Good news/Bad news about Multiple sclerosis research

The good news about Multiple sclerosis (MS) research is that there seems to have been a major breakthrough in treatment, the bad news is that research regarding demyelinating disorders which includes MS seems to have slowed down (1) – finding a solution, a medical answer, that isn’t politically approved of or one that is able to be easily patent protected may be the reason for the bad news. Finding an answer that you don’t like shouldn’t mean we stop asking the question. Work is progressing on genetic modification of mitochondrial DNA differences that can cause demyelination disorders and success has been seen in animal models for disease. Aging increases the risk for different types of mitochondrial DNA changes that can cause a variety of symptoms and diseases. (mitoTALENS/session by Moraes/28)

(Ubiquitin (a protein, not the same as CoQ10/ubiquinone, an electron carrying quinone involved in energy metabolism, 29) is needed for identifying which mitochondria are damaged and need to be recycled in the normal way, by autophagy/mitophagy, which involves the debris being taken into a container particle called lysosomes – imagine a cellular vacuum cleaner that can then recycle any useful material and discard any non-useful, potentially toxic material. See the session on Mitochondria in Parkinson’s Disease/Youle: 28)

Cannabinoids seem to be the good news treatment for MS in humans, whether as purified extracts of medical marijuana or as the whole product which can contain many cannabinoids and medically active terpenes.  An overview published in 2016 regarding the role of cannabinoids in neurology in various types of autoimmune disease: (2). An overview of the role of cannabinoids in neuroinflammatory conditions published in 2008: (3). An opinion article published in 2018 regarding the potential role of cannabidiol ( a non-euphoric cannabinoid) to improve mobility for patients with Multiple sclerosis: (4).

What is Multiple sclerosis?

Multiple sclerosis is a chronic condition that seems to be autoimmune in nature where the body is breaking down the protective coating around the branching segments between nerves. The coating is called the myelin sheath and it acts a little like the plastic coating around an extension cord. Myelin on a nerve fiber or plastic on an extension cord keeps the electrical signals on the inside and out of danger of creating sparks elsewhere along the path of the cord or nerve fiber.

What are cannabinoids?

Cannabinoids are directly involved in making strong and flexible cell membranes as they are building blocks that make up portions of the membrane, like bricks in a wall. They can also be signaling chemicals that can be activated when released from the membrane. Excess calcium inside of a cell can be a signal that causes the release of cannabinoids. Once they are released they break down into their two basic components, phospholipids and a free fatty acid, often arachidonic acid. The problem is two part – 1) both of the components of cannabinoids once they are released from the membrane can become signaling chemicals that can lead to increased inflammation, NSAID pain killers (aspirin, naproxen, ibuprofen helped reduce level of fatigue experienced by MS patients) may help block the negative effects of excess free arachidonic acid (21); 2) if too many bricks are released from the wall, then the wall may no longer function – the plastic coating on the extension cord may allow sparks through that can be a risk for an electrical fire. In the case of Multiple sclerosis the nerve damage and lack of myelin sheathing around nerve fibers causes difficulties with muscle control and the patient may have increasing difficulty walking and doing other normal daily tasks.

Preventing the increased release of cannabinoids from the membrane walls would likely to the best plan for preventing the resulting increase in inflammatory signaling chemicals they form and the reduction in membrane function. The amount of cannabinoids present can cause opposite effects, small or medium amounts can have beneficial effects while large amounts may have significantly different effects. Mitochondria are the main energy production center of the cell, where sugar is turned into a usable form of energy with the chemical shorthand name ATP or ADP. Both are phosphochemicals differing in the number of phosphate groups, adenosine tri-phosphate and adenosine di-phosphate. The amount of calcium within the cell and within the mitochondria may be different and cannabinoid can affect the movement across the mitochondrial membrane and cause differenct effects depending on the amount of calcium in each area and the amount of cannabinoids that are present. It’s complicated is the short story. This article goes into a longer  but still simplified description of the chemistry. (23)

And part of the point is that having adequate cannabinoids and adequate phosphonutrients and adequate but not excessive calcium are all important for cellular health and the ability to produce energy – and to not be fatigued – excessively tired all of the time. And in order to have adequate calcium but not excessive the cells need adequate magnesium and adequate protein and phosphonutrients in order to hold it ready for use – like taxicabs circling the block ready to discharge magnesium as a free ion when and where it is needed. The topic of magnesium, and the need for protein and phosphonutrients was introduced in a recent post. Magnesium blocks entry of excess calcium from being able to enter the interior of the cell, where it can cause increased release of cannabinoids from their storage positions within the cell membranes. Ibuprofen, but not other NSAIDs such as naproxen, also help reduce the amount of breakdown of cannabinoids. (pp 82-83, 24)

What are oligodendrocytes?

A type of specialized brain cell called oligodendrocytes are responsible for building or repairing the myelin sheath. Multiple sclerosis involves increased loss of oligodendrocytes. The specialized cells have calcium permeable glutamate receptors and are more susceptible to oxidative stress than average cells so they are particularly at risk for being damaged by ongoing emotional or physical stress or a traumatic brain injury. (6) Sphingomyelin is one of the building blocks of the myelin sheath, (7),  and is formed by oligodendrocytes. (8)

The body is complicated and needs many/all of the nutrients for optimal health. More nutrients and other lifestyle issues that may benefit myelin production or increase risk are discussed in a list of tips for regenerating myelin, phosphatidylserine, a phospholipid, is one of the recommendations; other conditions that may include myelin breakdown besides Multiple sclerosis are also mentioned: (22). 

Problems with vitamin D availability may also be involved in the body being more prone to autoimmune reactions by the immune system (attack on our own healthy cells instead of only attacking foreign or damaged cells); and on the natural building or repair of the myelin sheath. (5) And just to keep things interesting – iron is important but too much within the oligodendrocytes may increase risk for MS; polyunsaturated fats are also important but their reactivity may increase risk to the oligodendrocytes from oxidative stress; lack of Nrf2 may be involved in the susceptibility to oxidative stress in the development of MS due to damage to the oligodendrocytes; and the oligodendrocytes have an abundance of calcium permeable glutamate receptors so excess glutamate may increase risk of excess calcium entry into the cells which can lead to cell death. (8)

