Category Archives: phospholipid

Looking up an itch found a synthetic cannabinoid in clinical trial for four diagnoses; Resunab

Cannabinoids are the active phytochemicals found in marijuana which include the euphoric THC and many, many non-euphoric types. A synthetic version of one of them has reached trial stages for autoimmune and skin related diagnoses and for the life shortening genetic condition Cystic fibrosis.

I stumbled across the information while looking up whether marijuana has been found helpful for preventing or treating eczema or the autoimmune skin condition psoriasis, [link] – yes was potential answer and a specific synthetic cannabinoid was mentioned: Ajulemic acid.

A 2007 study published in the Journal of Dermatological Science found that Cannabinoids, having anti-inflammatory properties, work to inhibit the proliferation of skin cells called keratinocytes, which play a role in causing psoriasis. [link]

Its Wikipedia page led me to the company and the clinical trials. The synthetic molecule is being purified and called Resunab by the company Corbus Pharmaceuticals. They have already been approved for Phase Two trials for the drug for four different serious diagnoses: Cystic Fibrosis, Systemic Sclerosis, Dermatomyositis, Systemic Lupus Erythmatosus. The synthetic cannabinoid activates the CB2 receptors and does not cause symptoms of euphoria as does THC, the euphoria promoting chemical found in marijuana. [Read more regarding Resunab and the clinical trials by Corbus Pharmaceuticals]

And why was I looking up eczema and psoriasis and cannabinoids? – the incredible itchiness I’ve been experiencing since only a few days off of my medical marijuana. Some autoimmune symptoms are worse and a previously tiny itchy spot is now raised scabby patches over a large area of my back – arrgh. (It’s talk like a pirate day.) My genetic study and personal life experience has proven to my satisfaction that my body needs an external source of cannabinoids — and a non-euphoric source would be nice but a euphoric source in the meantime is less itchy than having no source – for me at least and maybe for the other psoriasis patients who participated in previous research studies.

Take home point for patients with one of the four diagnoses in Stage 2 trials – contact the company for more information regarding whether they are still looking for patients to participate.

Take home point for me – I’m not 100% sure but my back is itchy, and I think the take home point is that my body needs an external source of cannabinoids and I should just accept that and adapt my life to the current realities of limited legality, limited access, difficulty traveling legally, etc. Marijuana has been found to help promote brain cell growth, prevent cancer, and help reduce inflammatory symptoms associated with autoimmune disease. And previous reading had suggested that I have a genetic problem in my keratinocytes that may be associated with, drum roll,  migraines, TMJ, IBS, and eczema. I have had all of those problems for many years of my life, decades of discomfort, hours of lost time with my children, hours of reduced productivity at work.

But marijuana is a powerful drug and the strains and quality of what is available to medical patients varies greatly. It is safest when the strain has a good balance of euphoric and non-euphoric cannabinoids — both types have medical properties and affect the neurotransmitters in the brain and throughout the nervous system.

Previous (very messy collections of notes) posts on keratinocytes:

  1. Substance P, neuropathic pain, migraines, and the cannabinoid system
  2. An article on Morgellons; a link, and a comment I added re keratinocytes

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.

 

An article on Morgellons; a link, and a comment I added re keratinocytes

Morgellons, chapter from a book, skeptic busting or quack busting, but open-minded regarding the sufferers having a real itch problem rather than a delusional psychiatric disorder as the mainstream medical world is treating the condition. Sufferers have lost jobs due to a condition that has no physical diagnosis:[https://medium.com/matter/the-itch-nobody-can-scratch-4d980e3ac519#.tcwvu9neq]

It is horrible to have physical symptoms that are dismissed as “all in your head,” — that is no help if there is pain in your skin or under your skin.

I added a comment, slightly edited here:

Maybe they have overactive keratinocytes that produce Substance P and causes itch and neuropathic pain. Magnesium deficiency can lead to increased production of Substance P.

“Keratinocytes are able to detect itch-associated signals by expression of protease-activated receptor-2,[11] opioid,[12] cannabinoid[13] and histamine H4 receptors.[14] By responding to these signals, keratinocytes can modulate itch in many ways. For example, keratinocytes can release neurotrophins including NGF[15,16] and neurotrophin-4[17] (Fig. 1), lipid mediators[18] or endothelin-1,[19] which can either directly activate itch fibres in the skin or activate mast cells to release pruritogenic mediators. In addition, neuropeptides including substance P have been shown to significantly increase the release and production of NGF of human cultured keratinocytes, indicating a neuroimmune interaction mechanism between sensory nerves and keratinocytes[20] (Fig. 1). Interestingly, keratinocytes can also inhibit itch through the release of endocannabinoids, which bind directly to inhibitory receptors on sensory nerves.”

— so maybe the Morgellons sufferers have a defect or insufficiency in endocannabinoids. Epsom Salt baths for magnesium in case gastrointestinal absorption of magnesium is a problem might help, and supplements with phospholipids like phosphatidylcholine or phosphatidylserine might help if endocannabinoid deficiency is a problem — or chocolate, rosemary and nutmeg are food sources.

Excerpt from: “Pathophysiology of Itch and New Treatments,” Ulrike Raap; Sonja Ständer; Martin Metz, Curr Opin Allergy Clin Immunol. 2011;11(5):420–427. [http://www.medscape.com/viewarticle/749608_2]

/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./

Substance P, neuropathic pain, migraines, and the cannabinoid system

Our bodies don’t have specific receptors just for sensing “pain.” Pain is a sign that something is wrong in the body and is sensed in a variety of ways. In medical terminology there are two main types of “pain.” Nociceptive pain is associated with physical damage to the body or by sensations of pressure or heat or extreme cold. It might be due to pressure from a cancer tumor. Nociceptive pain might be described as “sharp, aching or throbbing.” Neuropathic pain is caused by physical damage or pressure on nerves. It might also be due to a cancer tumor but one that is pressing on a nerve. Nerve damage can also be due to some nutrient deficiencies such as vitamin B12, [B12}, or other “Nutritional imbalance, alcoholism, toxins, infections or auto-immunity.” Neuropathic pain often is described as “a burning or heavy sensation, or numbness along the path of the affected nerve.” [http://www.medtronicneuro.com.au/chronic_pain_commontypes.html]

Some types of pain such as migraine headaches may involve both nociceptive pain due to the pressure of inflammation or dilation of blood vessels an neuropathic pain from pressure on nerves by dilated or inflamed blood vessels.

