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)

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.

Reference List

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    1. Figure 3, https://europepmc.org/articles/PMC2515933/figure/F3/
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  3. Glycerophospholipid biosynthesis, reactome.org, https://reactome.org/PathwayBrowser/#/R-HSA-1483206
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  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/
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  19. Lysophosphatidylethanolamine, sciencedirect.com, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/lysophosphatidylethanolamine

Cannabinoids & blood vessels – and LongCovid.

I have been experiencing blood vessel breakdown and edema – in my fingertips, since stopping THC (medical marijuana) to travel in non-legal states, I continued CBD though. My genetics make me equivalent to a knockout mouse – I can’t make endocannabinoids & need an external source. Medical marijuana products have the most, a few foods or spices have a little. (Symptoms of Clinical Endocannabinoid Deficiency & Phospholipid food sources (post))

Gist of my Thread * – hypoxia, low oxygen, plus low THC/anandamide -> increased blood vessel breakdown. My solution was to increase motion in my fingers – ‘jazz hands’ & hold the steering wheel very gently. My fingers hurt, still do. Haven’t gotten back on THC yet. *The pain got better when I got back to using medical marijuana. (*This post is based on a Twitter Thread I wrote Sept 1,, 2020, and added too Sep 18, 2020; more recent info reminded me of it and led to this post)

The Endocannabinoid system has a role in vascular health and regulation of inflammation.

Summary point – excess inflammation causes breakdown of the cell membranes to release stored endocannabinoids for use as messenger chemicals – able to directly cause actions or after having been transformed into another chemical such as eicosanoids. Endocannabinoids are also used within membranes and release of too many can cause membrane breakdown.

Anandamide (natural cannabinoid) boosts the body’s Nitric oxide, helping: muscular tone of blood vessels, healthy insulin secretion, healthy muscular tone of our airway pathways, a healthy digestive tract, & new blood vessel & healthy nerve development. ” – Dr. Caplan, @drcaplan. (16)

Anandamide is the THC equivalent endocannabinoid and has also been found protective of the blood vessel membranes involved in the blood brain barrier, (17) – what protects our heart helps protect our brain and lungs too. They are the three critical organs most protected during a drowning in freezing water situation. We have instinctual responses that help protect our brain’s circulation at the expense of blood flow reaching our fingers and toes. During a freezing incident damage to fingers and toes can be extensive and lead to amputations of some of the frozen digits.

Low oxygen levels can affect blood vessels by affecting the cannabinoid system. (3)

Cannabinoid control is varied, and may modulate – cause different actions based on need. The endocannabinoid system involves type 1 and type 2 cannabinoid receptors and TRPV ion channels which are activated by different cannabinoids. Cannabinoid receptor activity may lead to reduced blood flow in some situations and increase it in others, as needs change. CBD and THC can activate both CB1 and CB2 receptors and THC can also activate the TRPV channels. (3)

Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation. ” (3)

CBD oil helped protect cells during low oxygen, hypoxia, in a study regarding refractory epilepsy – resistant to treatment. ~ Fewer seizures if cells are protected from hypoxia & influx of extracellular chemicals. (1)

In addition to hypoxia – oxygen levels, the balance of cannabinoids, THC/CBD, may be important for blood vessel membranes.

Results section: “Experimental data suggested dynamic regulation of endocannabinoids and their receptors in the vascular system [16]. Therefore, we investigated the components of the endocannabinoid system in human aorta and found significantly higher mRNA levels of the cannabinoid receptors CB1 (Figure 1(a)), CB2 (Figure 1(b)), TRPV1 (Figure 1(c)), and GRP55 (Figure 1(d)) in the aneurysms as compared to the samples from controls. Expression of related factors 5HT1A and PPARα was comparable between the groups (data not shown) Mass spectrometry measurements of endocannabinoids showed a significantly lower level of anandamide (Figure 1(c)) & a significantly higher level of 2-arachidonoyl glycerol in aneurysms (Figure 1(d)). Interestingly, aneurysm samples contained a significantly lower amount of the endocannabinoid degradation product arachidonic acid (Figure 1(e)) and palmitoylethanolamide (Figure 1(f)) than the control samples. Therefore, aortic aneurysm showed not only increased level of cannabinoid receptors, but also a different amount of ligands & decreased level of of their degradation products suggesting differentiated, persistent action of endocannabinoids in the aortic wall.” – (C. Gestrich, et al, 2015) (10)