Summary points for protecting oligodendrocytes –

  • all nutrients are important, (22), but balance is also important.
  • Avoid excess emotional and physical stress if possible.
  • Adequate iron is important because the oligodendrocytes need more than average in order to be able to make the myelin sheath. Some patients may have an underlying genetic difference that leads to their needing supplementation of a well absorbed form of iron throughout their life. Genetic screening and individualized metabolic guidance may be needed for optimal treatment of patients with MS as it may have differing causes. A true autoimmune antibody/antigen has not been identified. (10)
  • In general however, avoid excess iron (fortified breakfast cereals and meats for example; men and menopausal women who eat large servings of very iron-fortified foods or large servings of iron rich meats can be more at risk for iron overload. Donating blood occasionally can benefit society and may help protect against the risk of iron overload for people who do not menstruate. Food sources of iron and more information about donating blood: (9) Iron overload can be a cancer risk and tends to be more common than iron deficiency in the non-menstruating population.(11))
  • and avoid excess free glutamate (frequently used in seasonings and naturally found in fermented products such as soy sauce. It is in many processed foods, (12)).
  • Eat a balance of omega 3, (22), and omega 6 polyunsaturated fatty acids.
  • Eat plenty of antioxidant rich foods regularly that also include Nrf2 promoting phytonutrients and other phospholipid containing nutrients. Here is some Nrf2 promoting foods and menu ideas: G10: Nrf2 Promoting Foods.
  • And cannabinoids or other phospholipid/phosphonutrient containing foods include these, many of which are also Nrf2 promoting foods:

Food Sources of Phospholipids and other phospho-nutrients, a partial list:

Hemp seed kernels and oil; Artemisia turanica/wormwood leaf; amaranth seed; asparagus; avocado fruit or the inner kernel, dried and powdered; beans/legumes; cardamom seeds and powder; carrots; celery stalks and leaves; cocoa beans and cocoa powder, baker’s chocolate, dark chocolate and to a lesser amount milk chocolate and chocolate syrup; coconut; cumin seed/powder; fennel seed, flax seed, pine nuts; sesame seeds, pumpkin seed kernels, squash seeds; butternut squash and pumpkin; gingko leaf; grapefruit and orange juice with the pulp; Jerusalem artichoke (this is a root vegetable rather than a green artichoke); lettuce, spinach and mustard leaves and other leafy green vegetables and herbs; nuts/peanuts, cashews, walnuts; oats; okra seeds; onion root, leek leaves, garlic;  parsnip root; pomegranate seeds and pomegranate peel extract;rice, white or brown but the bran is the best source; rosemary; sorghum;  sweet potato or yam; buckwheat (a seed botanically that is not wheat and is gluten free); wheat. (G.26)

The current treatments for Multiple sclerosis are very costly, and may not help all patients while also tending to cause negative side effects.

Returning to the original question – why has the ratio of research being published about demyelinating disorders declined since 2013? It is possible that the answer might be that medical marijuana or a recommendation to eat more dark cocoa and beans, nuts, and seeds is not as profitable as the older MS treatments may average $60,000 per year and newer treatments cost 25-60% more than that, (13), which would be an average prescription cost of $75,000-96,000 per year per patient with Multiple sclerosis. Good quality cocoa is expensive but can fit within most grocery budgets. Being a medical marijuana patient might cost around $12,000 per year for a patient using it several times each day. Use of ibuprofen daily might cost a few hundred dollars per year depending on the amount used and whether it was a name brand or off brand. (21(24) (Note – long term use of ibuprofen may cause intestinal problems, ginger (about 1/2 teaspoon) can be healing for the intestines and help with pain relief as well as ibuprofen and provided better pain relief when used in combination with ibuprofen in a study with arthritis patients. Ginger may be reducing inflammation by reducing the amount of cannabinoid breakdown to free arachidonic acids and preventing transformation into inflammatory eicosanoids. (27))

Efficacy and negative side effects are also worth considering – for that $60,000-96,000/year price tag only half of the patients may gain health benefits while many will experience negative side effects in addition to needing time and copays for office visits to receive some types of treatments. Fewer than half of patients receiving interferon-β treatment were found to benefit medically and many experienced side effects. (13)

The pharmaceutical industry frequently does medical research involving new drug treatments. The use of medical marijuana for the treatment of Multiple sclerosis or other demyelinating disorders is not legal at the Federal level as the herb is still scheduled as a substance with no medical benefit. Private research in states that have legalized medical use could possibly be performed however. Enrolling patients would likely need to be by self selection though, and for comparison purposes an experimental group of patients could be given a phospholipid rich diet plan to follow and a control group of patients receiving standard pharmaceutical treatments could also be followed to compare health outcomes with the current standard of care.

How many patients have Multiple sclerosis?

More math – there are about 400,000 people in the U.S. with Multiple sclerosis and about 10,000 newly diagnosed patients each year. (14) Averaging the cost of standard treatments to $78,000 per year would mean the 400,000 patients require $31,200,000,000 per year in pharmaceutical care. Thirty one billion dollars would buy a lot of cocoa. The number of patients living with the condition globally is estimated to be around 2.3 million people. (15) If they all received treatment at the average U.S. cost it would require $179.4 billion in care.

People living farther from the equator tend to have a greater risk for developing Multiple sclerosis so vitamin D deficiency may be involved.

Looking at the global distribution map on the link does visually suggest that vitamin D deficiency may be involved – it is not as much of a risk for nations around the equator where more sunshine would consistently be available.  Genetic differences may also be involved as it is more of a risk for Caucasians and people of central and northern European descent. It is rare for Inuits, Aborigines and Maoris. (14) (The Inuit native diet is rich in vitamin D from seafood sources.) A map of distribution risk across the U.S. also suggests a sunshine factor – rates below the 37th parallel are reduced compared to farther north. (15)

Sphingomyelin is found in the diet but needs to be made by the oligodendrocytes.

Why discuss eating cocoa or sources of phospholipids or vitamin D? Why not just eat sphingomyelin? We do eat some but our digestive systems break it down into smaller types of fats, (16), and then our oligodendrocytes have to rebuild it. Sphingomyelin tends to be found with cholesterol within the body, and both can affect the digestion of the other. (16)

Genetic differences may be involved in risk for MS. Variations in genes involved in Vitamin D metabolism may be a risk factor. There also may be differences in the cannabinoid metabolism involved or in other metabolic pathways.

Vitamin D can be made out of cholesterol when our skin is exposed to adequate sunshine. Genetic differences in vitamin D metabolism may be why some people are more prone to developing multiple sclerosis than others – speculatively. Genetic differences in vitamin D metabolism have been studied in relation with multiple sclerosis risk and a correlation was found however studies with supplementation have been inconclusive. (17) One nutrient solutions can not solve multiple nutrient problems – adequate iron but not too much, adequate balance of polyunsaturated fats to promote health without increasing inflammation, avoiding excess free dietary glutamate, and having adequate phospholipids and Nrf2 promoting foods in the diet may also all be important – in addition to having adequate vitamin D in the diet or from sunshine or tanning lights.

Vegetarian based diets include many foods that help reduce inflammation & protect against oxidative stress, & may save money.

