Full Extract Cannabis Oil (FECO) and Cancer

The “C” word instills dread in all, as it did with my Father's cancer diagnosis. Continually listed as the second leading cause of death for Americans, Cancer is a proven killer that does not discriminate. Even with today’s modern medicine, the fight against Cancer with early diagnosis and aggressive treatment can still lead to an early demise.

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Cancer is a genetic disease, caused by changes to genes that control the way our cells function, especially how they grow and divide. Genetic changes that cause cancer can be inherited. They can also arise during a person’s lifetime as a result of errors that occur as cells divide or because of damage to DNA caused by certain environmental exposures. Cancer-causing environmental exposures include substances, such as the chemicals in tobacco smoke, and radiation, such as ultraviolet rays from the sun. (1)

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We are not aware of any cancer in his family history. He lived a clean life of no smoking, very little drinking and stayed in shape playing tennis. However, for twenty years he worked in the front office of an iron works company with more-than-you-can-count cancer causing chemicals floating around. He was diagnosed with Stage 4 Renal Cell Carcinoma more than a decade after retirement from the company. Did his exposure to those chemicals cause his cancer?

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Each person’s cancer has a unique combination of genetic changes. As the cancer continues to grow, additional changes will occur. Even within the same tumor, different cells may have different genetic changes. In general, cancer cells have more genetic changes, such as mutations in DNA, than normal cells. Some of these changes may have nothing to do with the cancer; they may be the result of the cancer, rather than its cause. (1) These unique combinations of genetic mutations in tumors and cancers can determine what chemotherapies work and which ones don’t.

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The Diagnosis

I always worried about my dad having a heart attack due to stress but once he reached his seventies, really thought he could live to be an very old man. His diagnosis at age 75 caught the family off-guard and unprepared. Unfortunately, his case was our learning experience. He was given two traditional chemotherapy options; each with low efficacy rates failed. He also tried a several varieties of Full Cannabis Extract Oils (FECO), also known as Rick Simpson Oil (RSO) which provided great palliative care. But we couldn’t defeat the cancer and lost after 17 months.

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Why did my Father die of cancer after treatment with Cannabis oil? Each individual is unique including their Endocannabinoid System (ECS), a principal endogenous signaling system that appeared early in evolution and has important regulatory functions throughout the body. (2, 3, 4, 5) Each cancer is unique with its mutation combinations. Each Cannabis flower is unique with its Cannabinoid, terpene, and flavonoid ratios. And to note, investigators do not know how terpenes and flavonoids affect the interaction of the Cannabinoid molecules with the ECS.

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The Heterogeneity and Complexity of Cannabis Extracts as Anti-Tumor Agents

The mainstream conversation of Cannabis revolves around the two major Cannabinoids, Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD), however; the Cannabis plant contains over 500 different compounds including over 120 identified as phytocannabinoids. (2) Included in these compounds are terpenes and flavonoids, the molecules that define the aroma and taste of the flower. Why mention them? Because they are important, yet investigators do not know their exact role in the interaction with Cannabinoids and ECS. How important are they? Researchers have identified and classified a common terpene, Beta-caryophyllene, found in Cannabis, black pepper, and basil as a dietary Cannabinoid. (6) And recently, investigators announced that a Cannabis derived flavonoid demonstrated therapeutic potential in preclinical models of metastatic pancreatic cancer. (7)

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A study recently published in Oncotarget demonstrates the diverse characteristics and complexity of the Cannabis plant and its extracts in fighting various cancer cell lines. Cancer cell lines are cancer cells that keep dividing and growing over time, under certain conditions in a laboratory. Cancer cell lines are used in research to study the biology of cancer and to test cancer treatments. (8) Investigators in Israel examined 124 different Cannabis extracts, choosing a select 12 to monitor on 12 Cancer cell lines. Some of the cancers represented in the study were colon carcinoma (HT-29), breast carcinoma (MCF-7) and prostate carcinoma (LNCaP).