  1. G. La Rana, et al., AM404, an anandamide transport inhibitor, reduces plasma extravasation in a model of neuropathic pain in rat: Role for cannabinoid receptors, Neuropharmacology, Vol. 54 Issue 3, March 2008, Pages 521–529 Abstract opening: “Neuropathic pain consequent to peripheral nerve injury has been associated with local inflammation. Following noxious stimulation afferent fibres release substance P (SP) and calcitonin-gene related peptide (CGRP), which are closely related to oedema formation and plasma leakage. ” Read more, Abstract available:[http://www.sciencedirect.com/science/article/pii/S0028390807003504]
  2. Paul L. Durham, Ph.D., Calcitonin Gene-Related Peptide (CGRP) and Migraine, Headache. 2006 Jun; 46(Suppl 1): S3–S8. Excerpt: “Activation of trigeminal sensory nerve fibers causes a pain response to be conveyed to the brainstem (and from there to higher brain centers) and evokes release of vasoactive peptides such as substance P and CGRP from trigeminal fibers. These peptides exacerbate vasodilation and cause neurogenic inflammation characterized by vasodilation, leakage of blood vessels, and degranulation of mast cells.4 ”  Levels of CGRP increase in people who suffer from migraines and a type of prescription medication, called sumatriptan, which has been found helpful to stop migraine pain, has also been found to inhibit the release of CGRP in migraine patients. The medication may be inhibiting the release of CGRP by increasing intracellular levels of calcium (*which might then be causing an increased release of endogenous cannabinoids from membrane storage.) “The cytokine TNF-α was studied in view of previous observations that it is among the most consistently elevated cytokine in migraine and that it, like nerve growth factor in the experiments described above, activates MAPK pathways in various cell types including neurons.19 The results of the investigations reveal that TNF-α-1 receptors were present on most CGRP-containing rat trigeminal ganglia neurons. In addition, CGRP release from cultured trigeminal neurons was increased after treatment with TNF-α or ceramide, an intracellular signaling intermediate from the TNF-α-1 receptor.“Read more, Full text available:[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134175/] (*TNF = Tumor Necrosis Factor. Increased levels of ceramide are found in Alzheimer’s and it is involved in the cannabinoid membrane system also. Ref’s: Surprising finding provides more support for Alzheimer’s being an autoimmune disease  ,  *Activating cannabinoid receptors type 1 –> production, which mediates cannabinoid induced apoptosis – p67 )
  3. Calcitonin is a hormone released by the thyroid that promotes lower blood calcium levels by reducing bone resorption (bone resorption: breakdown of the bone and release of minerals). [http://medical-dictionary.thefreedictionary.com/calcitonin]
  4. Calcitonin Gene-Related Peptide 1 and 2 cause dilation of blood vessels in the heart and brain and throughout the body. Its prevalence in the Central Nervous System (CNS) also suggests that it may also have a neurotransmitter or neuromodulator role. [http://www.uniprot.org/uniprot/P06881] [http://www.uniprot.org/uniprot/P10092] CGRP is produced by nerve cells in the brain and throughout the body. The protein has a role in sensations of pain. It is a member of the calcitonin family of proteins and exerts its effects at receptors that are formed from two other types of receptors including the “calcitonin receptor-like receptor (CALCRL) and a receptor activity-modifying protein (RAMP1).[7] ” ”  The alpha form of the protein may help reduce pain while the beta form is associated with migraine, temporomandibular joint (TMJ) pain, psoriasis (an eczema-like condition believed to be autoimmune in nature), and irritable bowel syndrome (IBS). The beta form is largely produced in keratinocytes found in the epidermis layer of skin. The alpha form is the type produced more within sensory nerves.[https://en.wikipedia.org/wiki/Calcitonin_gene-related_peptide] *Note to self — ouch. I have had severe migraines, TMJ, symptoms like IBS, and severe eczema throughout much of my life. My keratinocytes may be the common element.
  5. Quanzhi Hou, et al., Keratinocyte expression of calcitonin gene-related peptide β: Implications for neuropathic and inflammatory pain mechanisms, Pain, Vol 152, Issue 9, September 2011, Pages 2036–2051, Keratinocytes also express the two types of receptors that form the CGRP receptor. Read more, Abstract available:[http://www.sciencedirect.com/science/article/pii/S0304395911003137]
  6. Xiaoyou Shi, et al., Neuropeptides Contribute to Peripheral Nociceptive Sensitization by Regulating Interleukin-1 Beta Production in Keratinocytes, Anesth Analg, 2011, July 113(1) 175-183, This article includes a discussion of Substance P and CGRP levels in a type of chronic peripheral pain condition and whether Substance P and CGRP might cause an increased production of IL-1beta. The discussion mentions that an abnormal response to capsaicin is observed in patients with the chronic peripheral pain condition called “complex regional pain syndrome (CRPS).” [Capsaicin is the active phytochemical found in hot peppers which can also be a trigger for symptoms of Irritable Bowel Syndrome. https://en.wikipedia.org/wiki/Capsaicin] Full text available: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123433/]
  7. Capsaicin is the active phytochemical found in hot peppers which can also be a trigger for symptoms of Irritable Bowel Syndrome. Except probably not in birds: “The seeds of Capsicum plants are dispersed predominantly by birds: in birds, the TRPV1 channel does not respond to capsaicin or related chemicals (avian vs mammalian TRPV1 show functional diversity and selective sensitivity).” [https://en.wikipedia.org/wiki/Capsaicin]
  8. I love search engines and the large volume of knowledge available online. Somewhat related posts on this site:  1) And what do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids have in common? (Answer – TRPV1 channels and Irritable Bowel Syndrome.) 2) Links about magnesium deficiency and Substance P, a neuropeptide associated with inflammation, .

Time for an Epsom bath perhaps.

Epsom salt baths can be a well absorbed source of magnesium because skin absorption will bypass a problem of poor intestinal absorption of magnesium. Calcium tends to be preferentially absorbed by the intestines, especially when there is an imbalance in vitamin and hormone D levels and poor intestinal absorption of magnesium over time can easily lead to symptoms of magnesium deficiency. Symptoms of magnesium deficiency are usually labeled something else by the medical profession because the problem is not obvious on lab tests until it is quite severe because the body takes more magnesium from the bones as needed up until the point where osteoporosis is severe  enough to cause a shortage of stored magnesium.

Soaking in a bathtub for twenty minutes that has one cup of Epsom salt to a half full bathtub, and one teaspoon of a cooking vinegar such as apple cider vinegar to balance the alkalinity of the Epsom salt, can be a cure for a bad mood as well as various achy muscle cramps if magnesium deficiency is an underlying problem. Negative symptoms can occur if you stay in the bath too long. Excess magnesium absorption can cause loose watery stools for an entire day, not just once. Falling asleep in the bath can also lead to more life threatening symptoms of a weak, and fluttery heart rate, or even lead to coma and/or death — so twenty minutes to forty minutes is probably safe for a deficient person while someone who isn’t deficient might notice a weak slowing heart rate sooner than the twenty minute average that a person deficient in magnesium might find only as calming and soothing to  their mood and muscles. A person who was deficient but who then started taking the baths regularly might start noticing the weak heart rate sooner — get out of the tub then, even if its not been twenty minutes — shower and rinse time. Research on the therapeutic use of Epsom salt baths recommended one cup Epsom salt to the half full/full bath and use up to three to four times per week, but not daily.

I can’t find the actual research study among the following posts of mine (see below) but Dr. Oz has an article on the baths also and recommends the twenty minutes a few times a week also: [http://blog.doctoroz.com/oz-experts/restoring-magnesium-levels-with-epsom-salt-baths]

Previous posts on magnesium deficiency and Epsom salt baths:

1) Autistic kids wash up happier in an Epsom salt bath, .

2) Hypomagnesemia symptoms and causes list, .

3) Magnesium deficiency can cause irritability, anxiety, and chronic degeneration, .

4) Note to self: Epsom salt bath first, keyboard second; Irritability, Schizophrenia, T. gondii, and hormone D, .

An update on schizophrenia, unrelated to Substance P, migraines, or Epsom Salt baths:

5) The voices that people with schizophrenia are hearing are probably their own inner thoughts, .

/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./

Ibuprofen may reduce pain and inflammation due to it helping prevent breakdown of cannabinoids within the body

In a recent post I mentioned that the over-the-counter medication ibuprofen might be helpful for people who are trying to withdraw from the prescription medication olanzapine/Zyprexa (TM) because ibuprofen also helps prevent the breakdown of cannabinoids within the body but without affecting mental health symptoms. I didn’t have the citation about ibuprofen handy but have since found it.

The post mentioning ibuprofen was the third in a series about the prescription medication olanzapine/Zyprexa (TM):

  1. “Quit stalling,” is also a handy phrase; or Olanzapine may be dangerous to individuals and others, ,
  2. Zyprexa, $4.8 billion in prescription sales in 2007, and diabetes may also become a side effect, ,
  3. So, “we have nothing to fear but fear itself,” psychiatrists and their prescription pads, an unhealthy microbiome, and the occasional suicide bomber, . This is the post that mentions ibuprofen.

Excerpts from p83 and 82, Editors, Emmanuel S. Onaivi, Takayuki Sugiura, Vincenzo Di Marzo, Endocannabinoids: The Brain and Body’s Marijuana and Beyond, (Taylor & Francis Group, 2006, Florida), pages 82 and 83 are from Chapter 3, by: E.S. Onaivi, H. Ishiguro, P. W. Zhang, Z. Lin, B. E. Akinshola, C. M. Leanoard, S. S. Chirwa, J. Gong, and G. R. Uhl, Chapter 3, Endocannabinoid Receptor Genetics and Marijuana Use.

A note before typing the excerpt about ibuprofen: Fatty acid amide hydrolase (FAAH) is a primary enzyme for breaking down cannabinoids whether they are from internally produced (endogenous) sources or from external foods or other substances such as medical marijuana or the prescription medication for Multiple sclerosis called Sativex (TM).

“In addition to PMSF, numerous compounds have been identified that block FAAH reversibly and irreversibly. Among these is ibuprofen, which is an active inhibitor, but not other nonsteroidal anti-inflammatory agents (NSAID) such as naproxen.” [Onaivi, et al., 2006, p83]

The paragraph doesn’t explain what PMSF is but according to the search engine it is likely to be a serine protease inhibitor used in biochemistry to “prepare cell lysates” — which means to split cells open by causing their membranes to breakdown. “phenylmethane sulfonyl fluoride or phenylmethylsulfonyl fluoride (PMSF),” [https://en.wikipedia.org/wiki/PMSF] [https://en.wikipedia.org/wiki/Lysis]

Cannabinoids are not only messenger chemicals that can trigger actions within the body, they are also building blocks for strong and flexible membranes. Cannabinoids are released from the membranes as needed  individually rather than being stored in bulk and released in batches the way brain neurotransmitters are stored.

