Zinc Deficiency: Taste Buds Stop Working, & When Severe, Food is Revolting


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Hypogeusia

A Case Report

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The diagnosis came from a non-medical book:

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Remove zinc from your diet and you will get a condition known as hypogeusia, in which your taste buds stop working, making food boring or even revolting, but until as recently as 1977 zinc was thought to have no role in diet at all.The quote leaped from the page of a book “At Home” by Bill Bryson.

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Food aversion. Revulsion toward food.

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Hypogeusia is a diminished sense of taste resulting from zinc deficiency. The patient slowly, week after week, developed a severe aversion to all food groups except cappuccino (arginine).

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Month after month it became severe before the patient was finally able to identify a descriptive term “food aversion.” Hunger was severe. Patient was desperate to find fuel for body that was not revolting.

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Not anorexia – means loss of appetite. The patient was starving.

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Not anorexia nervosa – a distorted body image in which patients severely restrict food intake and can starve to death.

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Not depression – depressed mood often associated with poor appetite or stress eating.

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Food aversion was bizarre, going to bed starving while the best foods were sitting in the fridge untouched and literally repulsive even to think about. For months, walking up and down grocery aisles, repulsed by the thought of the finest foods despite hunger, craving to find some form of fuel that was not revolting. Months and months went by as it became severe. Past favorite foods might as well have been poison. Flavor was wanting.

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Specialists and literature searches commonly view food aversion as psychosomatic or the bizarre cravings of pregnancy. Females are at particular risk of being assigned psychological diagnoses. We do our patients a disservice failing to appreciate the complexity of human physiology with our limited understanding of evolving science. The human body is complex.

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To complicate matters, it’s not easy to diagnose depression – not all patients recognize it in themselves. Further, zinc deficiency induces depressive behaviors, plays a major role in major depressive disorder and is a risk factor for treatment resistance — referenced below at end. 

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Aversion became extreme before the patient could name the correct term: food aversion, no doubt why it is barely mentioned in medical searches: a condition must have a name before it can exist, before it can be identified and understood as a symptom. Hunger at times was severe, but just the thought of driving to the grocery store was troubling and wasted hours. Complicating the picture, the coexisting autoimmune disorder also caused anorexia, i.e. loss of appetite.

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Then that sentence leaped from the page naming the cause: Zinc deficiency. What causes zinc deficiency? Malnutrition, medications. You have to string together the right words in order to search the publication leads. Thus, when you specifically search food aversion and prednisone:

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“Food aversion is found among people who take Prednisone, especially for people who are female, 60+ old , have been taking the drug for 1 – 6 months, also take medication Methotrexate, and have Osteoporosis.”

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There it was: prednisone and methotrexate, elderly female. Prednisone depletes zinc.

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The patient stopped methotrexate. Six weeks went by before a small number of foods could be added to milk and eggs. Unfortunately, the only foods tolerated were easily digestible ice cream (protein), pasta and sweets, which leads me to recall patients with autoimmune disorders whose diet consisted of processed carbs such as English Muffins, bread, pasta, who complain they cannot eat anything yet they are obese. They cannot seem to change food choices. How many cancer patients have this problem from chemotherapy?

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Vegetarians are at risk of zinc deficiency since Zinc is available primarily in oysters, meat, and poultry. Among the many causes of gustatory (taste) dysfunction in Table 6 from 2013 American Family Physician, besides malnutrition are cancer, radiation, etc, a long list of medications are listed:

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Medications

Intranasal zinc, chlorhexidine (Peridex), chemotherapy, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, diuretics, antimicrobials (macrolides, terbinafine [Lamisil], fluoroquinolones, protease inhibitors, griseofulvin, penicillins, tetracyclines, nitroimidazoles [metronidazole (Flagyl)]), antiarrhythmics, antithyroid agents, antidepressants, anticonvulsants, lipid-lowering agents

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Chemotherapy, statins, antidepressants, blood pressure medications, antibiotics – many commonly used medications can cause deficiency, yet zinc deficiency is said to be rare. Are we failing to recognize this in our patients?

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If dysfunction occurs, stop the offending medication. Regarding chemotherapy, “These effects are usually transient and resolve within three months of treatment cessation. This adverse effect is most likely caused by toxicity to olfactory and gustatory receptor cells that have the ability to regenerate.”

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“Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes [1,2] and it plays a role in immune function [3,4], protein synthesis [4], wound healing [5], DNA synthesis [2,4], and cell division [4]. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence [6-8] and is required for proper sense of taste and smell [9]. A daily intake of zinc is required to maintain a steady state because the body has no specialized zinc storage system [10].”

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Immune function

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“Severe zinc deficiency depresses immune function [48], and even mild to moderate degrees of zinc deficiency can impair macrophage and neutrophil functions, natural killer cell activity, and complement activity [49]. The body requires zinc to develop and activate T-lymphocytes [2,50]. Individuals with low zinc levels have shown reduced lymphocyte proliferation response to mitogens and other adverse alterations in immunity that can be corrected by zinc supplementation [49,51].”

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DIAGNOSIS

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Serum levels of zinc and copper can be tested but do not reflect levels in the body as they are stored in tissue.

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Information below is from a review in J Clinic Toxicol by Osredkar J, Sustar N (2011) Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance. 

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“The ratio of copper to zinc is clinically more important than the concentration of either of these trace metals. Zn is the second most abundant transition metal in organisms after iron and it is the only metal which appears in all enzyme classes, while copper is present in every tissue of the body, but is stored primarily in the liver, with fewer amounts found in the brain, heart, kidney, and muscles.”

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…The optimal plasma or serum ratio between these two elements is 0.70 – 1.00 [1]….

“There are 2-4 grams of Zn distributed throughout the human body [2]. Most zinc is in the brain [primarily hippocampus, the limbic system], muscle, bones, kidney and liver, with the highest concentrations in the prostate and parts of the eye [3]. It is the second most abundant transition metal in organisms after iron and it is the only metal which appears in all enzyme classes [2,4].

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Copper is also a vital dietary nutrient, although only small amounts of the metal are needed for well-being [5]. Although copper is the third most abundant trace metal in the body [behind iron and zinc], the total amount of copper in the body is only 75-100 milligrams [6]. Copper is present in every tissue of the body, but is stored primarily in the liver, with fewer amounts found in the brain, heart, kidney, and muscles [7]….

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Diagnosing zinc deficiency is a persistent challenge. Zinc nutritional status is difficult to measure adequately using laboratory tests due to its distribution throughout the body as a component of various proteins and nucleic acids [18,136].”

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Plasma or serum zinc has poor sensitivity and specificity – these levels do not necessarily reflect cellular zinc status due to tight homeostatic control mechanisms.”

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Zinc and Vegetarian Diets is reviewed in 2012 with recommendations to minimize deficiency.

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“Since plant sources of zinc contain phytate and other inhibitors of zinc absorption, vegetarians and vegans may potentially be at risk of zinc deficiency.”

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Special cases such as those with inflammatory bowel disease, those with profuse diarrhea, or who have had bariatric surgery should consult with a nutritionist.

 

Zinc Therapy in Dermatology: A Review from 2014 is an open access PDF. Zinc is discussed in various conditions including eczema, psoriasis & psoriatic arthritis, acne, alopecia, seborrheic dermatitis, dandruff, etc.

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“It maintains macrophage and neutrophil functions, natural killer cell activity, and complement activity. It activates natural killer cells and phagocytic function of granulocytes and stabilizes the plasma subcellular membranes especially the lysosomes. It inhibits the expression of integrins by keratinocytes and modulates the production of TNF-𝛼 and IL-6 and reduces the production of inflammatory mediators like nitric oxide. It is also proposed that it is toll-like receptors mediated regulation of zinc homeostasis which influences dendritic cell function and immune processes [2]. Zinc also possesses antioxidant property and has been found useful in preventing UV- induced damage and reducing the incidence of malignancies. It has also been demonstrated to possess antiandrogenic properties as it causes modulation of 5𝛼-reductase type 1 and 2 activity [1, 3, 4].”

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2. H. Kitamura, H. Morikawa, H. Kamon et al.,“Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function,” Nature Immunology, vol. 7, no. 9, pp. 971–977, 2006.

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TREATMENT

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Based on limited reading, for zinc deficiency – NOT routine use – consider 20 to 50 mg zinc with 2 mg copper for a limited time. Follow cautiously for toxicity. HIGH AMOUNTS OF ZINC ARE UNSAFE.

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From Penn State Hershey Medical Center

 

Available Forms

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Zinc is available in several forms….

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More easily absorbed forms of zinc are zinc picolinate, zinc citrate, zinc acetate, zinc glycerate, and zinc monomethionine. If zinc sulfate causes stomach irritation, you can try another form, such as zinc citrate.

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The amount of elemental zinc is listed on the product label (usually 30 – 50 mg). To determine the amount to take in supplement form, remember that you get about 10 – 15 mg from food. [if you eat oysters, meat, poultry]

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Zinc lozenges, used for treating colds, are available in most drug stores. There are also nasal sprays developed to reduce nasal and sinus congestion, although they may have some safety issues (see “Precautions”). [Avoid nasal sprays as it destroys the olfactory nerve, the sense of smell.]

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How to Take It

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You should take zinc with water or juice. If zinc causes stomach upset, it can be taken with meals. Don’t take zinc at the same time as iron or calcium supplements.

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A strong relationship exists between zinc and copper. Too much of one can cause a deficiency in the other. If you take zinc, including zinc in a multivitamin, you should also take copper..

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Take copper on an empty stomach. The tablets I have seen are so tiny they stick in the throat. Copper is water soluble but dissolves better in hot water.

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Memorial Sloan Kettering Cancer Center [MSKCC] has important Cautions not to take, and also Warnings on taking zinc if you have certain medical conditions or take certain medications. Bear in mind, the highest concentration of zinc is the prostate. I strongly recommend reading all zinc sections from MSKCC.

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“Consumption of zinc >100 mg/day may increase the risk of prostate cancer (31).

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Although human studies have been equivocal, patients should take zinc 2 hours before or after foods that are high in calcium, phosphorus, bran fiber, or phytate to avoid nonabsorbable complexes (45) (67).

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When taken orally at large doses (100-300 mg/day), zinc can cause chronic toxicity including copper deficiency, depressed immune function, headache, chills, fever, and fatigue (58) (59).”

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“Intake recommendations for Zn are provided in the Dietary Reference Intakes developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies…. U.S. National Research Council set a Tolerable Upper Intake for adults of 40 mg/day[82,83].

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Zinc Fact Sheet for Health Professionals, NIH Office of Dietary Supplements  

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Recommended daily allowance for Zn

RDAs 8 mg/day for female, 11 mg/day for male

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Recommended intake for copper

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The 10th edition of Recommended Dietary Allowances (RDA) did not include an RDA for copper; rather a safe and adequate daily intake was suggested…. The following Table 2 provide the Recommended daily dietary intake (RDI) of copper for children and adults and Tolerable upper intake levels for copper [83,85].

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Recommended daily intake RDI’s

90 mcg

Tolerable upper intake levels TUL
10,000 mcg”

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Of interest, a 2005 publication, Re-establishment of olfactory and taste functions describes results of treatment. Very small numbers were tested limiting interpretation. Were large doses complicating the results, causing toxicity and/or copper deficiency?

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In an open study (n=119; idiopathic taste disturbance, n=45; drug-induced taste disturbance, n=38; zinc deficiency, n=36), taste improvement by 50% was achieved after 4 weeks and by 80% after 8 weeks of treatment with zinc sulfate (100 mg, three times daily) [201]. In a double-blind, placebo-controlled study (n=73; idiopathic taste disturbance, n=48; lowered zinc levels, n=25), treatment with zinc picolinate (30 mg, three times daily) for 3 months did not improve subjective taste assessment or taste performance in the entire mouth, although the group receiving zinc picolinate performed significantly better than the placebo group in the filter paper test [202]. However, both the double-blind study by Henkin et al. [171] and the double-blind study in 65 patients by Yoshida et al. [203] failed to confirm this difference. Nevertheless, if the patients with drug-induced taste disturbances were excluded and only the patients with idiopathic taste disturbances and zinc deficiency were analyzed, the result was significant [203]. A double-blind study in hemolized patients (n=22) with low zinc levels demonstrated a significant improvement in response to zinc (50 mg/day) given for 12 weeks [204]. Similarly, preliminary findings from a double-blind study with zinc gluconate by Heckmann et al. seemed promising in idiopathic dysgeusia [205], [206].

 

 

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Zinc: an Antidepressant by a psychiatrist writing in Psychology Today in 2013,  zinc is anti-inflammatory and antidepressant. “Inflammation is the primary driving mechanism behind the whole shebang and may decrease brain zinc levels all on its own.”

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“300 or more enzymes in our bodies use zinc as a buddy to help them do their thing, making DNA, protein synthesis, cell division, all hugely important stuff. Zinc is also critical to cell signaling (a major receptor motif, the “zinc finger” is as famous as the G protein in cell biology circles). The highest amount of zinc in the body is found in our brains, particularly in a part of our brains called the hippocampus [limbic system]. Zinc deficiency can lead to symptoms of depression, ADHD, difficulties with learning and memory, seizures (2), aggression, and violence (3).”

 

“…As always, there is a sweet spot of zinc consumption, and more is not always better. More than 50 mg a day can lead to improper copper metabolism, altered iron function, and reduced immune function. We need enough zinc in the right place at the right time…a typical zinc supplement pill of 25-50mg is probably best taken only every few days, unless you are an oyster connoisseur, in which case no supplementation is necessary.” [oysters are highest in zinc]

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That author reviews this 2013 publication: Potential roles of zinc in the pathophysiology and treatment of major depressive disorder.