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The complexity of Cannabis extracts was evident in the researchers recently developed liquid chromatography mass spectrometry. From the 124 natural and decarboxylated Cannabis extracts, 89 Phytocannabinoids were identified with 54 Cannabinoids appearing on a heat map which demonstrated the significant differences in the extracts. The heat map identified 5 major clusters characterized by patterns of Phytocannabinoid compositions. As previous research indicates, it is apparent that minor constituents can also significantly contribute to the variance among Cannabis extracts. (2, 9)

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The five clusters of Cannabinoids are:
Cluster 1: CAN 10, highest concentration of Cannabigerol (CBG)
Cluster 2: CAN2, CAN3 and CAN9, more Cannabidiol (CBD) and Cannabichromene (CBC) type and degradation products
Cluster 3: CAN1 and CAN8, large concentrations of Cannabidiolic Acid (CBDA) and degradation products including Cannabielsoic Acid (CBEA)
Cluster 4: CAN5, CAN7 and CAN12, higher concentrations (>35%) of Delta-9-Tetrahydrocannabinol (THC)
Cluster 5: CAN4, CAN 6 and CAN11, relatively higher concentrations of (-)-Delta-9-Tetrahydrocannabinolic Acid (THCA) and degradation products Cannabinolic Acid (CBNA) and (+/-)-Trans-Cis-Cannabitriolic Acid (CBTA)

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Effect of Cannabis Oil on Cancer Cell Line Survival

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The complexities of Cannabis is immense; what is not addressed in the research study is the impact of the "other" elements contained in the flower. Mentioned earlier, terpenes and flavonoids add to the entourage effect, yet scientists do not know the method of action of these molecules and how they affect the Endocannabinoid System. Different strains of Cannabis contain different ratios of Cannabinoids, terpenes and flavonoids.

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The twelve chosen Cannabis extracts (CAN1 - CAN12) effects were examined on the survival of 12 well-characterized cancer cell lines. The cells were exposed to increasing concentrations and monitored. The figure shown to the right are the effects of the 12 Cannabis extracts on the survival of A549 cancer cells, a lung carcinoma. As shown, one can see the variation of cancer cell survival. Extracts CAN8 (high CBDA) and CAN11 (high THCA) did not significantly affect cancer cell viability, while CAN7 (high THC) at the lowest dose appeared to greatly affect the viability of A549 but at higher doses became slightly less effective. The three extracts that affected the lung cancer cells the least were inactivated Cannabinoids, Cannabidiolic Acids THCA and CBDA.

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After review, it was determined that CAN5 and CAN7, each tested high for THC, were the most potent as an anti-tumor agent affecting the survival of the most cell lines. It's noted that the 14 THC-rich extracts seemed to possess similar Cannabinoid profiles. What is not noted is the terpene and flavonoid profile of each extract, a missing link in both this research study and in how do they affect Cannabinoids on the ECS receptors.

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The graphic below shows the variety of results the 12 Cannabis extracts exhibited against 12 different Cancer cell lines; some samples showing small results against a small number of cell lines, while others Cannabis extract samples are more prolific in their apoptosis levels. Unfortunately, on Cancer cell line HT-29, a human colorectal adenocarcinoma displayed no reaction to all of the Cannabis extract samples.

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Battling Cancer is a complex set of variables, an intense game of chance. These include type of Cancer and timing of the diagnosis, the mutations within the Cancer and traditional chemotherapies. The variables for introducing Cannabis are Cannabinoids, terpenes, flavonoids and delivery methods. Currently, Cannabinoids are only being considered in treatments with few exceptions.

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Rick Simpson aka Full Extract Cannabis Oil

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We decided to incorporate Cannabis into my dad's chemotherapy and researched Rick Simpson Oil commonly referred to by its acronym, RSO. RSO is now also referred to as Full Extract Cannabis Oil or FECO. This type of Cannabis extract oil was re-discovered by a man named Rick Simpson who used it to cure his Melanoma (skin cancer) and has claimed to have consulted thousands of patients with success. Rick Simpson advises to use a heavy Indica strain that is high in THC; his theory behind using heavy Indica dominant strains is that it would produce a more sedative effect compared to Sativa leaning flowers. These 'effects' are thought to be the result of the entourage effect determined by the terpenoids, flavonoids and other compounds present in the Cannabis oil. The terpenes, Myrcene and B-Caryophyllene are commonly found in Indica leaning Cannabis strains with more sedative or "couch lock" characteristics. As mentioned previously, B-Caryophyllene is categorized as a dietary Cannabinoid.

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Fighting Cancer with FECO is not covered by insurance and is potentially, an expensive therapy protocol for the average household. Whether buying it off the shelf with no discerning information, making it yourself or consulting a professional for personalized care, treatment can start as low as $30 - 50 for a gram to into the thousands and easily reach $7,000 to $10,000 for a 60 gram in 90 day regimen. My family learned many things in our fight and though we didn't win against Cancer, doesn't mean Cannabis wasn't a win for my family.