Some more good news – a vegetarian based diet can provide many of those dietary factors and save money (about $750/year, (18)) compared to a meat based diet (which tends to be more inflammatory – i.e. oxidative stress promoting). More math – the economical vegetarian diet (2015 U.S. prices) was estimated to cost about $2,762/year which would add up to $6,353 million per year for the 2.3 million global population of people with MS instead of the $179.4 billion that would be needed for current pharmaceutical treatments for Multiple sclerosis. Phosholipid rich, Nrf2 promoting foods can also provide a good balance of omega 3 fatty acids and include sources of vitamin D and iron and tend to include many high quality vegetarian sources of protein such as nuts, beans, and seeds.

Cocoa has been found to reduce fatigue for MS patients and is a good source of phospholipids and Nrf2 promoting flavonoids.

Better news – cocoa, which is made from a bean that is rich in flavonoids, which are Nrf2 promoting phytonutrients, G10: Nrf2 Promoting Foods, and is a good source of phospholipids, (G.26), has been found to help reduce fatigue levels in patients with Multiple sclerosis while not increasing high blood sugar risk factors. (19)

Skip the sugar if possible, Insulin resistance may increase breakdown of the myelin sheath.

I add a spoonful of dark cocoa powder (unsweetened Baking cocoa) to my coffee – like mocha coffee without the syrup. Once you stop using sugar your taste buds adjust to not needing as much sweet taste – or add a little sugar or honey but artificial sweeteners may not be that helpful because the sweet taste is still signaling the body to increase insulin levels which then increases appetite and studies have found snacking calories are then increased -resulting in no overall reduction in calorie intake. Avoiding insulin resistance, frequently a problem with Type 2 Diabetes and Metabolic Syndrome, may also help protect against Multiple sclerosis risk as it may have something to do with the breakdown of the myelin sheath. (20)

/Disclosure: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes. Thanks./ 

  1. James Lyons-Weiler, *A graph of all research studies regarding demylinating disorders such as Multiple sclerosis as a ratio of all medical research studies over time – there has been a significant decrease in the ratio since 2013. The graph begins with approximately 4/100,000 studies in 1944, peaks at approximately 46/100,000 in 1998/1999 and drops to approximately 7/100,000 in 2017/2018.   https://twitter.com/lifebiomedguru/status/1021794538682236929 (1)
  2. Katz D, Katz I, Shoenfeld Y,  Mini Review, Open Access, Cannabis and Autoimmunity – The Neurologic Perspective: A Brief Review. June 2, 2016, J Neurology, Neuromedicine. http://www.jneurology.com/articles/cannabis-and-autoimmunity–the-neurologic-perspective-a-brief-review.html (2)
  3. G. A. Cabral, L. Griffin-Thomas, Cannabinoids as Therapeutic Agents for Ablating Neuroinflammatory Disease. Endocr Metab Immune Disord Drug Targets. 2008 Sep; 8(3): 159–172.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750822/ (3)
  4. Thorston Rudroff, Jacob Sosnoff,Cannabidiol to Improve Mobility in People with Multiple Sclerosis. Opinion Article, Front. Neurol., 22 March 2018.   https://www.frontiersin.org/articles/10.3389/fneur.2018.00183/full (4)
  5. Cell-based study reveals that vitamin D can drive the activity of neural stem cells that promote myelin repair, MS Society of Canada, March 30, 2015, https://mssociety.ca/research-news/article/cell-based-study-reveals-that-vitamin-d-can-drive-the-activity-of-neural-stem-cells-that-promote-myelin-repair (5)
  6. Attila Köfalvi, Cannabinoids and the Brain, Springer Science & Business MediaDec 22, 2007, pp 342 and 344, https://books.google.com/books?id=ZNIorLciZCoC&pg=PA342&lpg=PA342&dq=myelin+sheath+cannabinoid+metabolite&source=bl&ots=t0vcsRm2HK&sig=oDbCl2JBArCt9s5KT8xawwBrv5M&hl=en&sa=X&ved=0ahUKEwjf2MS3xbrcAhUBI6wKHdIEDbUQ6AEISDAE#v=onepage&q=myelin%20sheath%20cannabinoid%20metabolite&f=false (6)
  7. ElenaPosse de Chaves, Simonetta Sipione, Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction. Frontiers in Membrane Biochemistry, FEBS Letters, Vol 584, Issue 9, 3 May 2010, Pages 1748-1759, ScienceDirect,   https://www.sciencedirect.com/science/article/pii/S0014579309010564
    (7)
  8. Arundhati Jana, Kalipada Pahan, Sphingolipids in Multiple sclerosisNeuromolecular Med. 2010 Dec; 12(4): 351–361.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987401/ (8)
  9. Iron-Rich Food-List of Meats, Vegetables and Meals, American Red Cross, https://www.redcrossblood.org/donate-blood/blood-donation-process/before-during-after/iron-blood-donation/iron-rich-foods.html (9)
  10. Susan J. van Rensburg,Maritha J. Kotze, Ronald van Toorn, The conundrum of iron in multiple sclerosis – time for an individualised approach. Metab Brain Dis. 2012 Sep; 27(3): 239–253.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402663/ (10)

  11. Iron: The Double-Edged Sword, The Physician’s Committee for Responsible Medicine, https://www.pcrm.org/health/cancer-resources/diet-cancer/nutrition/iron-the-double-edged-sword (11)
  12. Dr. Amy Yasko, Detecting Neuro-Provoking Foodshttp://www.dramyyasko.com/wp-content/files_flutter/1279663001Neuroprovokers8.pdf (12)
  13. Daniel M. Hartung, PharmD, MPH, Dennis N. Bourdette, MD, Sharia M. Ahmed, MPH, Ruth H. Whitham, MD, The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: Too big to fail?,  Neurology. 2015 May 26; 84(21): 2185–2192. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451044/ (13)