Significance – the ratio: “Mass spectrometry measurements of endocannabinoids showed a significantly lower level of anandamide (Figure 1(c)) and a significantly higher level of 2-arachidonoyl glycerol in aneurysms (Figure 1(d)).” (10) >> Too little of the THC equivalent (anandamide), excess of CBD equivalent cannabinoid (2-AG).

Human Endogenous Retroviral Syncytin-1 protein is also found on the SARS-CoV-2 Spike protein.

The protein Syncytin-1 is present in the spike of SARS-COV2 and is also part of the human genome and is involved in development of the human placenta (13) during conception and pregnancy. “Indeed, alignment of the endogenous elements Syn1 found on human chromosome 7, or Syn2 found on chromosome 6, or HERV-K expressed from chromosome 6, all show a number of sequence motifs with significant similarity to nCoV2019 spike protein.” (12) Anandamide, the THC equivalent endogenous cannabinoid, down-regulates activity of the Syncytin-1 and 2 proteins during development of the placenta. (14)

Syncytin is the endogenous gammaretrovirus envelope that’s encoded in the human genome … We know that if syncytin … is expressed aberrantly in the body, for instance in the brain, which these lipid nanoparticles will go into, then you’ve got multiple sclerosis. The expression of that gene alone enrages microglia, literally inflames and dysregulates the communication between the brain microglia, which are critical for clearing toxins and pathogens in the brain and the communication with astrocytes. It dysregulates not only the immune system, but also the endocannabinoid system, which is the dimmer switch on inflammation.” (15)

The endocannabinoid system is dysregulated in multiple sclerosis and seems to have excess of the THC equivalent, anandamide, and too little of the CBD equivalent, 2-AG. (18)

– Might infection with SARS-CoV-2 be causing changes with the syncytin retrovirus protein in the Spike protein gene that might leave Long-Covid patients with inhibition of the endocannabinoid system and symptoms of cannabinoid deficiency? Over active mast cell symptoms and blood vessel breakdown symptoms might involve reduced cannabinoids or malfunctioning endo cannabinoid system.

Hypoxia seems involved in COVID toes/fingers – the balance of endogenous cannabinoids being produced/released from cell membranes may also be a factor.

COVID19 toes or fingers (reddened & painful) may be hypoxia combined with cannabinoid deficiency leading to worse blood vessel breakdown & even more hypoxia.

Frostbite is a bigger risk for the toes, fingers, because they already may get less circulation, especially in low oxygen & cold situations because the body can protect the brain, heart, and lung’s circulation over the rest of the body – why people can survive cold water drowning. My first job was as a Lifeguard and Water Safety Instructor & learned about frostbite & drowning for that training.

What seems like Covid fingers suddenly became a problem for me when I stopped medical marijuana a couple days ago. Pain, inflammation a little pinker, each fingertip feels bruised and hurts to touch or hold things.

In balance & inhaled, THC & CBD help preserve blood vessel membranes & reduce mast cell activation. mast cell part is in second half of this post: https://transcendingsquare.com/2020/11/10/glyphosate-increases-histamine-both-may-be-a-factor-in-covid19/… I had a little recently – it helped with sensation in my fingers, and has since – symptoms return when I discontinue use and get better when I have medical marijuana products daily. I was a medical marijuana patient while sick with untested CoV19 like infection in Feb/March 2020 and had to quit smoking as a method of intake as respiratory symptoms worsened.

Cannabinoids might help treat a SARS-CoV-2 infection but avoiding smoking it would be better with the respiratory symptoms. (11)

Raynaud’s syndrome – may be autoimmune but is still not well understood – seems like the Covid fingers/toes problem too. (9)

Getting to the point, what have I been doing for my fingers?

