Simply Calming


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First, an introduction or just skip below to web link, below, of the sweet Suzuki Roshi breathing practice of exhalation. It is so simple people with Alzheimer’s can do it. So instantly calming.

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It is best to practice while we are young and build a solid practice, make it part of being with your Self. The Divine Self. It is so simple and so sweet. It is who we are.

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A wonderful practice and highest teaching. We are all the divine essence, the serene soul. Enjoy how simple and calming…..relax and be in the moment of which the highest teachings speak, as far back as the Vedas and Upanishads, Buddha and all spiritual traditions have taught. 

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There is no god but God. There are no other gods. Not dreamy woo woo stuff. It just Is. Omnipresent. 

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“This is no world. It is God Himself. In delusion we call it world.” Vivekananda (6:371) “Complete self-surrender is the only way to spiritual illumination. Vivekananda (5:258)

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Acceptance. Enjoy who you already are. 

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Just be. You are That. We forget our true self. This is real. No kids play. 

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We all experience these moments. Being. Just being. Simple as breathing. 

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“ There is no question that breathing is taking place. Can you see that there is no breather to be found anywhere? The body is empty, the breath is empty and you are empty.” 

 

The Upanishads describe that stage as turiya pure consciousness. Turiya is the background that underlies and transcends the three common states of consciousness.

Buddhists call this emptiness. Advaita calls it fullness. The Divine Essence. God. The self that merges into the Absolute beyond, time space and causation Beyond name and form there is nothing else but the Self, Existence-Consciousness-Bliss. And this pure simple breathing out brings it into this very moment.

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from the dharma message of Zen priest and teacher White Lotus Judith Ragir.

click above name to go directly to the website for this  dharma teaching – it will be easier to read. 

 

Exhaling and dissolving.

Here are some quotes from Suzuki Roshi in “Not Always So” (chapter: Calmness of Mind) that emphasize working with the exhale while meditating:

Calmness of mind is beyond the end of your exhalation. If you exhale smoothly, without even trying to exhale, you are entering into the complete perfect calmness of your mind. You do not exist anymore. 

Inhaling without effort you naturally come back to yourself with some color or form. Exhaling, you gradually fade into emptiness – empty, white paper. That is shikantaza. The important point is your exhalation. Instead of trying to feel yourself as you inhale, fade into emptiness as you exhale. 

To take care of the exhalation is very important. To die is more important than trying to be alive. When we always try to be alive, we have trouble. Rather than trying to be alive or active, if we can be calm and die or fade away into emptiness, then naturally we will be all right. Buddha will take care of us. Because we have lost our mother’s bosom, we do not feel like her child anymore. Yet fading away into emptiness can feel like being at our mother’s bosom, and we will feel as though she will take care of us. Moment after moment, do not lose this practice of shikantaza.” 

This is very impressive quote to me. It is in alignment with the fourth Tetrad of the Anapanasati Sutra. The Anapanasati Sutra is composed of sixteen contemplations, which divide rather neatly into four sets of four: The body group, the feelings group, the mind group, and the wisdom group. They are in a “somewhat” developmental order in that mindfulness of the physical movements of the breath is the first emphasis in any concentration practice. The feelings group is ***becoming sensitive to rapture and joy in meditation***and then calming or letting go of rapture. The third group is the mind group – becoming aware of the mind, gladdening the mind, steadying the mind, and liberating the mind. (See “Breath by Breath” by Larry Rosenberg. This is a book Clouds in Water studied several years ago).

The fourth group the wisdom group is very similar to Suzuki Roshi’s quote above.

From a Thich Nhat Hanh translation:

13. I am breathing in and observing the impermanent nature of all dharmas. I am breathing out and observing the impermanent nature of all dharmas. He practices like this.

14. I am breathing in and observing the fading of all dharmas. I am breathing out and observing the fading of all dharmas. She practices like this.

15. I am breathing in and observing liberation (cessation). I am breathing out and observing liberation (cessation). He practices like this.

16. I am breathing in and observing letting go (relinquishment). I am breathing out and observing letting go (relinquishment). She practices like this.

This sutra demonstrates how the breath can take you all the way to the deepest realizations. The breath often is used as the first object of concentration. But it also can practiced as a complete teaching which leads to insight.

In Larry Rosenberg’s book, he writes about Buddhadasa’s approach to breath practice and its use for going all the way to realization. He writes:

“ When we got to the thirteenth contemplation – which concerns impermanence, this is where real vipassana begins – he said that Anapanasati was one of the simplest and most effective means for realizing emptiness.” 

Buddhadasa said: “There is no question that breathing is taking place. Can you see that there is no breather to be found anywhere? The body is empty, the breath is empty and you are empty.” 

Perhaps this is where Zen and Vipassana meet. Where the Mahayana and the Theravada come to the same conclusion.

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.http://www.judithragir.org/2014/01/exhaling-and-dissolving/

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Ketamine’s effects tied to opioid system in brain


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Stanford announces:

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Ketamine’s antidepressive effects

tied to opioid system in brain

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“Ketamine’s antidepressive effects require activation of opioid receptors in the brain, a new Stanford study shows. The surprising finding may alter how new antidepressants are developed and administered in order to mitigate the risk of opioid dependence.”

 

 

…”The study enrolled adults with treatment-resistant depression, meaning their condition had not improved after multiple treatment efforts. Twelve participants received infusions of ketamine twice — once preceded by naltrexone, an opioid-receptor blocker, and once with placebo. Neither the study participants nor the researchers were told whether active drug or placebo was administered during each test. The researchers found that ketamine reduced depressive symptoms by about 90 percent for three days in more than half of the participants when administered with a placebo, but had virtually no effect on depressive symptoms when it was preceded by naltrexone.”

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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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Cannabidiol (CBD) FDA Approved for Epilepsy – May Help Pain, Mood – Costs Review


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Epidiolex from GW Pharmaceuticals, is a cannabidiol (CBD) recently approved by FDA for treatment of epilepsy. Others have found CBD helpful for pain, migraine, and mood disorders. CBD is one of the more than 80 known cannabinoids in the cannabis plant, the marijuana plant. It has no psychoactive effect, that means it does not make anyone “high”. But urine drug tests will be positive for marijuana and anyone may risk losing their job if their employer checks – some drug tests do not specify marijuana.

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Medications can be prescribed off-label by your doctor for conditions other than the FDA approved epilepsy in this case, and hopefully covered by healthcare insurance. Below are costs of the Epidiolex brand reviewed by O’Shaughnessy’s newsletter, the newsletter originally for California cannabis doctors.

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FDA approval means CBD now has accepted medical use and should be no longer classified as Schedule I, though the ruse will likely be continued by congress.

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GW Pharmaceuticals PLC said it plans to charge about $32,500 per patient annually in the U.S. for its new treatment for rare forms of epilepsy, the first prescription drug derived from the marijuana plant.

Chief Executive Justin Gover said in an interview Wednesday that the company set the price to be in line with other brand-name epilepsy drugs, such as H. Lundbeck A/S’s Onfi. He noted that the FDA designated the product an “orphan drug,” meaning it treats rare conditions, and that some other orphan drugs carry higher prices.