The paragraph actually started on page 82 and explains that FAAH is a membrane-associated serine hydrolase found primarily in brain and liver. And research with rat brain activity has shown that the enzyme is most prevalent in areas that also have many CB1, Cannabinoid Receptors type 1:

“The currently known endocannabinoids, derived from membrane phospholipids that contain arachidonate (Mecholam et al., 1998) are metabolized by FAAH (Deutsch and Chin, 1993), which is a membrane-associated serine hydrolase enriched in brain and liver. There is an overlap of the distribution of FAAH and its activity in the rat brain with the expression of CB1, which has led to the suggestion that FAAH is probably the major enzyme in the brain responsible for inactivation of fatty acid amides (Elphick and Egertova, 2001). This, in the human brain the distribution of CB1R and the FAAH enzyme frequently overlap in many structures.” [Onaivi et al., 2006, p82]

Excerpts from p83 and 82, Editors, Emmanuel S. Onaivi, Takayuki Sugiura, Vincenzo Di Marzo, Endocannabinoids: The Brain and Body’s Marijuana and Beyond, (Taylor & Francis Group, 2006, Florida), pages 82 and 83 are from Chapter 3, by: E.S. Onaivi, H. Ishiguro, P. W. Zhang, Z. Lin, B. E. Akinshola, C. M. Leanoard, S. S. Chirwa, J. Gong, and G. R. Uhl, Chapter 3, Endocannabinoid Receptor Genetics and Marijuana Use.

Now I just have to re-trace my steps to find the information about olanzapine and anandamide because I’m not sure where that citation was from. The anti-psychotic activity of the drug is believed to be due to it affecting dopamine and serotonin levels within the brain. [https://www.pharmgkb.org/chemical/PA450688#tabview=tab3&subtab=31]

My research into how olanzapine worked was a while ago. Wikipedia also just mentions the dopamine and serotonin affects but also includes more information about the Eli Lilly company’s lawsuits. The company settled 8000 lawsuits with $700 million in 2006. They are also stated to have agreed to pay $500 million more to settle 18000 other lawsuits in 2007 but that factoid says [citation needed]. More recently in 2009 the company plead guilty to a misdemeanor charge regarding marketing Zyprexa for off-label use and agreed to pay $1.4 billion. [https://en.wikipedia.org/wiki/Olanzapine]

I thought the mechanism involved inhibiting the enzyme that breaks down cannabinoids but obviously I need to search a little harder or this series of posts about olanzapine/Zyprexa (TM) will be based on [citation needed]. Yeah, I am saved by the search engine combined with perseverance with assorted search terms:

Cannabinoids may be responsible for weight gain associated with schizophrenia,” February 5, 2015,  “After the treatment, [16 weeks on olanzapine] the researchers observed hyperactivation in the left amygdala (limbic region) in, relative to a control group of healthy subjects. These brain changes were associated with increased levels of glucose, triglycerides and anandamide,” [http://medicalxpress.com/news/2015-02-cannabinoids-responsible-weight-gain-schizophrenia.html]

A different article about the same research group’s findings:

“Average blood oxygenation level-dependent signals revealed that limbic brain regions in the left amygdala and right insula became hyperactive to appetizing rather than neutral images after olanzapine treatment, and increases in activity were significantly higher than in control participants.”

“These brain changes were associated with increased levels of glucose, triglycerides, and anadamide, the primary cannabinoid neurotransmitter, binding to the cannabinoid 1 (CB1) receptor.”

— from the article by Liam Davenport on Medscape.com, “Antipsychotic-Related Weight Gain Explained?,” February 12, 2015, [http://www.medscape.com/viewarticle/839713]

/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./

And what do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids have in common?

// 7/1/16 addition: This post is for people suffering from Irritable Bowel Syndrome (IBS) which is not well understood, easy to diagnose or treat, and can be life threatening when more severe symptoms continue long term. The condition can continue for years or be a life long issue that flairs up at times and is less severe at other times.   http://www.news-medical.net/news/20160629/Treatment-for-IBS-proves-difficult-survey-reveals.aspx?platform=hootsuite

Dietary tips can be helpful but why some foods seem to trigger symptoms while others don’s has not been well understood either. The common factor underlying why some foods seem to be triggers for many people may be the TRP channels that are found in cells throughout the intestines and actually in most cells of most life forms. //

So what do osmo-mechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common?

They all may be able to overstimulate Transient Receptor Potential channels (TRP channels) within the gastrointestinal system and cause severe diarrhea in susceptible individuals.

In many cases, the activation mechanism of TRP channels is unclear (Figure 1), but known activators include specific agonists such as mustard oil (TRPA1) and capsaicin (TRPV1), an increase in intracellular Ca2+ (TRPM4, 5), temperature (heat: TRPV1, 2, 3, 4, TRPM4, 5; cold: TRPM8, TRPA1), mechanical or osmotic stress (TRPV4, TRPCs?) and phospholipase C (PLC) activation. TRP channel activity can be further modulated by intracellular phosphatidylinositol phosphates, such as PI(4,5)P2 and membrane potential, but also by inflammatory mediators, cannabinoids and steroids (Nilius, 2007; Rohacs, 2007; Nilius and Voets, 2008).” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012403/]

The TRP channels are a large group found in many species of life from yeast, to worms, fish and mammels. The agonists/activating chemicals for many of the types of TRP channels have not all been identified as of yet. [http://molpharm.aspetjournals.org/content/75/6/1262.full]

One type of TRP channels were formerly called Vanilloid Receptors, and are now called TRPV channels. Vanilloid Receptors were known to be activated by capsaicin found in hot peppers and chili powder. And more recent or less well known research has also found that they can be activated by cannabinoids and steroids, (see the link from the excerpt above), and osmomechanical stress.

Osmo-mechanical stress might be a precursor to edema, excess fluid in the extracellular space; if an organ or cell over fills with fluid it would mechanically be adding physical pressure to the organ or cell — and instead of popping like an overfull water balloon the TRP channels open in response to the physical pressure and let the excess fluid leak out into the extracellular space or into the area surrounding the heart for example. [http://www.ncbi.nlm.nih.gov/books/NBK92821/] Fibrotic heart disease would be adding mechanical stretching stress within the heart. TRP channels are being studied for possible use in preventing fibrotic heart disease. From that research article, we are told that changes in temperature may also activate them:

The activation mechanisms of TRP channel are highly diversified. Some TRP channels appear to be constitutively active, whereas others are activated by Gq-linked receptor activation, oxidative stress, changes of temperature, or an elevation of intracellular Ca2+ [126128]. All the TRP channels appear to be regulated by PIP2 [134137] .” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874073/]

PIP2 = phosphoinositides = phosphatidylinositol phosphates (PIPs) = phosphorylated deriviatives of phosphatidylinositol (PI) [http://www.annualreviews.org/doi/abs/10.1146/annurev.cellbio.21.021704.102317]

PIP2 = phosphatidylinositol-4,5-bisphosphate and PI, and phospholipase C (PLC) from the first excerptare involved in cannabinoid metabolism within plasma membranes: [page 9 Kendall et. al., Behavioral Neurobiology of the Endocannabinoid System (Springer, 2009, New York)]

Steroids and hormone D function similarly. And Benicar and curcumin can function similarly to hormone D. And curcumin is a medically active extract from turmeric, a powdered spice that is a main ingredient in curry powder. Turmeric is made from the root of a plant that is biologically very similar to ginger,  which is also a root that is used as a dried spice or  may be used as a chopped vegetable in stir-fry dishes and other foods. Ginger has over 400 active phytochemicals, and one of them might be acting similarly to the curcumin — but that is speculation based on the similarity of symptoms of Irritable Bowel Syndrome that both ginger and curry powder stimulate.

Because — what else do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common? — They all may irritate Irritable Bowel Syndrome, (IBS), for some people, along with emotional stress and other things like eating fructose in much quantity (example: from a piece of fruit or fruit juice) or gassy vegetables like cabbage and cruciferous vegetables and beans (gas would be adding mechanical pressure to those TRP channels which might be an over-active culprit in IBS patients).

The book, “Tell Me What to Eat If I Have Irritable Bowel Syndrome; Nutrition You Can Live With; Including Dozens of Healthful Mouth-Watering Recipes,” by Elaine Mager, M.P.H., R.D., includes dietary advice and other information about Irritable Bowel Syndrome (IBS). (Warning – most of the recipes contain gluten

/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./

What do we have in common with pine trees and ticks?

Cannabinoids is the short answer.