  • Exercise-jazz hands- to increase circulation & blood flow to the fingers & am trying to hold my car steering wheel as gently as possible – bruising has occurred basically of all my finger tips. The pinkie fingers are the worst.
  • I have also been trying to eat adequate protein foods as you can’t repair anything in the body without some protein building blocks. & Other nutrients, vit C, B’s, etc. also help.
  • I also picked up some legal everywhere CBD oil drops. The initial pain severity has improved. ** I eventually stopped the CBD drops, we may need the THC in balance for blood vessels: aortic aneurysm was found to have an excess of the CBD equivalent and a lack of the THC equivalent endocannabinoid. (10) Cannabinoids can be released from cell membranes in inflammatory situations – leaving less stable membranes perhaps if too many cannabinoids are released from storage.
  • Stress, physical or emotional, also increase cannabinoid release from membranes. Positive mental attitude, focusing on gratitude and love, has also helped. Quote: “If we have a positive mental attitude, then even when surrounded by hostility, we’ll not lack inner peace. But if our attitude is negative, influenced by fear, suspicion, or helplessness, even when surrounded by our best friends, in comfortable surroundings, we won’t be happy. ” – Dalai Lama @DalaiLama
  • EMF from WiFi exposure can also increase membrane openings and excess chemical flow into cells which can lead to increased membrane breakdown, so I try to use an EMF blocking case when holding my smartphone. The finger positions where I hold the phone most often is where there are sore finger areas too.
  • I have also been using my dielectric orgone blanket wrapped around the sore hands/wrist/left shoulder, about a 30 minutes or so for each area. Gets warm & may help by increasing electrical field activity which might stimulate healing. How to make one: Dielectric Orgone Blankets.
  • Stretching exercises that include the shoulders may help finger numbness problems as a pinched nerve in the shoulder can increase nerve issues in the fingers, ‘pins and needles‘ or numbness & pain. See: Is Your Shoulder Pain Related to Your Numb Hands or Fingers? (2)

Cannabinoid deficiency may also increase pain signaling and… Cannabinoids are part of cell membranes & inflammation causes release of them from membrane storage. Excess release of them may also be adding to blood vessel breakdown.

Magnesium is also essential to control influx of chemicals across the cell membrane. The US standard diet may be more unhealthy for people with African ancestry, who may conserve calcium and waste magnesium more than other ethnic groups, (5), and the US diet is high in calcium and frequently can be low in magnesium. Low magnesium levels could be increasing COVID19 severity, by decreasing apoptosis capability of white blood cells (WBCs).

The genetics of renal calcium sparing at the expense of magnesium may be more common in African ancestry than other ethnic groups leaving them more at risk for low magnesium levels, and reduced ability to fight an infection.

Other APOL1 gene variants may increase risk of chronic kidney disease by 15% and the gene variants are more common in people of African ancestry. (5) The gene difference might provide increased protection against a type of parasite common in Africa: “APOL1 variants may confer resistance against Trypanosoma brucei rhodesiense, the parasite that causes African sleeping sickness.” John Herrmann, PhD, @ablT315I. The gene variants may be increasing risk for more severe COVID19 illness with renal damage. (6) Magnesium wasting might be involved, it would be more alkaline – lower acid production was found with the gene variant:  “However, a recent study suggested that the APOL1 high-risk genotype was associated more strongly with CKD progression among blacks with low net endogenous acid production (NEAP).16” (7)

Magnesium is necessary also, to help keep membrane channels closed. Without it excess as calcium or other chemicals may be able to overload the cell where the calcium acts as a stimulant & can overactivate the cell to point of cell death. One type of magnesium channel is called the MgtE. (8)
Excess calcium may flow into the cell if there isn’t an atom of magnesium to “lock” the channel “doorway.”

*Low vitamin D levels may also be more of a risk for people with darker skin tones who live in northern climates.