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Abstract

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Incomplete response to monoaminergic antidepressants in major depressive disorder (MDD), and the phenomenon of neuroprogression, suggests a need for additional pathophysiological markers and pharmacological targets. Neuronal zinc is concentrated exclusively within glutamatergic neurons, acting as an allosteric modulator of the N-methyl D-aspartate and other receptors that regulate excitatory neurotransmission and neuroplasticity. Zinc-containing neurons form extensive associational circuitry throughout the cortex, amygdala and hippocampus, which subserve mood regulation and cognitive functions. In animal models of depression, zinc is reduced in these circuits, zinc treatment has antidepressant-like effects and dietary zinc insufficiency induces depressive behaviors. Clinically, serum zinc is lower in MDD, which may constitute a state-marker of illness and a risk factor for treatment-resistance. Marginal zinc deficiency in MDD may relate to multiple putative mechanisms underlying core symptomatology and neuroprogression (e.g. immune dysfunction, monoamine metabolism, stress response dysregulation, oxidative/nitrosative stress, neurotrophic deficits, transcriptional/epigenetic regulation of neural networks). Initial randomized trials suggest a benefit of zinc supplementation. In summary, molecular and animal behavioral data support the clinical significance of zinc in the setting of MDD.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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Cannabis That Can Stop the Munchies? What is THCV?


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MEDICAL MARIJUANA

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Cannabis is legal in California for adult use as of January 1, 2018. This may be helpful to someone you know. It is a most important drug. Below you can find a few pointers that are basic to understanding what strains to try. Distributors are swamped with ten times as many buyers as last week, prices are doubled, taxes are very high, it is very expensive and you will need to test many strains before you find what works for you without making you stupid with euphoria that lasts 12 hours. Do be warned of turning the body into sofa-size obesity overnight. Munchies occur with high THC strains. To discuss below how to avoid that torture and still relieve pain or muscle spasm.

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Horvath et al at Yale in 2015 found cannabis stimulates hunger and arousal in hypothalamic neurons. Here’s the YaleNews on the multi-authored work.

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Horvath is the Jean and David W. Wallace Professor of Neurobiology and of Obstetrics, Gynecology, and Reproductive Sciences, director of the Yale Program in Cell Signaling and Neurobiology of Metabolism, and chair of the Section of Comparative Medicine.

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To orient you in the quote below, cannabinoid receptor 1 (CB1R) is one of the two known cannabinoid receptors in the brain. Others are located outside brain, throughout the body.

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“The Pomc gene encodes both the anorexigenic peptide α-melanocyte-stimulating hormone, and the opioid peptide β-endorphin. Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for the central regulation of food intake. CB1R activation selectively increases β-endorphin but not α-melanocyte-stimulating hormone release in the hypothalamus, and systemic or hypothalamic administration of the opioid receptor antagonist naloxone blocks acute CB1R-induced feeding.

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Interesting. Low dose naltrexone, which is essentially long acting naloxone, may block munchies in humans? At what dose? Please comment if you take naltrexone 4.5 mg or 15 mg (anti-inflammatory doses) or 28 mg (weight loss dose) or 50 mg and above doses of naltrexone (high doses for addiction).

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One strain that is better at stopping or reducing the munchies, and that is believed due to a cannabinoid in the strain called THCV. You can always do a search for THCV.

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Cannabis is one of the few medications that can relieve some of the worst side effects of opioid withdrawal. Many patients find they need to use fewer opioid pills for pain or can stop them altogether; they need to use fewer muscle relaxants; and they can eat or sleep better if they use cannabis. Once cannabis became legal, many alcoholics were able to give up alcohol because their first preference is cannabis.

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Get a low cost recommendation for medical marijuana in minutes at home from your mobile phone. The best source for recommendation is : HelloMD.

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Cannabis may be legal in all states once tobacco companies toss some money at Congress. Could cannabis be related to the vow of Phillip Morris and a wave of big tobacco companies to stop selling cigarettes this year?

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It is dreadfully expensive and heavily taxed. All states should adopt New Mexico’s law that allows healthcare insurers to reimburse patients who have paid for medicinal cannabis. Voters…

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Cannabis is made by the body and the brain makes two of the endogenous cannabinoids. If is highly anti-inflammatory, and profoundly important mainly in the immune system but also in bone turnover. You have more cannabinoid receptors in your body than any other kind. It is as old as sponges, an ancient medicine.

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A WORTHY READ

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Mr. X – by Carl Sagan who describes his experience with marijuana at length and used it creatively for decades opening his brain to experiences he was otherwise not oriented to at all.

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MUNCHIES

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Fear the munchies. Cannabis, medical marijuana, can cause the munchies, an overwhelming desire to eat nonstop, usually all the most high calorie things your desperately fevered brain can dream of cramming in.

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Certain strains of cannabis can be life saving for those who have loss of appetite from conditions such as cancer, HIV/AIDS, depression, inflammatory conditions, etc. But the munchies can be disastrous when you cannot afford to gain weight due to pain or disability or simply wish to develop an important standard to maintain best health which means good lean body weight. The best way to reduce inflammation is to avoid obesity, avoid sugar, avoid diabetes, heart attacks, strokes. Remember inflammation is the root cause of 90% of the conditions we die of: diabetes, cancers, Alzheimer’s, Parkinson’s, autoimmune disease, atherosclerosis, etc.

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Those with an eating disorder should scrupulously avoid those strains that are highly rated for helping anorexia, loss of appetite.

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CHOOSE STRAINS THAT STOP THE MUNCHIES

STRAINS WITH HIGH THCV  OR HIGH CBD 

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If needing high THC for pain or appetite, for example, then a strain with high THC and high THCV is Durban Poison. Read in detail about strains on leafy.com using the search function and it will find dispensaries in your area.

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If low THC is all you need, then Leafly discusses high CBD strains with low THC currently available. Google it or ask the dispensary.

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I am not going to do more than mention these three cannabinoids: THC, CBD, THCV. You can google them but do glance at my outdated 2009 cannabis website – CBD has vastly changed since then, available even at farmer’s markets and nutrition departments of groceries.

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The cannabis plant has 400 chemicals of which about 86 are known cannabinoids but we focus on just a few and hybrids have been bred to display many qualities and various percentages of cannabinoids.

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THC

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THC, tetrahydrocannabinol, can cause euphoria and is the principal psychoactive ingredient useful for pain, depression, appetite, multiple sclerosis, fatigue, stress, and many conditions including just to have fun, be giggly or creative. For the California Medical Board, a strain with 18% THC is considered high, but some strains such as Holy Grail have 27% or more THC. Some strains are noted for causing more anxiety or paranoia due to THC content. It is widely said THC is necessary for pain relief but… see CBD below.

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CBD

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CBD, cannabidiol, a non-psychoactive cannabidiol that blocks the psychoactive component of THC so that you may be able to mix with THC in order to use a stronger dose of THC for the underlying condition —  find your best ratio of CBD to THC. Or use 100% CBD. Among strains of flower sold at dispensary, I’m not sure what % CBD

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Some people are highly sensitive to THC (paranoia, panic attacks, anxiety) and cannot use any THC or only very tiny amounts of THC with higher percentage CBD.

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Some use pure 100% CBD which is said to be useful for Crohn’s Disease, PTSD, multiple sclerosis and certain seizure disorders, the severe childhood Dravet Syndrome. There is a recent single report of an adult who failed all anticonvulsants and responded to CBD alone. I have seen a patient with depression after 2 years of severe disability from 4 major chronic pain conditions, surprisingly all pain 100% relieved by CBD. It is widely said that THC is essential for pain relief but for this case not needed.

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Some dispensaries will mix liquid CBD:THC in ratios of 15mg/mL CBD to 0.1 mg/mL CBD all the way up to ratio of 15:15 or more. Use topically, under tongue or swallow. One patient dilutes and uses topically. Very expensive!!! It is the only thing helping his extremely painful autoimmune neuropathy.

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THCV

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Leafly discusses ten strains that will not make you (as) hungry

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After discussing high CBD strains, then turn to high THCV:

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High THCV Sativa Strains

“By now you know what THC and CBD is, but you may not be familiar with the less ubiquitous THCV, a related chemical that suppresses appetite. While most strains on the market today tend to test anywhere between 10-20% THC, what’s considered a high THCV content might only hit a high-water mark of 5%. THCV tends to be more abundant in sativa strains, and it’s possible you’ve noticed that sativas tend to provoke hunger less than indica strains. The unique metabolic effects of THCV even have researchers considering its utility in treating obesity and diabetes.”

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Durban Poison is the name of the strain with highest THC and THCV, and a good profile detailed on Leafly: Maximal effect is Energetic > happy > uplifted >> focused >> euphoric. Not everyone may have all these effects.

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Always check Leafly’s negatives for each strain and look at the bar graphs — how severe are the side effects? Note that always worst is dry mouth. Half as bad are dry eyes for this strain – at least not as bad as dry mouth; and much lower in incidence is dizzy, anxious, paranoid. Overall a very good profile for a high THC strain.

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RISKS

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Note, those with Sjogren’s Syndrome who have dry eyes are at risk for corneal transplants and who have dry mouth are at risk for all teeth crumbling, so choose and treat accordingly.

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Cannabis can increase pulse and blood pressure which can be a risk of heart attack and stroke for any age. It is especially likely if you are naive to the drug, i.e. have never used it or have not introduced it to your system for decades. Check blood pressure and pulse before use and after you feel the peak effect.

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The youngest person I found on the internet who died of heart attack caused by cannabis was a healthy 17 year old male, possibly a false report, but cardiac arrhythmias can be fatal and there are undiagnosed cardiac conditions in young athletes who may be likely to use cannabis.

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Cannabis can interfere with memory.

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The adolescent developing brain may be vulnerable to harmful effects.

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HOW TO USE IT

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Vaporize it. Avoid 4 toxins. Rapid onset, short duration of effect.

If smoking, you will inhale 4 major toxins.

Use under tongue or topically on skin.

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If you swallow cannabis, you will not feel effect for 90 to 120 minutes so allow 2 hours before you add more or you may seriously overdose. Duration of effect may be 4 to 12 hours or more – overdosing can last days.

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5 mg oral THC may be too much for a starter dose for some people, but may be average for many, and some may need 10 mg. But heavy users need far, far more: TOLERANCE DEVELOPS!!! Money down the drain. Use only as much as you need or you will develop tolerance and require more frequent and higher and higher doses to reach same effect. That can be unaffordable for the average middle class person. 

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And yes, it may appear in urine for 30 to 60 days, possibly more.

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Cannabis is still a schedule I drug. The Emperor has no clothes. Do not take it onto planes or attempt to mail it.

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Do read more about it on my cannabis website linked above. It is a drug. You will benefit from learning how to use it.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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Anger


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Anger at the failure of our medical system to support research and treatment of pain, anger at failure of the few currently available analgesics, anger at lack of interest or funding from Pharma – it requires at least $10,000,000 more to finish one important human treatment before submitting to FDA – that’s just one study. Pharma does not care, the price is peanuts to them. At one point, a company bought it, intending only to bury it. They do that for rheumatology treatments too, both the innate immune system and the adaptive immune system are being ignored. What could be more powerful than the immune system?

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Anger

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Anger at the failure of most medical organizations to discuss cannabis, medical marijuana. Training in cannabis is imperative.

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I am thrilled that Scripps Memorial Hospital Grand rounds in 10 days is a one hour lecture by the doctor who is head of HelloMD, national leaders in physician approval for medical marijuana, and in education.

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Anger at the destruction of the field of pain management. I posted on this two days ago, top left column. Anger at the greed in the medical system where pharma can buy whatever they want by sprinkling money at congress who will never ever ever do anything about the unholy prices of drugs. Certain elements in power will never stop trampling on the poor and the disabled. They will never treat the addicts. There is no will, they are paid off and nobody wants to help the disabled, the unwell, the poor. Not in  the U.S. Voters do not want to hear it.

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Anger says step back, surrender.

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There is nothing anyone can do. The swamp is exhausting, dirty, dangerous and black.

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I have tried 7-1/2 years to introduce a new paradigm. At various lifetimes in medicine, I have had funding, sat on boards of companies, and panels at FDA. I have witnessed the destruction of what it once was 43 years ago when I entered practice. A long and tortured history, but still the most exciting thing in the world is medicine, science. So what? They shut off the field of pain and are killing it. The world is the world. Always was, always will be. Lust and greed, says the sage. You cannot uncurl the curly tail of a pig, says the sage. Always was, always will be. Do your duty. You cannot escape it. But surrender to love.

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Surrender. Do what you can and surrender the results to the Infinite.

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Read these books:

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Dying to Get High, Marijuana as Medicine

by Wendy Chapkis and Richard J. Webb

NYU Press 2008

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From back leaf:

“How can a substance that is no mystery to half of all adults in the United States prompt such confusion and misrepresentation in the realms of law, medicine, and policy?…. Offering nuance in place of slogans, Dying to Get High tells an inspiring story of the tactics and philosophies of a little-understood health movement.”

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“A beautifully written account from the front lines of the struggle between a federal drug war complex determined to keep demonizing marijuana and the growing movement of patients and doctors who have found marijuana to be a valuable medicine.”

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“….. Provides a human element to the history, pharmacology, psychology, and politics of medical marijuana in a way that no other work has. I loved reading it.”

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Heroin Century

by Tom Carnwath and Ian Smith

Routledge Press, London

2002

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This is an extremely important, amazingly interesting, readable book for everyone.

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From back cover:

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Is heroin really dangerous? Or Is it just dangerous because it is illegal?

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Page-one 93,

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“The income of the drug barons is an annual $254 thousand million dollars, greater than the American defense budget.”

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Read this book. A page turner! Exciting! fast paced, awesome! mind boggling!

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And just because you might flash some anger to propel you to actually do something, don’t get stuck there. Be at peace. Work hard. Use your expertise. Surrender to the Infinite.

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While you are thinking about it, tell Congress to make pain management a mandatory course in more than the current 3% of medical schools, less then 30 hours in 4 years. Fund research and treatment of neuropathic pain such as CRPS, Complex Regional Pain Syndrome because it can be so disabling – the same neuropathic pain can occur from strokes. Don’t we deserve better? Not even cancer pain is taught, let alone grade schoolers who should be taught about the body, about addiction, drugs, sex. Teach all that opioids cause pain because they trigger inflammation in the immune system and that stimulates pain. The more opioid you give, the more the pain. Teach about the brain’s pleasure centers and addiction, how drugs and food and cigarettes work there and how addiction kills.