Out-of-pocket costs for patients taking Epidiolex could range from $5 to $10 a month for those in state Medicaid programs to as high as $200 a month for some private insurance plans, Julian Gangolli, president of the company’s North America unit, said on a conference call with analysts Tuesday. Uninsured patients may qualify for receiving the drug free.

Dr. Jacqueline French, chief scientific officer of the Epilepsy Foundation, said there are low-cost generic epilepsy drugs on the market, but many patients with the rare forms of the disease have already tried them and the drugs didn’t help much.

Dr. French said Epidiolex improved symptoms for many children in clinical trials, and she is happy the price isn’t significantly higher.

The company expects to make the drug available after the U.S. Drug Enforcement Administration assigns it a controlled-substance classification, a decision expected by late September. GW Pharmaceuticals will distribute the drug through specialty pharmacies that ship directly to patients and caregivers.

FDA approval of a CBD extract means that cannabidiol now has an acknowledged medical use and therefore doesn’t fit a key criterion of Schedule I status. DEA rescheduling is supposed to follow as day follows night. Logically, the DEA resked should apply to cannabidiol, the molecule. But fixisin.com says CBD will remain on Sked I, with an exception created for CBD in an FDA-approved pharmaceutical.”

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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.

~~~~~

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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Memantine for Neuropathic Pain & Complex Regional Pain Syndrome, CRPS


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Neuropathic pain syndromes show an over-expression of NMDA receptors in the brain in animal models. Ketamine blocks the NMDA receptor. Another medication with the same mechanism, but in pill form is memantine. This report on six patients of the use of memantine for Complex Regional Pain Syndrome (CRPS) from 2007 in the Clinical Journal of Pain, six months after treatment with memantine, showed significant decrease in pain, improved motor symptoms and autonomic changes, and fMRI changes on the affected side improving, comparable to the unaffected side of the brain.

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It was approved for Alzheimer’s dementia gradually titrating to a dose of 28 mg/day, but for decades has been very useful off label for neuropathic pain including but not limited to CRPS, at a dose of 55 mg/day, and in recent years often prescribed for migraine.

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Ketamine is highly successful also for treatment resistant depression, and one patient, a psychiatrist disabled from the unfortunate triad of intractable neuropathic pain, migraine and treatment resistant depression, while slowly titrating to a dose of 55 mg/day, a process that takes almost 3 months, found depression relieved for the first time in decades at the dose of 35 mg. It was highly effective as one component of the multi-pronged approach for all three conditions.

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This life is a hard fact. We all need all the help, encouragement and positive attitudes we can get. Complex intractable pain and/or depression requires rational polypharmacy, selectively chosen based upon well known mechanisms, neurotransmitters, receptors, hormones, stress reduction, cognitive behavioral therapy, physical therapy, occupational therapy, nerve blocks, and spiritual understanding, etc. Several choices were summarized almost two years ago here.

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In my experience, memantine is very well tolerated with few if any side effects but covered by insurance only for mild to moderate dementia. Thus, not only is it highly challenging to treat neuropathic pain, but important to creatively meet the challenges of our backwards medical system that barely recognizes the needs of those with chronic pain.

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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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Ketamine for Bipolar Disorder Fear of Harm Phenotype Saved This Man’s Life


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Ketamine has given life back to so many who have been disabled by treatment resistant depression, bipolar disorder or intractable pain. It was approved in 1970 as an injectable anesthetic. It can be prescribed off-label from a compounding pharmacy inexpensively as a nasal spray or sublingual liquid or sublingual tablet for outpatient use or it may be given I.V. in a clinical setting. A patented nasal spray may be available soon (see below) for use only in a clinical setting.

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For many posts on ketamine since May 2009, use search function within this site at top left above small photo.

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NPR Morning Edition news today on ketamine for bipolar disorder “fear of harm phenotype.”

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For six years now, life has been really good for James. He has a great job as the creative director of an advertising firm in New York City. He enjoys spending time with his wife and kids.

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And it has all been possible, he says, because for the past six years he has been taking a drug called ketamine.

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Before ketamine, James was unable to work or focus his thoughts. His mind was filled with violent images. And his mood could go from ebullient to dark in a matter of minutes.

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Ketamine “helped me get my life back,” says James….

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…pharmaceutical companies are testing several new ketamine-related drugs to treat depression. Johnson & Johnson expects to seek approval for its nasal spray esketamine later this year, though the approval would be limited to use in a clinical setting.

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Meanwhile, doctors have begun trying ketamine on patients with a wide range of psychiatric disorders other than depression. And there is now growing evidence it can help people with anxiety, bipolar disorder, post-traumatic stress disorder, and perhaps even obsessive-compulsive disorder.

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“I think it’s actually one of the biggest advances in psychiatry in a very long time,” says Dr. Martin Teicher, an associate professor of psychiatry at Harvard Medical School and director of the Developmental Biopsychiatry Research Program at McLean Hospital.

James found his way to Dr. Demitri Papolos, an associate professor of clinical psychiatry at Albert Einstein College of Medicine.

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“He was like a whirling dervish when he came into my office,” Papolos says. “He was extremely fearful and scanning the environment all the time and he overheated at the drop of a hat.”

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Papolos diagnosed James with a variant of bipolar disorder he calls the “fear of harm phenotype.” It typically appears in childhood and often doesn’t respond to traditional psychiatric drugs.

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But Papolos has found that the condition does respond to ketamine. “It’s been transformational,” he says.

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In January, Papolos published a study of 45 children with the problem. They inhaled a nasal mist containing ketamine about twice a week. Nearly all got dramatically better.

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Scientists still aren’t sure why ketamine works, but there’s evidence that it encourages the brain to rewire, to alter the connections between cells. That process has been linked to recovery from depression. And it may also explain why ketamine helps people who have symptoms associated with several different psychiatric disorders.

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“I think it’s having multiple effects, and that means it’s probably useful for multiple different disorders,” Teicher says.

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One of those effects involves a part of the brain involved in temperature regulation. And that could explain why patients like James usually stop overheating once they are taking ketamine.

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James started taking a ketamine nasal spray every other day. He says his response was dramatic….

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Ketamine Relieves Depression By Restoring Brain Connections

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NPR All Things Considered published on ketamine 3/20/2017:

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Ketamine For Severe Depression: ‘How Do You Not Offer This Drug To People?’

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Gerard Sanacora, a professor of psychiatry at Yale University, has treated hundreds of severely depressed patients with low doses of ketamine, an anesthetic and popular club drug that isn’t approved for depression.

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“If you have patients that are likely to seriously injure themselves or kill themselves within a short period of time, and they’ve tried the standard treatments, how do you not offer this treatment?” he says.

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Why insist someone be suicidal? How do you not offer it to people who have failed all treatments and are disabled by intractable pain or treatment resistant depression? 

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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:  

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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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Oxytocin for Pain, Treatment Resistant Depression and Bipolar Disorder


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Recent publications on Oxytocin are listed below. It is a very effective hormone made by the brain. It is NOT the opioid oxycodone and NOT oxycontin.