Reference List

  1. Auzmendi Jeróni Magnesium is also essential to control influx of chemicals across the cell membrane. mo, Palestro Pablo, Blachman Agustín, et al., Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions. Frontiers in Behavioral Neuroscience 2020;14, 32 pages, https://www.frontiersin.org/articles/10.3389/fnbeh.2020.00032/full
  2. Amy Haddad, Is Your Shoulder Pain Related to Your Numb Hands or Fingers? sports-health.com, 11/28/2016 https://www.sports-health.com/blog/your-shoulder-pain-related-your-numb-hands-or-fingers
  3. Benyó Z, Ruisanchez É, Leszl-Ishiguro M, Sándor P, Pacher P. Endocannabinoids in cerebrovascular regulation. Am J Physiol Heart Circ Physiol. 2016;310(7):H785-H801. doi:10.1152/ajpheart.00571.2015 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865067/#!po=1.46104
  4. Erin Cline, Clinical Endocannabinoid Deficiency Syndrome: Can CBD help?, cbdhacker.com, Oct. 10, 2018 https://cbdhacker.com/clinical-endocannabinoid-deficiency-syndrome-can-cbd-help/
  5. Dummer PD, Limou S, Rosenberg AZ, et al. APOL1 Kidney Disease Risk Variants: An Evolving Landscape. Semin Nephrol. 2015;35(3):222-236. doi:10.1016/j.semnephrol.2015.04.008 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562465/
  6. Juan Carlos Q. Velez, Tiffany Caza, Christopher P. Larsen, COVAN is the new HIVAN: the re-emergence of collapsing glomerulopathy with COVID-19 Nature Reviews: Nephrology, 2020; October 2020, pp 565-567 https://www.nature.com/articles/s41581-020-0332-3.pdf via https://twitter.com/EricTopol/status/1290659983890227203?s=20
  7. Pike M, Stewart TG, Morse J, et al. APOL1, Acid Load, and CKD Progression. Kidney Int Rep. 2019;4(7):946-954. Published 2019 Apr 4. doi:10.1016/j.ekir.2019.03.022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611987/
  8. Fei Jin, Minxuan Sun, Takashi Fujii, et al., Cryo-EM structure of the MgtE Mg2+ channel pore domain in Mg2+-free conditions reveals cytoplasmic pore opening. bioRxiv 2020.08.27.270991; doi: https://doi.org/10.1101/2020.08.27.270991 https://www.biorxiv.org/content/10.1101/2020.08.27.270991v1
  9. Raynaud’s Disease, medlineplus.gov, https://medlineplus.gov/raynaudsdisease.html#:~:text=Raynaud’s%20disease%20is%20a%20rare,areas%20turn%20white%20and%20blue
  10. Christopher Gestrich, Georg D. Duerr, Jan C. Heinemann, et al., Activation of Endocannabinoid System Is Associated with Persistent Inflammation in Human Aortic Aneurysm. BioMed Research International, Special Issue: Novel Biomarkers and Treatments of Cardiac Diseases Volume 2015, Article ID 456582, https://doi.org/10.1155/2015/456582 https://www.hindawi.com/journals/bmri/2015/456582/
  11. Sainz-Cort, A., Heeroma, J.H. The interaction between the endocannabinoid system and the renin angiotensin system and its potential implication for COVID-19 infection. J Cannabis Res, 2, 23 (2020). https://doi.org/10.1186/s42238-020-00030-4 https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00030-4
  12. profbillg1901, Response to nCoV2019 Against Backdrop of Endogenous Retroviruses. Feb 2020, https://virological.org/t/response-to-ncov2019-against-backdrop-of-endogenous-retroviruses/396
  13. Ruebner M, Langbein M, Strissel PL, Henke C, Schmidt D, Goecke TW, Faschingbauer F, Schild RL, Beckmann MW, Strick R. Regulation of the human endogenous retroviral Syncytin-1 and cell-cell fusion by the nuclear hormone receptors PPARγ/RXRα in placentogenesis. J Cell Biochem. 2012 Jul;113(7):2383-96. doi: 10.1002/jcb.24110. PMID: 22573555. https://www.researchgate.net/publication/224933500_Regulation_of_the_Human_Endogenous_Retroviral_Syncytin-1_and_Cell-Cell_Fusion_by_the_Nuclear_Hormone_Receptors_PPAR_gammaRXR_alpha_in_Placentogenesis
  14. Szilagyi JT, Composto-Wahler GM, Joseph LB, et al. Anandamide down-regulates placental transporter expression through CB2 receptor-mediated inhibition of cAMP synthesis. Pharmacol Res. 2019;141:331-342. doi:10.1016/j.phrs.2019.01.002 https://pubmed.ncbi.nlm.nih.gov/30610963/
  15. Joseph Mercola, How COVID-19 ‘Vaccines’ May Destroy the Lives of Millions. Feb 14, 2021, mercola.com, https://articles.mercola.com/sites/articles/archive/2021/01/31/covid-19-vaccine-gene-therapy.aspx?cid_source=twitter&cid_medium=social&cid_content=twitterhealth&cid=lead_20210131
  16. Maria Grazia Signorello, Giuliana Leoncini, Anandamide Induces Platelet Nitric Oxide Synthase through AMP‐Activated Protein Kinase. Lipids Vol 53, Issue 9, Sept 2018, pp 851-861 https://aocs.onlinelibrary.wiley.com/doi/abs/10.1002/lipd.12100?hss_channel=tw-65498903&utm_medium=social&utm_content=80709643&utm_source=twitter
  17. Calapai, F.; Cardia, L.; Sorbara, E.E.; Navarra, M.; Gangemi, S.; Calapai, G.; Mannucci, C. Cannabinoids, Blood–Brain Barrier, and Brain Disposition. Pharmaceutics, 2020, 12, 265. https://doi.org/10.3390/pharmaceutics12030265 https://www.dropbox.com/s/v4z1uumek52yesv/pharmaceutics-12-00265%20%281%29.pdf?dl=0
  18. Centonze D, Bari M, Rossi S, Prosperetti C, Furlan R, Fezza F, De Chiara V, Battistini L, Bernardi G, Bernardini S, Martino G, Maccarrone M. The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis. Brain. 2007 Oct;130(Pt 10):2543-53. doi: 10.1093/brain/awm160. Epub 2007 Jul 11. PMID: 17626034. https://pubmed.ncbi.nlm.nih.gov/17626034/
  19. Mass Cell Activity and Hyperexcitable Mood, https://transcendingsquare.com/2020/11/21/mast-cell-activity-hyperexcitable-mood/