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Have a wonderful life all of you. There’s a lot of work to take up. You will meet great people. Can’t wait to see what a little anger will do.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~

Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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A New Class of Pain Medicine from Cancer Cells – PD-L1 inhibits acute & chronic pain


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For the nonscientist, this report may explain better:

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Cancer actually yields a painkiller

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Scientists have discovered a potent painkiller in an unlikely place — cancer cells.

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This painkiller strongly inhibits acute and chronic pain in mouse models of melanoma, according to a study published Monday in Nature Neuroscience.

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Called PD-L1, the molecule is known to inhibit immune function, which helps cancers evade immune surveillance. It’s also produced in neurons. If it can be used to make an analgesic drug, it would represent a new class of painkillers, something badly needed.

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The molecule acts by targeting a cellular receptor called PD-1 and has been a longstanding target of cancer therapies called checkpoint inhibitors seeking to activate the immune system. But its painkilling effect is news.

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Ru Rong Ji of Duke University was senior author. Gang Chen and Yoang Ho Kim, also of Duke University, were first authors. The study can be found online at j.mp/cancerspain.

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…..Dr. Patel, oncologist from UCSD says: “This could result in a therapy that helps patients in a year or two years, just because so much has been done in the field.”

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The relationship between cancer and pain is complex, Patel said. PD-L1 suppresses inflammation, which activates the immune system, and also causes pain, Patel said. But there are other ways of activating the immune system, such as with the new cancer immunotherapy treatments, which don’t increase pain, he said.

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….The increased pain response is also caused by the cancer drug nivolumab. The drug, sold under the name Opdivo, targets PD-1 and shows success in treating melanomalymphoma and lung cancer. It produced strong allodynia for five hours in the mice, according to the study.

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Nivolumab is one of the new checkpoint inhibitor cancer drugs that targets PD-L1 receptors with immunomodulatory antibodies that are used to enhance the immune system. They can produce a wide spectrum of side effects termed immune-related adverse events (irAEs) with inflammation due to immune enhancement involving several organ systems.

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This is not my field and perhaps I am wrong. But if treating those cancers with immunotherapy causes the worst known neuropathic pain by blocking checkpoint inhibitors, is it possible that a new pain drug having the opposite mechanism could relieve pain but cause cancer?

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This Nature publication references the growing body of work from the lab of Linda Watkins, PhD, et al, published in 2014:

.Pathological pain and the neuroimmune interface

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Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms. Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~

This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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Cannabis risk, death from fungal infection, demanding peer reviewed science. Not even billions can buy CBD if it is classed as Schedule I


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“IMPROVING MICROBIAL DETECTION STANDARDS FOR CANNABIS”

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The full article in O’Shaunessy’s is recommended. I’ve extracted a few parts.

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“If the government is going to tax us, in return they’ve got to provide us with needed services. And that means well-equipped analytic test labs run by disinterested technicians.” [emphasis mine]

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“Let’s make measured changes before another patient is harmed while demanding peer reviewed science is used to guide the regulatory process. In an era of fake news, science by press release with “beliefs” derived from companies that have a vested interest in seeing more cannabis safety testing should be hyper scrutinized.”

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“I think the cannabis-testing labs should be operated by the Department of Public Health, overseen by Commissioner Raber (and equally proficient chemists in every city and state) and staffed by well trained and well paid technicians whose pensions are secure.”

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The importance is that many patients who are immunosuppressed use medical marijuana, and need to use it safely because nothing else helps as well, including those who are immunosuppressed and don’t know it. For example, many do not know that diabetics are immunosuppressed. Those with autoimmune diseases, chronic renal disease, may be using medical cannabis and should demand testing be done with their taxed dollars as should we all. This has been one of the most useful herbs in history, for thousands of years, and can give balm and relief even to shattered nerves, especially now that healthcare insurers are denying to pay for pharma’s gobsmacking overnight billious costs.

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gobsmacking billious costs

vs

getting up to speed on legal cannabis &

 research on endocannabinoid systems

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This is a timely issue. Discuss with your doctor, get your representatives to help to legalize it nationwide. It may be the only thing that can help, or the only one that doesn’t constipate or cause erectile dysfunction or interact with other drugs. We don’t want our medication infected, even if we want to use cannabis for relaxation and pleasure. The Xanax’s and Ativan’s could be improved upon if only the right science is funded.

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“On February 7, the Daily Mail reported a cancer patient in northern California died from a fungal infection that authorities suspect was caused by the inhalation of contaminated medical cannabis.”

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snip

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“Furthermore, molecular techniques can be used to assess whether this cancer patient’s infection was actually cannabis derived. This is possible by using PCR and sequencing as performed by Remington et al. on the cannabis material and on the patient to confirm such an event.”

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“Rather than jumping to conclusions from a news story about cannabis contamination (which may in fact be the case), officials should confirm, via molecular methods, that a fatal infection occurred from the consumption of contaminated Cannabis or from another source, such as a hospital acquired infection. Once confirmed, the scientific data can help drive the appropriate regulations forward to ensure patient safety.  Unfortunately, most regulations passed to date for microbial detection do not appropriately address patient safety and often suggest the use of antiquated, inaccurate technologies.  For instance, we have peer-reviewed evidence that the currently accepted 48-hour Petrifilm-based method currently in use fails to detect some of the most harmful microbes found on cannabis. The State of Colorado has recently come to similar conclusions and has moved their Petrifilm detection times from 48 hours to 60-72 hours while referencing a paper suggesting 120 hours may be required.  And even with these adjustments to the regulations, Petrifilms will never give as accurate results as PCR.” [emphasis mine]

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“All technologies used to ensure product quality and patient safety should be peer reviewed. DNA-based methods are imperative to patient safety, as they are accepted, peer reviewed, and have been used for decades in other industries for similar purposes.”

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Kits to perform qPCR-based microbial testing on cannabis are commercially available at medicinalgenomics.com. We hold the largest sequence database of microbes found on cannabis and have kits that perform these tests in hours as opposed to days.”
[emphasis mine]

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“The technology exists to ensure safer cannabis for patients. Let’s make measured changes before another patient is harmed while demanding peer reviewed science is used to guide the regulatory process. In an era of fake news, science by press release with “beliefs” derived from companies that have a vested interest in seeing more cannabis safety testing should be hyper scrutinized. This extends to our own work at Medicinal Genomics and underscores our publication history in this space.”

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snip

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O’Shaughnessy’s retro message:

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Medicinal Genomics’s qPCR technology is undoubtedly superior and would have picked up the aspergillus that may have been fatal to the California  patient. But how widespread is the danger, really? In San Francisco in the ’90s, many thousands of AIDS patients whose immune systems were beyond “compromised” smoked untested crude herb, and I only heard of one rumored instance in which aspergillus may have been involved in a death. Donald Abrams, MD, might be able to confirm or correct my reassuring recollection.”

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“That said, of course the labs testing cannabis should employ the best available technology. The question, is who should pick up the tab?” [emphasis mine]

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“When I was working for the San Francisco District Attorney in ’01 or ’02 I called on Josh Bamberger at the city health department on Grove Street and asked if their lab would take on the testing of cannabis being sold at dispensaries. He said he didn’t have the budget or the personnel.  In the years ahead I was surprised that nobody from the movement/industry ever made the demand —not even the request— that a government agency take responsibility for testing medical cannabis. No patient advocate declared, “If the government is going to tax us, in return they’ve got to provide us with needed services. And that means well-equipped analytic test labs run by disinterested technicians.” [emphasis mine]

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“All around the world, PRIVATIZATION is the overwhelming socioeconomic trend of our time.  The Power Elite have done such a thorough job of selling off the commons and undermining the public sector that everybody now simply assumes that for-profit labs can and should take on the responsibility of protecting public health. “

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“I think the cannabis-testing labs should be operated by the Department of Public Health, overseen by Commissioner Raber (and equally proficient chemists in every city and state) and staffed by well trained and well paid technicians whose pensions are secure. And while we’re at it, how about free public education and single-payer medical care?”

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I keep getting the suspicion billions are being funneled rapidly down new rabbit holes using fear to prevent science. We must be able to do more than just prescribe  opioids for severe pain. Opioids cause inflammation which causes more pain. Cannabis is anti-inflammatory, analgesic, etc etc etc, and not allowed in hospitals, SNFs, or in facilities that seniors can only dream of retiring to when they can no longer manage at home. We need medical better choices.

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Medicinal cannabis is a healing plant with cannabinoids like ones that your body makes that helps you feel healthy and somehow influences the immune system more than any other system, while also lifting mood. Wouldn’t it be nice to know? It has 400 chemicals, not just two synthetic ones pharma makes. An exciting new cosmos in the body’s realm of more than just neuroscience. We have more cannabinoid receptors than any other kind in our body. We need to learn.
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Stop this Schedule I nonsense. Legalize cannabis. Privatize and regulate it like big alcohol, but keep it apart from big pharma, and endow strong university ties. For pete’s sake, fund the research immediately. We need it. The immune system needs it. The pain matrix needs it. Why should we allow euthanasia when we can treat pain and symptoms. Grandmothers used to know how. We are living in the dark ages with cannabinoid systems science. It is in starving infancy, Israel’s Mechoulam lab pioneering this blossoming for decades.
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Don’t forget to tell your representatives that you hear you may benefit from medical marijuana. Cannabis, marijuana, just may help, as it helped so many little children having hundreds of seizures each day, helped by just one of the cannabinoids in the plant: CBD.  It has been reported to almost completely stop the hundreds of daily seizures in possibly 50% —wouldn’t it be important to do research on it?

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CBD  has no psychoactive power. There is no high, no hallucinations. It actually blocks the psychoactive power of THC. It should be legal. The plant should be legal. It helps many medical conditions. I have posted an astonishing case months ago 100% relief with CBD. Instead it, just the other day, CBD got clearly classified as Schedule I. This must go to the courts. This insanity about a healing plant can be sanely managed, just like alcohol is managed. Without privatized prison systems that waste taxpayer dollars.

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We see new funnels of big money going down the rabbit hole. The urgency to privatize. We have a lot of people who cannot afford the American medical system, cannot afford doctors, who may get some relief even as a muscle relaxant or for sleep or anxiety.

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How can anyone respect a legal system that does not even allow research on a healing plant so important to the immune system?

 

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No amount of billions can buy CBD if it is classed as Schedule I.