  14. MS Statistics, multiplesclerosis.net, https://multiplesclerosis.net/what-is-ms/statistics/ (14)
  15. Multiple sclerosis: Facts, Statistics, and You, healthline.com, https://www.healthline.com/health/multiple-sclerosis/facts-statistics-infographic#2 (15)
  16. Åke Nilsson, Rui-Dong Duan, Absorption and Lipoprotein Transport of Sphingomyelin, January 2006, The Journal of Lipid Research, 47, 154-171http://www.jlr.org/content/47/1/154.full (16)
  17. Shoemaker TJ, Mowry EM, A review of vitamin D supplementation as disease-modifying therapy. Multiple Sclerosis Journal, Volume: 24 issue: 1, page(s): 6-11 Jan 182018, http://journals.sagepub.com/doi/full/10.1177/1352458517738131 (17)
  18. Justin Caba, A Vegetarian Diet Can Save You Around $750 Each Year When Compared To A Meat-Eating Diet. Oct. 9, 2015, MedicalDaily.com, https://www.medicaldaily.com/vegetarian-diet-can-save-you-around-750-each-year-when-compared-meat-eating-diet-356670 (18)
  19. S. Coe, E. Axelsson, V. Murphy, M. Santos, J. Collett, M. Clegg, H. Izadi, J.M. Harrison, E. Buckingham, H. Dawes, Flavonoid rich dark cocoa may improve fatigue in people with multiple sclerosis, yet has no effect on glycaemic response: An exploratory trial. Clinical Nutrition ESPEN, Oct. 2017, Volume 21, Pages 20–25   https://clinicalnutritionespen.com/article/S2405-4577(17)30280-2/abstract (19)
  20. Kristina Fiore, Does Insulin Resistance Degrade Myelin? – Imaging study suggests insulin resistance is linked to loss of myelin., Oct. 23, 2015, MedPageToday.com, https://www.medpagetoday.com/meetingcoverage/sfn/54260 (20)
  21. Sara Palumbo, Chapter 7 Pathogenesis and Progression of Multiple Sclerosis: The Role of Arachidonic Acid–Mediated Neuroinflammation. from the book edited by Zagon IS, McLaughlin PJ, editors. Multiple Sclerosis: Perspectives in Treatment and Pathogenesis [Internet]. Brisbane (AU): Codon Publications; 2017 Nov 27. https://www.ncbi.nlm.nih.gov/books/NBK470143/ (21)
  22. Jordan Fallis, 27 Proven Ways to Promote the Regeneration of Myelin. Feb. 18, 2017, Optimal Living Dynamics,  https://www.optimallivingdynamics.com/blog/25-proven-ways-to-promote-the-regeneration-of-myelin (22
  23. Adrian Devitt-Lee, CBD Science: How Cannabinoids Work at the Cellular Level to Keep You Healthy, Project CBD,  Dec. 15, 2016, alternet.org, https://www.alternet.org/drugs/cbd-science-mitochondria-mysteries-homeostasis-renewal-endocannabinoid-system (23)
  24. Editors, Emmanuel S. Onaivi, Takayuki Sugiura, Vincenzo Di Marzo, Endocannabinoids: The Brain and Body’s Marijuana and Beyond, (Taylor & Francis Group, 2006, Florida), pages 82 and 83 are from Chapter 3, by: E.S. Onaivi, H. Ishiguro, P. W. Zhang, Z. Lin, B. E. Akinshola, C. M. Leanoard, S. S. Chirwa, J. Gong, and G. R. Uhl, Chapter 3, Endocannabinoid Receptor Genetics and Marijuana Use. https://www.crcpress.com/Endocannabinoids-The-Brain-and-Bodys-Marijuana-and-Beyond/Onaivi-Sugiura-Di-Marzo/9780415300087 (24)
  25. J. Depew, RD, G10: Nrf2 Promoting Foods, 2018, effectivecare.info, G10: Nrf2 Promoting Foods. Particularly helpful for an overview of plant phytonutrients groups: Maria de Lourdes Reis Giada, Chapter 4: Food Phenolic Compounds: Main Classes, Sources and Their Antioxidant Power, Biochemistry, Genetics and Molecular Biology » “Oxidative Stress and Chronic Degenerative Diseases – A Role for Antioxidants”, book edited by José A. Morales-González, ISBN 978-953-51-1123-8, Published: May 22, 2013    https://www.intechopen.com/books/oxidative-stress-and-chronic-degenerative-diseases-a-role-for-antioxidants/food-phenolic-compounds-main-classes-sources-and-their-antioxidant-power (G10.11)
  26. Arlen Frank, Chemistry of Plant Phosphorus Compounds, Elsevier, Jun 3, 2013, https://books.google.com/books/about/Chemistry_of_Plant_Phosphorus_Compounds.html?id=6btpFSV1T2YC (G.26)
  27. Ginger Decreases Colon Inflammation, Prime Endoscopy Bristol, Oct. 12, 2011,  http://www.primeendoscopybristol.co.uk/ginger-decreases-colon-inflammation/ (27) 
  28. From Pediatric Encephalopathy to Alzheimer’s: Linking Mitochondria to Neurological Diseases. 2016 Neurobiology of Disease Workshops, Neuronline.sfn.org, http://neuronline.sfn.org/Articles/Scientific-Research/2017/From-Pediatric-Encephalopathy-to-Alzheimers (28)

Is it Addiction or Starvation?