Excerpts from p59 and p62, Editors, Emmanuel S. Onaivi, Takayuki Sugiura, Vincenzo Di Marzo, Endocannabinoids: The Brain and Body’s Marijuana and Beyond, (Taylor & Francis Group, 2006, Florida), pages 59 and 62 are from Chapter 3, by: E.S. Onaivi, H. Ishiguro, P. W. Zhang, Z. Lin, B. E. Akinshola, C. M. Leanoard, S. S. Chirwa, J. Gong, and G. R. Uhl, Chapter 3, Endocannabinoid Receptor Genetics and Marijuana Use,

“This chapter discusses the current state of description of the genes encoding the CBRs, [cannabinoid receptors], from their serendipitous identification to the existence of an EPCS, [Endogenous P_?__ Cannabinoid System – I can’t find the acronym spelled out within the text]. This previously unknown but ubiquitous EPCS consists of the membrane cannabinoid receptors, their ligands, endocannabinoids that are known to act as retrograde messengers, and the associated proteins for their biosynthesis, e.g., phospholipase D, and for their inactivation, e.g., fatty acid amide hydrolase (FAAH) and monoacylglycerols.” (p59)

Cannabinoids are essential throughout the body and in most forms of life, including plants, animals and some insects:

“The occurrence of a novel cannabimimetic molecule 2-scia-donoylglycerol (2-SG) in the plant seeds of umbrella pine (Sciadopitys verticillata) has also been reported (Nakane et al., 2000). 2-SG was found to have effects on the CB1R similar to, but with lower activity than, 2-AG, demonstrating the occurrence of these interesting molecules, not only in plants and animals but also in disparate organisms such as ticks. This widespread occurrence of endocannabinoids and related fatty acid amides and their receptors appears to be highly conserved in nature, indicating a fundamental role in biological systems. For example, the salivary glands of ticks, which are ectoparasitic and obligate blood-feeding arthropods, can make endocannabinoids and their congeners with analgesic and anti-inflammatory activity, which possibly participate in the inhibition of the host defense reactions (Fezza et al., 2003).” (p 62)

Ticks know that cannabinoids have medical properties – are U.S. politicians dumber than ticks? – or are they just under the control of corporate profit influence? The Eli Lilly company made $4.8 billion off of the cannabinoid system in 2007 alone with the sale of olanzapine/Zyprexa.

The paragraph continues:

“Apparently, the EPCS plays a critical role in the survival and mechanisms of cell death.”

In other words the endogenous cannabinoid system is essential for controlling apoptosis – the enzymatic blast of death that white blood cells can deliver to infected, cancerous, or otherwise damaged cells. The cure for cancer has always been within us – when we are well nourished and functioning correctly.

The paragraph continues (it’s a long paragraph, which actually started half way up the previous page, but this does include the rest of the paragraph.):

“Previously, the existence of anandamide analogs in chocolate had been demonstrated (di Tomaso et al., 1996). It is thought that chocolate and cocoa contain N-acylethanolamines, which are chemically and pharmacologically related to anandamide. These lipids could mimic cannabinoid ligands either directly by activating CBRs or indirectly by increasing anandamide levels (Bruinsma and Taren, 1999). These observations demonstrate that endocannabinoid analogs exist in plants and animals and further illustrate that evolutionary conservation of the cannabinoid system in nature. In this section, we will briefly review the properties and functions of these endocannabinoids. Thus, the EPCS represented by CBRs, endocannabinoids, and enzymes for the biosynthesis and degradation of these ligands is conserved throughout evolution. Endocannabinoids are present in peripheral as well as in brain tissues and have recently been demonstrated to be in breast milk. In addition, the recent demonstration of the expression of functional CB1R in the preimplantation embryo and synthesis of anandamide in the pregnant uterus of mice suggested that cannabinoid ligand-receptor signaling is operative in the regulation of preimplantation embryo development and implantation (Paria and Dey, 2000). 2-AG has been characterized as a unique molecular species of the monoacylglycerol isolated from rat brain and canine gut as an endogenous CBR ligand (Sugiura and Waku, 2000). 2-/ag also exhibits a variety of cannabimimetic activities in vitro and in vivo, and clearly further studies are necessary to determine the relative importance of 2-AG and anandamide in the human body and brain. This is because the levels of anandamide (800 times lower than the levels of 2-AG) found by some investigators in several mammalian tissues, and its production mainly in the postmortem period in the brain, have led to questions about the physiological significance of anandamide, especially in the brain, despite its high-affinity binding to CBRs (Sugiura and Waku, 2000). These research findings undoubtedly have advanced cannabis research and have allowed us to hypothesize that the EPCS consists of a previously unrecognized but elaborate network of endocannabinoid neuromodulators complete with their accompanying biosynthetic, uptake, and degradation pathways just like the monoaminergic and opiodergic systems.” (p62)

So olanzapine/Zyprexa prevents the breakdown of anandamide – which normally becomes more elevated in the postmortem (dead) brain while a different endocannabinoid – 2-AG – is normally more elevated in the live brain. Personally I like my brain to function more like a live brain than a dead brain, as I’m not partial to zombies or negative side effects such as diabetes, suicide, or homicide. So the Eli Lilly company may be similar to blood sucking parasitic ticks in that they are pleasuring some patients to the point of sickness or death with the prescription medication olanzapine/Zyprexa.

There was a warning from the FDA about Zyprexa in 2005, but regarding a problem with it being given in error to people who actually had been prescribed the allergy medication Zyrtec. Zyprexa causes many negative side effects and Zyrtec doesn’t cause any — at least for me, I’ve used it for allergies in the past. Zyprexa is described within the FDA warning as being an anti-psychotic that is only for the short term or maintenance management of schizophrenia or for the short term use for manic episodes associated with bipolar disorder. So be sure to check your Zyrtec bottle every time you refill it, just in case the pharmacist makes a mistake and grabs Zyprexa instead or couldn’t read a hand written prescription accurately and thought that it did say Zyprexa.[http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152869.htm]

The medication, in an injectable form, was also under FDA review due to two patient deaths — autopsy found higher than expected levels in the blood of the two patients a few days following a standard injection (a one month sustained release dose is given as a intramuscular injection). The FDA required animal studies which showed that some animals did have increased amounts of the drug in their blood following death. No changes were required for the medication’s patient care or label requirements. The article includes the information that since 2011 that total sales of olanzapine had dropped for the year 2014, due to an increase in the use of generics. “Zyprexa’s 2014 sales have fallen to $1.04 billion from $4.62 billion in 2011, primarily due to competition from generic medications, Reuters reported. ” [http://www.biospace.com/News/deaths-review-of-eli-lillys-antipsychotic-zyprexa/369798?type=twitter_zyprexalilly032415]

The two patients are still dead though. Maybe enough patients complained to their doctors in 2012 and 2013 about the negative side effects of the medication to cause the large increase in use of different generics. — No that isn’t what happened, the FDA approved a generic form of olanzapine in 2014, so now Eli Lilly isn’t the only parasitic tick pleasuring patients to sickness or death. [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm277022.htm]

Obviously Eli Lilly and the generic drug company is making billions off of our cannabinoid system — so clearly cannabinoids have medical uses within the body.

Cannabinoids are essential throughout the body and not all people can make them from other molecules. They may have a deficiency of the nutrient since birth, due to genetic defects, or some people may have been able to make adequate cannabinoids when they were young but then they may have lost the ability later in life due to malnutrition, disease, or aging. So for some individuals from birth and for others later in life cannabinoids are an essential nutrient that has to be obtained from external sources. The nutrient guidelines need to be changed to reflect the fact that some people and some babies may need an external source of cannabinoids in their diet or with an alternate external source, (such as medical marijuana or the prescription Sativex which contains a balanced amount of THC and CBD extracted from medical marijuana), and all infant formula should be required to have cannabinoid content equivalent to what would be provided naturally within breastmilk.

The herb rosemary, from the pine family, is a natural source of cannabinoids, so is nutmeg, cardamom, chocolate and cocoa, buckwheat, the inner germ of corn, and some seeds such as cucumber seeds and pomegranate seeds.

Sources: 1. Weihrauch et al, 1983 The Phospholipid Content of Foods (JAOCS, vol 60, no. 12 (December 1983) and 2. James Duke – Greenpharmacy.com for the herbal plants, Ethnobotanical and Phytochemical Database of medicinal plants and chemical activities, (This website still exists, however the Database is no longer available.)

See a couple of my older posts for more information and excerpts about the phospholipid content of many foods:

/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./

 

Omega 3 and omega 6 fatty acids aren’t just fats, they can activate cell receptors

Me 5:41am:

I didn’t know the history of omega 3 recommendations. Thanks for sharing.  The balance of omega 3 to omega 6 may be part of the issue – not just take more of one thing (omega 3 fatty acids) but also have less of the other thing (omega 6 fatty acids).

From (2002):
http://www.ncbi.nlm.nih.gov/pubmed/12442909

“Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today’s Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a low omega-6/omega-3 ratio) exert supressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial”

~~~~
 A response, 10:41am:
But is omega-6 itself a problem, or is it simply an measurable indicator that an individual has a high-fat diet?    Dietary science seems to suffer from ‘observability bias’; that is, being unable to observe actual chemical process in the body from consumption through mortality, researchers are forced to wring as much causality (and as many conclusions) as possible from a few metrics, without experimental confirmation of the actual biochemistry.
 ~~~~~~
Me 1:42pm:

Some of the omega-3 fatty acids can activate some cell receptors that have powerful anti-inflammatory effects. “Stimulation of GPR120 by DHA has been shown to inhibit both the TLR2/3/4 and TNF-a proinflammatory cascades.”  Any chemical that can act as a signaling device may also have risks if too much is consumed.  (TNF-a = Tumor Necrosis Factor – alpha – an important signal to tell white blood cells to kill infected or damaged cells.)http://www.themedicalbiochemistrypage.org/omegafats.php

I’m still reading re the omega 6 question.