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.
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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.
~~
This site is not for email and not for appointments.
If you wish an appointment, please telephone the office to schedule.
~~~~~
For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.
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PEA in US (palmitoylethanolamide), PeaPure in Netherlands – DO NOT BUY OTHER SOURCES


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PEA in US is palmitoylethanolamide from Vitalitus

PeaPure in  Netherlands

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DO NOT BUY OTHER SOURCES

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PEA is thankfully available in the US since Spring 2016 from ONE company: Vitalitus. It is a trusted source. Buy PEA only from Vitalitus in the US, others are fraudulent sources.

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I strongly recommend that you AVOID any product with a “PEA-type” name trying to sell elsewhere in the US or on the web.

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One such fraudulent source is a foreign entity pretending to be in the US, and they are now listing a US address on Brickell Avenue, Miami, FL 33131 United States. But that is a virtual office address which is still listed for rent at $60/month.

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It looks like they’ve morphed the website and their product label. Very professional looking but AVOID THEM LIKE POISON. They keep trying to post comments on my website. They may even be buying advertising on my free site – anyone can advertise but I do not endorse products with this one exception, PEA, because it is unique.

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I have also seen “PEA-type” powder available on the web. Do not buy powders claiming they are pure palmitoylethanolamide. They are not trustworthy sources.

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Make sure your PEA comes only from a trustworthy source. In the US, that is Vitalitus. PEA works on the innate immune system, mast cells, and much more. There are more than 400 scientific publications on palmitoylethanolamide since it was rediscovered by a Nobel Prize Winner in 1993. Vitalitus’ PEA capsules are 100% palmitoylethanolamide. Pain relief is one of its immune functions. Your body makes it, plants make it, it has no toxicity, but follow directions or capsules will not fully absorb.

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~
This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~
This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please ignore the ads below. They are not from me.

 

NFL – Prevent &Treat Chronic Traumatic Encephalopathy, CTE – Opioids Blamed Wrongly


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Crowdfunding Needed

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Prevent and Treat

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Chronic Traumatic Encephalopathy

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C.T.E.

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Opioids Wrongly Blamed

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Leagues may have known about this technology since 2002 publications

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Football players have demonstrated ability to influence others

and raise money for important medical causes.

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This is not about class action law suits.

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This can be imaged early and likely treated.

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It’s about science and bringing medicine into the 21st century.

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A paradigm shift began with the discovery

of the innate immune system by internationally recognized scientists in 1991.

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The clock has been turned off.

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We can change this now.

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Funding is needed for internationally recognized leaders to continue this work.

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The tragic deaths of former NFL football players from repeated concussions has led to brain damage and death from Chronic Traumatic Encephalopathy (CTE). Suicide profoundly shocks us when many players like Junior Seau at age 43 and now Tyler Sash, die at age 27. He is the youngest found to have such extensive brain damage, as bad as that seen in Junior Seau. So much can be done with state of the art science now that has been ignored.

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Disclosure: I was asked by a research institute if I would evaluate retired NFL players. I chose not to do that so that I might be free to post unbiased information that is not subject to being manipulated by either side in the ongoing appeals for compensation that must be going on with the NFL for $70 million. Tragic that this is such a fight. Even more tragic, this may be diagnosed early and treated.

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Pearls

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Fear of compensation claims after concussion injury prevents imaging of football players and veterans early, while still treatable, before severe changes and death.

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Fear of compensation claims has prevented decades of research funding by internationally recognized scientists. Could politics at NIH & the VA have turned off funding for veterans with pain and with concussion blast injuries? Does cancer and heart disease forever lock up all the research money and now it shifts to stem cells?

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It is inaccurate to say that CTE cannot be diagnosed except after death at autopsy.

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PET scan imaging of glia can show changes early, while alive.

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The ligand PK1195 must be used for PET scan to image glia, available for years in Australia, not yet in America.

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FDA approval must be obtained for the ligand PK1195 before it is used to  image glia in the United States.

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CTE can be diagnosed early.

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CTE is likely to be treatable.

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Internationally distinguished scientists have shown reversal of complete paralysis in rat models of multiple sclerosis in 2010, a so called “degenerative” neurological disease.

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Intractable pain and treatment resistant depression can be put into remission with glial modulators. Surely CTE and other neurological diseases can be approached with scientifically recognized mechanisms and treatments – even if doctors are not aware of the paradigm shift and how to modulate neuro-inflammation. See years of posting on this site since 2009 based on the most important finds in the field of neuroscience for more than 100 years: the innate immune system, glia, neuro-inflammation, and ability to use glial modulators, to modulate intractable conditions that are known to lead to suicide and/or death.

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Paradigm shifts in all fields including medicine, fail to be recognized.

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CTE gives opioids a bad name and misled Taylor Sash and likely others from the diagnosis of CTE that caused years of severe forgetfulness and behavior changes. He may have chosen suicide by opioid.

 

 

 

FACT:

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Trauma such as concussion or infection or stroke triggers inflammation in the brain:  “cytokine storm”

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Inflammation kills brain cells

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Inflammatory cytokines (inflammation) are produced by glia that has been activated by trauma or other causes such as infection, stroke, etc.

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Activated glia produce neuroinflammation and cell death.

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Inflammatory cytokines produce pain and “degenerative” neurological and psychiatric disorders including dementia, depression, anxiety, delirium and death.

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Neuro-inflammation in brain has been found in teens with early signs of schizophrenia, in rats made depressed, and rodents with chronic pain.

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Glia have been detected in life, in vivo, with PET scan imaging, by internationally-recognised radiologist working at Imperial College London, now based in Australia.

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PET scans require a ligand, PK1195, approved for years in Australia – must be approved by FDA in the United States before it can be used here.

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There is good clinical data and publications in animal models to show that damage in brain and spinal cord produced by activated glia can be reversed.

E.g., In 2010, total paralysis has been completely reversed in a rat model of multiple sclerosis by internationally-recognised glial researcher who, in 1991, transformed the understanding of glia that comprise 85% of the brain, since then known to be the innate immune system.

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Publications have shown that patients with major depressive disorder and patients with chronic low back pain have memory loss and brain atrophy.

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Opioids cause pain by stimulating production of inflammatory cytokines that are known to damage neurons in brain and spinal cord – and must be tapered off. We have better treatment for pain.

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Insurance carriers routinely deny payment for recognized medications and procedures to relieve pain.

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CDC is planning a nationwide experiment to radically limit opioids.

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Treatment with glial modulators that reduce neuroinflammation has been shown clinically to relieve treatment resistant major depressive disorder, PTSD, bipolar depression and intractable pain. They are neuroprotective.

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We need to be able to flag players off the field early and intervene with treatment such as glial modulators either before, during or after repeated injury.

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GOALS

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1.  PK1195, a ligand for PET scans, must be tested and approved by FDA. Approval is mandatory for all medications or substances injected into vein or body.

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It simply “tags” the PET scanner to image glia, the cells of the innate immune system that are activated by trauma, infection, stroke, etc.

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2. Do serial PET scans using PK1195 to image glia in NFL players and veterans after blast injury.

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Trauma from concussion is causing cytokine storm, killing brain cells –> ultimately end stage dementia, anxiety, depression, suicide

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3. Flag that player off the field. Follow glial changes during treatment to determine if able to return or if permanent, but prior to end stage damage.

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4.  Treat with glial modulators preventively, early, middle, and/or late

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This subject will be continued. My apologies for lack of time to delete and edit. Days pass by quickly to post brief comments. Time is limited. Please send comments, below.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

Relevant comments are welcome.

If any questions, please call the office to schedule an appointment.

This site is not email for personal questions.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please be aware any advertising on this free website is

NOT advocated by me and NOT approved by me.

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Be the change you wish to see – or walk away. Money at NIH


 

 

A Turning Point

 

$$$$$ MONEY $$$$$

 

at NIH

 

May not come this way again

 

NIH developing

5-year NIH-wide Strategic Plan

 

 

 

Donate to organizations, below

They can provide feedback to NIH via the

RFI Submission site


 

 

 

John C. Liebeskind, 1935 – 1997, distinguished scholar and researcher, past president of the American Pain Society, had the radical idea that pain can affect your health.

 

Research decades ago by an Israeli team at UCLA and others had shown “that pain can accelerate the growth of tumors and increase mortality after tumor challenge.” Decades ago Professor Liebeskind lectured all over the country: Pain kills.

 

He wrote an editorial in 1991, summarizing a life’s work:

 

“Pain and stress can inhibit immune function.”

 

 

Quoting John Bonica, the father of modern pain management, he wrote:

 

“Bonica has long argued that the term ‘chronic benign pain’ (used in distinction to pain associated with cancer) is seriously misleading.  Chronic pain is never benign, he contends; “it is a ‘malefic force’ that can devastate its victims’ lives and even lead to suicide.”

 

 

Liebeskind continues, “It appears that the dictum ‘pain does not kill,’ sometimes invoked to justify ignoring pain complaints, may be dangerously wrong.”

 

Pain mediates immune function

 

Importantly

 

  Opioids mediate the suppressive effect of stress on natural killer cells,

 

 published in 1984, immune system.

 

Alcohol increases tumor progression, 1992, immune system.

 

It used to be news.

He did not live to see change.

 

People just want to go on doing what they’re doing.

They want business as usual.

 

 

After 1991, we saw the great discoveries of neuroinflammation, pioneered by Linda Watkins, PhD, the early understanding of the innate immune system, its involvement in chronic pain and depression, and a few weeks ago, a British team showed neuroinflammation in teens with early signs of schizophrenia and DNA markers.

 

 

Major Depression has the same neuro-inflammation found in chronic pain, often responding to same medications, in particular glial modulators – immune modulators. Now, perhaps early schizophrenia will respond to glial modulators, reducing inflammation seen on scan in teens, before they become homeless and burned out by antipsychotic drugs

 

Inflammation out of control destroys neurons

 

Fire on the brain

 

 

We must be the change we wish to see

 

It’s not just the Bern. It’s been starting. Forces are finally coming together. We want change. It’s been too much. Too long.

 

We won’t take it anymore.

 

I figure if I tell you about it, you might just mention it to someone to pass it on. That is all. One small action may lead to change. Activate inputs to the NIH strategic plan.

 

 

~ Action needed ~

 

Prices of drugs becoming unaffordable

No new drugs for pain or major depression

Research to repurpose existing drugs

Expose the politics destroying our compounding pharmacies

 

Above all

The #1

Major Priority:

Request NIH to solicit priority call for research on

Glial modulators of the

Innate immune system

 

 

Why?

 

Glia modulate

chronic pain, major depression

and almost every known disease

 

Glia are your innate immune system

 

Inflammation kills

 

 

 

 Stress kills. Inflammation kills.

 

 

Pain kills

 

In the 1970’s, Professor Liebeskind and an Israeli team at UCLA injected cancer cells to two groups of rats that had sham surgery. Cancer spread much faster and killed far sooner in the group with poor treatment of surgical pain.

 

 

~ Pain kills ~

 

He lectured all over the country

 

Forty five years ago

 

 

I’m gonna be dead before I see this country do anything but unaffordable opioids and the magical ineffective trio of gabapentin, Lyrica, Cymbalta to treat chronic pain. The devastating, blind, nationwide emphasis does nothing to address the cause: inflammation, the innate immune system gone wild.


 

 

Innate immune system in action

 

Untreated pain suppresses the hormone systems too.

 

Untreated depression – same inflammation kills lives.

 

Where’s the money?

 

We are the change we wish to see. It’s pitiful I am so lazy. Suddenly, too late, we may need something, but, aha, no new drugs in the pipeline.

 

 

 

~ Make a joyful cry to NIH ~

 

They are soliciting input from professional societies

 

If your condition has failed all known drugs for pain or major depression, then make a joyful cry to NIH, now, before they give away all that nice new $$$$$money$$$$$.

 

 

Follow and join

 

American Pain Society

 

 

International Association for Pain

celebrating 40 years of pain research

 

 

Reflex Sympathetic Dystrophy Syndrome Association

help for CRPS/RSD  

 

 

 

The key to CRPS/RSD pain will apply to all forms of chronic pain, in particular the most difficult form, neuropathic pain. RSDSA funds research into all forms of chronic pain, not only Complex Regional Pain Syndrome (CRPS/RSD). Their scientific board members are not funded by opioid money.

 

 

 

Exactly

what is the annual cost of care

as fraction of GDP

for the growing population of Americans on opioids

for one year, for lifetime?

 

 

People are dying from prescription opioids and those who need them find they don’t work well enough. Prescriptions opioid costs must be a huge fraction of the medical costs in the United States GDP. You are required  to see a doctor every single month each year, often lifelong, just for one opioid, 12 months a year x 30 years x tens of millions of people and increasing – a growth industry. Not even counting $600 a day for the opioid, what the cost of monthly visits for 30 years? Not counting the army of DEA, FDA, CDC agents watching the opioids like a hawk. We all have to be sharp, addiction is growing. Addiction aside, deaths from prescription opioids are shaking up the CDC forcing urgent change this coming month.

 

 

 

Opioids do not work well for chronic pain

We need better

It’s not just the $600/day price

They just don’t work

 

 

donate

 

 

Raise a joyful noise at NIH now or write back at us readers with comments and better suggestions. Tell others what you’d like to see. Which politicians do you know would be most interested in this at national levels and organizations?

 

You may never see this change unless you do it now. Other forces will get this new money.

 

 

Turning point now

May not return

 

 

We are at a turning point and we will fail to catch the sail that’s coming fast to carry all research money in their shiny big stem cell direction. They never look back.

 

 

There is so many medications we can use today, FDA approved drugs that can be re-purposed and applied to recent cutting edge science. Someone must pay to do the work to study this.

 

 

Re-purpose old drugs

 

 

Stanford just showed a popular generic drug improved recovery of stroke paralysis in mice to begin at 3 days rather than 30. Old drug, new purpose, of course more years of testing to confirm in humans. Brilliant team applying new science.

 

 

Request
NIH to solicit a

Special Invitation

for 30 good protocols to

repurpose old drugs

 

 

Hundreds of old drugs, already approved, could be involved in mechanisms we have recently learned about. Speak up or money will go to shiny new stem cells. None for chronic pain or major depression. No company will find this profitable – it must be funded by NIH. A popular generic sleeping pill can bring astonishing return from stroke paralysis.

 

 

Congress has not opened this new money to NIH in many long years. How often will there be extra money?

 

 

donate

 

 

Lawrence A. Tabak, D.D.S., Ph.D.
Principal Deputy Director, NIH, solicits you to

Review the NIH Strategic Initiative Plan and their

Request for Information (RFI) and the NIH website

and provide your feedback via the RFI Submission site

 

 

This is for “stakeholder organizations (e.g., patient advocacy groups, professional societies) to submit a single response reflective of the views of the organization/membership as a whole. We also will be hosting webinars to gather additional input. These webinars will be held in early to mid-August.

 

 

 

Be the change you wish to see

Donate to those organizations

to solicit the change you wish to be

 

 

 

Happy New Year

Rejoice!

There’s money at NIH

 

 

 

 

 

 

The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

Relevant comments are welcome.

If any questions, please schedule an appointment with my office.

This site is not for email.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

 

 

 

 

Proposal: A 5-Year Study of Best Methods to Treat Intractable Pain


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PROPOSAL

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A controlled trial to improve care for chronic pain:

The study to understand prognoses and preferences for

outcomes and risks of treatments

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Model after Joanne Lynn’s 1995 SUPPORT Study

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A controlled trial to improve care for seriously ill hospitalized patients:

The study to understand prognoses and preferences for

outcomes and risks of treatments (SUPPORT)

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Proposal

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A controlled five-year trial to improve care for outpatients with chronic pain. The study will be designed to understand prognoses and preferences related to the outcomes and risks of various treatments.

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The focus:

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Intractable pain, those who have failed pain medications and procedures or those with moderate to severe pain who only partially respond.

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Study polypharmacy, compare medications that may show synergy or that additively improve relief.

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Study and search for glial modulators – medications that reduce proinflammatory cytokines.

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Problem

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Research is needed to give persons with intractable pain the data and the confidence that they can affordably use to choose the best treatment needed to get their lives back again. They have already spent tens of thousands. They may be unable to work. We all need these options.

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There are a few small islands in this country doing a radical experiment in managing pain without opioids [narcotics, the police term] as discussed in the New York Times in May 2014, and the 2008 Mayo Clinic study. Efforts such as these need to be supported with data as soon as possible in order to reduce the burden of disability and pain in our society, especially our youth, our children, our veterans, our aging seniors, well everyone. We can be productive and we want to be.

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I have seen remarkable outcomes, pain that failed to respond to all known pain medications, going into partial and even total remission, lives restored after weaning off opioids and appropriate treatment given.

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We cannot expect any medication to work every time. How often can we achieve better results after opioids are tapered off? Opioids may prolong pain in Complex Regional Pain Syndrome where remission seems possible only after they are stopped, yet opioids may be essential in many forms of chronic pain. We need data on the radical experiment to manage pain without opioids, and determine how best to manage chronic pain with them.

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Opioids have a long history of being the drug of choice to treat chronic intractable pain by doctors who lack information and training about other exciting options now coming to the fore. Compounding the problem is the fact that physicians do not know how to diagnose musculoskeletal pain and do not know how that good physical therapy is actually effective.

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Healthcare providers need data about all the options to begin to address the toll that chronic intractable pain exacts and government worldwide need to know what is cost effective and possible. Many countries cannot obtain opioids.

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We must not be insensitive to the financial burden that frustrates patients when they spend tens of thousands of dollars for drugs that provide little if any benefit.

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Investment in developing nonopioid treatments for pain does not even begin to compare to the investment in opioids for pain. The few medication choices we have are not enough. Often they fail to help. Expensive drugs are not the best choice if they are not affordable or they are limited to diabetic neuropathy when more than 100 types of peripheral neuropathy have been identified, plus many more types of even more severe neuropathic pain not classified as neuropathy. Shall we continue to ignore all those because FDA has classed these few new drugs for diabetic neuropathy exclusively?

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Let me be clear, prescription of opioids is justified and they are valuable. Opioids are on the World Health Organization list of ten essential drugs. BUT there is little or no research on treatment of intractable pain without opioids.

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Neuropathic pain, nerve pain, is the most difficult to treat. Neuropathy, radiculopathy, transverse myelitis, adhesive arachnoiditis, central pain, RSD, Guillain-Barre, trigeminal neuralgia, Tic Douloureaux, post herpetic neuralgia, to name a few. It is not enough to limit research of neuropathic pain to diabetic neuropathy when it fails to address all other causes. When FDA approves a drug only for diabetic neuropathy, insurers deny the drug for the other 95% of you without diabetes. Insurers may choose to read guidelines as mandates, fiats,  marching orders.

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Neuropathic pain is not the only concern. Physicians do not know how to diagnose musculoskeletal pain. How can they if only 3% of medical schools teach pain management and when doctors do not know how to assess ineffective physical therapy when they have never seen better.

A patient dislocated her hip 7 times, manually repositioned each time in ER. The 6th surgeon impinged a wide band of muscle in the joint causing muscle all down the thigh to bulge 5 to 7 mm high, of rock hard spasm with intense relentless pain. The 7th surgeon had the gentle ability to restore position and release the entrapment. A light touch across the thigh even through clothing can detect the cause. Would a surgeon have discovered to release the entrapment unless she had dislocated a 7th time? Simple muscle strain, undiagnosed by a surgeon who deals with muscle all the time, was not even noticed and he ignored the acute pain it caused. She has now learned how to avoid dislocating that new hip. Had the muscle not been appropriately identified as cause, she would not be able to move by now. But the surgeon should have had the skills to notice instantly before those muscles became chronically strangled. She was referred for manual physical therapy and thankfully, before all else could occur, she dislocated and was repositioned by the 7th surgeon. A wonderful teaching case for a teaching hospital that should be every hospital. Grand Rounds for pain cases.