Hope – is the future, is teamwork to build a better future.

“Nothing that is worth doing can be achieved in our lifetime; therefore we must be saved by hope.

Nothing which is true or beautiful or good makes complete sense in any immediate context of history; therefore we must be saved by faith.

Nothing we do, however virtuous, can be accomplished alone; therefore we must be saved by love.

No virtuous act is quite as virtuous from the standpoint of our friend or foe as it is from our standpoint. Therefore we must be saved by the final form of love which is forgiveness.”

― Reinhold Niebuhr, The Irony of American History (goodreads.com)

We are blessed,
a loving eye in the sky
Shines forth, glory is ours.

Teamwork – requires communication and working together in spite of differences. Diversity within a team can improve the variety of skills, experience and ideas available to the team. Teams do not all have to be best friends to work together, adult maturity looks at that long view, the whole is greater than any of the parts.

In the recent post: Strategic Mindset & Grit – try, try, try again, but a little bit better each time, we learned that the people who built Stonehenge (U.K.) took approximately 1175 years to complete the various phases of its development into the world’s largest astronomical calendar. Now that is teamwork, and dedication. They may have hoped to improve crop production due to a lengthy change in the weather to cooler temperatures that supported fewer crops. The people of the time increased their use of grazing animals for their survival during the long cold snap (~700 years or more, I’m not a historian).

Miracles exist
In our hearts and in our minds,
One life at a time.
Many lives over all of time.

None of us is as smart as all of us” – Ken Blanchard

We got this, the world
In the palms of our hands, all
Joined together, One.

On the other side of darkness is light – let there be light for growth and discovery, and let there be darkness for rest and recovery.

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.