Tag: THC

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G3.6.1: “Calcium sparklets” and Oxidative Stress

G3.6.1.1: “Calcium sparklet” – a burst of energy from a TRP channel; can be measured but not seen.

Calcium and magnesium are both electrically active ions – ions are atoms of an individual element rather than being a more complex molecule that is made of a combination of several different elements. Water is made of one atom of oxygen and two atoms of hydrogen for example. Calcium and magnesium are both individual elements rather than being molecules. They are both considered to be essential trace minerals that we need in our diet on a regular basis or we would get sick and eventually die without enough of either one. They each have an ionic charge of +2 and can exchange one or two electrons.

Ions can typically donate or receive electricity by sharing or receiving one or two electrons. Sodium and potassium are essential trace minerals with a charge of +1, they can exchange one electron. the energy is in the form of electromagnetic radiation, which is also what make “light., (G3.105), so while our human eyes may be too big to detect the “light” of a microscopic burst of energy from the flow of calcium across a TRP channel – maybe a tiny spark might be visible to that microscopic world.

Magnesium sparklers – a spark of life.

Many people may be more familiar with holiday “magnesium sparklers” than with “calcium sparklets” as the mineral magnesium is flammable and can be used to make Fourth of July sparklers, which are a festive sight during celebrations of the U.S. Independence Day.

 

G3.6.1.2: Calcium sparklets can be caused by high blood sugar – hyperglycemia. (G3.108)

  • Calcium and diabetic vascular dysfunction, Focus on “Elevated Ca2+sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells: “This report is also the first to describe a molecular mechanism by which hyperglycemia produces increased [Ca2+]i in VSM and suggests that this mechanism of Ca2+ sparklet activation may be uniquely initiated by hyperglycemia.” (G3.108)

Calcium sparklets are not a good thing, not in excess at least, they represent an open gate into the interior of the cell, allowing a crowd to enter instead of invited guests only. (G3.106, G3.107, G3.108) Too much energy or other types of chemicals suddenly being available on the interior of a cell can over activate it and even lead to the death of the cell.

“Excitotoxins” refers to chemicals that can cause a cell to become overactive if the chemical is allowed to enter the interior of the cell. TRP channels are the gateway that selectively lets in some things and keeps out everything else. If TRP channels aren’t able to do their job properly, then too much of “everything else” is able to rush into the cell and that may be what happens for some people more than others. If the everything else includes MSG from a recent meal or the alternative sweetener aspartame then overactivity of the cell may result.

Calcium itself acts as a messenger chemical that can trigger action when it is on the interior of the cell and can act as an “excitotoxin” and lead to the death of cells. During normal health magnesium is in greater abundance inside of the cell and calcium is found in larger amounts than magnesium in the fluid surrounding the cells and within blood plasma.

The alternative sweetener aspartame, brand name Nutrasweet, or the more concentrated version Neotame may both act as excitotoxins. The food flavoring ingredient monosodium glutamate also may over excite cells. What they have in common is a free amino acid that can act as a signal to the brain cell to tell it to get busy doing whatever it usually does, “just get busy, go, keep going, there’s no “off” here, move it . . .” an excitotoxin is the worse drill sergeant ever, and eventually the cell runs out of nutrients and/or builds up waste products of metabolism, and may even die. That’s a dramatization, but roughly that is the story – “oxidative stress” equals “waste products of metabolism.”

G3.6.1.3: Oxidative Stress > metabolic waste products > “TRPA1 sparklets.”

To return to the excerpt and list from the previous section, the first list of chemicals known to activate TRPA1 channels included waste products of metabolism. Metabolism is the chemical deconstruction of a larger molecule into smaller parts. Enzymes are necessary that are specific to the exact type of chemical transformation. Toxins can collect without enough of the right type of enzyme to metabolize them into smaller chemicals that are safe or can be excreted more easily by the kidneys.

  • The summary and excerpt: The TRPA1 receptor is directly activated by calcium levels inside of the cell, and a variety of toxins or “noxious” (irritating) substances that are produced as a normal part of “oxidative stress” otherwise known as “inflammation” including, “4-hydroxy-2-nonenal, hydrogen peroxide, hypochloride, hydrogen sulphide, 15-delta prostaglandin J2 [25–28].” and irritants from the environment or diet can also activate the TRPA1 receptor, *1.“mustard oil (allyl isothiocyanate: AITC) [29], *2. cinnamaldehyde [30, 31], *3. allicin [32, 33] and *4. formalin [34]…”. (G3.25) Serotonin and other “Inflammatory mediators, such as bradykinin…[19, 35]” (G3.25) can make the receptors more sensitive which can lead to increased responsiveness of nerve endings – more pain (G3.25) or itch. (G3.24)
  • And a new excerpt about oxidative stress and metabolites that are produced within the body, some would activate TRPA1 channels: “Reactive oxygen species (ROS)”(G3.93) formed from oxidative stress were found to activate the TRPA1 channels in the cerebral arteries but not in other areas of the vascular system, “NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries.” (G3.93).