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Use search function top left above photo to see previous postings on oxytocin since 2013. It can be extremely important in the treatment of intractable pain, treatment resistant depression, bipolar disorder or anxiety.

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Once you titrate to the proper dose for each person —from 10 to 100 u’s, relief is quite astonishing, with rapid onset in a few minutes when given under the tongue – only after reaching that person’s dose, simple, without side effects. May use as needed 3 or 4 times per day. There is no withdrawal.

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Avoid use if polycystic ovary syndrome (PCOS). 

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Oxytocin must be made by a compounding pharmacy. Healthcare insurance refuses to reimburse for any compounded medications though they are far less expensive even than gabapentin that fails to help so many with pain, and oxytocin is far more effective. 

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Every time you hug someone, you are giving each other oxytocin. When your dog and you stare at each other, oxytocin is being stimulated. Having discussed that with one of my patients, he came back one month later to say he and his wife had fallen in love again after almost 50 years of marriage because they’ve been hugging every day: hugs stimulate oxytocin. 

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Behavioral effects of oxytocin are highly context- and person-dependent. You are not going to fall in love with someone you do not like. 

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Rash, JA, et al: Oxytocin & Pain, A Systematic Review & Synthesis of Findings. Clin J Pain 30(5):453-462, May 2014.

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Xin Q et al: The Analgesic Effects of Oxytocin in the Peripheral and Central Nervous System. Neurochemistry Intl 103:57-64, 2017.

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Paloyelis Y et al: The Analgesic Effect of Oxytocin in Humans: A double-blind, placebo-controlled, cross-over study using laser-evoked potentials. 

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MacDonald K, Feifel D. Oxytocin’s role in anxiety: a critical appraisal. Brain Res 2014; 1580: 22–56.

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Churchland PPS, Winkielman P. Modulating social behavior with oxytocin: how does it work? What does it mean? Horm Behav 2012; 61: 392–399.

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Bethlehem, R A I  et al: Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women, Translational Psychiatry, 2017, 7, 4, e1099 ********excellent********

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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!

.

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

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After Ketamine for pain, complaints of depression dropped in half & pain reports were lower


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KPBS Radio highlighted a new study today by UCSD School of Pharmacy

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San Diego Scientists Find Further Evidence A Club Drug Could Treat Depression

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In a new analysis published Wednesday in the journal Scientific Reports, UC San Diego researchers said millions of FDA side effect records reveal that people who took ketamine for pain relief reported lower rates of depression.

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“The occurrence of complaints about depression dropped in half after ketamine administration,” said UC San Diego Skaggs School of Pharmacy professor Ruben Abagyan, who led the study.

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The researchers focussed on the FDA’s Adverse Effect Reporting System, a database that tracks negative side effects among people who take various drugs. But the researchers were not primarily interested in bad outcomes.

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Instead, they looked for a positive outcome: declining rates of depression among people taking drugs not typically thought of as antidepressants.

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They found signs that other common drugs — including Botox, a pain reliever called diclofenac and the antibiotic minocycline — also reduced depression among patients in the FDA database.

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[minocycline is a glial modulator and it can prevent CRPS from spreading.]

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University of Miami psychiatry professor Charles Nemeroff wrote that the study was, “very interesting.”

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“The findings are of considerable interest. However the interpretation of the findings are key,” he wrote, saying it will be important to understand whether ketamine is directly treating depression or simply relieving pain, which can indirectly help people experience less depression.

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The UC San Diego researchers said they controlled for this variable by comparing people who took ketamine with those who took other pain medications. They said they still found a larger drop in depression among those who took ketamine.

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This is the open source (free) article in Nature with brief excerpts below:

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Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications

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.Isaac V. Cohen, Tigran Makints, Rabia Atayee, Ruben Abagyan

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We found that patients listed in the FAERS database who received ketamine in addition to other therapeutics had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain (LogOR −0.67 ± 0.034) (Fig. 1c). This reduction in depression is specific to ketamine and is known to be much more rapid than current antidepressants, making this observed effect very promising for treatment of patients with acute depressive or suicidal episodes. These patients cannot afford to wait up to six weeks for reductions in their depressive symptoms. Pain reports were also significantly lower for ketamine patients (LogOR −0.41 ± 0.019) (Fig. 1c).

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The analysis of the whole FAERS database revealed several other unintentional depression reducing drugs among antibiotics, cosmeceuticals and NSAIDS (Fig. 2). Our data supported previous studies that observed the psychiatric polypharmacology of minocycline [my emphasis], a tetracycline antibiotic14 (Fig. 2). The NSAID, diclofenac [that has highest incidence of heart attack and cardiac arrhythmia of any NSAID], was also observed to have some antidepressant properties (Fig. 2). It is theorized that both of these drugs may accomplish antidepressant effects through an anti-inflammatory mechanism. Because of the antidepressant activity of several NSAIDs, we further separated the non-ketamine pain cohort. Ketamine patients were then compared to patients who received any other combination of drugs for pain excluding NSAIDs. It was observed that depression event rates remained low (LogOR −0.56 ± 0.035) (Fig. 2)..The reduction of depression rates in ketamine patient records makes a case for study of ketamine as a psychiatric drug. These results imply that ketamine may be further explored as a monotherapy or adjunct therapy for depression. It should also be noted that FAERS data revealed that ketamine use [may] lead to renal side effects and awareness and caution in patients with renal or hepatic impairment may be warranted (Fig. 1a and b). [my emphasis].

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As an important side note, we also evaluated efficacy and side effects with the use of ketamine for pain management. We found that patients who were on ketamine had reduced opioid induced side effects including constipation (LogOR −0.17 ± 0.023), vomiting (LogOR −0.16 ± 0.025), and nausea (LogOR −0.45 ± 0.034) than patients who received any other combination of drugs for pain indications (Fig. 1d). Our data supports ketamine’s opioid-sparing properties and alludes to the fact that patients may receive benefits of improved pain, reduced requirement of opioids, and ultimately less opioid reduced side effects.

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The results of this study support previous small scale studies’ conclusions that ketamine is a good monotherapy or adjunct therapy for depression. In clinical practice ketamine would be especially useful for depression because of the quick onset of its action compared to existing first line therapies. Regardless of the causative mechanism ketamine appears to have therapeutic potential for TRD. Further, the potential to reduce many of the most complained side effects of opioid treatment makes ketamine adjunct therapy for pain seem desirable.

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Overall, this study demonstrates that the therapeutic potential of ketamine can be derived from appropriate statistical analysis of existing population scale data. This study also outlines a methodology for discovering off label pharmacology of existing approved drugs. This method can be applied to other indications and may reveal new important uses of already approved drugs, providing reliable justification for new indications without large investments in additional clinical trials.

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FDA Adverse Event Reporting System. The FAERS database was created to support FDA’s post marketing surveillance on drugs and biologic therapeutics. It contains adverse reaction and medication error reports sent to the FDA through MedWatch, the FDA Safety Information and Adverse Event Reporting Program. Reporting is voluntary and is done by patients, family members, legal representatives, doctors, pharmacists and other health- care providers. If any party reports an adverse effect to the manufacturer, the manufacturer is legally obligated to forward the report to the FDA. Data is available online in quarterly format for AERS from the first quarter of 2004 to the third quarter of 2012 and for FAERS from the fourth quarter of 2012 to the first quarter of 2016.

