EPIGIRL 2

EpiGirl is a fictional character in the SPARS epidemic scenario that was published in 2017. EpiGirl collates the adverse reaction reports from VAERS and other patient forums and it seems worse. The scenario works through that issue by suggesting it was duplicated records.

2017 SPARS Report –

A database is needed, collecting data is needed – that is basic to experimental design – collect data, all the data. And in this case, all the data includes adverse reactions in the experimental group or in those with passive exposure reactions. That is even stated in the branded experimental design literature. In this case data is not being collected and definitions are being changed so the data that is being collected does not match the redefined label.

A whistleblower nurse shared what is happening with the data regarding who is in the hospitals with Covid currently – the experimental group (vac) or the control group (unvac)? The definition was changed to call anyone within 14 days of an injection unvaccinated, allegedly because their antibodies wouldn’t be expected to be elevated enough to be protective yet. That may be true but it doesn’t change the fact the person was in the experimental group – did receive an injection, or a second injection – they are no longer in the ‘unvaccinated’ control group immediately after getting the first injection.

The adverse reactions tend to occur early also, within the first few days after an injection, or second one, according to the nurse. See the full story here: twitter.com/AxelSavage4/status/1437624425281511429?s=20.

From the replies:

Benny Nomad@BennySeattle· Replying to @AxelSavage4 : “Have you considered that what you are describing is fraud? They are calling everyone who has had their first shot un-vaxxed, and if they have had the second shot, for the following 14 days they are still considered un-vaxxed. How is that not fraud?

LibertySavage@AxelSavage4·That’s exactly what it is”

The first injection or exposure can prime an allergy-like over response of the immune system to occur the next time the antigen is present in the body. People who were already sick with CoV may be at more risk of an over-reaction to an injection, because their immune system was primed by the earlier sickness.

Another medical professional shared concerns over underreporting of adverse reactions, to the US VAERS adverse reaction database. Doctors are being threatened to not report cases to the system. See: EXCLUSIVE: COVID Whistleblower Claims the VAERS Reporting Database Tracking Vaccine Complications is WRONG and Undercounting by a Factor of 100! (thegatewaypundit.com/2021/09)

170,000 comments about adverse reactions have been submitted to a news website:

News article about the ABC website postings: Unexpected and heartbreaking: Thousands flood ABC affiliate’s Facebook page with vaccination horror stories. (Sept 13, 2021, worldtribune.com) “39,000 responses (as of mid-day Sept. 13)

We need reliable data that has been double checked for identity, confidentially, in order to prevent duplication of record entries. We need reliable data that is contained in a cybersecure location on a hosting platform that is independent from technology that may be compromised regarding reliability, on Linux systems for example.

  • *Guidance is being provided on Telegram, if you are interested in learning about using Linux instead of Windows type systems. Sign up on Telegram first, and then search for and follow ‘Jeffrey Peterson,’ in his pinned posts look for the discussion Chat room link: @jptchat. People are helping each other get set up and Jeffrey also provides guidance and has tutorials.
  • Invite link: JP’s technology chat: https://t.me/jptchat

EPIGIRL 2 will need funding and a lot of volunteers around the world. These adverse reactions are happening around the world. The injection batches were not claimed to be or required to be, all the same product, so different locations may have been test cases for different experimental batches. Adverse reactions may cluster by batch/location, not just by ethnic/genetic or health differences. Without reliable data at an international level, those patterns will not be revealed. Giving us the need for EPIGIRL 2 – Epidemiologic Patterns in Genetics; Injection Reaction Log – an Extremely Professional, International, Giant, Injection Reaction Log. EPIGIRL squared – two names to represent the two strands of the double helix of a DNA molecule.

The recommendations made by the committee investigating adverse reactions should be included as the basis of EPIGIRL 2 (from the last post, Chimeric Spike, with Prion-like areas). If we are to follow the ‘science’ – that is what the science says:

Immunization Safety Review Committee

  • Surveillance of adverse events related to vaccines is important and should be strengthened in several ways:
  • The committee recommends that standardized case definitions for adverse events be adopted.
  • The committee recommends that formal guidelines or criteria be developed for using VAERS data to study adverse events.
  • The committee recommends the continued use of large-linked databases, active surveillance, and other tools to evaluate potential vaccine-related adverse events.
  • The committee supports the development of Clinical Immunization Safety Assessment (CISA) centers to improve understanding of adverse events at the individual level.
  • One area of complementary research that the committee continues to recommend is surveillance of ASD* as exposure to thimerosal declines. (*Autism Spectrum Disorder)
  • The committee recommends increased efforts to quantify the level of prenatal and postnatal exposure to thimerosal and other forms of mercury in infants, children, and pregnant women. 
  • 2. Excerpt : Immunization Safety Review: Vaccines & AutismBOX 2, Comm. Conclusions & Rec. Institute of Medicine (US) Immunization Safety Review Committee. Washington (DC): National Academies Press (US); 2004. https://www.ncbi.nlm.nih.gov/books/NBK25349/#a2000af8fddd00068

The SPARS report predicted an EpiGirl – we need her, badly, desperately – truthfully. This is dangerous, and is a genocide because some are more at risk than others.

Methylation: Anyone with methylation gene defects would be more at risk for epigenetic gene changes which can lead to conditions like POTS. See: Epigenetic changes may also be involved in Covid19 or LongCovid, Nov 18, 2020. They would be healthier by not taking standard B supplements which have unmethylated forms of B12 and folate. Instead seek out food sources that aren’t the supplement fortified types, and/or methylated forms of folate and B12 (not folic acid or cyanocobalamin – yes the standard form of B12 used in the US contains cyanide and taking too much of it for too long can lead to cyanide poisoning – does it make sense to use cyanide in a dietary supplement? NO, but that is off-topic.).

BHMT: People with a BHMT gene allele would also be more at risk for inflammatory membrane break-down. There is an ethnic difference in rate – people with Caucasian or African ancestry are more likely to have a defective BHMT gene allele than people of Asian ancestry. See: Cannabinoids are made with the BHMT gene (and others). Feb, 25, 2021.

