Clinical Endocannabinoid Deficiency, (CED), and phospholipids.

During normal health we make cannabinoids internally – endogenously, hence the term endocannabinoids in contrast to cannabinoids found in plants such as cannabis/marijuana/hemp. Most cannabinoids do not cause euphoria even though the group may be best known for that affect.

Anandamide (AEA) is the endocannbinoid that is chemically similar to the euphoria causing cannabinoid found in marijuana known as THC, tetrahydrocannabinol. Cannabidiol, CBD, is a non-euphoria causing cannabinoid found in some strains of marijuana. It is chemically similar to the endocannabinoid known as 2-AG which in times of normal health is found in greater concentration within the body than anandamide.

Cannabinoids within the body are found as a structural part of cell membranes. They also can be released from the membranes and used as signaling chemicals within the brain and peripheral nerves, affecting many things including memory, appetite, sleep, movement, and fertility. The cannabinoids when released from the cell membranes can also be modified into another type of signaling chemical that is important in immune health (eicosanoids).

Due to genetic changes or other issues with metabolism or health some people may not be able to make cannabinoids internally and would need an external source to maintain health. Due to marijuana having been listed as a controlled substance considered to have no medicinal value research has been limited to studies about toxicity and addiction. Research on the role cannabinoids plays in health is becoming more available but is still in early stages considering the many functions they have within the brain and body.

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.
  • 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).
  • 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.
Conditions that may involve Clinical Endocannabinoid Deficiency (CED)

Food sources of cannabinoids or phospholipids (a precursor chemical):

Cannabinoids, can be found in smaller amounts in foods than in medical marijuana or synthetic THC medications. Good sources include:

  • Chocolate, dark cocoa powder.
  • Seeds: hemp kernels, pomegranate, seeds & peel, pumpkin, sesame, flax, fennel, cardamom, cumin and coriander;
  • Grains: amaranth, rice bran, sorghum, buckwheat, wheat;
  • Beans/legumes;
  • Coconut/Nuts: pine nuts, peanuts, cashews, almonds;
  • Green plants: lettuce, spinach, mustard greens, leek greens, asparagus, avocado fruit and dried kernel, celery, carrots, onion, garlic. Squash, cucumber and okra seeds, butternut squash, pumpkin, sweet pototo or yams, parsnip root, Jerusalem artichoke root.
  • Herbs: Rosemary, Gingko leaf, Wormwood/Artemisia;
  • Grapefruit and citrus juice with the pulp.
Good Food Sources of Cannabinoids and/or Phospholipids

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Brain cells and aging

Within the majority of the brain the type of brain cells that send nerve signals generally do not get replaced, however they also generally don’t lose function. Dementia – loss of memory and other cognitive skills – is not a normal part of healthy aging. Age related forgetfulness has to do with loss of the connections between brain cells but the brain cells remain functional – so continuing to take part in learning and social activities may help prevent dementia and forgetfulness by helping to maintain current connections between brain cells and add new connections formed during learning or socializing. 

And yet Alzheimer’s dementia now “afflicts 5% to 10% of the U.S. population over the age of 65 and as much as 45% of the population over 85.” (page 694, Neuroscience, 6th. edition, 1)

Research for medications for Alzheimer’s treatment have focused on reducing the levels of certain types of protein that collect in the damaged areas of the brain of a patient with the condition, however even if successful at reducing the amount of the protein the medications have not been found very helpful for restoring the patient’s cognitive health. (previous post) People with normal brain function also can have excess of the protein and it is also found in the brains of people with autism disorder – confusing, yes. Adequate quality sleep may help the brain waste removal system keep the levels of excess protein from building up to damaging amounts. (previous post on sleep and the glymphatic system)

Things that may increase risk include chronic stress and the excess cortisol and inflammatory oxidative stress chemicals production. Moderate exercise may help reduce stress and promote detoxification of inflammatory chemicals. Staying socially and mentally active also may be protective of brain function. Prevention is the best medicine for conditions that cause irreversible degenerative changes such as the damage in Alzheimer’s Disease. Learning about new foods and recipes and then making healthy meals to share with others can be a way to combine physical and mental activity and gain from nutrients that help detoxify inflammatory oxidative stress chemicals. (previous post, Foods for beneficial T-cells) – (Nrf2 promoting foods)