1. Talk Therapy or “Just say no” can’t help a genetic difference.

Talk therapy is also beneficial but can not “cure” a biological difference in metabolism.
  • Looking up the definition of the word “disease” suggests that a genetic difference affecting a body wide receptor system might fit the term “body disease.” “Disease: a disorder of structure or function in a human, animal, or plant, especially one that produces specific signs or symptoms or that affects a specific location and is not simply a direct result of physical injury.” – Oxford Dictionaries (I.1.disease)
Redefining the neurobiological underpinnings and genetic risks of the behavior we call addiction could lead to more targeted help for the sufferers of addiction rather than continuing to treat them primarily by focusing on a discussion of their difficulties with motivation or impulse control.
Binge eating disorder for some sufferers may involve a genetic difference in the endogenous cannabinoid system which leaves the person unable to produce the cannabinoids normally and so they are left hungry, starving for the foods that are better sources of cannabinoids naturally.
Chocolate is the richest standard food source that isn’t a controlled substance but it isn’t a low calorie food (hemp oil and hemp seed products are not available in a limited quantity but they are still difficult for farmers to grow in all areas and medical marijuana is still considered a controlled substance at the U.S. federal level.) Less calorie dense foods than chocolate include pomegranate seeds, dark green leafy vegetables and herbs such as oregano and other green leafy herbs. So if binge overeating sounds sadly familiar, consider making an enormous salad and it may be just what your body needs. I use a half a pomegranate worth of seeds on my salad, which is about 1/2 cup of the seeds, and 1 teaspoon each of Italian Seasoning and Basil or Tarragon or some other leafy green herb. The enormous (a full dinner plate size is what I mean) salad might also help sufferers who are trying to resist the urge to over-consume alcohol or a few other addictive substances as well, if an underlying difference is present in their genetic code.
A dinner plate with a soup spoon and regular spoon for size comparison. Salad includes romaine lettuce, cilantro, tarragon, Italian seasoning, carrot, celery, avocado, pomagranite seeds, hemp seed and pumpkin seed kernels, lime juice and hemp oil and sea salt to taste.
The discussion of foods that are good sources of phospholipids or cannabinoids is not to suggest that medical marijuana patients should stop using their medication but simply to point to some food sources that might be available to most people where ever they live. Medical marijuana has significantly more cannabinoids than the foods that I mentioned in the previous paragraph or which will be mentioned later. My own physical symptoms are better helped by use of medical marijuana than by very large salads however the large salads are less expensive and have less effect on my mood. My previous use of the psychiatric medication Olanzapine has changed my withdrawal reaction to the medication and to marijuana significantly. I still have four months supply of the medication Olanzapine and plan to never ever use it again because its physical side effects while using it are very bad and withdrawal from it are much worse, frighteningly worse.
Medical marijuana patients who have never used olanzapine are unlikely to have the negative withdrawal reaction that I now experience within a few hours of my last dose. The strain of medical marijuana or type of synthetic or natural product is also important for any user in order to have a positive mental health reaction. Pure THC or the synthetic version, Dronabinol, can cause increased anxiety. Strains that have a mixture of cannabinoids and terpenes seem to help balance the mental effects in a way that is less likely to cause increased anxiety. Real lemon and lime products that contain the oil is one example of a easily available food substance that provides terpenes which help reduce the anxiety effects of medical marijuana or the synthetic Dronabinol. Terpenes and a link about lemon is included later in this post.
The Endogenous Cannabinoid System holds answers.
Background information:
  • Endogenous refers to something that can be made internally by our body rather than a chemical that is needed to be obtained from an external source on a daily or semi-regular basis. An example such as oxygen from the air we breathe is needed within every few minutes or cellular damage can start to occur; or trace nutrients such as essential fats or fat soluble vitamins may not be needed as often because they can be stored in the fat and membranes of the body. They may only need to be consumed in the diet every few days or weeks without resulting in negative health effects. The body can store extra vitamin D during summer months that can last most of the winter but does start to run out by springtime.
A person with a metabolic difference due to genetics, chronic illness, or the standard changes associated with aging may need an external source of nutrients that other people of average health would be able to make internally – “endogenously.”
  • Cannabinoids are a type of chemical called phospholipids which are formed from a lipid, a type of fat, and the mineral phosphorus.
I have a genetic difference in my ability to phosphorylate (I.2.wikigenes.BHMT) so that I am unable to make phospholiids endogenously and I have found that having an external source of cannabinoids in my diet every day helps my chronic illness conditions and improves my muscle and nerve control. I am registered as a Medical Marijuana patient in a state where it has been legalized for medical use.
     Some of my symptoms that are relieved by the herbal medicine have been troubling me since I was an infant. I had severe eczema throughout my childhood and severe congestion. Rarely could I breathe through both nostrils and nosebleeds were also common. The enzyme the BHMT gene produces when functioning incorrectly is associated with a risk for vascular problems – ie nosebleeds or easy bruising or spider veins or all of them.
     The protein that the gene normally produces is necessary in Glycerophospholipid biosynthesis, metabolism , and Phospholipid metabolism, (so a double mutation in this gene may make it difficult for me to make phospholipids endogenously), among 17 pathways in all – that is an important enzyme: (I.6.genecards.BHMT) And the CDK-mediated phosphorylation and removal of Cdc6 SuperPath involves 97 other pathways which include a Calcium2+ pathway and a Parkinsons Disease pathway and creatine metabolism (important for muscles) and synthesis of DNA and many other metabolic paths/chains of chemical events : (I.7.genecards.phosphorylation)
  • Phospholipids are found in human breast milk and helps stimulate the infant’s appetite and helps support adequate weight gain. The cannabinoids and phospholipid group perform two main functions – they are flexible and form a significant part of membrane walls, like building blocks or bricks; they can also be released from the membrane and act as messenger chemicals that can activate other systems or be modified slightly to become a different type of messenger chemical called eicosanoids.
  • Eicosanoids include the leukotrienes: Santa Cruz Biotechnology,(I.8.scbt.com)

2. It might be motivating to learn of an underlying cause to cravings.

It might help a person to learn that for a person with a genetic difference, difficulties with motivation or impulse control are likely due to an underlying deficiency of a substance they are missing, which would likely have helped them have better impulse control and to not have cravings for substances.
Someone without the genetic difference would be making the substances internally which would help them have good impulse control and not crave substances.
     Helping the person with substance abuse problems to find approved external sources of the substance (cannabinoids) seems like it would be more helpful and potentially more motivating for them to be able to view themselves as a worthwhile person with special dietary needs rather than as an unmotivated drug addict who just doesn’t try hard enough to change.
     Substance abusers likely quit using and relapsed again more times than anyone cares to count. every single time a chronic user runs out of their substance of choice they are “quitting” until they get more.
     Do you blame a hungry person for eating breakfast in the morning? Should a person just “quit eating” if they have an overeating disorder? Answer: No.
  • Cannabinoids might help some types of eating disorders and some types of drug or alcohol addictions by providing an essential nutrient that the person might not be able to make.
  • If the body can’t make an important substance or convert substances into active forms then it becomes an essential nutrient – essential for that specific person’s daily diet.