Glyphosate: Glyphosate residue is also likely a factor in rate of severe reactions in CoV illness or injection reactions. See: Glyphosate and COVID-19, Oct 25, 2020, it has dietary tips for trying to reduce glyphosate intake and improve the negative effects. Glyphosate can increase the risk of misfolded proteins and may be adding to the out of control inflammation. It also likely is increasing the risk of low vitamin D and minerals such as manganese and the amino acid methionine. Manganese is really essential for mitochondria to function normally. Tracking patterns of severity of illness over geographic regions that produce or use more biofuel made with biomass from glyphosate crops is a need. Asking people with adverse reactions, and the control group, those without, to have a urine test for glyphosate residue, is a need. Reliable data requires collecting data in a method that is consistent and has quality control standards to assure the results are reliable. How a sample is taken, stored, and tested, all may affect quality of the results.

Citric Acid Cycle Nutrients & Cofactors: The spike protein is harming mitochondria, which then the debris from the mitochondria, harms our cells. We need to protect our mitochondria as cancer and other chronic degenerative disease is preceded by dysfunction of mitochondria. They switch from using oxygen and the Citric Acid Cycle. For mitochondria to be able to perform the chemical reactions of Citric Acid Cycle they require that we have nineteen different nutrients and cofactors available to them – and in balance and in adequate amounts – not just ‘one’ nutrient. One problem/one cure – is not how the body works or how nutrition works.)

Cytokine storm risk: Ten to fifteen percent of the population are estimated to be at great risk for a severe cytokine storm reaction to ANY severe immune challenge, whether a vaccine or an infection. (5) See: Cytokine Storm, SIDS, autism and Vitamin C, March 29, 2020. Their bodies do not react normally to infection. Genetic screening is needed to identify the genes involved and then screen for those at risk.

In the meantime, high dose intravenous vitamin C (Marik Protocol) therapy does work well to reduce the cytokine storm from escalating and prevent the damage that can be caused by it. See: Bitter taste receptors in the lungs & Hesperidin’s decongestant properties. April 7,2020 < the food and supplement recommendations are still valid.

You can lead a horse to water, but you can’t make it drink.” Self care – includes the word self, because oneself, is in charge of self care. It is not about spa treatments or getting disabling nail extensions applied with potentially toxic chemicals. That is not self care in any kind of health sense.

The only problem with that plan is that the FDA is preventing use of the treatment for Covid related care. It does not have risky side effects and has a large amount of supportive research for similar cytokine conditions. There is no sensible reason to not approve it for use during an alleged pandemic emergency – if we have an emergency, then we should be providing emergency care to those who need it – NOT WITH-HOLDING IT, or criminalizing the use of it by independent physicians who deem it in their patient’s best interest.

Vitamin C given in advance of a vaccine may also help reduce the risk of an over-reaction of the immune system – even for animals that can make some of their own vitamin C (we can’t make any). From the post: “Giving extra vitamin C before vaccines was found to be protective even in lab animals that genetically can make vitamin C. (4)

If health is the goal – then why hasn’t everyone been told that taking vitamin C in advance of a vaccine can help prevent an over-reaction of the immune system?

If health is the goal – then why don’t we screen for the 10-15% who will have a very severe reaction, which may result in a neurological condition that lasts the rest of their life, and EXCLUDE them from being given an immune challenge? They likely would never get exposed to tetanus or many of the other rare conditions that many vaccines are designed to protect against.

If health is the goal – then why did 170,000 people reply to a news-site about the death of someone they know that occurred after a CoV injection? If the VAERS system is only collecting 1% of adverse reactions, and currently shows a death count of ~14000 (check this, yes, almost 15,000 now, and over 19,000 people were left permanently disabled after CoV injections).

If health is the goal – then why are the CoV injections seeming to be used as a euthanasia device?

Adverse reaction entry to VAERS, shared by AMM MD on Telegram, invite link if you are on Telegram:

AMM, MD
Covid vaccine AEs and other hidden truths
https://t.me/AMM_MD

WHY VACCINATE PEOPLE IN THE LAST DAYS OF THEIR LIFE? 🤬” (- AMM MD)
71 yo F “In her end days of lung cancer was not eating and drinking very little for 3d before vaccination was given. She became very ill as she was told she might and was unresponsive and in the hospice 2d later. [Died 6d after vax.]. The adverse effects of this vaccine served no purpose to be administered to an imminent end to this dying woman. The vaccines effects would never have gotten in her body till after she had died and only made her more sick and weak then she needed to be.
Write-up: Suddenly more weak , exhausted, all around much worse then she had been feeling as she was in her last days of lung cancer. Within hours of the vaccine she was worse and in 2d unresponsive and in a hospice. 4d [later] she died
.” 1637303″ (quoted from VAERS, the US adverse reaction database).

Health doesn’t seem to be the goal to me.

15 Signs That You Might Be an Abusive Government (or Relationship).
– guidance about emotional manipulation- domestic violence often dies not include outright hitting, may just be threats or verbal abuse, or silent treatment to ‘punish’ the victims.

American Frontline Doctors is a group working towards making early treatment available to anyone who wants it. Their site has a proposed Vaccine Bill of Rights: https://americasfrontlinedoctors.org/take-action/the-vaccine-bill-of-rights/

EPIGIRL 2 is needed, with a giant team, for a giant project, because a giant massacre is happening, and being lied about – ask yourself “What would Viktor Fankl do?

Answer – take notes, really good notes.

More info: Viktor Frankl on the Human Search for Meaning, Maria Popova, (brainpickings.org).

I have begun a Protocol on a supplement dispensing site – people who enroll as clients could order at a discount from the items I’ve prescreened and added dosing details for, or browse the catalog. People who enroll as clients could be later added to an EPIGIRL 2 database. Starting is a place to start.

The Protocol: Health Aids for Special Times – it has a lot of food and general health info also. I maxed out the memory and need to copy it over to a pdf though, and probably break the supplements and protocol into smaller groups. Important point to add – to detox – don’t overeat regularly. The body needs to get a little hungry to have the time and need for white blood cells to go looking around for cellular debris to clear up and reuse for nutrients. When we overeat the body and blood cells are busy coping with storing all the excess nutrients as fat or cholesterol plaque or excreting some of it.