The next paragraph reviews their role – fatty acids are building blocks of the membranes. Inflammatory signals can cause cell membrane breakdown which releases the omega 6 fatty acid ALA and leads to production of eicosanoids – which are also powerful messenger chemicals.

And part of the reason research is limited may be because the ALA and conversion to eicosanoids all has to do with endogenous cannabinoid system — and with reefer madness and the paper industry and the Marijuana Tax Act of 1937 causing decreased availability and increased illegality of marijuana.  Interestingly the physicians at the time didn’t like the law:

“The American Medical Association (AMA) opposed the act because the tax was imposed on physicians prescribing cannabis, retail pharmacists selling cannabis, and medical cannabis cultivation and manufacturing; instead of enacting the Marijuana Tax Act the AMA proposed cannabis be added to the Harrison Narcotics Tax Act.[34]”

https://en.wikipedia.org/wiki/Legal_history_of_cannabis_in_the_United_States

Me 1:59pm:
The ratio of omega 3 to omega 6 fatty acids is important because they compete with each other for use as building blocks of the membranes. So too much of one or the other might leave the membranes weaker or less flexible or might be causing more of one type of signaling messenger chemical to be produced at the expense of other types of signalling chemicals. btw that article doesn’t mention the endogenous cannabinoid link – I could give you links for that if you’re interested.
~~~~~~
 Response 2:12pm:
I fear you’ve lost me with the cannabis stuff…
 ~~~~~
Me  2:21pm:
The ALA omega 6 fatty acid, arachidonic acid, is actually part of two endogenous cannabinoids:  2-arachidonoylglycerol ether (noladin ether), N-arachidonoyl dopamine (NADA).
The endogenous cannabinoids are stored in the membranes and can be released by different inflammatory signals which can include having elevated intracellular levels of calcium.  Magnesium is an electrically active ion found in higher concentration within the cell while calcium is the electrically active ion found in higher concentration in blood plasma. After release the parts of the endogenous cannabinoid break apart so the arachidonic acid becomes a free fatty acid again.Endogenous cannabinoids are phospholipids which is chemically very special. They have a fatty acid end that likes to dissolve in oil and a phospho- end which likes to dissolve in water which makes them very useful for building membranes within a watery and oily environment.This is a continuing ed course and has lots of info:
http://www.netce.com/coursecontent.php?courseid=1129

 ~~~~~~~
Response 2:25pm:
Are we still talking about people not living longer when they take Omega-3 supplements,
~~~~~
Me 2:34pm:

Cannabis is not a bad plant or substance. Cannabinoids are in every cell of our body. They are in breastmilk. Babies don’t grow well and have reduced appetites when the mother is lacking endogenous cannabinoids. They are in pine trees,, nutmeg, rosemary, buckwheat, chocolate and in most life forms except insects. So hemp rope and paper was cheap in the 1930s and a paper industry executive managed to stigmatize cannabis as something that only those jazz musicians who steal your wife would use. (paraphrased)

Plastic nylon rope was also a new invention of the time – hemp and cannabis eventually were made illegal. But you can’t legislate physiology to just be something that it is not –  omega 6 fatty acids are used in the internal production (endogenous) of cannabinoids. People who are healthy, well nourished and without genetic defects in the endogenous cannabinoid system can make the chemicals themselves but the building blocks are becoming more rare in our food supply as the fertility of soil is depleted.

 Me 2:37pm:
The tl:dr = omega 6 fatty acids are part of cannabis and cannabinoids so limiting research in the cannabinoid system is also limiting research into the function and ideal ratio of omega 6 and omega 3 fatty acids.
Me 2:47pm:
And back to the article you linked to – the ideal ratio of omega 6/omega 3  to consume in the diet each day must be different for the Inuit than for other populations and is also likely a little different for different types of diseases based on one of the links I quoted.
 Me 2:49pm:
So why not call it buckwheat stuff or pine tree stuff or sea squirt stuff — or even better — human stuff?
~~~~~
Response 3:03pm:
I’m not sure I’m following.  Are you saying that because fish oil is useless, marijuana is useless?
~~~~~~
Me 3:09pm:
(but not in response to  the previous response – I had missed seeing it – this was just following up from my series of short comments following the last response. – My yes was not to that response but was saying yes to the last response – this all must have been confusing in many ways .):
Yes, all of that was talking about why people might not live longer if they take large quantities of omega 3 fatty acids when they are genetically not related to the Inuit.  Omega 3 and omega 6 can both be powerful signaling chemicals not just dietary fats. Limiting research in the endogenous cannabinoid system limited research throughout the body and throughout all areas of physiology because the cannabinoid receptors, cannabinoids, and eicosanoids do so many things for us – and for mosquitoes too.
Me 3:21pm:

From an evolutionary perspective – most native diets wouldn’t have supplied much omega 3 or omega 6. The Inuit diet would have had a lot of omega 3 from the fish and little omega 6. Other native diets wouldn’t have had a lot of omega 6 either because it is concentrated in our modern vegetable oils,.  A native diet would get it from eating sunflower seeds but that would take a lot of growing, harvesting, and shelling before you could consume a medicinal quantity of omega 6 from sunflower kernels.

A take home point might be to continue consuming some omega 3 and some omega 6 without overdoing either one — and more research is needed  😉

~~~~~
Response 3:29pm:
 I dunno…the way I’m reading it is, dietary researchers are biased towards finding dietary reasons for things that may have nothing to do with diet, and then dietary marketers take that misunderstanding and spin it into sales of the supplement du jour.
    I expect we’ll have a legalization of marijuana soon, and a decade or so of cannabis as miracle drug, and then someone will notice that it really makes no difference, and we’ll move on to mayfly extract or some such thing.
~~~~~~
Me 4:20pm:

I agree with you  that many supplement sales companies will push whatever supplement they can in whatever way they can — but so do pharmaceutical companies and our bodies actually are made up of cannabinoids, omega 3 and omega 6 fatty acids, and we are not made up of patent pharmaceuticals.

— Everything has to do with diet because we are actually made out of what we eat, drink, and breathe. Babies don’t eat or grow well and fail to thrive when their mother’s milk is deficient in cannabinoids. Cannabinoids are always going to make a difference in health because they make up our cell walls and our membranes and act as messenger chemicals. Non-euphoric strains have been developed and are being used with elderly patients in nursing homes in Israel.

– Genetic defects or malnutrition or older age and ill health may all limit our bodies ability to make the cannabinoids internally and so those individuals would need to consume an external source everyday for the rest of their lives in order to supply their bodies with the essential membrane building blocks. Research suggests we need about 600 mg per day which would be roughly equivalent to 1/8 ounce per day (which is a lot to consume per day and is expensive).

No one dietary supplement or extract is likely to be a cure-all by itself because the nutrients usually work together as teams. Research science got too thrilled by magic bullet medicines and seems to think nutrients also act by themselves — possibly because a few nutrients were discovered due to population wide nutrient deficiencies. – scurvy, pellegra, beri beri, and rickets.

It’s frustrating to me that physiology research and health care got derailed by the paper and rope industries.

Cannabinoids are not a fad supplement, They are always going to be essential for the health of humans, and for most of the rest of the life forms on our planet.

Disclosure: I am a dietitian and medical marijuana patient and have had chronic health issues since infancy (bottle-fed) which I believe may be related to genetic defects in my cannabinoid receptor system. An external source helps reduce my autoimmune thyroid disease symptoms and reduces symptoms of numbness in my fingers and toes. The chronic nerve degeneration disease ALS has a 19% comorbidity rate with the type of autoimmune disease I have – if medical marijuana can help prevent my becoming paralyzed than that seems like a good thing to me.

Sorry for the lengthy comments – the negative view of cannabis as only an addiction is so frustrating too me. Is starving infants really better than providing the body with all of the essential building blocks that it needs? If cannabinoids are naturally found in breast milk than we need to be adding them to infant formula and to the formula used for tube feeding paralyzed adults and others who can’t consume solid foods.

You can look forward to the mayfly extract,  😉 I’ll stick with rosemary, buckwheat and other natural sources of cannabinoids.

~~~~
Response 4:35pm:
  I’m not sure that individual practitioners in the dietary field are necessarily better than big drug companies; though; both seem to monetize the assumption that evolution has left the human body unable to meet its own dietary needs.

~~~~

Me 4:58pm:
The Linus Pauling Institute has very thorough information about nutrient needs and interactions and food sources for the nutrients. +Stephen L
http://lpi.oregonstate.edu/

or the DASH diet has been found effective and is fairly easy to follow.
http://www.dashdietoregon.org/why

If an individual dietary practitioner is pushing only supplements on you without mentioning any foods than find a different dietary practitioner would be my recommendation for you. Good ones would know that fiber and other phytochemicals in whole foods are also very beneficial and wouldn’t be available in a pill. And the supplemental fiber that is commonly used isn’t as good for the body as the many varieties that are found in produce naturally.

Funding is the problem – research is expensive and nutrients can’t be patented and sold at a huge profit.