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The study used over 8 million adverse event reports from first quarter of 2004 to the first quarter of 2016. All the quarterly files from 2004 to 2016 were combined into a master file which was used as the primary source for analysis. . . .

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Out of 8 million reports, 279,853 reports were used for analysis of ketamine in Fig. 1. Two cohorts for ketamine (K) patients and pain (P) patients with 41,337 and 238,516 patients respectively....

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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.

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

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Naltrexone in Low Dose Reduces Pain & Depression


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We’ve known LDN helps pain since the turn of the century. Stanford could really shake the research world if they trialed LDN for Major Depressive Disorder, not the depression that improves with less pain, or in Multiple Sclerosis clinics or the Parkinson’s or Inflammatory Bowel Disease clinics. Is it too much to ask for better quality clinical research, not just results of patients responding by click or touch on a computer touch pad?

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The astonishing promise of low dose naltrexone (LDN) research remains in its infancy since 1984, 33 years ago, when it was discovered to offer profound clinical relief for multiple sclerosis and other serious conditions. I have prescribed naltrexone in ultra low and low dose since 2003, and discussed its central anti-inflammatory glial modulating mechanisms in 2009:

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Low dose naltrexone, or LDN, has been prescribed “off label” for persons with many conditions including intractable pain, chronic fatigue syndrome, complex regional pain syndrome, RSD, Multiple Sclerosis, Parkinsons Disease, IBS, inflammatory bowel disease, autoimmune diseases and Crohn’s Disease to mention only a few. Low dose naltrexone is not a cure but may be potentially helpful for selected persons with these conditions. It appears to have little or no toxicity at this low dose – a few persons report transient insomnia, nausea or vivid dreams.

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The same year in 2009, soon after my post on LDN, Drs. Younger and Mackey of Stanford Pain Center reported a double blind study of low dose naltrexone in persons who had fibromyalgia more than 10 years and showed 30% improvement in pain and fatigue.

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In 2016, five Stanford authors including Dr. Mackey published a poster presentation. At least the 2009 study was double blind; not this one. It was open label.

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A novel glial cell inhibitor, low dose naltrexone, reduces pain and depression, and improves function in chronic pain: A CHOIR study

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Poster presented at: Annual Meeting of the American Pain Society; May 11-14, 2016; Austin, TX. Poster 418.

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Authors: K. Noon,  J. Sturgeon, M. Kao, B. Darnall, S. Mackey

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Stanford University Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford, CA

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Funding received from NIH and the Redlich Pain Endowment

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NIH funding should lead us forward, not back to a single open label study. One would hope Stanford would do the larger study they recommended 7 years ago. This adds to the CV of five researchers, but

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  • does it help millions with chronic intractable pain?

  • does it add to the growing body of clinical LDN experience worldwide?

  • when will the mechanism and uses of LDN, the TLR4 receptor and the powerful innate immune system be taught by healthcare providers in academia, in practice, and in pharmacies, not just in basic science?

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The poster highlights the Stanford CHOIR Information Registry (discussed below), but provides almost nothing new despite the computing power of CHOIR that likely cost small fortunes. Patients are asked to enter clinic data into a convenient handheld click- or touch-based input device. What could be easier? We look forward to better studies from Stanford’s CHOIR devices and we long for the days when doctors publish better data that addresses the disabling pain, depression and needs of millions of our patients with chronic intractable pain.

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Stanford’s CHOIR Information System

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“We modified and implemented an existing, web-based system that administers computer-adaptive PRO questionnaires, called the Collaborative Health Outcomes Information Registry (CHOIR).  Next, we developed a messaging interface to send PRO results from CHOIR to the UF Health Epic EHR.

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The CHOIR system was developed at Stanford University by a team of informaticists and physicians who provided a no-cost license for our implementation. CHOIR utilizes a client-server architecture with web-based clinician and patient interfaces that use open source technologies, including jQuery mobile and Google Web Toolkit. Users can access CHOIR via web browsers on desktop or mobile devices. The primary patient user function is the completion of computer-adaptive PRO assessments using a click- or touch-based input device ( Figure 1 ).  Clinical user functions include registering patients to complete a PRO assessment, reviewing individual and summary PRO assessment results, longitudinal outcomes tracking, and clinical decision support through the aggregation of PRO result sets.”

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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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This site is not for email and not for appointments.

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

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Microbiome, Metabolome & Disease


 

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Many of us have followed the research in this field for health, happiness and well-being. Today’s questions and answers from an expert on microbiota in Reddit Science is of great interest and something I wanted on these pages for future reference. I sifted through the pages to condense the questions, leaving answers intact. AMA is short for Ask Me Anything. Where Professor Barrett’s  responses to questions are clear, I have omitted the questions; where not clear, questions are abbreviated and/or added. I am sure we would all like much more information on inflammation and the inflammasome, the gut and brain and health. Support science. Be careful of low quality journals and quackery. She says even some yogurts have no bacteria.

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Science AMA Series: I’m Kim Barrett, Professor of Medicine at the University of California, San Diego and Editor of The Journal of Physiology. This week, we published an issue on the microbiota [editorial free], so I thought it would be a great opportunity to discuss how our microbes influence our well being. AMA!

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This is her main message, again and again:

[–]Kim_Barrett

Eat a well-balanced diet, including cultured/fermented foods, and avoid excessive fat and processed carbohydrates..

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[–]Kim_Barrett

Thanks to both. There is a lot of epidemiological evidence for the health benefits of all of these fermented foods, which may deliver bacteria similar to probiotics as well as beneficial metabolites that have greater bioavailabilty. These foods have been consumed by humans for millennia but were less prevalent in the diet as society discovered refrigeration etc. But studies to actually prove efficacy and mechanisms of action remain in their infancy. This is an area where the National Center for Complementary and Integrative Health is placing a lot of emphasis for research funding.

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Q Nose/sinuses:

[–]Kim_Barrett

Yes, this is a less appreciated area but rapidly growing area of study. I definitely would encourage you to look at our special issue of the Journal of Physiology, which has short reviews on the oral, skin and vaginal microbiota. Our external cavities all have their own distinctive microbiotas, but in aggregate they may encode many of the same sorts of metabolic capacities as seen in the gut. The specific populations may also depend on the type of environment – for example, the bugs on your forearm are different from those on your forehead. Lots more work to be done.

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there is not a simple way currently of knowing about our microbiota’s composition, but general indices of gut health may give some clues. Likewise, finding effective probiotics may be a bit of a case of trial-and-error, but there is good epidemiological evidence for a beneficial effect of fermented foods like Kombucha.

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Q on IBS:

[–]Kim_Barrett 

Serotonin is a major controller of gut motility and sensation, and alterations in serotonin signaling have been documented in irritable bowel syndrome. The cells that make serotonin in the gut have been shown to express receptors for short chain fatty acids (SCFAs), which are major products of bacterial metabolism of undigested carbohydrates. Finally, some gut bacteria metabolize the serotonin precursoe, tryptophan, which in turn has implications for the production of appropriate gut levels of serotonin.

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Q:  Sometimes, when I am constipated, I can perceive a certain taste and smell that arrives internally. Have direct nerve connections between the bowel and the brain been identified? What role to microbiota play in perception of satiety? What is the importance of the neurological phenomenon vs the blood chemistry in controlling weight gain or loss?

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[–]Kim_Barrett 