3. Genetics of the cannabinoid system and binge eating disorder, alcohol abuse and drug addiction.

“It is important to note that, as with alcohol, marijuana, and heroin, a human genetic variant of the cannabinoid CB1 receptor gene CNR1 has been associated with susceptibility to cocaine and amphetamine dependence (Ballon et al. 2006, Comings et al. 1997; Zhang et al. 2004).
  • Behavioral Neurobiology of the Endocannabinoid System; Ch.13: Drug Addiction, (page 334, I.9.Searchworks)
Endocannabinoids: The Brain and Body’s Marijuana and Beyond is a reference textbook available online as a pdf. (I.10.Endo.pdf)  It includes information regarding the genetic differences known to be associated with binge eating disorder and other drug addictions affected by rimonabant, a chemical which inhibits the endogenous cannabinoid system. Use of rimonabant affected craving for food/sucrose and alcohol in animal research, and it was found to reduce rewarding effects of morphine/opioids, amphetamine, cocaine and diazepam in other studies.
  • Rimonabant is not in use for drug addictions because it is associated with a significantly increased risk for suicide. This is an important point to note – blocking the endogenous cannabinoid system is associated with a significant risk for suicide.
The problem with addiction to some substances or to eating excess food for some cases of over eating disorders is an underlying inability to make the cannabinoids but a remaining need for them and a hunger, an urge for “something,” something that is unknown however. And what people choose to consume in order to try to quench that unknown hunger varies from food and alcohol, to the rest of the drugs that are commonly abused.
     Dietary sources are needed instead. However our food supply has limited sources. Vine ripened produce or lemon oil, rich in aroma, are examples of a food containing cannabinoids or a similar group of aromatic and medicinal phytochemicals called terpenes. Chocolate and the herb rosemary are two other food sources. The spices cardamom, cloves, and nutmeg are also sources. Non-euphoric cannabinoids also exist and may have medicinal benefits depending on the patient’s condition. Copaiba oil is a food grade essential oil that can have non-euphoric cannabinoid content with medicinal benefits.
     Wouldn’t it be nicer to tell starving people that they are starving rather than that they are poorly motivated?
  • For more information regarding binge eating disorder, drug addiction and rimonabant: See Ch.3: Endocannabinoid Receptor Genetics and Marijuana Use, (p72-73 & 91, I.10.Endo.pdf) and Ch.13: Behavioral Effects of Endocannabinoids, mentions that research with rimonabant has helped show excessive alcohol drinking behavior and development of alcoholism may be related to genetic differences in the CB1 receptors. (p319, I.10.Endo.pdf)
  • Impulse control deficits may involve the cannabinoid system: See Ch.13: Behavioral Effects of Endocannabinoids, (pp325-330, I.10.Endocannabinoids.Full Text.pdf).
  • Schizophrenia may be related to a deficiency in the cannabinoid receptors themselves rather than being due to a deficiency in cannabinoids: See Ch.15, Neuropsychiatry: Schizophrenia, Depression, and Anxiety,; of the book Endocannabinoids: The Brain and Body’s Marijuana and Beyond: (p378, I.10.Endocannabinoids.Full Text.pdf)
More recently a gene has been identified in binge eating disorder, the gene for the cytoplasmic FMR1-interacting protein 2 (CYFIP2). (I.11.sciencedaily) The gene has a number of known variations and has allso been associated with Fragile X, an autism like condition, ADHD, autism, obsessive-compulsive behavior, and Prader-Willi Syndrome.. (I.12.ncbi.FragileX)
     The enzyme the gene CYFIP2 produces when functioning normally is involved in many metabolic pathways in the body including one that plays a role in myelination of nerve cells and one in phospholipid metabolism. (I.13.reuters) (I.14.genecards.CYFIP2)
     So an external source of cannabinoids might help a person with a problem in their CYFIP2 gene to have normal appetite control and also to protect their nerves from multiple sclerosis – which causes degeneration of myelin.  Myelin is similar to the lipid part of some of the phospholipids of the endogenous cannabinoid system. Multiple sclerosis has been associated with social anxiety and eating disorders (I.15.omicsgroup) which are also conditions associated with gene differences in the cannabinoid system. Myelin is made with sphingomyelin which is made of sphingolipids. (I.16.sphingolipids) Easy right? (I.17.mpcfaculty.lipids) Even easier – coconut oil is about 50% phospholipids and is a good source of sphingolipids. (I.18.coconut)
     I don’t know if I have any differences in my CYFIP2 gene; it was not one of the 30 genes that were included in the Nutrigenomic Screening I had done for my personal use for the “purposes of research.” Genetic screening is only used for certain conditions in standard health care currently and some types of health care claims can not be made by practitioners about genetic screening for other conditions – no guarantees in life or lab tests. The screening I had was designed to test genes commonly found to have differences associated with autism. (I.33.Nutrigenomic Screening) (p22, I.34.example of the genetic screening I had)
     I have a genetic difference in my ability to phosphorylate (I.2.wikigenes.BHMT) The gene I have a double malfunction in, BHMT, is also associated with multiple sclerosis except it seems to be with an over activity rather than too little function. Methionine and homocysteine metabolism and vitamin B12 may be involved. (I.19.BMHT.MS) Hypothyroidism may be associated with over expression of this gene: (I.20.wikigenes)
     The enzyme BHMT/1 (Call – T), Betaine-homocysteine methyltransferase (BHMT), in normal health helps produce the amino acids methionine and Dimethylglycine (DMG).
     DMG has been found helpful in ADHD, autism, allergies, alcoholism drug addiction, and chronic fatigue syndrome among other chronic issues. Methionine has been found helpful in treating depression, allergies, alcoholism and schizophrenia among other chronic issues. Since learning of the difference in my genetics I have been taking the two amino acids in a powder form that I add to a glass of water. It doesn’t taste good but it leaves me feeling more energetic and with a more positive mood.
     What it tasted most like was a tart red wine and the nutrient content of red wine does contain free amino acids, so someone with a problem with the BHMT gene may have problems with unidentified cravings that wine seem to help. While I did love red wine, it didn’t love me. It was one of the first triggers for severe migraines that I identified and started avoiding. A painkiller did help with migraine pain somewhat but zero time spent with a migraine is my goal.
     I found based on the information that is available regarding dose, that a half teaspoon of each of the amino acid powders helped my mood without causing such an energy boost that it caused an increased heart rate or prevented me from going to sleep. I tried one teaspoon of each initially and found that it was too much of an energy boost. Both amino acids can act as activating chemicals within the brain.
     I have early symptoms of neuropathy, I would rather prevent multiple sclerosis than to learn more about it first hand. Taking the supplemental methionine may be helping my body do what it needs to do to prevent an autoimmune breakdown of my myelin.

4. Sometimes people are wrong – Nixon was wrong.

If the good people, in their wisdom, shall see fit to keep me in the background, I have been too familiar with disappointments to be very much chagrined.” – Abraham Lincoln (1809-1894), (p 634, I.23)
Hemp fiber was essential for rope and strong fabric. Thomas Jefferson grew hemp and is said to have smoked it too. It is time to stop being disappointed in loved ones who are likely suffering from a metabolic deficiency that leaves them susceptible to substance abuse or overeating and instead start accepting that they have needs that a person of average health doesn’t have or may not have to the same extent. Many nutrients are needed in a just right amount, not too little or too much.
     Cannabinoids are powerful and can be consumed in excess however it does not have the toxicity and deadliness of many other substances that are abused, including alcohol.
     The American Medical Association has recommended that marijuana be rescheduled as an herb with medicinal benefits. (I.24.AMA resolution) (I.25.veteransformedicalmarijuana)
     Rescheduling marijuana as a medicinal plant would free academic researchers to study its medicinal benefits. As a “Scheduled Substance” currently research studies are only supposed to assess toxicity and rehabilitation areas rather than design experiments assessing the medicinal value. Currently the synthetic form of the main euphoric cannabinoid, THC, is listed at a “safer” level of risk than the marijuana plant itself.
     The synthetic forms can be even more dangerous as they are more concentrated and are in isolation rather than also providing the non-euphoric cannabinoids that are found in most strains of marijuana and which have calming effects. Synthetic THC or THC in excess can cause paranoia and other mood symptoms that would have been unknown to Thomas Jefferson when he enjoyed smoking marijuana that was milder in the amount of THC it likely contained and more likely to be balanced with non-euphoric cannabinoids.
     The problem with black market development of a product is that it is often being designed to maximize the “buzz” or “euphoria” rather than the medicinal or pain killing effects. However, there is not that much “euphoria” felt by the person with chronic illness who is using a larger quantity of marijuana everyday due to an underlying inability to make cannabinoids because a tolerance is built up and they simply need some of the herb or other concentrated sources of cannabinoids every day just to maintain a state of health and function that is a little closer to everyone else’s “normal function“.    