Disclaimer: 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.

Glycine – good for our extracellular matrix & for immune protection against viral infection.

The extracellular matrix is very important for our immune defense as white blood cells actively patrol the areas surrounding cells for pathogens to remove, such as virus. Deficiency of glycine may be involved for patients with more severe COVID-19. “Glycine intake as nutritional supplement was very effective against virus infections.” (1)

Glycine is an amino acid and is important in the structure of protein chains because it is small in size and can allow folding of the long chain into a three dimensional shape. (See post: Glyphosate & COVID19) It is important within proteins (such as collagen) that help stabilize the gooey gelatin like fluid that supports the areas within our cells and surrounding our cells. There can be a thicker layer immediately surrounding cells which is called a glycocalyx, a term also used to describe the gel coating that surrounds bacteria.

Biofilms formed by an alginate-overproducing strain of Pseudomonas aeruginosa have a complex structural architecture that allows them to more resist tobramycin than biofilms formed by an isogenic nonmucoid strain. This suggests that an altered structure of biofilms cause increased resistance of pathogens against antibiotics.182 ” (9)

It helps protect our cells from bacteria, virus and other pathogens. A stronger extracellular matrix, made possible with daily supplements of 10 grams of glycine, was found to help protect against viral infection. (1)

Glycine is used often in the assembly of collagen proteins. The small glycine molecules help stabilize the triple helix shape of the long column like folded protein. The long sturdy fiber like proteins help add stability and structure to the three dimensional woven mesh of the fluid gelatin like extracellular matrix or cytoplasm within cells.

Glycine is utilized to synthesize serine, sarcosine, purines, creatine, heme group, glutathione, and collagen. Glycine is a major quantitative component of collagen. In addition, the role of glycine maintaining collagen structure is critical, as glycine residues are required to stabilize the triple helix of the collagen molecule.

The collagen fibers can be chemically stained for viewing on microscope slides. In an image here (7, 8) the collagen fibers are greenish and surround the cells that each have a brownish-black nucleus in the middle.

Extracellular matrix – our glycocalyx – our jelly lining.

We need a healthy extracellular matrix that is not too sticky and dehydrated to prevent easy flow of fluid and cells and not too watery as some solid support is needed. We are almost 70% water but it doesn’t seem like it. Magnesium is also essential for the structure of the gelatin like matrix within and surrounding cells. Each atom of magnesium can hold 18 molecules of water in an electrically stabilized cloud of water surrounding the magnesium atom. Sulfates are also essential for the stability of the matrix structure. Monosaccharides, single molecules of sugars, are also an important part of the glycocalyx on cell surfaces. Different types of monosaccarides are combined into surface glycoproteins that tell the immune system information about the cell – whether friend or foe.

Many of the extracellular proteins, such as sialic acid, also carry a negative electrical charge so there is a slight magnetic like repelling against other cells. This is critically important for holding vessel walls open – the negative charge surrounding the interior repels the other wall from collapsing inward. Some food additive emulsifiers may be too effective and also may emulsify our intestinal lining and cause bowel troubles such as diarrhea and discomfort. Gumbo file is a very healthy emulsifier from nature -powdered sassafras leaves – used by indigenous Americans.

Cells encounter surrounding surfaces first through their glycocalyx and therefore it may substantially contribute to crucial physiological and pathophysiological processes. The glycocalyx is a carbohydrate-enriched sugar coating that covers the surface of many cells, including cancer cells, presumably greatly influencing cellular interactions with their environment at the molecular scale. Its components are glycolipids, glycoproteins and glycosaminoglycans (GAGs). Glycocalyx contains large amounts of chondroitin sulfate (CS), dermatan sulfate, heparan sulfate, sialic acid, and hyaluronic acid, all negatively charged at neutral pH21.” (4)

The amino acid Glycine – available in supplements as Dimethylglycine (DMG) and Trimethylglycine (TMG).

Glycine is available as a bulk powder available from protein supplement companies focused on the weight lifting industry. Betaine is the more common name for Trimethylglycine (TMG), it and Dimethylglycine (DMG) are available as supplements in tablets or powders. It may be helpful to have both as they are used for different purposes and are not exactly equivalent. DMG can cross the blood brain barrier so it is helpful when the calming inhibitory effects of glycine are needed within the brain. (2)

Dimethylglycine (DMG) is an amino acid found naturally in plant and animal cells and in many foods such as beans, cereal grains, and liver. It is used to improve energy, boost the immune system, and to manage seizures and autism. There are some positive reports of DMG efficacy on the immune system.” (3)

DMG may be helpful for people with seizure risk – it was found to help some patients but not showing conclusively positive results overall. Some patients may have a genetic difference and need an external supply. (3)

People with a BHMT gene allele (like myself) would need an external source of DMG as the BHMT enzyme is needed to breakdown betaine to DMG. You can see the chemical steps in a graphic here: (6). From a previous post: “DMG has been found helpful in ADHD, autism, allergies, alcoholism, drug addiction, and chronic fatigue syndrome among other chronic issues.” See #3. BHMT in this post: Methylation Cycle Defects – in me – genetic screening “for research purposes only” A more recent post goes into further detail about the BHMT enzyme’s role in the production and breakdown of endocannabinoids. Cannabinoids are made with the BHMT gene (and others).

I have a double BHMT gene allele – I need an external source of DMG and methionine and it helped my mood immensely. It helps me feel more cheerful as well as more energetic. I take about a half teaspoon of each once or twice a day. A teaspoon at a time was too much energetic, seemed to cause a racing heart rate. The total amount a person needs per day may be more than that. Capsules would be giving a smaller amount, I didn’t notice much effect at all from taking a little tablet supplement and the price was significantly larger. A half teaspoon of a powder is about 2.5 grams, a tablet is usually about 500 milligrams, 0.5 grams.