Lots of nerve connections between the brain and gut, and gut nerve endings have been shown to sense bacterial metabolites. To the extent that the microbiota and their metabolites control the secretion of GI hormones, they clearly participate in satiety perception, but this still needs further study. And weight gain/loss is such a complex phenomenon, also encompassing societal and behavioral aspects, that the relative contributions of the factors you mention have not been worked out by any means.

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Good and bad may be too simplistic. A “good” bacteria may be bad for you if in the wrong place. As for substrates and products, this is probably too big of a topic to tackle right now, but I would direct you to the work of Eugene Chang at the University of Chicago who has done a lot of work in this area. Gut permeability is also clearly important. We have done work to show that certain commensal and probiotic species can tighten the gut barrier so that pathogens and toxic metabolites are less able to penetrate and initiate inappropriate inflammatory reactions and a vicious cycle of further weakening of the gut barrier.

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Q   Strong evidence correlates aberrations in gut diversity with certain diseases. Phylogentitcally speaking, it seems to matter more that the microbiome is diverse and less important which species are specifically there. The hypothesis being that the gut microbial metabolome is relatively stable, regardless of specific species present. http://go.nature.com/2iQLOu1

Q1 – Have clinicians started to take the next step, looking at disease correlations with perturbation of the microbial metabolome?

Q2 – If so, what have they found? Do probiotics replace those missing metabolic pathways?

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[–]Kim_Barrett 

Absolutely agree with your comments about the metabolome. However, most of this work at present is still in preclinical models, although there has been a lot of attention to the way in which metabolic pathways change after bariatric surgery, for example.

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Q:

When I was very young, I had a few instances of food poisoning visiting family in Mexico, I even contacted tuberculosis. I, of course, was given many antibiotics. I’ve had a lot of digestive issues since then, it was always a problem. I’m 36 now, and adopted a very low carb diet 3 years ago. During the initial transition, I had, to put it succinctly, severe dhiarrea. Like stuff was probably dieing off. And then, 4 months in, I had more energy, metal alertness, and general feeling of being present. And I no longer had crippling depression. From a completely anecdotal standpoint, I think that changing my diet also drastically changed my gut biome, and that, in turn, actually effected my brain function. It seems like what you’re research has shown is that this isn’t some woo-woo thinking, but an actual thing?

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Q does Kefir boost gut bacteria?

[–]Kim_Barrett

Yes, along with other related foods.

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Q are we discovering new categories of bacteria in the body?

[–]Kim_Barrett 

This was a big sticking point in the field initially since many of the bacteria cannot be cultured. Now they are identified by sequencing. The estimate is that healthy individuals harbor at least 1000 different species. Not to mention viruses, fungi, protea….we’re just getting started, and as you imply, the bioinformatics challenges are huge.

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[–]Kim_Barrett 

There’s quite a bit of evidence that mixtures of different bacteria are more effective than single bacteria. Perhaps they have complementary metabolic functions, or mutually help each other to colonize the gut.

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Q  research of healthy bacteria for auto immune disease?  Crohn’s disease?

[–]Kim_Barrett

Others are exploring a role in asthma.

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Q: studies in which obese mice had received gut flora from lean mice and subsequently lost weight, and vice versa. Does this imply that a microbial treatment for obesity in humans could be developed, and if so, is there any interest in this?

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[–]Kim_Barrett 

A lot of people are looking for just such a treatment!

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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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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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Caffeine May Reduce Age-Related Inflammation, Stanford Aging Study


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Caffeine may be able to reduce inflammation.

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Inflammatory immune molecules increase as we age and are associated with mortality from all causes, Alzheimer’s disease, stiffening of arteries, hypertension and cardiac disease. Inflammation kills. Yesterday Stanford and colleagues from University of Bordeaux published results of a long term aging study of 114 patients in Nature Medicine (paywall):

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Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states

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For nonscientists, see below. Caffeine may block inflammation. Adenosine and adenine are known to stimulate the inflammasome. Caffeine blocks the effect of adenosine.

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“They found that older people between the ages of 60 and 89 tend to ramp up production of immune molecules in a complex called the inflammasome. That’s a clump of immune proteins inside cells that activate one of the immune system’s big guns, called interleukin 1 beta or IL-1B. It’s an important molecule for fighting off infection, but too much of it for too long has been linked with chronic diseases like heart diseasecancer, and Alzheimer’s disease.

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Among the older people in the study, 12 of them made much more of these inflammatory molecules, and 11 people made much less. The less-inflamed group was also healthier, with lower blood pressure, more flexible arteries, and more relatives who lived past age 90.

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They also had lower levels of the breakdown products of DNA and RNA circulating in their blood, including one molecule called adenine, and another called adenosine — which is adenine attached to a sugar molecule. These molecules are known to stimulate the inflammasome, and lower levels of them could explain why this group was less inflamed. In fact, treating cells with these breakdown products made them churn out more inflammatory molecules, and made mice more inflamed, with higher blood pressure.

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HIGHER BLOOD LEVELS OF CAFFEINE CORRELATED WITH LESS INFLAMMATION

That’s where the caffeine comes in. Caffeine is known to block the effects of adenosine in the brain — that’s how scientists think it keeps us awake. So, the researchers suspected that it’s possible that it could block the effects of adenine and adenosine on immune cells, too, and reduce their ability to cause inflammation. According to a questionnaire, people in the less inflamed group consumed more caffeinated beverages like coffee, soda, and tea. In fact, higher blood levels of caffeine and other caffeine breakdown products correlated with lower production of inflammatory molecules like IL-1B.

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When the scientists treated cells with adenine and another molecule known to trigger the inflammasome, the cells that were soaking in caffeine produced far lower levels of inflammatory molecules. The researchers still haven’t fully explained how caffeine is interfering with inflammation. And the results aren’t enough to base any behavioral recommendations off of; but it’s comforting news for those of us who were already reaching for that second hit of caffeine, anyways.”

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Many articles on pro-inflammatory cytokines IL-1β, IL-6, and TNF-α are found in the setting of chronic pain and in depression:

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IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress.

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Depressed rodents shown to have inflammation, published by Yale and NIMH a few years ago.

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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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This site is not for email and not for appointments.

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

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

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Got no business feelin’ down – Music


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I got no business feeling down. Music can be fun. Turn on the best. Find your self. Have some fun here. Stop that freekin gloom.

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It will take some work. Words have power.

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Music

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Y’all know the Abyssinian Baptist Gospel Choir don’t you? What do you think they’re singing about? There’s better ways to be happy than to allow the mind to sink back down to the world. It’s the spirit!

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The Beatles, “I Wanna Hold Your Hand. And when I touch You, I feel happy inside. It’s such a feelin that my love I can’t hide. Yeah you, you’ve got that something, I think you’ll understand.”

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Whatever that Infinite is, that Bliss, the only way to know It is to BE It. You already are. You, I, we are infinite. So make happy. You can’t destroy the ones you hate, we gotta love em. They are us. They are god too. You cannot divide infinite by 2, it’s still 2. It’s all Infinite. Just run from the danger gods.

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How to understand this? “The seeds of love I sow, ” Led Zeppelin, Physical Graffiti,”Let music be your master. Will you heed the Master’s call?