Me 6:14pm:

I was looking through the extremely long  comments and saw that I missed one of your comments – no I was not saying that because omega 3 fatty acids haven’t proven to prevent heart attacks as hoped that cannabis is also going to be useless – sorry my responses must have been confusing because they had nothing to do with that comment – I only just saw it. I was saying that the two chemicals are related/work together so limiting research in one area, cannabinoids, may have limited research advances being made with the other, omega 3/omega 6 fatty acids and the importance of having them in balance in moderate amounts.

— vegetable oil = fried food, chips, etc – things we tend to eat to much of. So salmon or sardines a couple times per week is still probably healthy amount of omega 3 and eating moderate amounts of fried foods and chips would help keep omega 6 intake more in balance with the omega 3.

The comments are from this post.
““““
Eicosanoids were also a Fringe Topic: Eicosanoids are made from eCBs from the membrane
/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./

Magnesium deficiency is bad for a good mood, and can be dangerous in combination with THC

     A modern day cannibal such as the homeless man in a recent news story may not be infected with anything contagious but could be overreacting to acute magnesium deficiency. The homeless man may have been under the influence of a synthetic street drug commonly referred to as “bath salts,” a chemical substance based on the structure of the euphoric cannabinoid THC contained in medical marijuana. A study on cannabinoid effects found that research animals would kill other smaller animals when deficient in magnesium but not otherwise. Typically a mellow couch potato is the stereotype rather than raging maniac yet even mild magnesium deficiency made small doses of the THC turn the nutrient deficient animals into killers.
Education on the risks of magnesium deficiency would make a starving rage less likely to occur no matter what other chemical effects might be going on. Magnesium deficiency rage is part of the problem with alcohol abuse. Other pharmaceuticals also can deplete magnesium stores and coffee, carbonated beverages and the act of smoking also cause magnesium stores to be used for buffering the removal of waste.
The following excerpt from an endogenous cannabinoid textbook does make regulation of bath salts seem like a good idea. I am not familiar with the chemistry of the drug being sold as “bath salts” or the current news stories but I felt it necessary to mention magnesium deficiency in relation. Preventing magnesium deficiency would help prevent rage. Promoting safe access to medical marijuana products which contain a good balance of the euphoric THC and the more calming non-euphoric cannbinoids for those with documented chronic medical needs would help make a black market less profitable and reduce the risk of there even being a black market for the higher risk synthetic THC/bath salts (legal because it isn’t marijuana and is sold as “bath salts” or by some other name).
Education about stress coping skills and plenty of community support centers would help reduce demand for and support of a black market in artificial enhancements to life of whatever type – gambling, incessant video game playing or other escapes from reality.
In the excerpt below it mentions that magnesium deficiency alone could cause rodents to kill and eat other rodents. A large dose of THC given to hungry isolated rodents led to them killing other rodents when. Smaller doses of THC did not cause rodent killing unless the rodents had also been on a magnesium deficient diet for six weeks prior to the smaller dose of THC.

65. Marie-Hélène Thiébot, Frédérique Chaperon, Ester Fride, and Emmanuel S. Onaivi, Endocannabinoids : The Brain and Body’s Marijuana and Beyond, Chapter 13, Behavioral Effects of Endocannabinoids, (2006 by Taylor and Francis Group, LLC)  (p 310)

 “In isolated rats, food deprived for 22 h and then fed ad libitum for a 3-h period, a single injection of D9-THC (11 mg/kg) induced mousekilling (muricidal) behavior with enhanced aggressiveness, as indicated by the dramatic increase in the number of attacks on the dead mouse until it was completely torn in pieces (Bac et al., 1998). These authors also showed that D9-THC, at doses (2, 4, and 8 mg/kg) inactive to induce muricidal behavior in control rats, became efficient in rats suffering a magnesium (Mg2+) deprivation for 6 weeks. A severe Mg2+ deficiency (50-ppm diet) induced killing behavior by itself, and D9-THC exacerbated further attacks on the dead mouse. A moderate Mg2+-deficient diet (150-ppm) alone did not produce muricidal behavior, but all the rats became mouse killers when given D9-THC, whatever the dose. These results suggest a potentiation between both treatments to elicit aggressiveness. D9-THC would act as a trigger to induce aggression in Mg2+-deficient rats and reciprocally Mg2+ deficiency would reveal the potential neurotoxicity of a low dose of D9-THC (Bac et al., 2002).” (p310)

  • A recent study found no difference in crime statistics around medical marijuana dispensaries in the year 2009, “Report: Medical Marijuana Dispensaries Not Linked To Neighborhood Crime,” by Jason Koebler, (June 6 2012), US News: [usnews.com/news/articles/2012/06/06/report-medical-marijuana-dispensaries-not-linked-to-neighborhood-crime]
  • 2016 update – states that have legalized marijuana have not had increased crime rates due to marijuana, http://www.attn.com/stories/6042/legal-marijuana-and-crime, but there may have been an increase in traffic accidents related to marijuana use – or an increase in testing for it, more research is needed because cannabis affects the body differently between individuals and is very different than the effects of alcohol.
  • Driving under the influence of marijuana is less associated with weaving between lanes than with alcohol use and is more likely to promote driving slower than average http://www.livescience.com/54693-high-drivers-double-after-marijuana-legalization.html (which can also be dangerous if significantly slower than the flow of traffic, http://www.dailymail.co.uk/news/article-2016721/Slow-drivers-dangerous-roads-cause-crashes.html).
  • There have been an increase in emergency room visits due to marijuana products which suggests to me that strains and products are being produced that have too much THC and not enough of the non-euphoric cannabinoids that promote more of a calming and relaxing effect on the brain. This report from 2015 states a problem with increased teen use but I’ve seen other articles that suggest there hasn’t been a significant increase in use by teenagers.  http://denver.cbslocal.com/2015/09/15/feds-release-marijuana-stats-to-show-negative-effects-of-legalization/
  • THCV is one of the non-euphoric cannabinoids that help balance the stimulating effects of the euphoria producing THC. Some strains of sativa type cannabis plants contain THCV while indica strains do not. https://www.whaxy.com/learn/thcv-buffers-psychoactivity-of-thc-study.
  • Cannabinoids are made up of phospholipids and arachidonic acid or another fatty acid. The combination forms a flexible building block for cell membranes that can be released from storage when needed as an active messenger chemical. Many types of cannabinoids exist besides THC and they all have roles throughout the body’s organ systems and in every cell of the body. Some people are born with genes that don’t function normally and the inability to produce cannabinoids has been associated with eating disorders, cigarette smoking, alcohol abuse, and to a lesser extent with cocaine use and other drug use.
  • Some tips from pros in the field of weed (pun intended) for people who have over imbibed sativa and are paranoid is to first not panic, it will pass. Knowing that the symptoms are due to too much THC may help with the feelings of anxiety. Other tips include eating a little black pepper or lemon juice/lemon peel. Both substances contain terpenes that may help balance the anxiety producing aspects of some sativa strains. Eating may also help with sativa anxiety but time may be necessary for the mood to pass. Too much of an Indica strain is likely to just cause munchies, coach lock (sleepy mellowness with no interest in moving) until sleep occurs.  https://www.whaxy.com/learn/what-to-do-if-you-get-too-high.

The act of smoking in itself can lead to reduced levels of magnesium and vitamin C whether tobacco cigarettes or other herbs are being smoked. The craving for food a few hours after smoking marijuana commonly known as “the munchies” is related to a drop in magnesium levels. It is better for the brain and body to eat rather than to try to resist the messages of hunger – the body is hungry for magnesium though so choose foods that contain some such as whole grains, popcorn or corn chips, beans, nuts, seeds, potatoes or sweet potatoes, green leafy vegetables, bananas, figs, yogurt, chocolate,  and many other foods contain small amounts. https://draxe.com/magnesium-deficient-top-10-magnesium-rich-foods-must-eating/

Having a good balanced meal before consuming marijuana may also help reduce the risk of having the munchies later. And different strains of marijuana may contain more or less of certain types of cannabinoids or terpenes which may also increase appetite for other reasons than the drop in magnesium in which case, snacking on carrots and celery sticks would contain fewer calories and have less risk of leading to excess weight gain.

Another way to improve the mood if magnesium deficiency is a problem is to take a hot bath with real Epsom salt, details here: http://transcendingsquare.com/2016/07/12/nerd-does-not-stand-for-nearest-emergency-room-department/.