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MAJOR FUNDING DECLINE IN PAIN RESEARCH

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 BEFORE 2008

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 BEFORE CONGRESS CUT NIH BUDGET BY UNTHINKABLE 30% IN 2010

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Perhaps the biggest impediment to gathering data about pain management is the lack of government funding for pain research and lack of a Pain Institute at NIH. If not, funding will continue to be fragmented and split elsewhere, not to learn about one of the most costly problems in every society.

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In 2008, before the worldwide depression, pain research was in major decline. The AAAS, the American Association for Advancement of Science told us then:

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“Federal funding for pain research is declining sharply, more than 9 percent a year since 2003, according to a new study published in The Journal of Pain. Pain research, as a result, now accounts for only 0.6 percent of all grants awarded by the National Institutes of Health (NIH), despite the high prevalence of chronic pain in the U.S.

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“This startling finding shows the government’s meager investment in pain research is seriously out of proportion with the widespread chronic pain incidence in our society, which is estimated at one in four Americans and accounts for more than 20 percent of all physician office visits,” said Charles E. Inturrisi, president of the American Pain Society and professor of pharmacology at Weill Cornell Medical College, New York. “And this disparity is not attributable to years of budget cuts at NIH because the Journal of Pain study clearly shows pain research has a higher percentage decline than the overall NIH budget. So the drop in agency funding has not affected all research areas equally.”

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[emphasis mine.]

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Research in pain was sharply declining prior to 2008. Then a 30% cut across the board in 2010. Thank the American Pain Society for those ancient 2008 figures. No one had ever asked – which is why we need a Pain Institute at NIH.

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Frustration is compounded the last few years by insurers no longer willing to authorize many opioids and non-opioid medications, even generics.

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As for the cost of opioids,  a single opioid for one patient may exceed $80,000 per month when the patient is required to use with another long acting opioid, and often several nonopioid adjuncts just to bring pain down from 9 on scale of 10, to a slightly more bearable 7 or 8 which is severe, relentless and prevents sleep and ability to concentrate. One drug that costs pennies to make, sells for $80,000 a month to allow 4 a day when at least 6 a day are needed and it is only one of many for pain every day.

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Prescription of opioids is justified and may be invaluable.

but there is little or no research on

 treatment of intractable pain without opioids.

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We need national consensus guidelines based on data

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We must do a better job treating intractable pain. We need guidelines that have more to offer than the few opioids and few adjuvants we now have, so few in number, so great the need. Can we know when is it true that opioids are indicated? Our use is many times more than all the other First World countries?

 

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Treatment must be individualized

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Data is needed to guide choice

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Compounded Medications are among the

most useful drugs we have for treatment of intractable pain

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Compounded medications may be the only ones that help, and can reduce pain to zero. We can re-purpose the delivery of any medication, as long as it has been FDA approved. But the last few years insurers have been discontinuing coverage for compounded medications and Medicare has never covered them.

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This must change. Who is funding that political blockade that denies coverage for compounded medicine? The cost may be $120 for one compounded medication vs $80,000 for one opioid. Either way, the person with intractable pain likely needs 3 or 4 or 5 or 6 medications, compounded or not. Who can afford $400 per month out of pocket for compounded medications that work, when insurance will not cover the affordable drugs. Who can afford that out-of-pocket expense if insurers cover nothing for your pain, neither the bright shiny opioid or the compounded sprays, capsules, suspensions, creams, troches, as well as the essential solutions instilled into the bladder for interstitial cystitis?

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This must change. Lawmakers must be called to account for allowing and perpetuating the inhumane taking advantage of those who suffer intractable pain.

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A first step in getting lawmakers to pay attention is to amass a body of compelling data.

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BALANCE IS NEEDED

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The United States as a society cannot afford for pain research to die and go bankrupt and leave only opioids as the standard treatment for hundreds of types of pain. Someone has to begin the needed studies. It does not just bankrupt the patient, it leaves us all bankrupt, the country most importantly. It ends marriages, tears apart families. To be struck down as a child with intractable nerve pain the rest of your life, or be struck in your prime, is devastating. And disability gets routinely denied for pain. Why? Perhaps because pain is taught in only 3% of university medical schools. How are doctors to imagine that pain can end lives when they have no experience seeing how disabling it can be?

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 If doctors cannot see the devastating toll that pain takes,

how can we expect accountants to see it?

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The Study We Need

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Solution

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 To gain a comprehensive and compelling picture of how pain impacts the population and how to effectively treat it we need a large-scale study:

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  • Five years in duration

  • 10,000 outpatients – statistically this must be adjusted to obtain multiple outcomes

  • At five major university teaching hospitals for regional differences

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 Outcomes

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The study will yield important information about the following:

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  • Efficacy

  • Pain Numeric Rating Scores, Percent Improvement

  • Functional Improvement, etc

  • Compounded medications

  • Racial and Gender Disparities

  • Addicts who have chronic pain

  • Top notch manual physical therapy* [see below], not for what passes in most places. This must change ASAP. United States is far behind other countries. Even if the condition is neuropathic, it often becomes musculoskeletal after splinting for months, years

  • Interventional procedures

  • Meditation

    How you brain can heal your body and your body heal your brain.

  • Pain changes DNA, neurotransmitters. Have we permanently changed them with opioids?

  • Polypharmacy. When employing one drug alone is unlikely to lead to a successful outcome.

  • Stem cells for joint pain – autologous lipid derived mesenchymal stem cells

  • rTMS, experimental after 20 years, is it still better for acute than for chronic pain?
    Who will benefit, for how long? How many weeks of relief for that $15,000 investment?

  • Glia, the Innate Immune System

Opioids create pro-inflammatory cytokines that create pain and opioid tolerance.

Restore cytokine balance, reduce inflammation and pain.

Which of our existing medications either trigger or reduce inflammatory cytokines in the CNS?

  • Pain in the person with Alzheimers dementia

  • Danger of combining opioids with benzodiazepines

  • Danger of long term use of opioids (regardless if short or long acting)

  • Appropriateness of using opioids as a first choice in acute pain (loss of a milk tooth, sore throat in a teenager, acute back pain, ankle strain, etc.)

  • Appropriateness of opioid holidays.

  • Post op pain can be avoided completely with combined use of oral low dose naltrexone and ketamine IV anesthesia. Patients discharged directly from recovery room with no need for pain medication for months or years

  • Cost Benefit Analysis

 

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Five Conditions Will Be Studied

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Strong emphasis must be placed on neuropathic pain that so often fails to respond to any intervention

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1. Complex Regional Pain Syndrome

The Netherlands invested €25 million over 5 years to study this one devastating pain condition, far out of proportion to the incidence in that small country. There are pain specialists who cannot recognize it and/or doctors who routinely deny disability for this devastating pain, like death in life.

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2. Low Back Pain

Define criteria for surgery.

If we wait too long before surgery is done, will we ever reverse the chronic pain that has set in?

Have we condemned that patient to monthly visits for opioid the remaining 50 years of their life?

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3. Other neuropathic pain conditions such as adhesive arachnoiditis, trigeminal neuralgia, transverse myelitis, Tic Douloureaux, Post Herpetic Neuralgia, Interstitial Cystitis, Vulvodynia, Proctalgia, Pudendal Neuropathy


4. Painful peripheral neuropathy nondiabetic and Painful Small Fiber Neuropathy  all forms of painful neuropathy

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5. You choose – central pain?

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What We Must Do Now

 

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  • Find a pain advocate like the cancer advocate of the 1950’s that changed attitudes for research

  • Fund the pain SUPPORT study

  • This will spin off enormous research ideas that we must begin separately to implement with research as each develops, the need is beyond urgent. How many more years can we make everyone wait?

  • Write letters, to congress, the White House. Real letters, not email, not signature lists. Congress will not hear us unless we speak in very, very large numbers.

  • Help the topic of intractable pain become a part of the 2016 presidential conversation.

  • Incentivize teaching hospitals to teach pain management and to develop options for nonopioid treatment of chronic intractable pain. Pain is a multidisciplinary field, not limited to Anesthesiology procedures.

  • Create an Institute for Pain Management in addition to the 28 institutes at NIH, three of which are for addiction, none for pain. Pain is the number one reason people seek medical help.

  • Require that pain specialists sit on the FDA advisory committees for pain medication – none recently.

  • Require insurance coverage for compounded medications.

  • Prevent FDA from limiting medication to cancer pain.
    Cancer pain does not exist.

    There are basic types of pain that occur in persons who have cancer, neuropathic pain being worse than other forms of “cancer pain.” It has the same medication response or failure to respond as persons whose pain is not due to cancer.

  • How do we restrict the use of opioids to severe pain when there is nothing else to offer and after everyone is started on opioids by their family doctor years before they see a pain specialist?

  • Novel and ancient methods for treatment of pain should be explored including cannabis and possibly hallucinogens

  • Isolation of pharmacologically important medicine from rainforest and deep seas must be done before they disappear.

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Physical Therapy is the #1 Key to Chronic Pain

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Manual Physical Therapy was introduced to the United States in the late 1970’s but is rarely practiced or not done well. It does not mean “hands on.” It derives from techniques brought to us by British Commonwealth and Scandinavian countries. Our healthcare providers do not know how to differentiate between good and useless practices. Fortunes and lives are wasted hinging on that distinction. Pills never can undo the harm brought about by common musculoskeletal issues – and our providers have no training in recognizing simple muscle trigger points, let alone intractable connective tissue contractures. My patients have been misdiagnosed as histrionic, drug seeking, personality disorders, and worse. It boils down to ignorance and lack of basic training, let alone believing what the patient says and not having the tools to help.

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The trend is for year long residency programs following the 3 year Doctorate of Physical Therapy (DPT).  The year long residency program is a very positive step.  The limitations are that it is a year with a clinical staff that may have a specific perspective.  The push towards evidence based practice is a reasonable step but should not exclude considerations of outside the box treatment options.

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The osteopathic manipulative technique has been a cornerstone of best education for physical therapists.  The craniosacral approach is an offshoot from that tradition.  When we get to visceral mobilization, the evidence is much harder to produce but that does not have me shy away from its application.

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Movement is critical for the hormonal regulation of the body.  Chronic stasis leads to numerous changes that compound an underlying medical diagnosis.  We see that with a 16 y/o female, Lyme’s disease, CRPS diagnosis, bedridden for years.  She is significantly benefiting from stretching dysfunction and improving axial extension.  Another who quit walking had global lower limb connective tissue contracture.  Walking is currently limited by soft tissue contracture through the tarsal tunnel, affecting the plantar nerves and the burning and tingling with walking greater than 5 minutes at a time.  Mobilizing the soft tissues will ultimately restore function. This 20 year old quit college due to pain and one first visit requested motorized wheelchair and Social Security Disability. This young person will walk again.

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There is no end point to this educational process except when we think we know it all.  No certification, no degree, no one course signifies competency.  Ongoing intellectual curiosity is the most important element in preparation.

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Prescription painkiller overdose epidemic in the U.S.

Not in other countries

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Pain Management centers at major universities closed in 1991. They lose money, are time consuming, require team conferences that are not reimbursable. Thus began the era when prescription opioids took off for noncancer pain, and no one was generating nonopioid approaches to chronic pain. Anesthesiologists shifted to procedures – that is their focus after all. Procedures are not applicable to many types of pain.

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“Since 1999, the amount of prescription painkillers prescribed and sold in the U.S. has nearly quadrupled, yet there has not been an overall change in the amount of pain that Americans report.”

from the CDC report of prescription painkiller overdose epidemic

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I feel I have failed when I have to point out to my own patient whose pain is severe, that the high dose opioid I have prescribed is not helping, or is creating pain; when I know there are other options which are not available because the FDA has not approved them or because they are prohibitively expensive. I have failed when so many medications I prescribe are not on the formulary.

 

We need a mandatory formulary available for those with intractable pain.

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There were 16,651 deaths from prescription opioids in the U.S.in 2010, “Starting with 4,030 deaths in 1999….” “…nearly 60 percent of the drug overdose deaths (22,134) involved pharmaceutical drugs. Opioid analgesics, such as oxycodone, hydrocodone, and methadone, were involved in about 3 of every 4 pharmaceutical overdose deaths (16,651).” It’s far higher now. A CDC report stated that one in every 20 U.S. adults has a history of [opioid] use – not abuse, but use.

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Monitor risk, yes, but that should not get all the investment. Many addicts would not be there if there were better treatments for pain, if they had not been given opioids after a minor procedure or injury that is better treated with real therapy, not drugs.

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People with pain do not mention the pain has taken their lives. We may see them as weak. That young child with fractures on the ball field is going to need the best care so pain does not become chronic. Give him or her opioids and opioids cause pain, pain becomes worse, intractable before the 6th grade. That is not an addict, but that child and his or her parents are often treated like addicts, at least with suspicion, drug seeking. What is best for that child with chronic pain when she becomes pregnant? When nursing? Think of our young veterans, some with 3 or 4 different pains, and each type addressed differently. What if either of them was an addict before the pain? If we don’t treat them, they will turn to drugs. What are the best, most efficient, options for treatment of intractable pain? When will we learn? We need to identify and treat before it becomes chronic.

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Chronic pain can be reduced or eliminated in many situations now even possibly without drugs, provided the issue is properly identified – and that will never happen until providers are educated in how to identify first class physical therapy. Further research will help to release persons with intractable pain from the prison that too often makes them feel that life is unbearable and that they can more easily face death. We all need to wake up to this situation.

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If we continue to passively allow nothing to be done, then there may be nothing to help us when we fall into the sudden bind of intractable pain when we wake up one day with shingles or a pinched nerve or when pain of the face prevents us from eating or sleeping or speaking or even wanting to live. It will be too late.

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Sharp like a razor’s edge is the path,
The sages say, difficult to traverse.

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Shall we let those we love hang on the edge while we fail to move this multi-tentacled monster forward? How do we light the fire that enables us to solve this fearful fragmentation of choices?

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See how beautifully it works when the right combinations are brought together?

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Yellow rose blue hibiscus

 

 

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~
This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please ignore the ads below. They are not from me.

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Ketamine – small doses work in depression and bipolar disorder


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Everyone is very edgy right now with depression. Media is sensationalizing, which is the worst thing to do. I even hesitate to write this now.

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Ketamine really does work

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Small doses may be all that’s needed. Even large doses are safe.

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Two Cases

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I hate to play on emotion that is strong right now, but Robin Williams might be alive today if his doctors prescribed ketamine nasal spray.

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Every one, doctors and patients alike, worry about ketamine. It sells newspaper headlines and distorted media coverage that then overtakes the life saving stories of its profound safety when used under good medical supervision. Experience helps.

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Two cases from yesterday and today really must be shared. These two patients would not be alive today if they did not have ketamine nasal spray for their depression.

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I don’t mean to say every one will respond to these extremely tiny doses, but it’s always exciting to hear the effective dose is simply so small.

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These details would make good case reports if time permitted, but there is never enough time. I wanted simply to say a few things now because these two patients were seen.

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**1**

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In May 2014, saw a fifty-ish woman who is now responding to 20 mg (4 nasal sprays) given as one dose every 48 hours. She has been treated at well known university psychiatry departments, failed ECT 9 or 10 times – memory loss was so bad she got lost in her own neighborhood. Received IV ketamine once or twice weekly for one year before I saw her.

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Diagnoses:  dysthymia as long as she can remember, and 25 years of Major Depressive Disorder, PTSD, anxiety, etc. Olympic level athlete —

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**2**

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Second patient now in late teens, Juvenile Bipolar Disorder/Fear of Harm phenotype, profound thermoregulatory changes respond in seconds to ketamine, dose of 10 mg nasal spray every 3 days. That’s it! Temperature responds in seconds, and the depression responds in 10 minutes in her case. She was so violent before treatment that she had been hospitalized 7 times in 2-1/2 years. Doing very very well. And the low dose naltrexone, by the way, is involved in thermoregulation.

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I should mention, no side effects whatsoever. I have never seen toxicity. I watch kidney and bladder function meticulously, and patients with massive pain on very high doses have never had any organ toxicity.

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NEURO-INFLAMMATION AND GLIA – brain on fire.

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I mention Olympic athlete because so many people I see with Complex Regional Pain Syndrome – the pain that so often leads to suicide, seems to occur more often in top level athletes, either state or national level, professional or sponsored in their teens. Yes, they occur in others, but there is a striking predominance in athletes for unknown reasons.

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Glia are triggered by trauma, then they become activated and produce pro-inflammatory cytokines. Inflammation is out of balance. Ketamine profoundly reduces the pro-inflammatory cytokines, and so does low dose naltrexone. I write about these mechanisms with more frequency that anything else. This is what we must address – the brain is essentially “on fire.” And this inflammation, these pro-inflammatory cytokines, are involved in almost every known disease: Alzheimer’s disease, Parkinson’s disease, ALS, chronic pain, major depressive disorder, cancer, autoimmune disease, and atheroscloerosis.

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Inflammation kills. Unfortunately this new research on glia and inflammatory diseases, these diseases could be called gliopathies, all based on new research since the turn of the century. We now know glia are your innate immune system in brain and spinal cord. They need a balance the anti-inflammatory cytokines with the pro-inflammatory cytokines. Inflammation may be lifesaving when you have caught a virus, but not as a steady diet. Give the brain a break or it leads to hyperexcitable glutamate that triggers calcium flooding into the neuron, cell death, brain atrophy and memory loss. Seen in people with Major Depression and those with chronic low back pain.

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Do doctors know about the innate immune system? or the receptor that won the Nobel Prize 2 and 1/2 years ago? or glia?

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Answer: no.

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Papolos et al have published Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype

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Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated.

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Dr. Papolos’ video on treatment points out, ketamine nasal spray is off-label

for Bipolar Disorder. And I add, ketamine is off-label for pain and for major depression.

He posts this:

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PUBLIC WARNING

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Public Warning: Ketamine is a controlled substance.

Administered improperly, or without the guidance of a qualified doctor,

Ketamine may cause injury or death.

No attempt should be made to use Ketamine

in the absence of counsel from a qualified doctor.

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“Off label” means it is FDA approved for another purpose, but he prescribes it for Juvenile Bipolar Disorder. I would add that in qualified hands, ketamine is one of the safest medications we have in our formulary.

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More later, as time permits.

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PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
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Ketamine is a controlled substance.
Administered improperly, or without the guidance of a qualified doctor,
Ketamine may cause injury or death.
No attempt should be made to use Ketamine
in the absence of counsel from a qualified doctor..

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The material on this site is for informational purposes only.

It is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