T cells are a type of blood cell with immune system functions. Beneficial T cells can help clear excess protein found in Alzheimer’s (2) while other types can increase inflammation and the types can transform based on the level of oxidative stress chemicals that are present so having antioxidants and other phytonutrients in daily meals can help signal the T-cells to take the beneficial forms instead of the inflammatory forms. (The non euphoria producing endogenous cannabinoid 2-AG (acts at the CB2 receptor, somewhat similar to CBD) may also help signal T cells towards the less inflammatory type, and reduce migration of them. page 96)

Nrf2 is a gene and protein that help promote the more beneficial types of T cells and help the immune system in other ways and also promote our own production of antioxidants for reducing the oxidative stress chemicals that are a natural waste product left from energy metabolism – when blood sugar is turned into a usable form of energy.

The long story is complicated, the short story remains,

  • include moderate exercise most days of the week,
  • have adequate sleep, 6-8 hours/night, ideally with complete darkness, blackout curtains and cover the light from an electric bedside alarm clock (put it in a nearby drawer or cover it with something),
  • get some natural sunshine or full spectrum light during the day if possible (may help with vitamin D, bioactive sulfate, and circadian rhythm metabolism within the body which includes production of melatonin,
  • stay mentally and socially active,
  • reduce stress when possible and/or practice relaxation techniques,
  • drink adequate water and regularly eat a good variety of colorful fresh produce, whole grains, nuts, beans, seeds, and include omega 3 fatty acid sources on a daily or weekly basis.
  • Clean air quality is also important. Formaldehyde (from secondhand smoke or even excessive use of decorative candles), and other air pollutants (released by plastics or new carpeting/flooring for example) can collect in poorly ventilated buildings. See this post for more information about formaldehyde sources and ways to reduce it: Formaldehyde: Health Risks, and Environmental and Dietary Sources.(effectiveselfcare.info)
  • Adequate water, not getting dehydrated regularly, is important enough to repeat because dehydration allows toxins within the body, including formaldehyde, to collect, instead of being removed by the glymphatic/lymphatic and vascular system, and to then be excreted by the kidneys. Brain Formaldehyde is Related to Water Intake Behavior, Ting Li, et al, 2016, (PubMed) A discussion of how much water is typically needed for health each day, and how much protein to eat for basic needs without being too much for long term kidney health, is available in a previous post: Make Every Day Kidney Appreciation Day. (effectiveselfcare.info)

More of the long story – the Cannabinoid Receptor Type 2 is also activated by a phytonutrient called beta-caryophyllene (BCP) which is found in many aromatic herbs and spices including: oregano, cinnamon,  clove , rosemary,  thyme, black pepper, (4), and copaiba oil. (5) Benefits may include reducing inflammation and pain, anti-anxiety, anti-cancer, (4), and protection of the brain by helping reduce increased activity after brain trauma which can lead to scar like tissue walling off the area of trauma instead healing.(5)

The problem in Alzheimer’s may not be the protein itself but instead the cells that over-actively making it in response to inflammatory signals so the solution would be not trying to remove excess protein but to stop the production of excess protein by signaling the overactive cells that all is well again, stop walling off the supposed injury. Formalin, a more dilute buffered form of formaldehyde was the toxin used to create inflammation in an animal based study of the potential benefits of beta-caryophyllene. A dose of 5 mg/Kg purified beta-caryophyllene essential oil given by mouth (rather than by an injection) was found to help reduce inflammatory pain from the formalin. (4) For a 75 kilogram adult that would be a capsule with 375 milligrams of the purified oil.

The herb rosemary is pine needle like plant that has been used as a pain killer in traditional folk medicine for arthritis pain and was thought of a s a memory aid. Studies more recently have found the essential oil beneficial for improving memory. (6)  **Use care when purchasing essential oils, some are intended only for external use either on the skin when diluted in a small amount of milder oil such as almond oil for massage or topical pain relief, or as an aromatic for scent (example, put a few drops on a cotton ball that is attached to a fan or on the outlet of a humidifier to circulate the aroma through a room).