/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./

Membrane Building Foods

I didn’t finish this list of foods rich in phospholipids, so I’m starting again at the top of the food chain with human milk. It contains more phospholipids than cow milk and has almost as much of the endogenous cannabinoid (eCB) precursor PE as it has PC, more commonly known as lecithin.
Abbreviations
PC – Phosphatidylcholine     PE – Phosphatidylethanolamine – part of Anandamide (AEA) an eCB
PS – Phosphatidylserine       PI – Phosphatidylinositol

Total Lipids (g/100 g)
Total Phos Lipids  (mg/100gr)
 PC
 PE
 PS
 PI
 SPH
Human Milk
3.800
60
17
15
Data NA
Data NA
Data NA
Whole milk
.
Cow
3.660
34
12
10
1
2
9
Sheep
7.000
51
15
18
2
2
15
Buffalo
6.890
29
8
8
1
1
10
Tot. L.
 Tot. Ph L.
 PC
 PE
 PS
 PI
 SPH

Organ and muscle and other tissues that have been tested across animal species are relatively similar in content. Note the brain is actually highest in the Phosphatidylethanolamine (PE -1948):

Beef Brain
12.1
5,433
1,307
1,948
871
242
944
Pork Organ:
PC
PE
PS
PI
SPH
Kidney
2.90
2,340
842
398
164
70
328
Liver
3.70
2,901
1,688
618
38
209
131
Lung
3.70
1,590
795
191
127
80
191
Spleen
2.45
1,240
409
174
161
25
236

The tables of data are not really meant to be a menu of food ideas itself. It is a dietitian type tool for more easily comparing the types of foods. There are more tables farther down the page. Yesterday’s list was a partial list of the plant foods and today’s focus starts with animal products. Organs and plant parts that are more membrane rich also deliver those building blocks in the food or concentrated supplement (bovine thyroid or adrenal extracts are available on the supplement market and may be helpful building blocks or may be contaminated byproducts full of contaminants – check the company and the source . Organ meats are concentrated in nutrients and toxins because they are also part of the detoxification process for the body (liver and kidney and spleen are detoxifiers, gizzard is a bird/reptile stomach.)

From (Weihrauch et al, 1983 The Phospholipid Content of Food) Excerpt [1]:

Data on organ meats are limited. Rouser et al. (29) determined the phospholipid distribution in human, bovine, mouse and frog liver, kidney and spleen. They reported among vertebrates little or no species variability of the phospholipid class distribution of organs and most subcellular particulates. The apparent connection between phospholipid function and phospholipid content and distribution in similar foods and tissues seems to be supported by the similarity of the respective data for the various milks, the eggs from various avian species, the livers of pork, chicken and turkey, the various beef muscles, the white (breast) and dark (thigh) meats of poultry, and the hearts and gizzards of poultry. Among animal tissues, beef brain contains the highest amount of phospholipids.”
*** We are what we eat. Looking at the average content of a type of organ can demonstrate the critical need that nutrient might play in a diseased condition of that organ. The beef brain is very rich in phospholipids and the endogenous cannabinoid building block, PE, and sphingomyelin (SPH) which suggests to me that myelin sheath problems in multiple sclerosis may have to do with lack of nutrients. Chronic degenerative disease happens slowly – breaking down is the same thing as not rebuilding as needed. Got to put the shingles back on after a wind storm or water leaks in and makes a worse mess.

Prevention of further damage and repair of damage might be possible with an increase in phospholipid foods. Bonus side effects would include pain killing, immune system strength, brain cell growth and prevention of stroke damage – and anticancer benefits to boot.

Excerpt [1]:

“Eggs, organ meats lean meats, fish, shellfish, cereal grains and oilseeds are good sources of phospholipids, especially the choline phospholipids. Leafy vegetables, fruits and tubers contain very low amounts of phospholipids.  (***yesterday’s list had some herbal and food sources not listed on the following charts)

More research is needed on the phospholipids in animal products such as beef, pork, lamb and fish. The effect of breed, age, sex, season and feeding habits need to be examined. More research is also needed on nuts, oilseeds, fruits and vegetables. Cultivar, geographical location and growing season may be some variables that should be examined.”

***I think we are still waiting. This article is fairly heavily cited by other authors and cost $34.95  – research isn’t cheap either.As a breast feeding educator and with five years personal experience, I am very comfortable in reporting that there is and is supposed to be wide variation in the lipid content in human milk – extensively researched. Fat content and type is supposed to vary with age and stage of the infant – premature infant milk is richest in fats, then newborn milk, and weanling milk has the lowest fat content. The types of essential fats in the mother’s diet will largely be what shows up in the milk for the baby. Malnourished women were found to have less of the endogenous cannabinoid content which can reduce the infant’s suckling and growth rates. Gently washing and massaging the infant may replicate the grooming/licking that stimulates the infant’s own production of eCBs. {the Endo textbook, Onaivi, et al, 2006}

A quote from a chapter; “Targeting the Cannabinoid System to Produce Analgesia” (Sager et al, 2009):

“In conclusion, the analgesic effects of cannabinoid-based medicines acting at CB1 receptors are well described, but limited by adverse side-effect profiles. The identification of alternative cannabinoid entities, such as the CB2 receptor and enzymes engaged in the catabolism of eCBs, offers further opportunity for the development of novel cannabinoid based analgesics with an improved side effect profile.” [3]

Let me give you a subtext interpretation – blocking CB1 didn’t work so let’s try to mess around with the CB2 system instead.

Rimonabant, a CB1 inhibitor, was recently ramping up for a big release when suicides and depression became a significant side effect. It is still for sale in countries besides the US. Rimonabant blocks – stops – deactivates the CB1 receptors throughout the body. Every cell has some, the brain is just the richest source. So the adverse side effect that was most debilitating was the suicides not euphoria from inhaling a little too much.

The CB1 receptors help control all four main brain neurotransmitters. So this patentable magic bullet was designed to promote weight loss because it was noticed that mice whose CB1 receptors were blocked got skinny. Yes, appetite can be decreased with marijuana as well as increased depending on whether a lot or a little of the CBs and which CBs interact with the receptors. The psychoactive CB that we all hear about the dangers of (mythic dangers largely) is delta-9 THC and it is the only euphoric/psychoactive one. The others are medicinal too. If pain killing without “adverse side effects” was the primary goal then why wouldn’t we simply extract or synthesize the pain killing CBDs that aren’t psychoactive and give them to patients? – $$$$$

We can’t simply extract plant parts without being able to charge extra for the little chemical tags that make each new rendition of a drug “unique” and ownable and profitable. It is too bad that health has become a commodity (dwindling).

We already know how to target the cannabinoid system to produce analgesia (pain killing) – just eat it or heat it. And now we know a few more foods to eat (besides special brownies).

The research thrust in science seems to be to find patentable magic bullet medications that go to a target and do one wonder action – but the body doesn’t really work that way. Also turns out that it would be hard to build a myelin sheath for a nerve cell with an aspirin or an opioid medication. Ibuprofen might help though, one of the ways it helps kill pain is to reduce breakdown of endogenous cannabinoids (now I know why it was always my favorite painkiller). This article isn’t where I read that – (Onaivi et al, 2006), however the (Sagar et al) article begins with the point that slowing the breakdown of eCBs also produces analgesic effects and inhibiting enzymes that metabolize them is a possible drug approach being considered.

I am instead considering buckwheat noodles and Shitake mushroom Tempura from a local Japanese take out restaurant or making corn bread and shredded barbecue turkey (a great way to use up the dark meat – unfortunately the turkey is still frozen).

In my post, Aftermath’s Fruit and Nut Course, I retold the vitamin D story instead of getting straight to the point that if for any reason the intracellular levels of calcium or glutamates increases too high then the membrane areas rich in endogenous cannabinoids will release them in order to be ready for use as messengers or as building blocks. We don’t need to know why the intracellular level of calcium or glutamates got elevated – the research exists that calcium or glutamates  are themselves powerful messengers within the cell fluid – they don’t belong there under normal conditions. Usually the membrane carefully controls the entry of calcium and free amino acids – large molecule compared to a single ion of calcium. The entry is controlled by channel shaped proteins in the membrane. The channels are normally powered by magnesium and controlled by eCBs and other messenger chemicals. What isn’t normal to the body are calcium channel blocker drugs. I personally prefer to think of food as maintenance medicine and magnesium as nature’s number one calcium channel blocker.

Egg yolks (PC source) and saturated fats got a bad reputation (usually also good source of arachidonic acid) and so did hemp/marijuana. Moderation is the key and pharmaceutical magic bullets aren’t moderate in price or side effect. Healthy foods come bundled with healthy side effects, help yourself to seconds.

However caution with seconds on liver and organ meats. They could deliver too much active vitamin A and D. Once a month serving of liver can deliver a boost of enzyme building blocks as well as the phospholipids. Any meat is best to think of as 1/4 of the plate, about the size of a deck of playing cards or 3-4 oz like a small chicken breast. Add some root vegetables (1/2-1 cup) and a green vegetable (1-2 cups) and a 1/2 cup of grain with a dash of good fats in the form of a few tablespoons of nuts or seeds or a tsp of oil. A fruit serving makes a good snack for later and water or herbal tea is always a good beverage for meals – easy on the digestive system.