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Ain’t no Judas. It’s all Love. Every last one. You don’t have to worry. It’s a movie. You are infinite, remember? It’s real and it’s a movie all at the same time. Step away for a bit and check out these lyrics I never heard til now.

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Love the Great Spirit, the Infinite, the Absolute, Truth, Consciousness. The world pulls us down. It succeeds! I got no business allowing that. I can do better. Just how to do that is this.

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Led Zeppelin, Physical Graffiti

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Houses Of The Holy  
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Let me take you to the movies. Can I take you to the show
Let me be yours ever truly. Can I make your garden grow
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From the houses of the holy, we can watch the white doves go
From the door comes Satan’s daughter, and it only goes to show. You know
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There’s an angel on my shoulder, In my hand a sword of gold
Let me wander in your garden. And the seeds of love I’ll sow. You know
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So the world is spinning faster. Are you dizzy when you’re stoned
Let the music be your master. Will you heed the master’s call
Oh… Satan and man
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Said there ain’t no use in cryin’ ‘Cause it’ll only drive you mad
Does it hurt to hear him lyin’? Was this the only world you had? oh-oh
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So let me take you, take you to the movie. Can I take you, baby, to the show
Why don’t you let me be yours ever truly.
Can I make your garden grow

you know.

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Kashmir
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Oh, let the sun beat down upon my face
And stars fill my dream
I’m a traveller of both time and space
To be where I have been
To sit with elders of the gentle race
This world has seldom seen
They talk of days for which they sit and wait
All will be revealed
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Talk in song from tongues of lilting grace
Sounds caress my ear
And not a word I heard could I relate
The story was quite clear.
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Ooh, baby, I been blind
Oh, yeah, mama, there ain’t no denyin’
Oh, ooh yes, I been blind
Mama, mama, ain’t no denyin’, no denyin’
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All I see turns to brown
As the sun burns the ground
And my eyes fill with sand
As I scan this razor line
Can I find, can I find where I’ve been
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Oh, pilot of the storm who leaves no trace
Like sorts inside a dream
Leave the path that led me to that place
Yellow desert stream
Like Shangri-la beneath the summer moon
I will return again
As the dust that floats finds you
Will move and search Kashmir
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Oh, father of the four winds fill my sails
Cross the sea of years
With no provision but an open face
Along the straits of fear
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Oh, when I want, when I’m on my way, yeah
And my feet wear my fickle way to stay
Ooh, yeah yeah, ooh, yeah yeah, but I’m down
Ooh, yeah yeah, ooh, yeah yeah, but I’m down, so down
Ooh, my baby, oh, my baby
Let me take you there
Come on, oh let me take you there
Let me take you there back to top
In The Light
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And if you feel that you can’t go on
And your will’s sinking low
Just believe and you can’t go wrong
In the light you will find the road
You’ll find the road
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Hey, ooh, did you ever believe
That I could leave you standin’ out in the cold
Hey, baby, I know how it feels
‘Cause I have slipped through
To the very depths of my soul
Oh, baby, I just want to show you what I’d give you
In case you ever been on the road
Now, listen, oh, as I was and would do for you, too
Honey, as you would do for me
I would share your load, let me share load
Ooh, let me share you load
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And if you feel that you can’t go on
In th light you will find the road
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Hey, oh the winds of change may blow around you
But that will always be so
Oh wo, when love is pain it can devour you
If you are ever alone
I’ll share your load, I will share your load
Baby, let me, oh let me, in the light
Everybody needs a light, oh yeah, oh baby
Everybody, everybody, everybody sure ’nuff they do
Light, light, light, in the light (Repeat)

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Be the witness. Watch the movie, don’t sink into it. It’s only the body. Step away for a few minutes. Be aware of love and consciousness of spirit. Expand consciousness as often as you can. Fill the heart with love. Practice this. Meditate from the heart. We get stuck but sometimes we need to break out some music. You are not the body or the mind. You don’t think God is fun? Infinite is more fun than imaginable, they say. You may have evolved in taste for music, Infinite Bliss has infinitely better, sages say.

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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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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 in Bipolar Depression – A Review


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An excellent review of Ketamine, a rapid-acting antidepressant and anti-suicidal agent, in Bipolar Depression

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Efficacy of Ketamine in Bipolar Depression: Systematic Review and Meta-analysis. 

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Parsaik AK1, Singh B, Khosh-Chashm D, Mascarenhas SS.

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OBJECTIVE: To consolidate the evidence from the literature to evaluate the role of ketamine in the treatment of bipolar depression.

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METHODS: Major databases, including MEDLINE, EMBASE, Cochrane, and Scopus, were searched through October 2014, for studies reporting the role of ketamine in the treatment of bipolar depression. Only randomized controlled trials were included in the meta-analysis. We calculated standardized mean differences (SMDs) with SE for each study included in the meta-analysis. A random effect model was used to calculate the pooled SMDs. Heterogeneity was assessed using the Cochran Q test and I statistic.

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RESULTS: Of the 721 articles that were screened, 5 studies that enrolled a total of 125 subjects with bipolar depression (mean age, 44.6+/-4.3y and 65.6% females) were included in the systematic review; 3 randomized controlled trials (69 subjects) were included in the meta-analysis. The meta-analysis showed significant improvement in depression among patients receiving a single dose of intravenous ketamine compared with those who received placebo (SMD=-1.01; 95% confidence interval, -1.37, -0.66; P<0.0001). The maximum improvement was observed 40 minutes after the ketamine infusion. No heterogeneity was observed between the studies (Cochran Q test P=0.38, I=0%). The 2 studies that were excluded from the meta-analysis also showed significant improvement in depression after ketamine therapy. Individual studies also reported improvement in anhedonia and suicidal ideation after ketamine therapy. None of the subjects had serious side effects, and the side effects were similar between the ketamine and placebo groups.

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CONCLUSIONS: This study suggests that ketamine is effective in treatment-resistant bipolar depression and may reduce suicidal ideation and anhedonia.

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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.

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

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The advertising below is not recommended by me.

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Veterans Suicides 20 per day – MD not paid in 12 months for 5 approved visits


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VA Conducts Nation’s Largest Analysis of Veteran Suicide

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Read the report all you want, but for 12 months I’m not reimbursed. And no explanation why. No wonder they can’t get doctors.

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Yet another call just now from TriWest asking me to treat a veteran. VA crisis lines leave vets in limbo. Calls go to voice mail. Veterans have killed themselves just after calls to crisis lines. A lot of these suicides are due to PTSD. Veterans cannot get the help they need.

 

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I believe it is TriWest who won the contract to schedule suicidal veterans who have Treatment Resistant Depression or PTSD or Bipolar Depression. I treat that. It works except in the most extreme cases, in minutes to just a couple days. It’s simple and safe for outpatient use. It has been tested at NIMH and Yale since 1991. The VA-UCSD psychiatrist referred him and then continued care.

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I will not see one more veteran until I am reimbursed for the 5 pre-approved visits for a veteran I treated 12 months ago. He was better in a few days, the first time in decades he had relief of depression. If you cannot pay me who can relieve treatment resistant Major Depression in 2 days, then honey, no wonder you can’t find docs to help. They limited me to their chosen codes for billing. I spoke to psychiatrists who work with veterans and they have never heard of those codes. I guess they just mean loud and clear: NO PAY. Fine. It was a pay cut to offer and took weeks of paper forms, months of approval – you have to really want to do it. With frequent help from a very experienced clerk and a doggedly informed veteran who knew all the ropes, it took months for paperwork to get rushed through. Plenty of doctors just graduating this month don’t know how many months paperwork takes and they won’t get paid.