“Increased TRPA1 sparklet frequency” (G3.93) can be caused by chemicals that are produced during oxidative stress – which can be caused by emotional or physical reasons. The significance is that it means more calcium or other chemicals could be rushing through the open channel in the membrane wall. Calcium can also be an activating substance as was mentioned in the first summary and excerpt. This is complex chemistry and is just meant to be an introduction to the topic of oxidative stress in relation to conditions of chronic pain and itch. That second excerpt is from an additional list and is about chronic migraine – who are the people who might be more likely to have overactive TRPA1 channels? – quite a few besides those with sensitive skin or pain problems. A more complete list is in the next section but it is likely an incomplete list.

G3.6.1.4: “People with overactive TRPA1 channels” may include people with symptoms of:

  • “chronic itch” (G3.24);
  • “chronic arthritis” (G3.25);
  • “inflammatory bowel diseases (IBD: ulcerative colitis, Crohn’s disease)” (G3.76);
  • people with an Irritable Bowel Syndrome (IBS) may also have had a history of child trauma, domestic violence or sexual abuse:  “As Leserman and Drossman (2007) note, patients with a history of physical or sexual abuse in childhood, or intimate partner violence, have 1.5 to 2 times the risk of reporting gastrointestinal symptoms or having a functional gastrointestinal disorder.,” (G3.94); and trauma survivors may also have comorbid chronic pain conditions such as fibromyalgia: “Van Houdenhove et al. (in press) found that 64% of patients in a group for FMS or Chronic Fatigue Syndrome had at least one type of either child or adult trauma. More concerning was that 39% of the group reported abuse during childhood and as adults, indicating a lifelong pattern of abuse. Although these findings are somewhat mixed,” (G3.94);
  • a medical hypothesis suggests TRPA1 channels may be involved in many chronic pain and airway conditions and also diabetes: “Furthermore, TRPA1 is also involved in persistent to chronic painful states such as inflammation, neuropathic pain, diabetes, fibromyalgia, bronchitis and emphysema.,” (G3.95);
  • symptoms of “diabetic hypersensitivity” (G3.96)  might feel or sound like: “Don’t touch me it hurts.” Symptoms of mechanical hypersensitivity may feel like being physically over sensitive to any sensation. Any touch may be experienced as “pain” or “itch” instead of being pleasant. Symptoms of hypersensitivity associated with diabetes have been found to respond to TRPA1 channel antagonists – chemical inhibitors – a medicine in other words. (G3.96) Reducing the over activity of the TRPA1 channels would help resolve the underlying problem but overmedicating would be a risk. Too much inhibition, too much of the medication could be dangerous to long-term health as the TRPA1 channels play important functions throughout the body.;
  • “chronic migraine,” “cluster headache,” (G3.77); “Reactive oxygen species (ROS)”(G3.93) formed from oxidative stress were found to activate the TRPA1 channels in the cerebral arteries but not in other areas of the vascular system, “NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries.” (G3.93);
  • preeclampsia may involve overactivity of the TRPA1 channel, it also has mechanico-sensitive properties or other TRP channels  – more research is needed: (G3.78, G3.79, G3.80, G3.81, G3.82, G3.83);
  • chronic respiratory conditions involving “airway inflammation” such as “asthma” or “COPD,” overly dry airways may be a problem causing difficulty with completely emptying the lungs (G3.84);
  • cardiac issues such as Congestive Heart Failure may involve TRPC channels, (G3.85), which are not activated by the food type items on the list below but which are likely to be activated by cannabinoids which are #8 on the list below, (G3.89, G3.90);
  • male infertility due to motility issues in the sperm, (G3.87, G3.88). TRPC channels (G3.89) can be activated by Phospholipase C (G3.90) which suggests they can be activated by other phospholipids as well. So a deficiency or gene difference affecting their production endogenously may be involved in male infertility involving motility. More research is needed. In the meantime formaldehyde is definitely not beneficial for fertility in women or men. There is more research available regarding exposure risks for female reproductive health (G3.91) than for males.(G3.92)

G3.6.1.5: People with overactive TRPA1 channels may be sensitive to:

And now we return to the list from the section on the last page. It is greatly expanded now with more food items and other possible substances that can activate TRPA1 channels and TRPC channels, gathered from the research about the list of conditions that might be at increased risk for overactive TRP channels. The TRP channels are all membrane channels but there are many individual types and several categories. The basic form and function is similar however and is described and illustrated in an article about the TRPC channel and cardiohypertrophy associated with Congestive Heart Failure, which was included in the previous list.  (G3.85)

