoxic chemotherapy and radiation. These patients usually need to extend the time and increased amounts of cannabis oil to treat the cancer. Depending on the damage done and the stage of cancer, it could take as much as 180 grams of cannabis oil over a 6-month period to be effective. Cannabis and cannabinoids offer potential applications as an antitumor substance, based on their ability to limit inflammation, cell proliferation, metastasis, angiogenesis, and cancer cell survival. Cannabis compounds have shown success in some cancers more than others. Bear in mind, the application of cannabis as treatment in cancer is still in its infancy. Though there is extensive evidence that cannabis can alleviate nausea, anxiety, seizure disorders, glaucoma, diabetes, and is helpful in pain management, less research exists on its treatment of various cancers. However, numerous antidotal success reports accumulate daily.
Lastly, it is said that laughter is the best medicine. Cannabis is famous for its mood-boosting, euphoric, and relaxing characteristics. Though subjective, many find these properties to be beneficial for maintaining mental health when dealing with a serious disease.
This article is designed to highlight the existing research findings of cannabis treatment in cancer. As with any cancer treatment, it is important to work together with an experienced physician or oncologist to design an individualized, personalized treatment program. 420Evaluations Online is a legal online site for finding a medical doctor experienced in cannabis treatment. Notes ______________________ 1. Bridgeman MB, Abazia DT. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017 Mar; 42(3):180-188. 2. Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol.Handb Exp Pharmacol. 2005; (168):657-90. 3. Pertwee RG. Pharmacological actions of cannabinoids. Handb Exp Pharmacol. 2005; (168):1-51 4. De Petrocellis L, Melck D, Palmisano A, et al. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc Natl Acad Sci U S A. 1998;95(14):8375–8380. 5. Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S, De Petrocellis L, Laezza C, Portella G, Bifulco M, Di Marzo V. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther. 2006 Sep;318(3):1375-87. Epub 2006 May 25. 6. Shrivastava A, Kuzontkoski PM, Groopman JE, Prasad A. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol Cancer Ther. 2011;10(7):1161–1172. 7. Sarnataro D, Pisanti S, Santoro A, et al. The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits human breast cancer cell proliferation through a lipid raft-mediated mechanism. Mol Pharmacol. 2006;70(4):1298–1306. 8. McAllister SD, Christian RT, Horowitz MP, Garcia A, Desprez PY. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Mol Cancer Ther. 2007;6(11):2921–2927.; McAllister SD, Murase R, Christian RT, Lau D, Zielinski AJ, Allison J, Almanza C, Pakdel A, Lee J, Limbad C, Liu Y, Debs RJ, Moore DH, Desprez PY. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res Treat. 2011 Aug;129(1):37-47. 9. Qamri Z, Preet A, Nasser MW, et al. Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol Cancer Ther. 2009;8(11):3117–3129. 10. Sánchez C, de Ceballos ML, Gomez del Pulgar T, et al. Inhibition of glioma growth in vivo by selective activation of the CB2 cannabinoid receptor. Cancer Res. 2001;61(15):5784–5789. 11. Jacobsson SOP, Rongård E, Stridh M, Tiger G, Fowler CJ. Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability. Biochem Pharmacol. 2000;60(12):1807–1813. 12. McAllister S, Chan C, Taft R, et al. Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. J Neurooncol. 2005;74(1):31–40. 13. Massi P, Vaccani A, Ceruti S, Colombo A, Abbracchio MP, Parolaro D. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. J Pharmacol Exp Ther. 2004;308(3):838–845. 14. Sarfaraz S, Afaq F, Adhami VM, Mukhtar H. Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res. 2005;65(5):1635–1641. 15. Mimeault M, Pommery N, Wattez N, Bailly C, Hénichart JP. Antiproliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: implication of epidermal growth factor receptor downregulation and ceramide production. Prostate. 2003;56(1):1–12. 16. Sánchez MG, Ruiz-Llorente L, Sánchez AM, Díaz-Laviada I. Activation of phosphoinositide 3-kinase/PKB pathway by CB1 and CB2 cannabinoid receptors expressed in prostate PC-3 cells. Involvement in Raf- 1 stimulation and NGF induction. Cell Signal. 2003;15(9):851–859 17. Nithipatikom K, Isbell MA, Endsley MP, Woodliff JE, Campbell WB. Anti-proliferative effect of a putative endocannabinoid, 2-arachidonylglyceryl ether in prostate carcinoma cells. Prostaglandins Other Lipid Mediat. 2011;94(1–2):34–43. 18. Carracedo A, Gironella M, Lorente M, et al. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Res. 2006;66(13):6748–6755. 19. Blázquez C, Carracedo A, Barrado L, et al. Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB J. 2006;20(14):2633–2635. 20. Xu X, Liu Y, Huang S, et al. Overexpression of cannabinoid receptors CB1 and CB2 correlates with improved prognosis of patients with hepatocellular carcinoma. Cancer Genet Cytogenet. 2006;171(1):31–38. 21. Friedman MA. In vivo effects of cannabinoids on macromolecular biosynthesis in Lewis lung carcinomas.Cancer Biochem Biophys. 1977; 2(2):51-4. 22. Alexander A, Smith PF, Rosengren RJ. Cannabinoids in the treatment of cancer. Cancer Lett. 2009;285(1):6–12. 23. Pisanti S, Malfitano AM, Grimaldi C, et al. Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Best Pract Res Clin Endocrinol Metab. 2009;23(1):117–131. 24. Sarfaraz S, Adhami VM, Syed DN, Afaq F, Mukhtar H. Cannabinoids for cancer treatment: progress and promise. Cancer Res. 2008;68(2):339–342. 25. Caffarel MM, Andradas C, Pérez-Gómez E, Guzmán M, Sánchez C. Cannabinoids: a new hope for breast cancer therapy? Cancer Treat Rev. 2012;38(7):911–918. 26. Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA. Antineoplastic activity of cannabinoids. J Natl Cancer Inst. 1975 Sep; 55(3):597-602. 27. Carchman RA, Harris LS, Munson AE. The inhibition of DNA synthesis by cannabinoids. Cancer Res. 1976 Jan; 36(1):95-100. 28. Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S, De Petrocellis L, Laezza C, Portella G, Bifulco M, Di Marzo V. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther. 2006 Sep;318(3):1375-87. Epub 2006 May 25. 29. De Petrocellis L, Melck D, Palmisano A, Bisogno T, Laezza C, Bifulco M, Di Marzo V. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc Natl Acad Sci U S A. 1998;95(14):8375–8380. 30. von Bueren AO, Schlumpf M, Lichtensteiger W. Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells. Anticancer Res. 2008;28(1A):85–89. 31. Laezza C, Pisanti S, Crescenzi E, Bifulco M. Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells. FEBS Lett. 2006;580(26):6076–6082. 32. Caffarel MM, Moreno-Bueno G, Cerutti C, Palacios J, Guzman M, Mechta-Grigoriou F, Sanchez C. JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008;27(37):5033–5044. 33. Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA. Antineoplastic activity of cannabinoids. J Natl Cancer Inst. 1975; 55(3):597–602. 34. Guzmán M. Cannabinoids: potential anticancer agents. Nat Rev Cancer. 2003;3(10):745–755. 35. Todaro B. Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting. J Natl Comp Canc Netw. 2012;10(4):487–492. 36. Doblin R. Marijuana as Antiemetic Medicine: A Survey of Oncologists' Experiences and Attitudes. AK. Journal of Clinical Oncology. J Clin Oncol. 1991 Jul;9(7):1314-9.