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San Diego VA has the worst reputation in the nation. I understand it is the San Diego VA that has the worst lag time delays of several months before veterans can even be seen. Worst in the country. Correct me if I’m wrong. And we have a lot more veterans because warm sunny weather is easier on their bones. Is that any excuse to dis-incentivise any doctor by not paying for services?

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The new veterans suicide hotline does not even return all calls. Public Radio just had an expose’ on this one or two weeks ago.

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Twenty veterans take their life daily.

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Only 30% of people with depression respond to antidepressants.

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Based on publications from major academic centers, treatment resistant depression, it seems, is diagnosed after failing as few as 3 or 4 antidepressants.

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Compare any antidepressant to ketamine with potential relief in hours to a couple days.

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It’s not like this is new. In 1991 ketamine was first studied at NIH for depression. Yale has carried the work forward with them. But people live at home and it has to be cost effective. It is unnecessary and/or unaffordable for most people including taxparers to be paying for IV infusions when many or most patients do well on sublingual or nasal use. It is the #1 drug of abuse in China, so don’t just offer it to any person who needs it. Make sure you understand how important glial modulators are in depression. See Yale with NIMH publication on inflammation in depression, I posted on these pages about 3 or 4 years ago when it came out.

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Yale with NIMH had published that ketamine rapidly creates synapses.

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And Yale has published:


Activation of a ventral hippocampus–medial prefrontal cortex pathway is both necessary and sufficient for an antidepressant response to ketamine

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In January 2012, I posted detailed information:

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Depression PTSD – Ketamine Rapid Relief

 

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  • PTSD has a more direct link to suicide than previously thought, a current Texas A&M University study concludes – references below.

  • A high lifetime risk of suicide occurs in women who have been sexually and physically abused as young girls.

  • More than 300,000 veterans have been diagnosed with PTSD or major depression – many not yet diagnosed.

  • Risk of suicide is the highest during the first month of standard antidepressant therapy, and a significant number of patients do not have adequate improvement even after months, resulting in harm to personal and professional lives.

  • Patients are at suicide risk upon discharge from psychiatric hospitals.

  • Significant predictors of both suicide attempts and preoccupation with suicide are guilt and anger and impulsive behaviors.

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  • Ketamine is the most important breakthrough in treatment of major depression with rapid and lasting effects.

  • Ketmine can help immediately, unlike all other antidepressants that may require weeks or months to work, if they help at all. See NPR report here – that appeared soon after I posted this (skip to their last section). It is FDA approved and legal. NPR again reports ketamine’s rapid relief of depression.

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  • snip

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    • The medical literature on ketamine use is profoundly important. There are over 6,800 medical publications. Ketamine has potent healing powers. Karl Jansen, psychiatrist in London, believes that “ketamine has potent healing powers when used as an adjunct to psychotherapy.” There is nothing like it; however, treatment for serious depression still requires team support, not medication only.

    •  The World Health Organization reports that disability to due depression is second only to heart disease.

    • Suicide is a catastrophic medical emergency. I cannot stress this enough. Depression is treatable.

    • Your death is unnecessary. It would be a terrible loss to all who love you.

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Please read that entire post January 2012 before you call to ask questions. The calls are very time consuming.

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There is no reason to restrict life and death matters to one drug, and then make it dependent upon only IV infusions. What kind of life is vegetating in depression for decades? It is a short acting drug. I have posted on why ketamine should never be used alone, but must be used with other glial modulators.

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Most troubling:

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Compounded Medications are Not Covered by Any Insurance

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Most people cannot afford compounded medications, especially if disabled due to Major Depression or PTSD or pain – same medications work on mood and pain.

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TAKE ACTION

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Healthy people can get back their lives. These simple steps can be taught across the nation. Millions are needlessly disabled, especially our young adults who are most vulnerable to these disorders, and several hundred thousand of our young veterans.

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An entire nation can get and breathe relief.

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DO THIS:

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Call your favorite politician and relevant organizations who care about healthcare and veterans to STOP the collusion and restraint of trade since all insurers began refusing to cover compounded medications. All these new $100,000 per year medications are paid for by the taxpayers and your insurance deductible that goes up every year. How long will you be able to afford medical care? How long can this restraint of trade be practiced under our noses unless we take action?

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Get this on the Democratic platform this presidential year. It’s a scam perpetuated by multibillion dollar pharma and their mighty rich contributions to congress who are killing affordable medical care.

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Affordable medical care

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These medications must be compounded. How many can afford $200 to $300 or more cash out of pocket just for medications? Or will this become another safe old drug that is bought by a financier, patented, and now they charge $100,000 a year? You know who pays for everything and it ain’t the 1%.

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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?

.

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

.

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

.

Activated glia produce neuroinflammation and cell death.

.

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

.

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

.

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.

.

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

.

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.

.

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.

.

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!

 

 

 

 

Health Insurance All But Useless with High Deductibles


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“High Deductibles in Health Insurance”

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Quoting from the New York Times today, a subject often encountered daily, so rarely discussed in the media. My own colleagues cannot afford health insurance deductibles, let alone the average person who is not a medical professional. Five compounding pharmacies have closed in the last few months! Compounded medications are no longer covered! My patients cannot afford the insurance denials for medications, and how are we practicing medicine when each visit must be taken up with prior authorizations? No wonder the cost of medical care has gone up. What do we do for chronic pain or treatment resistant depression when our people have failed all drugs? Research funding never seems to go toward pain or depression.

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To the Editor:

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Re “Many Say High Deductibles Make Their Health Law Insurance All but Useless” (news article, Nov. 15):

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My self-employed husband and I have found ourselves in this predicament: affordable health care premiums but a prohibitive $5,000 yearly deductible.
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Truly accessible health care cannot be achieved when insurance companies are the primary beneficiaries of policies and when those who are “insured” still cannot afford to see a doctor.

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SUSAN A. McGREGOR

North Kingstown, R.I.
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To the Editor:

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Your article does a good job of describing cost-shifting from insurance companies to medical consumers but doesn’t explore the issue of risk-shifting.

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People pay insurance companies premiums to take on risk. Insurance companies try to avoid as much risk as they can. High deductibles and co-payments are just part of the risk-shifting.
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Other strategies being used include narrow networks of doctors and hospitals, denial of access to high-quality and often high-cost specialists, questioning and limitation of access to expensive drugs, questioning and limiting high-cost testing, and even offering free health club memberships to screen out those with high-cost disabilities.
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At a health insurance fair in San Francisco earlier this month, participants selected from various plans offered through the Affordable Care Act. Credit Jim Wilson/The New York Times