  1. Mustard:  “mustard oil”, (G3.25); “Isothiocyante derivatives constitute the main pungent ingredients in wasabi (allyl isothiocyanate), yellow mustard (benzyl isothiocyanate), Brussels sprouts (phenylethyl isothiocyanate), nasturtium seeds (isopropyl isothiocyanate) and capers (methyl isothiocyanate). Allyl isothiocyanate is the major active ingredient in mustard oil.” (G3.67); Yellow mustard is the condiment used in many ways in cooking. It is a spice made from a small seed that is dried and powdered. It has medicinal value for a variety of conditions. Mustard oil applied topically as a massage oil is reported to provide relief for pain due to arthritis. (G3.68) Wasabi is a type of horseradish like seasoning used in Japanese cooking.It is a root vegetable that also has many medicinal benefits. (G3.72) Brussel sprouts are a vegetable that look like tiny cabbages and are botanically related to cabbage. They are very healthy in many ways and might be worth trying in smaller quantities, steamed more thoroughly rather than raw or lightly steamed or sauteed.(G3.71) Nasturtium seeds can be pickled and used in cooking similarly to capers. (G3.69) Capers are a pickled product with a peppery taste which resemble peppercorns, however they are made of the springtime buds of the caper plant which are picked when they are the size of peppercorns, and are preserved in a pickling brine. Capers are used in salads or savory dishes. (G3.70)
  2. Cinnamon:  “cinnamaldehyde”, (G3.25); Cinnamon is a spice used in cooking which is made from the inner layer of bark from a plant. It is dried and powdered and used in baking or savory dishes. Medicinally a ½ teaspoon of cinnamon per day has been found helpful for improving blood sugar control. A half teaspoon is a large amount for a single serving but some people enjoy it at breakfast stirred into a bowl of hot cereal. (G3.43, G3.67))
  3. Onion or Garlic: “allicin”, (G3.25); (G3.41) To be more precise – the raw garlic contains allicin; baked or roasted garlic would be less likely to still have allicin present. It would likely be similar for onion, raw or lightly sauteed might be a problem while caramelized, baked, or roasted might be tolerable. (G3.67)
  4. Formaldehyde: “formalin“, (G3.25); chemically the two are very similar: (G3.42); and formaldehyde is found in the environment and as a metabolite of some alternative sweeteners and other dietary sources. (G3.56) See the next section (which was posted first on this site) for more information on sources and ways to avoid Formaldehyde.
  5. “(Winter-green),” (G3.67); Wintergreen is a natural flavoring herb in the mint family. It is typically used as an essential oil as a flavoring in many foods and other types of products. It has medicinal benefits related to it containing the chemical that acts as the pain killing ingredient of aspirin.(G3.73)
  6. “eugenol (Cloves)” (G3.67); Cloves are used in a traditional holiday decoration to make an aromatic dried ornament from an orange. The tack like cloves are poked into the rind of a fresh orange and then the fruit is allowed to dry and it shrinks and smells good for a long time without spoiling if it was allowed to dry thoroughly. Cloves for use in cooking or baking are ground into a powder and used in baking and also in savory dishes and chutneys. The spice and essential oil also have medicinal benefits. The essential oil has numbing properties and in traditional medicine is applied topically to the gums for relieving the pain of a toothache.(G3.74)
  7. “and gingerol (Ginger).” (G3.67); – a root with medicinal properties and commonly used in cooking as a minced or chopped vegetable and is used in dried and powdered form as a spice in savory and baked dishes and may be served dried and candied and used as a candy or chopped and used in baked goods or chutneys.Ginger has many medicinal benefits and has been found helpful for the relief of arthritis pain when used in a quantity that would be equal to about a half teaspoon of the dried powder. Pregnant women should avoid large quantities of the herb or vegetable or candy as miscarriage may be a risk. (G3.75)
  8. “Δ9-tetrahydro-cannabinol (THC) and cannabinol (an oxidation product of THC).” (G3.67); The herb cannabis also known as marijuana has many medicinal benefits and  is the most significant source of THC but some foods also have some cannabinoid content. The topic of food sources of cannabinoids and risks and safe use warnings are discussed in the section I. Addiction or Starvation?. Medicinal benefits are discussed in detail in the textbook Endocannabinoids: The Brain and Body’s Marijuana and Beyond, editor and Chapter Three by Emmanuel S. Onaivi, et al., (CRC Press, 2006, Boca Raton, FL), which is available online as a pdf:  (I.Endocannabinoids: Full Text pdf)

See a healthcare provider for medical advice, diagnosis or treatment.

  • 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.
  • The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)

References: 

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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.
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. 

(I.26.fastcompany)

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)