~~~~~

Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

.

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Neuroimmunology’s Future – Bioelectronics Treats TNF Diseases – Will replace drug industry


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This is an earth changing, once in a century paradigm shift in medicine.

TNF Alpha Diseases

Bioelectronics reduces TNF alpha

Inflammatory Diseases treated without drugs.

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A novel therapy, never done before, is now in clinical trials with Rheumatoid Arthritis patients and it is working well  – with no medication. Electrical stimulation is reducing TNF-alpha, the inflammatory cytokines that underlie many diseases including pain, cancer, autoimmune diseases and major depression. This is a completely new field of medicine reported by The New York Times Magazine. I strongly recommend reading the entire article as I have only a small clip below.

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Several of the foremost neuroscientists are involved with this, starting with the research of Kevin Tracy in 1998 who proved that stimulating the vagus nerve with electricity would alleviate harmful inflammation. He is a neurosurgeon and President of the Feinstein Institute for Medical Research in Manhasset, N.Y.

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Today researchers are creating implants that can communicate directly with the nervous system in order to try to fight everything from cancer to the common cold. “Our idea would be manipulating neural input to delay the progression of cancer,” says Paul Frenette, a stem-cell researcher at the Albert Einstein College of Medicine in the Bronx who discovered a link between the nervous system and prostate tumors….

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The list of T.N.F. diseases is long,” Tracey said. “So when we created SetPoint” — the start-up he founded in 2007 with a physician and researcher at Massachusetts General Hospital in Boston — “we had to figure out what we were going to treat.” They wanted to start with an illness that could be mitigated by blocking tumor necrosis factor and for which new therapies were desperately needed. Rheumatoid arthritis satisfied both criteria. It afflicts about 1 percent of the global population, causing chronic inflammation that erodes joints and eventually makes movement excruciating. And there is no cure for it.

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In September 2011, SetPoint Medical began the world’s first clinical trial to treat rheumatoid-arthritis patients with an implantable nerve stimulator based on Tracey’s discoveries. According to Ralph Zitnik, SetPoint’s chief medical officer, of the 18 patients currently enrolled in the ongoing trial, two-thirds have improved. And some of them were feeling little or no pain just weeks after receiving the implant; the swelling in their joints has disappeared. “We took Kevin’s concept that he worked on for 10 years and made it a reality for people in a real clinical trial,” he says….

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…The biggest challenge is interpreting the conversation between the body’s organs and its nervous system, according to Kris Famm, who runs the newly formed Bioelectronics R. & D. Unit at GlaxoSmithKline, the world’s seventh-largest pharmaceutical company. “No one has really tried to speak the electrical language of the body,” he says. Another obstacle is building small implants, some of them as tiny as a cubic millimeter, robust enough to run powerful microprocessors. Should scientists succeed and bioelectronics become widely adopted, millions of people could one day be walking around with networked computers hooked up to their nervous systems. And that prospect highlights yet another concern the nascent industry will have to confront: the possibility of malignant hacking. As Anand Raghunathan, a professor of electrical and computer engineering at Purdue, puts it, bioelectronics “gives me a remote control to someone’s body.”

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Glaxo has also established a $50 million fund to support the science of bioelectronics and is offering a prize of $1 million to the first team that can develop an implantable device that can, by recording and responding to an organ’s electrical signals, exert influence over its function. Instead of drugs, “the treatment is a pattern of electrical impulses,” Famm says. “The information is the treatment.” In addition to rheumatoid arthritis, Famm believes, bioelectronic medicine might someday treat hypertension, asthma, diabetes, epilepsy, infertility, obesity and cancer. “This is not a one-trick pony.”

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…The subjects in the trial each underwent a 45-minute operation. A neurosurgeon fixed an inchlong device shaped like a corkscrew to the vagus nerve on the left side of the neck, and then embedded just below the collarbone a silver-dollar-size “pulse generator” that contained a battery and microprocessor programmed to discharge mild shocks from two electrodes. A thin wire made of a platinum alloy connected the two components beneath the skin. Once the implant was turned on, its preprogrammed charge — about one milliamp; a small LED consumes 10 times more electricity — zapped the vagus nerve in 60-second bursts, up to four times a day. Typically, a patient’s throat felt constricted and tingly for a moment. After a week or two, arthritic pain began to subside. Swollen joints shrank, and blood tests that checked for inflammatory markers usually showed striking declines.

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Koopman told me about a 38-year-old trial patient named Mirela Mustacevic whose rheumatoid arthritis was diagnosed when she was 22, and who had since tried nine different medications, including two she had to self-inject. Some of them helped but had nasty side effects, like nausea and skin rashes. Before getting the SetPoint implant in April 2013, she could barely grasp a pencil; now she’s riding her bicycle to the Dutch coast, a near-20-mile round trip from her home. Mustacevic told me: “After the implant, I started to do things I hadn’t done in years — like taking long walks or just putting clothes on in the morning without help. I was ecstatic. When they told me about the surgery, I was a bit worried, because what if something went wrong? I had to think about whether it was worth it. But it was worth it. I got my life back.”

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Prostate Cancer – Exercise Cuts Inflammatory Cytokines IL-6 & IL-8, reduces psychological distress


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American Society of Clinical Oncologists (ASCO) in Chicago yesterday report on exercise reducing psychological distress. Whether cancer outcome will be impacted is not yet known and will require study but inflammation may impact cancer progression.

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The usual treatments change metabolism, cause weight gain, “loss of lean muscle mass, change[s] lipids, increase[s] rates of diabetes, and it thins bones.”

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Exercise is even more critical in those undergoing hormone therapies.

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This was a small randomized study for seven weeks.

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Patients receiving usual care experienced a 0.08 log10 increase in pro-inflammatory interleukin-6 production, while patients treated with an exercise program experienced a 0.03 log10 decrease in IL-6 (P<0.05), said Charles Kamen, PhD, research assistant professor at the University of Rochester Medical Center in New York.

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In his oral presentation … Kamen and colleagues observed a similar relationship with another pro-inflammatory cytokine, interleukin-8. In the control patients, the researchers noted a 0.03 log10 increase compared with a 0.04 log10 decrease among the exercise group, Kamen said.

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Using the Profile of Mood States (POMS), the research team determined that psychological distress decreased 5.17 points among the exercise group but increased 2.43 points in the patients who were in the usual control group (P=0.02).

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“This study supports the use of exercise for cancer patients for reducing psychological distress and suggests a potential biological mechanism by which this improvement occurs, namely by reducing systemic inflammation,” Kamen said in his presentation….

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The POMS scores were overall significantly in favor of the exercise group, and the subscales all trended in favor of exercise, except for the anger subscale in which there was virtually no change, Kamen said.

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PEA Palmitoylethanolamide – “Glia & Mast Cells as Target, An Anti-Inflammatory & Neuroprotective Lipid Mediator”


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Another oustanding article on palmitoylethanolamide “PEA.” I have seen profound results with it relieving intractable neuropathic pain in a woman with CRPS for years, and I suspect it may help Major Depressive Disorder but that remains to be tested.

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I need to add that opioids create pain. One mechanism by which that occurs is that opioids create pro-inflammatory cytokines, which creates more pain. Patients may see no response to essential pain relieving medications untill they taper off all opioids and allow the system to stabilize. Otherwise, they will have pain forever and it may increase.

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Glia and mast cells as targets for palmitoylethanolamide,

an anti-inflammatory and neuroprotective lipid mediator

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Authors  Skaper SD, Facci L, Giusti P.