I am not taking enough DMG and I hadn’t realized TMG might be helpful too – what I also hadn’t realized is TMG is betaine – so I should be taking the DMG form, I get betaine from food and I don’t do well with too much of a good source (quinoa). We need about 10 grams of glycine per day from dietary sources, yet the typical diet only provides two grams. “Glycine produced by human metabolism is much lower than the cell’s needs giving a general glycine deficiency of 10 g/day in humans.” (1)

People who took ten grams of glycine per day as a supplement had fewer viral infections than the control group. (1) “Glycine intake at the afore-mentioned dose prevents the spread of viruses by strengthening the extracellular matrix barriers against their advance. ” (1)

Nutritional supplement, 10 g/day, Glycine, promotes young strong collagen, compared to old weak collagen formed from an un-supplemented diet (~2 gr/day) and our own metabolic pathways (~3 gr/day). Graphic from: “Glycine can prevent and fight virus invasiveness by reinforcing the extracellular matrix” (Meléndez-Hevia, et al., 2021) (1)

Gee, I do want “young, strong collagen” (see above image, (1)) , so I will have my glycine drink four times a day. Breaktime, be right back. I will be so cheerful it may be hard to recognize me. 🙂

  • My “Cheerful Juice” drink reminds me of red wine without the alcohol, ~ 10 oz water, 1/2 teaspoon DMG, 1/2 tsp methionine; a little of my coffee sweetener mix: Stevia, powdered cardamom, sage and oregano; 2 ounces pomegranate juice. If I had taurine and creatine on hand I would try adding that too, but amino acids are acidic. The beverage is tart and I sip it slowly.

People with a genetic problem with methylation may have problems making a variety of proteins, as well as people with a diet deficient in the methyl donating nutrients folate, B12, betaine, choline, and the amino acid methionine. “Studies that simulated methyl-deficient diets reported disturbances in energy metabolism and protein synthesis in the liver, fatty liver, or muscle disorders.” […] “Hypomethylation has a wide spectrum of effects that include genetic, epigenetic, and metabolic alterations.” (5) Someone with a genetic problem with methylation would need to take the bioactive, methylated form of B12 and folate. The standard supplement of folic acid and cyanocobalamin are unmethylated forms and would be not helpful for someone unable to remethylate them.

Summary – to fight virus well, we need a healthy extracellular matrix for white blood cells to be able to patrol easily — and to have that we need adequate glycine in our diet and the genetic ability to digest it to Dimethylglycine (DMG).

  • We also need to stay well hydrated, and to have adequate sulfate, magnesium, protein and ATP for magnesium storage, and a wide variety of monosaccharides to make surface glycoproteins that say and do the correct functions as cell surface immune markers.
  • Epsom salt soaks may be helpful as a topical source of magnesium and sulfate for people with poor intestinal absorption of magnesium, or sometimes there can be a genetic difference limiting intestinal absorption for the person’s whole life.
  • Fiber rich plant foods are also needed to support the extracellular matrix – similar to how gelatin is supported by fruit pectin fibers when making jams.
  • We can’t do much without B vitamins – they are the body’s energy providers, essential for our mitochondria. Lack can lead to mitochondria switching to anaerobic glycolysis which may be a risk for later transition to cancer. Methylated forms of folate and B12 are needed by people with certain gene differences. Niacin in a much higher dose than would be available from the diet can help reduce inflammation, (niacin post) and also help preserve tryptophan stores for use to make serotonin and melatonin (see last post).

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.

Reference List

  1. Enrique Meléndez-Hevia, Patricia de Paz-Lugo, Guillermo Sánchez, Glycine can prevent and fight virus invasiveness by reinforcing the extracellular matrix. J Functional Foods, Vol 76, 2021, 104318, ISSN 1756-4646, https://doi.org/10.1016/j.jff.2020.104318. https://www.sciencedirect.com/science/article/pii/S1756464620305429
  2. Is TMG or DMG more effective?, davincilabs.com, https://blog.davincilabs.com/blog/is-tmg-or-dmg-more-effective
  3. Dimethylglycine: Purported Uses, mskcc.org https://www.mskcc.org/cancer-care/integrative-medicine/herbs/dimethylglycine
  4. Kanyo, N., Kovacs, K.D., Saftics, A. et al. Glycocalyx regulates the strength and kinetics of cancer cell adhesion revealed by biophysical models based on high resolution label-free optical data. Sci Rep10, 22422 (2020). https://doi.org/10.1038/s41598-020-80033-6 https://www.nature.com/articles/s41598-020-80033-6
  5. Obeid R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients. 2013;5(9):3481-3495. Published 2013 Sep 9. doi:10.3390/nu5093481 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798916/
  6. Glycine formation from betaine-trimethylglycine. image https://www.researchgate.net/figure/Glycine-formation-from-betaine-trimethylglycine-BHMT-betaine-homocysteine_fig5_320773132 from Adeva, María & Souto-Adeva, G. & Ameneiros-Rodríguez, E. & Fernández-Fernández, C. & Donapetry-García, C. & Domínguez-Montero, A.. (2018). Insulin resistance and glycine metabolism in humans. Amino Acids. 50. 10.1007/s00726-017-2508-0. https://www.researchgate.net/publication/320773132_Insulin_resistance_and_glycine_metabolism_in_humans
  7. Collagen Fiber, sciencedirect.com, https://www.sciencedirect.com/topics/medicine-and-dentistry/collagen-fiber see,
  8. Michal Miko, Ivan Varga, Chapter 6 – Histologic Examination of Peripheral Nerves, Editor(s): RS Tubbs, E Rizk, MM. Shoja, M Loukas, N Barbaro, RJ Spinner, Nerves and Nerve Injuries, Academic Press, 2015, Pages 79-89, ISBN 9780124103900, https://doi.org/10.1016/B978-0-12-410390-0.00006-8. https://www.sciencedirect.com/science/article/pii/B9780124103900000068
  9. Baral B, Mozafari MR. Strategic Moves of “Superbugs” Against Available Chemical Scaffolds: Signaling, Regulation, and Challenges. ACS Pharmacol Transl Sci. 2020;3(3):373-400. Published 2020 Apr 13. doi:10.1021/acsptsci.0c00005 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296549/

Cannabinoids are made with the BHMT gene (and others).

Cannabinoids are complex molecules we can make when genetically and nutritionally, healthy and nourished. Various genetic differences are known that cause a deficiency in endogenously made cannabinoids – phospholipids. Lack of cannabinoids negatively effects many areas of health throughout the body and brain, the mood and decision making, and appetite, and movement are all affected by cannabinoid availability.