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POTENTIAL DRUG INTERACTIONS

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CBD is metabolized via the cytochrome P450 system (10), mainly by isozymes located in the liver (11). Most drug interactions are associated with concurrent use of other Central Nervous System depressants with Cannabis. In clinical research, drug interactions are rare and there is no drug that cannot be used with Cannabis, if necessary. Existing studies have not demonstrated toxicity/loss of effect of comitant medications, but still theoretically possible. A known exception is a high dose of CBD/Clobazam with a side-effect of drowsiness caused by a sedating metabolite, N-deesmethyl Clozabam that requires a dose reduction (12, 13, 14).

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If you are taking a medication that says "Do Not Take With Grapefruit", taking CBD in tincture, pill capsule or edible form could cause you to have too much of your medication in your bloodstream. This could cause unwanted side effects. This can happen with common drugs including warfarin, taken by millions for blood clots, and antidepressants like Zoloft. (15) Dr. Michele Ross, PhD writes in her book, Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency, ways to mediate the risk include lowering your dose of medication under your doctor's guidance or lowering your dose of CBD to a dose that causes minimal inhibition of P450 enzymes.

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If you take prescription medicines for blood pressure or central nervous system or are a sensitive patient, we recommend consulting a Medical Cannabis Practitioner (Canna-Nurse). CBD can lower blood pressure (16) precaution must be taken. My father, who was battling Stage 4 Renal Cell Carcinoma, had a blood pressure event when I switched his Full Extract Cannabis Oil (FECO), also referred to as Rick Simpson Oil (RSO), to a CBD dominant strain.

References
1) National Cancer Institute, What is Cancer? — Link
2) Liran Baram, Ella Peled, Paula Berman, Ben Yellin, Elazar Besser, Maya Benami, Igal Louria-Hayon, Gil M. Lewitus and David Meiri1, "The Heterogeneity and complexity of Cannabis Extracts as Antitumor Agents"; (2019). Oncotarget, 10(41).doi:10.18632/oncotarget.26983 — Link
3) Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2.; Pharmacol Rev. 2010; 62:588–631. doi.org/10.1124/pr.110.003004— Link
4) Pacher P, Bátkai S, Kunos G. The Endocannabinoid System as an Emerging Target of Pharmacotherapy. Pharmacol Rev. 2006; 58:389–462. doi.org/10.1124/pr.58.3.2. — Link
5) McPartland JM. Phylogenomic and Chemotaxonomic Analysis of the Endocannabinoid System. Brain Res Brain Res Rev. 2004; 45:18–29. doi.org/10.1016/j. brainresrev.2003.11.005. —Link
6) Ju¨rg Gertsch, Marco Leonti, Stefan Raduner, Ildiko Racz, Jian-Zhong Chen, Xiang-Qun Xie, Karl-Heinz Altmann, Meliha Karsak, and Andreas Zimmer; Beta-Caryophyllene is a Dietary Cannabinoid; PNAS , July 1, 2008, vol. 105, no. 26, 9099–9104 — Link
7) Michele Moreau, Udoka Ibeh, Kaylie Decosmo, Noella Bih, Sayeda Yasmin-Karim, Ngeh Toyang, Henry Lowe and Wilfred Ngwa; Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer; Frontiers in Oncology, 23 July 2019, doi.org/10.3389/fonc.2019.00660 — Link
8) National Cancer Institute, NCI Dictionary of Cancer Terms — Link
9) Berman P, Futoran K, Lewitus GM, Mukha D, Benami M, Shlomi T, Meiri D., A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis. Sci Rep. 2018; 8:14280. doi.org/10.1038/ s41598-018-32651-4. — Link
10) Russo EB (2016) Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues.; Front. Pharmacol. 7:309. doi: 10.3389/fphar.2016.00309 —Link
11) Ogu CC, Maxa JL. Drug interactions due to cytochrome P450.Proceedings (Baylor University Medical Center). 2000;13(4):421-423. —Link
12) MacCallum, C.A., Practical considerations in medical cannabis administration and dosing; European Journal of Internal Medicine (2018), https://doi.org/10.1016/j.ejim.2018.01.004 — Link
13)Ujvary I, Hanus L.Human metabolites of cannabidiol: a review on their formation, biological activity, and relevance in therapy.Cannabis Cannabinoid Res 2016;1:90–101. —Link
14) Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al.Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome.N Engl J Med 2017;376:2011–20. —Link
15) Ross, Michele N.,Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency; Greenstone Books, 2018
16) Jadoon, Khalid, A., Tan, Garry, D., O’Sullivan, Saoirse, E. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight. 2017;2(11):e93760. https://doi.org/10.1172/jci. insight.93760. — Link