Mol Neurobiol. 2013 Oct;48(2):340-52.  Epub 2013 Jun 28.

Abstract

Glia are key players in a number of nervous system disorders. Besides releasing glial and neuronal signaling molecules directed to cellular homeostasis, glia respond also to pro-inflammatory signals released from immune-related cells, with the mast cell being of particular interest. A proposed mast cell-glia communication may open new perspectives for designing therapies to target neuroinflammation by differentially modulating activation of non-neuronal cells normally controlling neuronal sensitization-both peripherally and centrally. Mast cells and glia possess endogenous homeostatic mechanisms/molecules that can be upregulated as a result of tissue damage or stimulation of inflammatory responses. Such molecules include the N-acylethanolamines, whose principal family members are the endocannabinoid N-arachidonoylethanolamine (anandamide), and its congeners N-stearoylethanolamine, N-oleoylethanolamine, and N-palmitoylethanolamine (PEA). A key role of PEA may be to maintain cellular homeostasis when faced with external stressors provoking, for example, inflammation: PEA is produced and hydrolyzed by microglia, it downmodulates mast cell activation, it increases in glutamate-treated neocortical neurons ex vivo and in injured cortex, and PEA levels increase in the spinal cord of mice with chronic relapsing experimental allergic encephalomyelitis. Applied exogenously, PEA has proven efficacious in mast cell-mediated experimental models of acute and neurogenic inflammation. This fatty acid amide possesses also neuroprotective effects, for example, in a model of spinal cord trauma, in a delayed post-glutamate paradigm of excitotoxic death, and against amyloid β-peptide-induced learning and memory impairment in mice. These actions may be mediated by PEA acting through “receptor pleiotropism,” i.e., both direct and indirect interactions of PEA with different receptor targets, e.g., cannabinoid CB2 and peroxisome proliferator-activated receptor-alpha.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Palmitoylethanolamide (PEA) – Boosting Its Anti-inflammatory Immune Response


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Discovery could lead to new immune-response drugs for allergies, illnesses and injuries

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Improved spinal cord injury & inflammation in mice

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Medical news November 17, 2009, announced that “UC Irvine pharmacology researchers have discovered a way to boost levels of a natural body fat that helps decrease inflammation, pointing to possible new treatments for allergies, illnesses and injuries related to the immune system.”

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“For decades, it has been known that this fat, called palmitoylethanolamide (PEA), is a potent anti-inflammatory substance that reduces both allergic symptoms and occurrences of rheumatic fever, but researchers understood little about how PEA works.”

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I”n a study appearing online in the Proceedings of the National Academy of Sciences, Daniele Piomelli, the Louise Turner Arnold Chair in Neurosciences at UCI, and colleagues found that levels of PEA are tightly regulated by immune system cells. In turn, PEA helps control the activity of these cells, which are called into action to fight infection, disease and injury in the body.”

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They found a protein, an enzyme that breaks down molecules that control cell inflammation and deactivates PEA. They then created a novel compound that prevents the breakdown.

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“When given to rodents, the compound increased the levels of PEA in their immune cells and reduced the amount of inflammation elicited by an inflammatory substance. Furthermore, when administered to the spinal cords of mice after spinal cord injury, the compound decreased inflammation associated with the trauma and improved the recovery of motor function.”

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UCI is collaborating with the Italian Institute of Technology in Genoa to develop a range of immune-response drugs. 

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Source: University of California – Irvine

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Refer an earlier post on PEA here.

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Palmitoylethanolamide is sold as PeaPure, a food supplement, available from the Netherlands and imported by a local pharmacy here. I have submitted a paper for publication on the treatment of vulvodynia and proctodynia with PeaPure and a topical cream. That source will be posted once it is accepted.

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I have been seeing some exciting responses to treatment of intractable pain with PeaPure. I invite others who use it to add comments below so that we may all learn from your experience.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~~~~

Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Oxytocin, Astrocytes, Modification of Amygdala Circuits and Pain – IASP Early Research Career Grant Report


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As a physician who prescribes Oxytocin [OT] and sees profound relief of many forms of intractable pain and/or relief of treatment refractory Major Depressive Disorder or Anxiety and Panic Disorder, this research on mechanisms is deeply meaningful and long awaited. Oxytocin is a hormone made in the brain, but also in the heart and other organs in women and men. It is rare to find work on glia and oxytocin.

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Today the International Association for Study of Pain announced the final report from their 2012 Early Research Career Grant:

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“Dr. Alexander Charlet of the Centre National de la Recherche Scientifique (CNRS) in Strasbourg, France, has submitted his final report for his project “Involvement of astrocytes in the endogenous oxytocin modification of amygdala microcircuits….”

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“Dr. Charlet’s project focuses on the functional consequences of endogenous OT release in amygdala microcircuits on nociception and pain. In addition, he aims to decipher the precise mechanism, cellular and molecular, by which OT exerts its action. Thus, the purposes of his project are to characterize in vivo and in vitro the effects of endogenous OT in the amygdala on pain-related symptoms….

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.….”In addition, he was surprised to discover that perceptions of his project’s importance grew once it was awarded and triggered future collaborations: a Marie Curie European Action Career Integration Grant and the French Initiative d’Excellence Attractivity.”

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“As a result, Dr. Charlet also received two major personal prizes: an award from Swiss Society for Biological Psychiatry in 2012 and award from the French Académie nationale de medicine with the prestigious Albert Sézary price in 2013. Finally, he has been recruited as a neurosciences permanent researcher by the CNRS and recently opened his independent lab.”

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~~~~

Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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PeaPure – Palmitoylethanolamide for Nerve Pain or Migraine


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PeaPure is a glial modulator. It is available in Italy and the Netherlands as a food supplement and has been studied in multicenter clinical trials in Europe for several years. It is well tolerated with no side effects and is very helpful for neuropathic pain, headache, and osteoarthritis. It is anti-inflammatory and neuroprotective.

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Because it inhibits astrocyte activation and the over-expression of pro-inflammatory molecules and signals, it is being investigated in Alzheimer’s Disease.

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The mechanism of action of PEA was discovered in 1993 by Nobel laureate Rita Levi-Montalcini in her work on nerve growth factors. She found it is involved in metabolism of mast cells and published a series of papers on its self-healing effect of the body in response to inflammation and pain. Two recent publications from Jan M Keppel Hesselink, MD, PhD, and his colleagues at the Institute for Neuropathic Pain, Amsterdam, The Netherlands, describe case reports, one of which is the case of a woman with CRPS.

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The purpose of this post is to clarify dosing of PeaPure and how to take it for a sudden flare of pain. My apologies for failing to recall the source of these instructions which I believe was from the manufacturer and from here and here. The latter includes an excellent review of its mechanism.

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Description of PeaPure® 400 mg capsules
PeaPure® is a food supplement based on a natural and fatty-acid like compound.
The substance palmitoylethanolamide (PEA) is a physiologically active molecule that the body produces naturally.
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What the user should know prior to ingestion:
•    There are no known significant side effects.
•    PeaPure® can be taken simultaneously with other medicine. In case of doubt, it is recommended to first consult your doctor or a pharmacist.
•    Use during pregnancy is NOT recommended.
•    PeaPure® does not contain sugar, yeast, allergens, sorbitol, magnesium stearate, povidone or other ingredients.

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Dosage and administration – please refer to the manufacturer.

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UPDATE SEPTEMBER 2014

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It is with a heavy heart that I report this news:

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Palmitoylethanolamide is

now available only from the Netherlands,

sold as PeaPure, a food supplement.

  It is no longer able to be imported by a pharmacy, but we are hoping

that may change if we can interest a supplement manufacturer to make it available for the US.

Patent rights, attorneys are far beyond the resources of my local pharmacy.

 

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I have published this year, 2014, on the treatment of

vulvodynia and proctodynia with PeaPure and a topical cream.

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There are no studies to show us how often it may relieve nerve pain, but it is astonishing when it works. No toxicity, no side effects. Your brain makes it, plants make it. There is a growing literature on it and I have posted on some of its mechanisms. And in particular, its Anti-inflammatory, Analgesic, Neuroprotective Mechanisms.

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The material on this site is for informational purposes only, and is not a substitute for

medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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RSD/CRPS, Multiple Sclerosis, LDN & Ketamine


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It is rare for me to see a patient who is not complex.

They have failed so many treatments for so many years before they call.

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This is the report of a lovely woman in her early 70’s with progressive Multiple Sclerosis for 30 years and paraplegia that has forced her to use an electric scooter the last 5 years, and power wheelchair the last 2o years. Because of total paralysis of the right lower limb, she fell and shattered her femur, the thigh bone, in August 2009. Tragically, and all too often, the surgeon failed to diagnose Complex Regional Pain Syndrome [CRPS], even failed to visit her in the hospital. CRPS increased the fatigue she had already had from Multiple Sclerosis.

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Thankfully a physical therapist suggested the diagnosis.

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Why is pain management not a required subject for physicians?

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I have written elsewhere that the American Pain Society discovered that our National Institute of Health, NIH, devotes less than half of 1% of their research dollar to pain research. Of 28 NIH institutes, none for pain, three for addiction. This will not change soon. The only hope is that RSDSA.org will succeed in collaborating with all pain organizations, groups with dystonia, chronic fatigue in order to give a voice and research dollar to advances.

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Before seeing me in September, she had 11 sympathetic blocks with no benefit.

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Does it make you wonder why 11 were done?

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How does insurance authorize 11 when 10 had no benefit? I have just learned that a doctor must indicate at least 50% relief before another will be authorized. That explains it.

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Then she was given opioids including tramadal and Butrans patch which rendered her a “zombie,” sedated, poor memory, unable to function. She tried 4 or 5 treatments of Calmare with no benefit but was advised she needed a clear neural pathway for it to work. That was not possible due to the Multiple Sclerosis.
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Lyrica caused severe edema. Gabapentin 1400 mg/day caused weight gain, increased her appetite  more than usual, but she remained on it. She craves sweets more than usual, at times uncontrollably. Perhaps it can be slowly tapered now. Advil 600 mg gave some benefit but caused ulcers that required Nexium.

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Since her initial visit a few weeks ago, she became 60% better during her two week stay.

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I will highlight only two of the new medications started.

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It may also be said that opioids are not the answer.

Opioids may perpetuate pain.
They may produce paradoxical pain or opioid induced hyperalgesia or windup.

They may block the effect of ketamine and other adjuvants that would otherwise lower pain.

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Of importance is that she was not able to tolerate clothing on her right lower limb for three years, not even a sheet, and now she is able to sleep through the night without pain for the first time in three years and able to wear a skirt. This allows her to go out with family to restaurants and even to enjoy shopping with her daughter. Her dose of ketamine is very small relative to most of my patients and she uses it only once or twice a day since most of the new medications have brought her pain down.

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At her first visit one month ago, she rated pain from 6 to 8 on a scale of 10, average 7/10. Now 60% better, ranging from zero to 7, average 4. Yes zero pain, sleeping through the night without pain and waking without pain. She had not been able to tolerate touch to the right thigh or foot and would pull her skirt above the thigh, removing her shoe.

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Now she indicates pain continues to improve.

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Of interest, despite an abundance of concern that low dose naltrexone [LDN] may flare her Multiple Sclerosis, we were easily able to increase the dose to triple what is usually called “LDN.” This did not flare her condition and may be one of the most effective medications she is taking for pain.

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What is LDN?

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The FDA has sanctioned its use in the USA only in doses of 50 to 400 mg for addiction to opioids and alcohol.

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Low dose naltrexone [LDN] is a fascinating medication. It has been used in low dose in persons with Multiple Sclerosis since 1985 when a Harvard trained neurologist in New York City, Dr. Bihari, first discovered that it relieved all disability in some patients with Multiple Sclerosis and prevented recurrent attacks. Since then, doctors in Scotland, where they have the highest incidence of Multiple Sclerosis, find that one of the earliest signs of recovery in this population is relief of neurogenic bladder. It is said that persons with Multiple Sclerosis must remain on LDN for 1.5 years before they might fully assess its value.

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 Multiple Sclerosis may be flared unless very small doses of LDN are used.

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Many with Mulitple Sclerosis cannot tolerate more than 2 or 3 mg, perhaps due to spasticity. There is a great deal of dogma on the web about its mechanism, dosing and timing for off label use. Use the search function on this site to review the prior discussions I posted on LDN, MS, CRPS.

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Naltrexone is a glial modulator.

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What’s that?!

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By serendipity, four years ago I discovered naltrexone in low dose may relieve chronic intractable pain. I had been using it for perhaps eight years in microgram doses but I found in milligram doses it is even more profound.

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The mechanism of naltrexone and a wee bit of glial research is discussed here. The Nobel Prize was awarded last year for the discovery that these glia are your innate immune system. They are profoundly important in many diseases including chronic pain, Major Depression, Multiple Sclerosis, Alzheimers, Parkinsons Disease, ALS, Autism. They produce inflammatory cytokines that lead to inflammation.

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Now that she has been home for two weeks, on a number of medications that I started, not just the ketamine and LDN, I hope she will comment on her experience and her progress since flying back to the east coast after her brief visit here.

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It is often essential to taper off opioids to allow other medication to work.

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I feel she was able to benefit from these low doses of medication because she tapered off all opioid medication prior to her visit, thus allowing her system to recover and respond to these medications. We will know more in the next few months as she slowly titrates up on some of the medications that were started.

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Next year on her return, we may be able to withdraw some of the medications depending on how well she is doing.

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Finally, ketamine does cause her to have brief side effects. Her husband likens the effect the same as half a glass of wine: “She’s really cute.” Thankfully, most people have no side effects and if they do, they rarely last more than 20 minutes.

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She sends an update below, 80 to 90% better. Hopefully this will continue to improve over the next months as she slowly increases the medication we started. And ketamine has an additive effect in some. It is anti-inflammatory.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

.

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Ketamine Intranasal for Rapid Relief of Pain and Depression


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Poorly managed pain can evolve into chronic disease of the nervous system

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Ketamine is an important analgesic, more important than opioids. It can dramatically reduce pain, and rapidly relieve depression and PTSD.  Please read my earlier posts here and here. And the NPR report here just after I posted this (skip to their last section). Yes, it is FDA approved and legal. One woman said:

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 ‘It was almost immediate, the sense of calmness and relaxation.