It is discrimination to prevent research from occurring into the medical benefits of cannabis and cannabinoids and to prevent people who need an external source from having access to it. Covid and LongCovid may be increasing the number of people who might benefit from an external source as epigenetic changes or some other effects of the viral infection may be causing dysfunction in normal production of cannabinoids or some other problem.

Cannabinoids and the Cannabinoid receptors perform many functions in the body.

Membranes and growth of tissue is affected directly as building blocks that are part of the membranes, and indirectly as messenger chemicals that help promote and guide growth.

Cannabinoids also have widespread effects on immune function in addition to brain and nerve function. Cannabinoid receptors are found throughout the brain and also on white blood cells, leukocytes. Our immune function also needs endogenous, internally made, cannabinoids, or would benefit from an external source if endogenous cannabinoids were not able to be made normally.

“In human leukocytes the expression of cannabinoid receptor mRNA has been reported to be lower than that found in brain tissue. The message has, however, been detected in all subsets of leukocytes examined. The message levels are greatest in S cells, followed sequentially by natural killer cells (NK), polymorphonuclear neutrophils (PMN), T8 cells, monocytes and T4 cells.” (11)

Leukocytes help us fight viral infections and patrol for other infectious pathogens or precancerous or cancerous cells. Nutrients work together, synergy – increased power together than any on their own. We need magnesium for leukocytes to be able to perform the killing, apoptosis, and we need niacin to help with the safe removal of debris or engulfing of virus or small cells. Cell contents that are spilt into surrounding tissue has to be removed or it causes more inflammatory damage and can lead to death of other cells.

Niacin reduces inflammation for us in some direct ways and indirectly by inhibiting the NF-kB inflammatory pathway. Deficiency may increase neurodegeneration as well as reduce immune function for fighting virus or cancer.

Reports suggest that deficiency of niacin can increase the risk of neurodegeneration, immunological disorder and inflammation stress [14]. Additionally, niacin exerts its anti-inflammatory effect by suppressing the NF-κB pathway [15].” (18)

The cannabinoid system is also involved in neurotransmitter levels.

According to previous studies, CB1r [Cannabinoid Receptor type 1] is located in the locus coeruleus (LC) and in the dorsal raphe nucleus (DRN), and it regulates noradrenaline (NA) and serotonin (5HT) release, respectively, by the modulation of GABAergic and glutamatergic terminals (117118).” (17)

Problems with the endocannabinoid system can affect mood such as changes in serotonin leading to anxiety or depression. Adequate niacin intake helps preserve our serotonin levels by sparing tryptophan.

Genetic studies pointed out interesting results regarding the involvement of polymorphisms or epigenetic modifications of CNR1 as susceptibility/risk biomarkers to develop anxiety disorders. Lazary and cols. analyzed the interaction of the promoter regions of the serotonin transporter (5HTT; SLC6A4) and CNR1 genes on anxiety. Specific constellations of CB1r and 5HTT promoters were closely associated with high or low synaptic 5HT concentrations, which could result critically in the vulnerability to experience an anxiety disorder (124). Hay and cols. employed CRISPR/CAS9 technology to disrupt a highly conserved regulatory sequence (ECR1) of the gene encoding CB1r (CNR1).” (17)

Cannabinoid system differences occur in ethnic & gender groups. We may be equal but we are not all the same.

Who has the gene differences may vary with ethnicity. “With 60 DNA samples (120 alleles) for each of the 4 ethnic groups studied, we had 90% power to detect a variant allele with a true population frequency of ≥ 2% [16]. ” “Twenty-five SNPs were observed in BHMT — 17 in AA, 8 in CA, 9 in HCA, and 10 in MA subjects (Table 1 and Fig. 2 upper panel).” (1) Number of cannabinoid receptors has been found to vary based on ethnicity and gender with people of Caucasian background having the most, people with African/black background having slightly fewer, and Asian having significantly fewer than those of people with Caucasian or African ethnicity. (11)

The relative levels of the 58 kDa CBI protein 1070 E.S. Onaivi et al. from the male volunteers were, 47.4%; 39.0% and 13.6% for the White, Black and Asian blood samples respectively as shown in Fig. 3. The relative levels of the Cl31 protein in the male and female volunteers were 49.6%, 32.2% and 18.2% for the white and black females in comparison to the black male blood samples respectively as shown in Fig. 4. Therefore in both males and females, the cannabinoid receptors appear to vary by gender and ethnicity, for example Fig. 3 show white male > black male > Asian male and Fig. 4 show white female > black female > black male.” (11)

African Americans were found to have variations in the BHMT gene almost twice as often than Caucasian and Mexican-American ethnic groups and Hans Chinese American were least likely (small group study). (1)

The BHMT gene and Endogenous Cannabinoid production & breakdown.

The BHMT gene encodes an enzyme involved in homocysteine metabolism and the production of amino acids methionine, and dimethylglycine from betaine. (2) The BHMT enzyme is visualized in a graphic of the folded shape, made up of four parts, monomers, coupled into two sets of dimers, figure C: (1.1).

The BHMT enzyme is also involved in about 60% of the glycerophospholipid production pathway (2) which means important cannabinoids may not be able to be made internally and would need to be obtained in the diet or other sources or suffer deficiency symptoms chronically. People with Cystic Fibrosis also can’t make cannabinoids however the fatty acid end of the molecule is what can’t be made normally. The BHMT gene difference would disrupt production of the glycerophosphate end of the larger cannabinoid molecule. PA, PE, PI, and PS production might be reduced or dysfunctional and breakdown of LPC and LPE which might lead to some types of cannabinoids being unavailable and others unable to be broken down and remove normally so excess might collect -unknown by me. (3)

  • Phospholipids: PA, phosphatidic acid; PE, phosphatidylethanolamine; PC, phosphatidylcholine; PS, phosphatidylserine; PG, phosphatidylglycerol; CL, cardiolipin; PI, phosphatidylinositol. (15)
  • LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine, (19)
  • PE is needed to make anandamide, (20), the endocannabinoid similar to the euphoria producing cannabinoid THC found in marijuana.
  • PI is needed to make 2-AG, (20), the endocannabinoid similar to the non-euphoria producing cannabinoid CBD, also found in marijuana.