Organic or home grown/small farm grown may have more nutrient diversity because the soil is likely to have more variety and higher amounts of trace minerals. A plant species may have special abilities to absorb a nutrient better than other plants but if the nutrient isn’t in the soil to gather then the food is going to be less nutritious. If our animals are fed those less nutritious plant foods then the animal is going to also have less nutrient building blocks. Both the plant and animal kingdoms are having mass die-offs due to infection. We are losing our trees to disease as well as paper towels.

Mitigation of construction zones is similar to chronic degeneration – the erosion control on the hillside prevents the sand from washing away to dirty the water below and leave the underlying roots unprotected. Someone had to walk miles and miles with supplies and shovels and put in that silt fence to shore up the exposed top soil. Without membranes to protect our underlying roots, all our nutrients can wash away, messing up our kidneys and leaving us open to invasive species eager to rush in and live off the exposed nutrients.

Enjoy some eggs  and potatoes again – it’s the bacon or sausage that’s really a treat food – as in don’t treat yourself that way too often – you don’t deserve the salt and preservatives. A sprinkle of sunflower seeds might be good for a little crunch and salt or toasted sesame seeds with seaweed flakes is a Japanese condiment loaded with nutrients (seemed slightly fishy in flavor to me, I couldn’t quite get used to it).

*** These data tables are a reference – a starting point.  I will be adding menu ideas and recipes using foods chosen for phospholipid content but also magnesium, B vitamins and other trace nutrients and I will be adding a list of foods that are rich in the special starches the sugars that aren’t glucose or fructose (mannose, fucose, glucosamine, xylose or some examples).

Eggs, wh
Total Ph L
PC
PE
SPH
Chicken
11.150
3,490
2,687
578
82
13.770
3,656
2,766
605
90
Goose
13.270
3,318
2,455
624
100
Quail
11.090
3,638
2,923
382
107
Turkey
11.880
3,540
2,885
457
74
Egg, chicken
Total Phos. Lip.
PC
PE
PS
PI
SPH
White
0.015
2.8
1.2
Tr
0.9
Yolk
31.800
10,306
6,771
1,917
64
486
Chicken
Tot. L. (g/100 g food)
Tot. Ph L
PC
PE
PS
PI
SPH
Thigh
3.26
1,386
662
352
186
Tr
101
Breast
1.12
782
391
187
100
Tr
56
Skin
13.73
906
316
247
82
Tr
124
Gizzard
2.54
1,153
353
368
102
Tr
165
Heart
3.20
1,718
675
509
227
Tr
195
Liver
5.60
2,542
1,120
829
146
Tr
291
Turkey
PS/PI
Thigh
2.48
526
282
137
34
53
Breast
0.73
418
231
92
33
43
Gizzard
1.35
1,000
422
465
113
Heart
2.93
2,125
1,117
646
362
Liver
6.02
2,875
1,655
818
402
Total Lipids (g/100 g food)
Total Phos.lip.
PC
PE
PS
PI
SPH
Beef muscle, L. dorsi
PC + LPC
PS + PA + CL
fattened
12.4
690
340
124
96
38
63
lean
1.7
597
260
106
48
37
99
Tot. L.
Tot. PhL
PC
PE
PS
PI
SPH
Calf, L. dorsi
1.13
853
318
197
95
49
60
Pork, L. dorsi
2.58
596
304
167
57  PS/PI
34
Rabbit Skeletal muscle
2.26
510
276
122   PE +PS
20
Fish
Tot. L
Tot. Ph.L.
PC
PE
PS
PI
SPH
Abalone
1.05
695
285
222
35
35
7
Clam
1.45
532
217
16
96
129
Cod
0.59
520
359
99
26
Crab,frw
2.52
696
362
188
14
28
28
Crab, marine
2.23
580
331
128
29
23
29
Crayfish
1.77
530
289
139
56 PI
Also
25
Eel, slt.w
18.3
1,684
596
180
264
325
Eel, fresh water
18.3
2,196
637
171
406
488
Herring, wh musc.
3.82
937
499
219
140
66
Herring, dark mus
19.61
2,584
1,384
686
360
115
Mackerel, wh musc
1.91
726
196
220
86
224
Mackerel, dark mus. Male fish
10.14
2,328
111
1,442
625
151
Mackerel, dark mus. Female
10.54
2,410
774
1,309
335
994
Octopus
0.79
618
260
185
31
24
19
Smelt
1.25
427
222
141
21
Squid, muscle
1.68
1,098
777
114
83
102
Trout, rainbow
2.1 fillet
347
231
74
15
6
6
Tuna, dorsal muscle
3.79
617
166
132
93
211
Tuna, Ventral muscle
13.9
1,938
641
503
194
153
Tuna, dark mus.
5.06
1,756
692
244
240
557
Tot. L
Tot. Ph.L.
PC
PE
PS
PI
LPE
Tot. L
Tot. Ph.L.
PC
PE
PS
PI
LPE
LPC
Barley, wh gr
3.0
506
258
45
29
8
145
Corn, wh comm. Hybrid
3.7
213
139
15
26
10
Corn Germ, amylomaize
41.6
1,077
331
153
201
10
8
Corn Starch amylomaize
0.9
187
14
161
Oats, dehulled
5.8
1,439
430
213
46
294 +LPE, +LPS
Rice, Brwn
2.1
85
29
33
3
2
Rice, Bran
17.9
365
153
148
23
tr
tr
Rye, wh gr flour
3.1
743
273
90
184
196
Rye germ
16.5
1,071
346
132
230
0
Triticale, wh gr flour
3.4
938
321
186
206
225
Wheat, wh gr, hard
2.5
1,060
164
56 +PG
64
408
Wheat starch
0.7
677
72
548

1. Weihrauch et al, 1983 The Phospholipid Content of Foods (JAOCS, vol 60, no. 12 (December 1983)

2. James Duke – Greenpharmacy.com for the herbal plants
Ethnobotanical and Phytochemical Database of medicinal plants and chemical activities

3. Devi Rani Sagar, Maulik Jhaveri, and Victoria Chapman, Targeting the Cannabinoid System to Produce Analgesia, from D. Kendall and S. Alexander 9eds.), Behavioral Neaurobiology of the Endocannabinoid System. Current Topics in Behavioral Neurosciences 1, DOI: 10.1007/978-3-540-88955-7_11, @ Springer-Verlag Berlin Heidelberg 2009 (page 283)

4. Onaivi, E. S., Sugiura, T., Di Marzo, V., (eds)  Endocannabinoids; The Brain and Body’s Marijuana and Beyond ISBN 0-415-30008-8 (CRC Press, Taylor and Francis Group, 2006)

/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./

Feed your membranes

~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~  ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~
Some membrane building foods with links to Amazon but you can look for similar items at your local market.Today’s list is of membrane building foods that are rich in phospholipids which make strong membranes that are also smart at their job of regulating what goes in or is allowed out of the cell. Some of the phospholipids can be assembled into endogenous cannabinoids and others are important for other types of membrane function. The foods were selected from searches for the individual phospholipids within Dr. Duke’s Phytochemical and Ethnobotanical Databases created by Dr. James Duke of The Green Pharmacy [greenpharmacy.com]. (Update: That database is no longer available but the website still has other information.)

~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~Beans – all of them, with cocoa bean at the top of the list (chocolate hold the sugar and milk/cream)

bean sprouts have an increased amount so soy bean and mung bean sprouts are rich sources

Nuts – not well documented on the individual basis but peanuts are very good and pine nuts are excellant so I don’t think I would be going out on a limb to say the group has got to be very good compared to apple or orange juice content (pine nut 1000 , orange juice 10, peanut 620, sunflower seed, 1092 mg/100 g food total phosholipid content)

Seeds   (note the fruits and vegetable included – the phospholipid content is in the seed)

Adlay Millet     Alfalfa seed     Cardamom (used as a spice)     Hemp     Sunflower      Flax

Cucumber Seed     Pomegranite seed      Grape seed

Grains (must be whole grain products that include the bran and germ, the richest sources – wheat has some too but more of the choline variety which isn’t directly part of the endogenous cannabinoids so wasn’t on my initial search term results. Besides we don’t really need help eating more wheat products, I would like to help give a few ideas for substitutes.):

Buckwheat      Corn     Oats      Rice      Rye     Triticale

(probably regular millet, amaranth and quinoa too but I haven’t done an individual search yet)

Fruits

Apple     Fig     Grapefruit *    Lemon *     Orange *   *pulpy juice is a source

Vegetables

Carrot     Cassava, leaf     Cucumber seed      Garlic, bulb     Green Bell Pepper     Green pea

Potato     Sweet Potato    Spinach     Shitake mushroom      Kelp,  Bladderwrack      Purslane

Musk okra

Angelica/Dong quai (an herbal supplement to me maybe it is a vegetable to some people),
Women’s blend tea bags with 40 mg Dong quai

Stinging Nettle plant on Amazon: [Amazon] and root  (also available as an herbal supplement)

Membranes do control life or death – we crawled out of the sea or womb at some point in our lives and had to take that first dry cold breath of air.

Feeding your membranes may be even smarter than I thought.

/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./