‘No more fogginess. No more heaviness. I feel like I’m a clean slate right now. I want to go home and see friends or, you know, go to the grocery store and cook the family dinner.’

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NPR again reports ketamine’s rapid relief of depression. A 28 year old man whose refractory depression began at age 15, after ketamine, says:

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‘I Wanted To Live Life’

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Stephens himself has vivid memories of the day he got ketamine. It was a Monday morning and he woke up feeling really bad, he says. His mood was still dark when doctors put in an IV and delivered the drug.”Monday afternoon I felt like a completely different person,” he says. “I woke up Tuesday morning and I said, ‘Wow, there’s stuff I want to do today.’ And I woke up Wednesday morning and Thursday morning and I actually wanted to do things. I wanted to live life.”.
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Since then, they treated him with Riluzole that is FDA approved for ALS and has one of the dirtiest side effect profiles I have ever seen in medicine with serious organ toxicity. Ketamine rarely causes mild transient side effects, usually none. It appears the concern is how ketamine is used on the street with potential for abuse. I do not see ketamine abuse in my patients, some of whom are on opioids for pain or Valium family medicines from their psychiatrist. All of those have a greater potential for abuse, also not occurring in my patients. Pain and/or depression can lead to suicide.
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About 18 months ago, researchers at Yale found a possible explanation for ketamine’s effectiveness. It seems to affect the glutamate system in a way that causes brain cells to form new connections.
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Researchers have long suspected that stress and depression weaken some connections among brain cells. Ketamine appears to reverse the process.

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It would be of interest to see a case report of the bladder problems they mention. Is this in a single drug addict who used many unknown medications on the street? Several physicians have infused IV ketamine for persons with pain for many years, in far higher doses than I prescribe, with no report of any but transient minor symptoms.

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David Barsook’s 2009 review, reference below, describes changes that cause memory loss and brain atrophy with chronic pain, in particular, Complex Regional Pain Syndrome (CRPS), and they also occur with chronic depression:

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With the onset of chronic pain (including CRPS) a number of changes in brain function occur in the human brain including but not limited to: (1) central sensitization ; (2) functional plasticity in chronic pain and in CRPS; (3) gray matter volume loss in CRPS ; (4) chemical alterations; and (5) altered modulatory controls. Such changes are thought to be in part a result of excitatory amino acid release in chronic pain. Excitatory amino acids are present throughout the brain and are normally involved in neural transmission but may contribute to altered function with excessive release producing increased influx of calcium and potentially neural death.

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Brain atrophy and memory loss has also been shown in chronic low back pain as well as in chronic depression.

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Barriers to management of chronic pain are many:

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Although opioids are effective for acute pain, effective treatment of chronic pain is often daunting, particularly neuropathic pain.

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Opioids have been shown to create pain causing imbalance in the glial cytokines that favor pain rather than relief of pain. Opioids carry the risk of opioid-induced hyperalgesia which is a severe pain sensitivity. They affect the brain and endocrine system. Opioids may fail to offer significant relief, fail to improve function, and risk misuse, abuse, diversion and death. Their costs are astronomic, insurance coverage is increasingly limited, the potential for complications may be life threatening in a hectic medical setting, side effects can be lethal, lack of physician training in use of opioids and alternatives to pain control lead to increasing deaths, addiction and diversion. It has become a national emergency and a trillion dollar war on drugs.

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Complications can be greatly reduced through use of a scrupulous history and physical examination, but reimbursement is directly proportional to the shortest time spent with a patient. Will that help assessment and care?

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Individuals may have dramatically different responses to opioid therapy; some may not tolerate any, and relief must be balanced with side effects that increase as the dose increases. Patient status may change and require IV, rectal or tube delivery instead of oral formulas; drug-drug interactions may require rapid changes, and disease of kidney, liver or brain may require modifications or stopping altogether. They may increase risk of falls and cause central sleep apnea with drop in oxygen because the brain fails to give a signal to breathe.

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Chronic pain can lead to loss of sleep, hopelessness, depression, anger and other mood disorders such as panic, anxiety, hypochondriasis and post traumatic stress disorder [PTSD]. Treatment of mood disorders are shown to profoundly reduce pain perception and/or ability to cope with pain.

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Ketamine is anti-inflammatory and can reduce the need for opioid use, thus reducing the pain and side effects caused by opioids.

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Nasal ketamine is more effective than oral ketamine for pain relief; oral dosing has no effect on depression.

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Nasal delivery of ketamine is now possible due to advances in metered nasal sprayers that deliver a precise dose. No needle is required, no IV access, no travel to a specialist needed.

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You can carry pain relief with you and use it as directed when it is needed.

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Ketamine is an NMDA antagonist: it antagonizes the NMDA receptor which plays a profound role in pain systems and centralization of pain.

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Ketamine is neuroprotective and it can help other disease states as noted by Barsook, 2009:

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Besides improvement in pain, “there may be lessons from other diseases that affect the brain; it is noteworthy that acute ketamine doses seem to reverse depression and ketamine decreased prevalence of post-traumatic stress disorder (PTSD) in soldiers receiving ketamine during their surgery for treatment of their burns. In addition ketamine attenuates post-operative cognitive dysfunction following cardiac surgery that has been known to produce significant changes in cognition. [emphasis mine] The data suggest that the drug can alter or prevent other conditions based on its NMDAR activity where other drugs NMDA receptor antagonists are perhaps not as effective in these or pain conditions. Lastly, NMDA antagonists have been used in degenerative disease (and pain may be considered a degenerative disease as defined by loss of gray matter volume, see above) with mixed effects perhaps relating to how they act on specific NMDA subtypes. Taken together, ketamine may act not only on sensory systems affecting pain intensity, but also on a constellation of brain regions that are involved in the pain phentype. [sic, phenotype]”

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Side Effects

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Ketamine is more frequently used in babies and children than in adults because high doses of ketamine can induce hallucinations in the adult. Importantly, it is used in high dose in adults for treatment of Complex Regional Pain Syndrome.

Low doses, cause little or no side effects in adults. If present, they are transient and often resolve in 20 minutes. Patient who respond to ketamine report good acceptance as they find the relief of pain and/or depression far outweighs any short term minimal discomfort.

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Pain care reform is urgently needed.

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Research funding for pain is less than half of one percent of the NIH budget. More research is needed, but research on low dose ketamine for treatment of pain and depression has gone on for twenty years.

The public health crisis of untreated pain, which often results in disability, parallels the country’s struggle to halt the cost of health care. The longer a person remains with untreated pain, the less likely they are to return to work or to be employable.

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Conclusion

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Pain control requires urgent attention. It is past time to put into practice the use of this valuable medication so people can get on with life instead of being mired in chronic pain that for many risks suicide and ensures continuing decades of disability. Academic studies are usually limited by defining a predetermined dose rather than clinically titrating to effect. Thus no surprise, they find no effect as every patient will have no response until they reach their dose. And that dose, in my experience, falls into a bell shaped curve. One size does not fit all. Some respond at very low dose, others require much more, and the majority fall between.

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In my experience prescribing ketamine for ten years, only a rare person has problems. Almost all find it has returned function or significantly relieved pain. Some have been able to entirely eliminate opioids that did nothing for their pain for decades, though they dutifully returned to the MD every month to chronicle that pain. Pain continued to be rated ten on a scale of ten; patient always compliant despite side effects of constipation and often depression. My patients find the benefits of nasal ketamine far outweigh the relief of oral ketamine and at much lower doses with fewer side effects.

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Further, while the pain relief may be short lived, some find it gets better with repeat dosing, and relief of depression may last one to two weeks with a single dose.

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References

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http://www.wjgnet.com/1007-9327/10/1028.asp  Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats.

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CONCLUSION: Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-a and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.

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http://informahealthcare.com/doi/abs/10.1080/J354v16n03_03  Ketamine as an Analgesic Parenteral, Oral, Rectal, Subcutaneous, Transdermal and Intranasal Administration

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Ketamine is a parenteral anesthetic agent that provides analgesic activity at sub-anesthetic doses. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with opioid receptor activity. Controlled studies and case reports on ketamine demonstrate efficacy in neuropathic and nociceptive pain. Because ketamine is a phencyclidine analogue, it has some of the psychological adverse effects found with that hallucinogen, especially in adults. Therefore, ketamine is not routinely used as an anesthetic in adult patients. It is a frequently used veterinary anesthetic, and is used more frequently in children than in adults. The psychotomimetic effects have prompted the DEA to classify ketamine as a Schedule III Controlled Substance. A review of the literature documents the analgesic use of ketamine by anesthesiologists and pain specialists in patients who have been refractory to standard analgesic medication regimens. Most reports demonstrate no or mild psychotomimetic effects when ketamine is dosed at sub-anesthetic doses. Patients who respond to ketamine tend to demonstrate dramatic pain relief that obviates the desire to stop treatment due to psychotomimetic effects (including hallucinations and extracorporeal experiences). Ketamine is approved by the FDA for intravenous and intramuscular administration. Use of this drug by the oral, intranasal, transdermal, rectal, and subcutaneous routes has been reported with analgesic efficacy in treating nociceptive and neuropathic pain.
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http://www.ncbi.nlm.nih.gov/pubmed/15109503  Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study  Daniel Carr, et al, 2004
Crossover, 20 patients. Ketamine reduced breakthrough pain within 10min of dosing, lasting up to 60min
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http://www.ncbi.nlm.nih.gov/pubmed/15288418  Safety and efficacy of intranasal ketamine in a mixed population with chronic pain
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The intranasal route for ketamine administration has been applied only for pain of dressing changes in a single case study (Kulbe, 1998). In this patient, oxycodone and acetaminophen were ineffective to control pain during burn dressing changes in a 96-year-old woman cared for at home. She tolerated the burn dressing changes after three intranasal sprays of 0.1 ml each, in rapid succession, each containing 5 mg ketamine (15 mg total) (Kulbe, 1998).
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http://www.acutepainjournal.com/article/S1366-0071%2807%2900167-2/abstract  Safety and efficacy of intranasal ketamine for acute postoperative pain
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Ketamine delivered intranasally was well tolerated. Statistically significant analgesia, superior to placebo, was observed with the highest dose tested, 50 mg, over a 3 h period. Rapid onset of analgesia was reported (<10 min), and meaningful pain relief was achieved within 15 min of the 50 mg dose. The majority of adverse events were mild/weak and transient. No untoward effects were observed on vital signs, pulse oximetry, and nasal examination. At the doses tested, no significant dissociative effects were evident using the Side Effects Rating Scale for Dissociative Anaesthetics.
The safety profile following treatment with ketamine was comparable to that seen with placebo.
Although patients did report side effects of fatigue, dizziness and feelings of unreality more often following treatment with ketamine than following treatment with placebo, no patient reported hallucinations and the side effects were generally reported to be of mild or moderate severity, and transient. No serious adverse events were reported and the incidences of associated adverse events were comparable for ketamine and placebo. Although study medication was administered intranasally, nasal signs and symptoms were few and inconsequential. A distinctive taste, however, was reported more often following treatment with ketamine than following treatment with placebo.In conclusion this randomized, placebo-controlled, double-blind study, in 20 patients, has demonstrated that intranasal ketamine is safe and effective for BTP [breakthrough pain]. Our findings augment an early but promising literature documenting the effectiveness of nasal administration of a variety of opioids for pain management in adults (Dale et al., 2002) .
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~http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875542/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875542/  Ketamine and chronic pain – Going the distance, David Barsook, 2009

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This important paper covers essential points not mentioned by many, thus quoted at length below:

“Ketamine, brain function and therapeutic effect – neuroprotective or neurotoxic

With the onset of chronic pain (including CRPS) a number of changes in brain function occur in the human brain including but not limited to: (1) central sensitization ; (2) functional plasticity in chronic pain and in CRPS; (3) gray matter volume loss in CRPS ; (4) chemical alterations ; and (5) altered modulatory controls. Such changes are thought to be in part a result of excitatory amino acid release in chronic pain. Excitatory amino acids are present throughout the brain and are normally involved in neural transmission but may contribute to altered function with excessive release producing increased influx of calcium and potentially neural death. Here lies the conundrum the use of an agent that potentially deleteriously affect neurons that may already be compromised but may also have neuroprotective properties by mechanisms that include reducing phosphorylation of glutamate receptors resulting in decreased glutamatergic synaptic transmission and reduced potential excitotoxicity . Alternatively, ketamine may affect glia regulation of glutamate and inhibit glutamate release within glia. However, by whatever mechanism ketamine acts on CRPS pain, there does seem to be a dose/duration effect in that longer doses at levels tolerated by patients seem to prove more effective in terms of the duration of effects.

So what could be happening in the brain and what is required to alter brain systems and reverse the symptomatic state? Ketamine may diminish glutamate transmission and “resets” brain circuits, but it seems that a minimal dose and/or duration of treatment is required. Alternatively, ketamine may produce neurotoxicity and damage or produce a chemical lesion of affected neurons. These two issues are important to be understood in future trials. Reports from patients who have had anesthetic doses have included prolonged pain relief for many months. While the authors did not address issues such as the effect of dosing duration or repetitive dosing at say 6weeks, they did show a level of efficacy based on NNT that equals or betters most drug trials for this condition.”

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“Conclusions

As a community we have a major opportunity to define the efficacy and use of a drug that may offer more to CRPS (and perhaps other) patients than is currently available. This is clearly an opportunity that needs urgent attention and a number of questions remain to be answered. For example, is ketamine more effective in early stage disease? How does ketamine provide long-term effects? Further controlled trials evaluating dose, duration, anesthetic vs. non-anesthetic dosing are needed. Few of us really understand what it is like to suffer from a chronic pain condition such as CRPS. Ketamine therapy may be a way forward that can be brought into our clinical practice through further controlled studies that will allow for appropriate standards for use in patients.”

 

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The material on this site is for informational purposes only, and is not a substitute for medical advice,
diagnosis or treatment provided by a qualified health care provider.
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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!
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