Research in cannabinoid chemistry was limited to toxicity or addiction due to the rescheduling of marijuana by the Nixon administration as nonmedical. Since the differences in function of the endocannabinoid system varies with ethnic group it is somewhat genetic discrimination to as well as racial discrimination to target an ethnic group with a law that wouldn’t affect all ethnic groups equally. Someone unable to make cannabinoids would have more craving and physical need for a rich source of phospholipids or cannabinoids, than a person with normal ability to make cannabinoids and/or a low or normal amount of cannabinoid receptors compared to someone with many of them.

Cannabinoid receptors effect mood, & may be involved in anxiety, depression, and possibly suicide.

Lysophosphatidylcholine, LPC, can cause an increase in calcium flow into cells at an atypical cannabinoid receptor GPR55 (4, 5) which is excitatory. Over activity, excess calcium entry, might be a negative to cell health. During normal activation levels the atypical cannabinoid receptor has anti-depressant effects and may help prevent suicide as the brains of suicide victims have fewer GPR55 receptors than typical. (14)

This result, plus the observation that GPR55 increases intracellular calcium, suggests that GPR55 activation enhances neuronal excitability. These findings, together with the preferential expression of GPR55 on large-diameter DRG neurons, which can be involved in nociception, particularly in neuropathic or inflammatory pain states (2931), suggest that GPR55 may have a pronocioceptive [pain increasing] role.” (5)

So overactivity of the GPR55 receptors might be perceived as chronic pain and might affect mood and suicidal ideation. Cannabinoid receptors in the prefrontal cortex (CB1) are also known to be involved with suicide risk from research with people suffering from anorexia (17) or alcoholism and depression. (16)

Cannabinoids also can reduce oxidative stress & inflammation, and may be helpful for preventing or treating neurocognitive degeneration conditions.

Calcium can cause oxidative stress damage and would be increased during times of strenuous activity or infection or other times of increased metabolism. THC can cross the blood brain barrier and can help reduce oxidative stress and may be helpful for treatment of neurocognitive degeneration. It was found to improve glucose use within cells and improve brain function in other ways with no toxicity problems in an animal based study. (12)

In silico analysis predicted THC to be permeable across the blood-brain-barrier. THC was also predicted to have an oral LD50 and toxicity class values of 482 mg/kg and 4 respectively. These results indicate that C. sativa improves glucose consumption with concomitant suppression of oxidative stress and cholinergic dysfunction, and modulation of purinergic and gluconeogenic activities in brain tissues.” (12)

Personal experience – I have a double BHMT allele – it isn’t something I would recommend trying yourself.

I have experience of a lifetime without typical cannabinoid production and the symptoms that may cause. There is a double allele of my BHMT gene which means I can not make some endocannabinoids and can’t break down others. A double allele means both copies contain the same difference from typical. (post, see # 3 in the first list) So I can’t make the BHMT enzyme at all. I supplement with dimethylglycine and methionine since finding out and it helped. I need to continue daily though as genetic metabolic differences mean lifelong symptoms of deficiency of the nutrients that are affected, or an excess of a chemical metabolite that normally would be broken down sooner so it wouldn’t collect.

Post: Clinical Endocannabinoid Deficiency, (CED), and phospholipids. Excerpt:

Conditions that may involve Clinical Endocannabinoid Deficiency, (CED):

Conditions that may involve a deficiency in cannabinoids chronically may include symptoms of pain, muscle spasms, nerve numbness, mood disorders, movement disorders, digestive and appetite problems, appetite and growth failure in infants or colic, menstrual problems and infertility/miscarriages and hyperemesis prenatally.

  • Pain/inflammation: Migraines, Fibromyalgia.
  • Mental health: Anxiety, PTSD, Major Depression, Bipolar disorder, Motion Sickness, The balance of cannabinoids (2-AG ~ noneuphoric CBD and anandamide ~ euphoric THC) is a problem in schizophrenia. There is too much of the anandamide, excess THC can cause schizophrenia like symptoms, and providing CBD may help patients. *See this post for more nutritional deficiencies that cause schizophrenia like symptoms, five or more may be involved, suggesting the problem is a symptom rather than a condition with a single cause – and a single cure: The voices that people with schizophrenia are hearing are probably their own inner thoughts.
  • Nervous system: Multiple sclerosis, Diabetic Neuropathy, Brachial plexopathy, Causalgia, Phantom limb pain, Glaucoma, Huntington’s, Parkinson’s, Cystic Fibrosis,
  • Appetite/digestive system: Anorexia & Bulimia, Neonatal Failure to Thrive, infantile Colic, Irritable Bowel Syndrome.
  • Fertility/reproductive system: Dysmenorrhea, Hyperemesis, repeated miscarriages (Russo 2016), (anandamide is needed for implantation of a fertilized egg in the uterus and development of the placenta to occur normally, too much or too little can disrupt the process, Fonseca 2013), male infertility due to sperm motility problems is associated with low levels of anandamide (AEA) (Amoako 2013), (too much can also negatively affect male or female fertility). *See this post for more details about infertility and phospholipids: (Phospholipid or phosphorylation deficiency: Potential symptoms)
  • Other food sources of cannabinoids exist in addition to marijuana or hemp however the amount provided is in lower concentrations so you might need a large salad that includes several sources at one meal, and other sources in beverages, supplements, or at other meals.

— Addition to the excerpt – the amount of cannabinoids in medical marijuana is a lot more, and more likely to be obviously helpful, than the amount of phospholipids or cannabinoids found in a few foods and spices. Sadly medical marijuana has been stigmatized and illegal for many decades. Research into medical benefits was prevented with Richard Nixon’s administration rescheduled cannabis as having no medical value. Research was only possible on addiction or toxicity. Marijuana/cannabis not only has medical value, it has been used medicinally or in other ways by humans for thousands of years. Paper and rope made from hemp fiber was also a large industry prior to making cannabis illegal.

Conditions I’ve had symptoms of which might be due to Clinical Endocannabinoid Deficiency.