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

  1.  Neuroscience, 6th Edition, Editors D. Purves, G.J. Augustine, D. Fitzpatrick, W.C. Hall, A.S. LaMantia, R.D. Mooney, ML. Platt, L.E. White, (Sinauer Associates, Oxford University Press, 2018, New York) (Barnes&Noble)
  2. Anna Mietelska-Porowska and Urszula Wojda, “T Lymphocytes and Inflammatory Mediators in the Interplay between Brain and Blood in Alzheimer’s Disease: Potential Pools of New Biomarkers,” Journal of Immunology Research, vol. 2017, Article ID 4626540, 17 pages, 2017. https://doi.org/10.1155/2017/4626540. https://www.hindawi.com/journals/jir/2017/4626540/
  3. edited by Karsten Sauer, Klaus Okkenhaug, Lipid Signaling in T Cell Development and Function, Frontiers Media SA, Nov 12, 2015 page 96
  4. A.-L.Klauke, I.Racz, B.Pradier, et al., The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. European Neuropsychopharmacology, Vol. 24, Issue 4, April 2014, Pages 608-620, https://www.sciencedirect.com/science/article/pii/S0924977X13003027
  5. Guimarães-Santos A, Santos DS, Santos IR, et al. Copaiba Oil-Resin Treatment Is Neuroprotective and Reduces Neutrophil Recruitment and Microglia Activation after Motor Cortex Excitotoxic Injury. Evidence-based Complementary and Alternative Medicine : eCAM. 2012;2012:918174. doi:10.1155/2012/918174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291111/
  6. Rachel Hosie, Surge in Rosemary Sales as Aromatic Herb Found to Boost Memory, May 19, 2017, independent.co.uk,  https://www.independent.co.uk/life-style/health-and-families/rosemary-sales-surge-herb-boost-memory-holland-barrett-a7745231.html

Endocannabinoids, retrograde signaling, and learning.

The endocannabinoid system is involved in our ability to learn. Use of medical marijuana, in quantity, is known to reduce short term memory but it may also be helping the body form long term memories. However our natural endocannabinoid system wouldn’t primarily use the equivalent to the euphoria forming THC called anandamide. That is used to reduce nerve cell signaling. It is the non euphoria causing 2AG that is used within our brains to cause stronger nerve cell signals – practice more and the cells are more active in a certain order and that pathway is strengthened so next the cells will fire in that order more easily. (Endocannabinoids Performance through Retrograde Signaling).

More information about nerve signaling between brain cell synapses see Neuroscience, 6th Edition, pages 85-112, 169-189, and 571-593, (1), or summary information and short video explanations are available online for the previous edition: Synaptic Transmission, Synaptic Plasticity, Modification of Brain Circuits as a Result of Experience.

2AG is more similar to the non-euphoric cannabidiol (CBD) that is found in varying amounts in certain strains of medical marijuana. Both 2AG and CBD can activate both the Cannabinoid Receptor 1 and the Cannabinoid Receptor 2. It can have pain relieving and anxiety relieving benefits. (About the Endocannabinoid System)

Phospholipids and cannabinoids can be found in some legally and commonly available foods in addition to medical marijuana or the non-euphoric hemp kernel or hemp seed oil. See this post for more information about the nutrient group and other important nutrients, our bodies need all or most of them on a daily basis: Macro- and Micro-nutrients: Description and Food Sources.

Happy learning!

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.

  1. Reference: pp 169-189 “Synaptic Plasticity“, pp 571-593 “Experience-Dependent Plasticity in the Developing Brain“, pp 85-112, “Synaptic Transmission,” Neuroscience, 6th Edition, Editors D. Purves, G.J. Augustine, D. Fitzpatrick, W.C. Hall, A.S. LaMantia, R.D. Mooney, ML. Platt, L.E. White, (Sinauer Associates, Oxford University Press, 2018, New York) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326841/ (Barnes&Noble)