Posted on by Jenny

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.

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. 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/