The conditions/symptoms I’ve had over my life from the above list include: Migraines, Fibromyalgia; Anxiety, PTSD, Major Depression, Bipolar disorder; Anorexia & Bulimia, Irritable Bowel Syndrome; and some nerve/numbness symptoms since childhood – dystonia.

The amount of cannabinoids a human needs if they are unable to make them internally/endogenously is not readily available information due to the lack of research. The amount of medical marijuana that I find necessary to feel nerve flow in my fingers and throughout my body and to have other symptoms improve is quite a bit each day. It adds up in money to buy, and time and stigma to use.

Smoking is frowned upon by society and cannabis use is still treated as if it is just an addiction or even criminal (which it still is at the Federal level), so it frightens some people to even learn that you use it, or have used it recently. Chronic users have adapted a tolerance to it (8), and mentally may be more used to functioning with some than going without. The type of strain is important for the terpenes that provide different aroma also provide different health effects. Some can be calming for anxiety (limonene), and another sleep inducing and pain relieving (myrcene).

Daily use every 2-4 hours is what I find helpful and smoking has benefits for dosing. Edibles take longer to feel an effect and then suddenly can be too much. Inhalation effects are fairly immediate and easy to know then when enough has been absorbed. The forms of cannabinoids that are absorbed may vary too with the different intake routes, and inhalation may be more effective for some types of health problems than edible/intestinal absorption. The healthiest I’ve ever felt was when I combined eating some fresh trim or immature buds everyday or edibles along with some smoked bud.

Smoke toxins are a negative that causes the “dopey” effect of the stereotypical marijuana user. Vaping devices exist that heat the bud to a lower temperature so the burnt toxins are not created, however some of the THC conversion occurs at higher temperatures so symptoms may not be helped as much. The vape oil products may have other negative effects on the lungs due to the oil and flavorings being inhaled into the lungs where it can add to pneumonia risk.

How much THC am I getting throughout a day then? Possibly 40% of whatever was in the marijuana you smoked – a lot is lost when you burn the buds. 8 There is approximately 525 mg in an eighth of good medical grade marijuana with 15% THC. (6) That eighth ounce might cost $45-60. One gram per day of 10% THC marijuana might provide 40% of the 100 mg of THC it contains, if smoked vs made into an edible. A quarter to half of a one gram joint every 2-4 hours might be giving 10-20 milligrams of THC each time. Strains that also provide some CBD are important as the cannabinoids work together to do somethings in the body such as inhibit mast cell activation.

Eighty to hundred milligrams of THC is suggested as possibly feeling like an excessive dose all at once for someone with increased tolerance, while 25-80 range might be the typical preferred dose. (8)

I have not calculated this for myself before so it does bring up an interesting question of whether I’m getting too much, or enough, or not enough – the fact that I felt best while also eating fresh trim and other edibles regularly would suggest to me that it is not enough when only smoking and that I do need quite a bit daily.

The non-euphoric CBD has been found safe for use even at 1500 mg per day, though 20-40 mg might be more typically used. (7)

Dronabinol is a capsule form of a THC like medication and it might be prescribed at a 2.5 mg dose twice per day. That might seem like a lot to a new user and not that big of a dose to someone else, although the lack of CBD may be a problem if anxiety is a side effect.

Tolerance levels can reduce after not using for a while and then build back up again. Doses that would seem intense for a new user would not really affect a long term user. (8) Genetics may play more of a role in these differences too, lack of research leaves some questions unasked.

Genetic differences occur in the number of cannabinoid receptors which can effect tolerance for a concentrated source such as medical marijuana.

There can be genetic differences where a person doesn’t make cannabinoids well and has lots of extra cannabinoid receptors, all wanting/ready for cannabinoid activation – but with none or to little available. They might tolerate and prefer a larger dose of THC. Other people might have normal amounts of cannabinoid production and like a smaller dose or none, might not like it. For me it provides feeling throughout my body in a way that I don’t have otherwise. It helps me for muscle knots or spasms and pain. Mentally it helps me with PTSD and anxiety and prevents mast cell histamine excess and hyperexcitability.

Cannabinoids help with learning & forgetting – reshaping nerve pathways – neural plasticity. Pain signal pathways can also be remade more easily with cannabinoids.

Cannabinoids help with learning and nerve flow, and with forgetting – changing nerve pathways to build new as needed and remove the old as they are not needed (old phone number for example). Neural plasticity – changing nerve pathways and synapses between nerves is a function involving cannabinoids. Pain and movement, appetite and growth, cannabinoids affect many functions of the body and neural plasticity can affect pain pathways too – remembered pain in an amputee’s healed wound, and maybe feelings of the missing limb still being there also.

The same team noted a baseline fragility of serotonergic systems in migraine and fibromyalgia [89], plus the co-occurrence of primary headache in 97% of 201 fibromyalgia patients. In a later study [67], they supported the concept that both disorders represented a failure of serotonergic analgesia and NMDA-mediated neuronal plasticity.” (9)

Synergy – many nutrients work together to perform any action in the body. Magnesium also helps inhibit excess pain nerve signals.

Pain conditions can be caused by deficiency of nutrients or chemicals that inhibit pain sensing nerves. Magnesium is needed to inhibit them as well as cannabinoids. Migraine pain may be not responsive to opiate pain killers. (9)

A trigeminovascular system has long been implicated as integral to the pain, inflammation and secondary vascular effects of migraine, linked through the NMDA/glutamate system [49]. Cannabinoid agonists inhibit voltage-gated calcium channels, and activate potassium channels to produce presynaptic inhibition of glutamate release [50], without dissociative effects noted with other NMDA inhibitors, such as ketamine.” (9)

*Having adequate potassium and magnesium in the diet and avoiding excess glutamate in seasonings and other dietary sources can also help avoid migraines – in addition to the cannabinoids or cannabinoid receptor agonists – activators.

Diabetes pain may also not be helped by opiates unless magnesium is also provided – and providing magnesium in a larger dose helped even more! (10)

Give the body what it needs to function and it functions. Miracle!