     The person with a chronic need wants an herbal medicine that has a balanced variety of cannabinoids that treats a variety of symptoms, not just the euphoria inducing THC that can lead to overdose symptoms of a racing heart, feeling very chilled, and paranoia or anger combined with extra energy, so manic behavior might be a risk with an overdose reaction. Real lime or lemon juice products that are concentrated rather than being a watery lemonade may help counteract some of the mood changes associated with an overdose of THC. More on lemon oil is included in the next section. 

5. Medical Marijuana helps reduce opioid use, which can save lives.

     We currently have an epidemic of deaths due to opioid medications, prescription and black market drugs. The increase in deaths is due in part to the over prescription of opioid painkillers by the medical community but it is also due to black market substitutes that have been introduced in recent years. One type is particularly potent and is being sold as something else so consumers wouldn’t even know that they were being given a stronger version of an opioid medication than the prescription medication they were told they were purchasing on the black market – key point – don’t buy drugs on the black market because you don’t know what they might contain.
     This likely seems an obvious point which, honestly, even the drug addict knows that but their need is great enough during withdrawal that they may be more likely to take risks.
     Women may be especially at risk for opioid addiction whether it is due to differences in size or physiology is unknown. Addiction to opioids seems to occur for women at lower doses of the medication that were taken for a shorter amount of time than for men who become addicted. Women may be more susceptible to the cravings for the drug. (I.27.jotopr)
     In states with medicinal marijuana sales of painkillers dropped,which would include the opioids. Physicians are not comfortable with the inability to “prescribe” a set dose. “Take two hits and call me in the morning?” was asked in jest or in seriousness by a psychiatry professor, Deepak D’Souza, who also has researched marijuana. (I.28.npr)
     Deaths due to overdoses of opioids have also decreased in those states. (I.29.nbcnews) The cannabinoid and opioid receptor systems may both be involved in the regulation of appetite. Levels of the hormone leptin may be increased in response to CB1 receptors in the hypothalamus. Leptin and other appetite hormones may then “control opioid-regulated feeding…(Verty et al., 2003).” See Ch.13: Behavioral Effects of Endocannabinoids, (p313, I.10.Endocannabinoids.Full Text.pdf).
     Since marijuana use seems to be saving lives and has low toxicity risks, it doesn’t seem like how big a dose is as big a question as how to get a safe reliable supply to more patients in pain. The answer does exist but it is one a physician or psychiatrist is unlikely to like – the dose varies based on the person’s genetics and metabolism, the supply of nutrients available, tolerance, etc.; the answer is “It depends.” But the medication is so safe that worries about “too much” are really unnecessary, except possibly for more concentrated synthetic sources or extracted cannabinoid oil products.
     Signs of “too much” THC or synthetic THC can include a racing heartbeat, which very, very rarely has caused a couple/very few deaths. To the user first experiencing the racing heartbeat of excess THC, it may be frightening and feel like a panic attack. Relax it slows down again and only people with a pre-existing heart condition may be at risk during the time that the heart-rate is rapid.
     So if you have a weak heart – avoid excessive amounts of THC. The rapid heart-rate doesn’t occur at low doses. It may be accompanied a feeling of being chilled, and suddenly needing a jacket. Anxiety or anger may occur with excess THC or synthetic THC or during withdrawal from an excessive amount.
     The aromatic terpenes in citrus oil can have a calming effect if anxiety is a problem after consuming marijuana. Pinene from pistachio nuts may also be helpful, but a glass of lemonade might help the mood more quickly than eating pistachios because they would take longer to digest. (I.26.fastcompany)
     Artificial lemon flavored products wouldn’t help, only real lemon or lime juice products would help calm a mood unsettled by an excess or imbalance of THC. The plant contains many active phytochemicals which can include terpenes and other cannabinoids that are calming to the mood rather than causing euphoria. THC is the only cannabinoid in marijuana that causes euphoria.
     Opioid medications also cause euphoria – so why is one more socially acceptable than the other? Smoking is dirty and smelly and – the easiest way to not overdose.
     Eating products or the concentrated synthetic dose in one single sitting can leave a person feeling symptoms of overdose about one hour later, far too late to stop at half a serving or a small taste to see how you might handle that particular product and/or the strain that was used in it. Different strains of the plant can cause very different symptoms and help different types of symptoms, so the question of “how much” is less significant than which strain to use and the method to use to consume it.
     Smoking provides fairly instant changes to the mood so it is easy to tell if you’re getting more anxious or developing a rapid heart rate. Strains of marijuana can vary a lot, some types may cause the anxiety symptoms, while others would just cause the stereotypical “couchlock” – falling asleep. While setting fire to the couch might be a very real risk, otherwise, no danger other than possibly drooling a little and looking stupid. Looking stupid is better than looking dead from an opioid overdose – in my opinion – and I am a medical marijuana patient who has experienced these symptoms and read research about safe use.

6. Resources for help or just someone to talk to:

  • National Helpline: Substance Abuse and Mental Health Services Administration: “SAMHSA’s National Helpline, 1-800-662-HELP (4357), (also known as the Treatment Referral Routing Service), is a free, confidential, 24/7, 365-day-a-year treatment referral and information service (in English and Spanish) for individuals and families facing mental and/or substance use disorders.” (1.30samhsa.org)
  • Rape, Abuse and Incest National Network, RAINN Hotline: 1-800-656-HOPE, (1.31RAINN.)
  • U.S. National Suicide Prevention Hotline: “Call 1-800-273-8255, Available 24 hours everyday.” (1.32.suicidepreventionlifeline.org)

Help is only helpful when you accept it. Recognizing that you need it is the first step.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Links and References:

(I’ll finish this list later, I’ve learned a lazy editing tactic is to skip the footnote numbers until the final draft is complete.)

  1. Disease,” Oxford Dictionaries (I.1.disease)
  2. BHMT,” wikigenes.org, http://www.wikigenes.org/e/gene/e/635.html (I.wikigenes.BHMT)
  3. Glycerophospholipid biosynthesis,
  4. metabolism ,
  5. Phospholipid metabolism,
  6. (I.6.genecards.BHMT) [http://www.genecards.org/cgi-bin/carddisp.pl?gene=BHMT] (I.6.genecards.BHMT)
  7. (I.7.genecards.phosphorylation) [http://pathcards.genecards.org/card/cdk-mediated_phosphorylation_and_removal_of_cdc6] (I.genecards.phosphorylation)
  8. Leukotriene,” (I.8.scbt.com)
  9. Behavioral Neurobiology of the Endocannabinoid System; Ch.13: Drug Addiction, (page 334, I.9.Searchworks)  Behavioral Neurobiology of the Endocannabinoid System, Editors David Kendall and Stephen Alexander (Springer, 2009, Nottingham, U.K.). (I.Searchworks)
  10. Endocannabinoids: The Brain and Body’s Marijuana and Beyond, (CRC Press, 2006, Boca Raton, FL), Chapter Three, Endocannabinoid Receptor Genetics and Marijuana Use, editor and chapter by Emmanuel S. Onaivi, et al., (pages 72-73, 91, and 333), Chapter 15, Neuropsychiatry: Schizophrenia, Depression, and Anxiety, chapter by Ester Fride and Ethan Russo, (page 378), (I.10.Endocannabinoids: FullText pdf)
  11. (I.11.sciencedaily) Genetic risk factor for binge eating discovered. Sciencedaily.com, Oct. 26, 2016,  https://www.sciencedaily.com/releases/2016/10/161026170543.htm (I.sciencedaily)
  12. (I.12.ncbi.FragileX) Sabiha Abekhoukh and Barbara Bardoni, CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome, Front Cell Neurosci. 2014; 8: 81., ncbi.nlm.nih.gov https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973919/ (I.ncbi.FragileX)
  13. (I.13.reuters) Pathway Maps: G-protein signaling_RAC1 in cellular process, Life Sciences Research, thomsonreuters.com, http://lsresearch.thomsonreuters.com/maps/383 (I.reuters)
  14. (I.14.genecards.CYFIP2) CYFIP2, genecards.org,  http://www.genecards.org/cgi-bin/carddisp.pl?gene=CYFIP2 (I.genecards.CYFIP2)
  15. (I.15.omicsgroup) Shahla Mohamadirizi1*, Vahid Shaygannejad2, Soheila Mohamadirizi3 and Marjan Mohamadirizi4, Eating disorders in a multiple sclerosis clinical population and its association with social anxiety.   https://www.omicsgroup.org/journals/eating-disorders-in-a-multiple-sclerosis-clinical-population-and-its-associationwith-social-anxiety-2376-0389-1000183.php?aid=82623 (I.omicsgroup)
  16. (I.16.sphingolipids)
  17. (I17..mpcfaculty.lipids)
  18. (I.18.coconut) Handbook of Plant-Based Fermented Food and Beverage Technology, Second Edition, edited by Y. H. Hui, E. Özgül Evranuz  CRC Press, May 17, 2012, https://books.google.com/books?id=5fvRBQAAQBAJ&pg=PA669&lpg=PA669&dq=sphingolipids+in+coconut&source=bl&ots=QlgC46XLn8&sig=Y5AiDM4oUTBp9BS3aOKCtWK0Fbk&hl=en&sa=X&ved=0ahUKEwiQuL-wmdbVAhUG7CYKHXZCCxsQ6AEILjAB#v=onepage&q=sphingolipids%20in%20coconut&f=false
  19. (I.19.BMHT.MS) Naveen Kumar Singhal, et al., Changes in Methionine Metabolism and Histone H3 Trimethylation Are Linked to Mitochondrial Defects in Multiple Sclerosis. J of Neuroscience Vol 35, Issue 45, 2015 PAGES: 15170-15186 ISSN: 0270-6474 https://www.researchgate.net/profile/Rohan_Dassanayake2/publication/283710653_Changes_in_Methionine_Metabolism_and_Histone_H3_Trimethylation_Are_Linked_to_Mitochondrial_Defects_in_Multiple_Sclerosis/links/5693c64508aeab58a9a2aaf3.pdf (I.BMHT.MS)
  20. (I.20.wikigenes)
  21. ( methionine )
  22. ( Dimethylglycine (DMG).
  23. John Bartlett, Familiar Quotations, 14th Ed., 1910, (p 634, I.23)
  24. (I.24.AMA resolution) American Medical Association Medical Student Section, Resolution 2, JUne 8, 2008, http://www.oregon.gov/pharmacy/Imports/Marijuana/Public/AMA_MedStudentSectionResolution.pdf (I.AMA resolution)
  25. (I.25.veteransformedicalmarijuana) AMA Votes to Reschedule Medical Marijuana, VMCA, http://www.veteransformedicalmarijuana.org/node/67 (I.veteransformedicalmarijuana)
  26. (I.26.fastcompany) Chris Dannen, Three Beginner Mistakes to Avoid When Eating Cannabis, fastcompany.com Sept. 10, 2014, https://www.fastcompany.com/3035175/three-beginner-mistakes-to-avoid-when-eating-cannabis (I.fastcompany)
  27. (I.27.jotopr) Karen Barth, New Study Shows Women are Hit the Hardest as Opioid Epidemic Sweeps the Country. Jotopr.com, Feb. 27, 2017, https://jotopr.com/new-study-shows-women-are-hit-hardest-as-opioid-epidemic-sweeps-the-country/?utm_source=ReviveOldPost&utm_medium=social&utm_campaign=ReviveOldPost (I.jotopr)
  28. (I.28.npr) Shefali Luthra, After Medical Marijuana Legalized, Medicare Prescriptions Drop for Many Drugs. npr.org, July 6, 2016, http://www.npr.org/sections/health-shots/2016/07/06/484977159/after-medical-marijuana-legalized-medicare-prescriptions-drop-for-many-drugs (I.npr)
  29. Reuters, Legalized Marijuana Could Help Curb the Opioid Epidemic, Study Finds. March 27, 2017,nbcnews.com,  http://www.nbcnews.com/health/health-news/legalized-marijuana-could-help-curb-opioid-epidemic-study-finds-n739301 (I.29.nbcnews)
  30. National Helpline: Substance Abuse and Mental Health Services Administration: 1-800-662-HELP (4357), (1.30samhsa.org)
  31. Rape, Abuse and Incest National Network, RAINN Hotline: 1-800-656-HOPE, (1.31RAINN.)
  32. U.S. National Suicide Prevention Hotline:  1-800-273-8255, (1.32.suicidepreventionlifeline.org)
  33. Amy Yasko, Nutrigenomic Testing, Holistic Health International, http://www.holisticheal.com/health-tests/nutrigenomic-testing (I.33.Nutrigenomic Screening)
  34. Amy Yasko, Methylation Analysis Pathway: John Doe, Neurological Research Institute, http://www.holisticheal.com/media/wysiwyg/John_Doe_MPA_05.19.17.pdf (p22, I.34.example of the genetic screening I had)