Sunshine might be part of the miracle too – vitamin D represents a group of chemicals which may aid us in ways we don’t know yet. Supplementing with one – vitamin D, may not be providing us others that we would have made if sun or full spectrum/UVB containing light is available. (13)

We need cannabinoids too – and some of us genetically can’t make them – since birth, and potentially – epigenetic changes might be occurring that cause dysfunction in a person’s ability to make cannabinoids at some point later in their life. Is that happening in LongCovid survivors? -discussed in the last post.

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.

Reference List

  1. Li F, Feng Q, Lee C, et al. Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization. Molecular Genetics and Metabolism. 2008 Jul;94(3):326-335. DOI: 10.1016/j.ymgme.2008.03.013. https://europepmc.org/article/med/18457970
    1. Figure 3, https://europepmc.org/articles/PMC2515933/figure/F3/
  2. BHMT Gene (Protein Coding), Betaine–Homocysteine S-Methyltransferase: BHMT Pathways & Interactions, genecards.org, https://www.genecards.org/cgi-bin/carddisp.pl?gene=BHMT#pathways_interactions
  3. Glycerophospholipid biosynthesis, reactome.org, https://reactome.org/PathwayBrowser/#/R-HSA-1483206
  4. Drzazga A, Sowinska A, Krzeminska A, Rytczak P, Koziolkiewicz M, Gendaszewska-Darmach E. Lysophosphatidylcholine elicits intracellular calcium signaling in a GPR55-dependent manner. Biochem Biophys Res Commun. 2017 Jul 22;489(2):242-247. doi: 10.1016/j.bbrc.2017.05.145. Epub 2017 May 26. PMID: 28552522. https://pubmed.ncbi.nlm.nih.gov/28552522/
  5. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A. 2008;105(7):2699-2704. doi:10.1073/pnas.0711278105 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268199/
  6. Understand Cannabis Weights & Calculate THC Dose, June 5, canuvo.org, https://canuvo.org/cannabis-weight-calculate-thc-dose/
  7. CBD Dosage: Figuring Out How Much to Take, healthline.org, https://www.healthline.com/health/cbd-dosage#safety-and-side-effects
  8. Barreda AR, De Leon K and Urmasa S., A simple guide to pot, THC and how much is too much. April 20, 2018, latimes.com, https://www.latimes.com/projects/la-me-weed-101-thc-calculator/
  9. Russo, Ethan. (2008). Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?. Neuro endocrinology letters. 29. 192-200. 10.1522/cla.roj.let. https://www.researchgate.net/publication/5448843_Clinical_Endocannabinoid_Deficiency_CECD_Can_this_Concept_Explain_Therapeutic_Benefits_of_Cannabis_in_Migraine_Fibromyalgia_Irritable_Bowel_Syndrome_and_other_Treatment-Resistant_Conditions
  10. M. Bujalska, H. Makulska-Nowak, S.W. Gumuka,  Magnesium ions and opioid agonists in vincristine-induced neuropathy, Pharmacol Rep. 2009 Nov-Dec;61(6):1096-104. http://www.ncbi.nlm.nih.gov/pubmed/20081245
  11. Onaivi ES, Chaudhuri G, Abaci AS, Parker M, Manier DH, Martin PR, Hubbard JR. Expression of cannabinoid receptors and their gene transcripts in human blood cells. Prog Neuropsychopharmacol Biol Psychiatry. 1999 Aug;23(6):1063-77. doi: 10.1016/s0278-5846(99)00052-4. PMID: 10621950 https://www.researchgate.net/publication/12692236_Expression_of_cannabinoid_receptors_and_their_gene_transcripts_in_human_blood_cells
  12. Erukainure OL, Matsabisa MG, Salau VF, Islam MS. Tetrahydrocannabinol-Rich Extracts From Cannabis Sativa L. Improve Glucose Consumption and Modulate Metabolic Complications Linked to Neurodegenerative Diseases in Isolated Rat Brains. Front Pharmacol. 2020;11:592981. Published 2020 Nov 24. doi:10.3389/fphar.2020.592981 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774498/
  13. Vitamin D and your health: Breaking old rules, raising new hopes. Updated May 17, 2019, Published Feb. 2007, health.harvard.edu, https://www.health.harvard.edu/staying-healthy/vitamin-d-and-your-health-breaking-old-rules-raising-new-hopes
  14. Wróbel A, Serefko A, Szopa A, Ulrich D, Poleszak E, Rechberger T. O-1602, an Agonist of Atypical Cannabinoid Receptors GPR55, Reverses the Symptoms of Depression and Detrusor Overactivity in Rats Subjected to Corticosterone Treatment. Front Pharmacol. 2020;11:1002. Published 2020 Jul 8. doi:10.3389/fphar.2020.01002 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360849/
  15. Image/ Figure “General structure of phospholipids and common head groups.” source: Membrane lipids in Agrobacterium tumefaciens: Biosynthetic pathways and importance for pathogenesis researchgate.net, https://www.researchgate.net/figure/General-structure-of-phospholipids-and-common-head-groups-PLs-contain-two-fatty-acids_fig1_261605192
  16. Hungund BL, Vinod KY, Kassir SA,, et al., Upregulation of CB1 receptors and agonist-stimulated [35S]GTPS binding in the prefrontal cortex of depressed suicide victims. March 2004, Mol Psychiatry 9(2):184-90 DOI: 10.1038/sj.mp.4001376 https://www.researchgate.net/publication/8692237_Upregulation_of_CB1_receptors_and_agonist-stimulated_35SGTPS_binding_in_the_prefrontal_cortex_of_depressed_suicide_victims
  17. Navarrete Francisco, García-Gutiérrez María Salud, Jurado-Barba Rosa, et al., Endocannabinoid System Components as Potential Biomarkers in Psychiatry. Frontiers in Psychiatry Vol 11, 2020, 31 pp, DOI=10.3389/fpsyt.2020.00315 https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00315/full
  18. Li R, Li Y, Liang X, Yang L, Su M, Lai KP. Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets [published online ahead of print, 2020 Nov 10]. Brief Bioinform. 2020;bbaa300. doi:10.1093/bib/bbaa300 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717147/
  19. Lysophosphatidylethanolamine, sciencedirect.com, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/lysophosphatidylethanolamine
  20. Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry. 2016;79(7):516-525. doi:10.1016/j.biopsych.2015.07.028 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789136/