This process is about a lot more than high deductibles. But the end result is that good people are not getting the care they thought that they paid for. And the political leaders of both major parties approve these hassle factors — as our courts do — in the name of preserving America’s global competitiveness.
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BRANT S. MITTLER

San Antonio

The writer is a cardiologist and a lawyer.
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To the Editor:
.
So at the end of the day, health care is no more affordable than it was before Obamacare was enacted! Why should we be surprised?
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Several decades ago, in an effort to promote “wellness,” we saw an increasing trend to encourage people to visit their doctor more regularly and more often, by offering plans that covered basic health maintenance costs. State regulations demanded coverage of some services, and the Affordable Care Act only added to the list that must now be provided without cost to the user.
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Insurance in the traditional sense provides coverage for the unforeseen event. In health care, that would be serious injury and catastrophic disease. What we have today is what the insurance industry refers to as “trading dollars.”
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Imagine if car insurance covered all basic services to reduce the risk of future damage, like oil changes, new brakes and even periodic visits to the car wash. We would see huge increases in the cost of car insurance, although we would also see policies that are offered at low premiums but with high deductibles and high co-payments.
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MICHAEL A. SMITH

Wells, Me.

The writer is a retired equity research analyst who covered the insurance industry.
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.
To the Editor:
.
Your article about high deductibles in health insurance was accurate as far as it went, but a complete discussion of the benefits of health insurance coverage would have included the fact that insurers negotiate substantially reduced payments for in-network medical services for the insured.
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I have a high-deductible policy, but the payments I have to make to an in-network provider are usually only 40 to 50 percent of what I would have paid if I had been uninsured.
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An emergency room physicians’ bill here on my desk lists $632 as the charge, for which the insurer’s negotiated rate was $273.27, a 57 percent discount.
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My high-deductible health insurance policy is a membership in a huge discount medical services program. This is an important consideration that should be discussed more openly. The uninsured, by paying full freight, are subsidizing health care for those of us who are insured.
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DAVID MAIER

Richmond, Va.”

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Insurers Refusing to Cover Pain Medication – Morphine 100 mg per Day Maximum – Opioid Wake up Call – New Nationwide Standard? DEA Mandate


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The FDA mandated 22 manufacturers of long acting opioids

to fund a program on opioid prescribing.

FDA dictated the content.

~

I attended the SCOPE of PAIN program Friday November 6, from 8 to 12:30, taught by an Addictionologist from Portland with our local Southern California DEA. Continuing education credit was given by Boston University. The first grant recipient was in 2012.  

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My take:

I think we will rapidly see a 100 mg per day

maximum morphine equivalent allowed

Could I be interpreting this wrong?

Insurers simply deny paying for high doses. They have begun already.

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I am exhausted from ICD10 diagnosis coding – complex patients !!! – that has taken away any possibility I could leave my desk until 4 AM for the last four weeks, in midst of moving office to much better place, and midst the only two computer crashes I have ever had in my pursuit of efficient tech, plus dental fracture, so much more….perfect storm. The paragraphs could be edited and rearranged, so they would be in sequence but they’re not.

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I hope others will give me their take on this. It has been getting worse since almost all university interdisciplinary pain clinics were closed in 1991. Insurers, i.e. managed care clerks, are practicing medicine mandates set forth by anonymous committees looking at spreadsheets not at our complex care. Insurers could save many billions if they invested a few billions in education. Insurers wrote Obamacare. They could write it better. Congress wants all of us to do our part. Surely business too?

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Based on this series of opioid conferences, my guess is their first step is to chop opioid prescribing down to 100 mg morphine equivalents. But what about untreated pain at the heart of the epidemic of suicide? I see it among all classes of people, because we’ve focused on opioids too long to the exclusion of research and exclusion of a whole world of medications now generic, no longer on patent therefore inexpensive, FDA approved medications. The biggest shock: Valuable compounded medications are no longer on formularies of insurers! Our most affordable FDA approved medicines are no longer covered by insurance.

.

Where is the data that we must limit the dose to 100 mg per day morphine equivalent?

Is it too much pain medicine or is it untreated pain?

Is it lack of medical care?

or is it lack of affordable medical care?

.

 

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My comments arise from grave concern the Insurers and FDA are overlooking the needs of my pain patients. I must speak up now despite need to recover in the next few days.

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Where is the concern for the pain patient

in this multimillion dollar pharmaceutical-company-funded opioid conference?

FDA mandated that manufacturers of extended release opioids fund the conferences.

Where are the millions that need to be spent on

rational interdisciplinary pain management,

rather than just opioid management?

.

We need more than just studies of suicides and opioid changes.

We need hospitals and insurance systems

to recognize legitimate therapies that work for real people.

Would the epidemic of addiction

go down if people could get treatment for their pain?

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I posted this week on a new study, an epidemic of suicide in Caucasian middle aged Americans. The results were a shock to Case and Deacon, the Princeton Economists who did the research that merited two articles in the New York Times.

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..

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Epidemic of suicide

deaths as high as in the AIDS epidemic,

driven by pain, disability, loss of job, drug abuse, other.

By too many opioids or by untreated pain?

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That is why, a few days ago I posted on that epic study by Princeton economists: the suicides in middle aged Caucasians now comparable to deaths during the AIDS epidemic. I posted how that can change. In that article and for years with this blog, I post about medications that work more effectively than opioids, i.e. glial modulators, and the need for compounded and herbal medications from approved highly reputable small local pharmacies need to be covered by insurers and allowed on hospital formularies.

.

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Epidemic of suicide – could it be due to lack of pain treatment

not due to an epidemic of opioids?

Is it too much pain medicine or is it untreated pain?

Is it lack of medical care?

Or is it lack of affordable medical care?

.

 

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The key figure from the Case-Deaton study on epidemic of suicides in white middle-aged Americans –  bigger than deaths at the height of the AIDS epidemic. The question is why?

Andrew Gelman, statistician at Columbia University and writer for the Washington Post, argues in his blog against the rate being higher at all. His conclusion: “…death rates among middle-aged non-Hispanic whites in the U.S. slightly increased, even while corresponding death rates in other countries declined by about 30%.”

Screen Shot 2015-11-05 at 7.53.11 PM

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Regardless of the argument, untreated pain is a big problem. It causes suffering and joblessness, and can lead to addiction and suicide.

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Does it matter which side of the argument is right?

Pain management is being taught in only 3% of American medical schools.

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births.

.

Where is the data that we must limit the dose to 100 mg per day morphine equivalent?

Is it too much pain medicine or is it untreated pain?

Is it lack of medical care?

Or is it lack of affordable medical care?

Insurers are not willing to pay for larger doses of opioids

and deny prior authorization.

Does this lead to suicide?

Money is the root of some of this.

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The cure for suicide is not just to take a sword and slice off the top doses of morphine, and treat everyone with the same low doses, whether you have herniated discs or sprained ankle or RSD.  Sprained ankles may be already getting too much.

.

 

Why blame it all on over-prescribing? How about suicide due to under-prescribing, or suicide from not treating pain at all because healthcare insurance and unemployment don’t mix?   

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Are they blaming high doses as cause of suicide? How about when high dose opioids fail, when all drugs fail, we see no new drugs on the horizon for pain control. That does not fill those patients with hope.

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Of course it is important to acknowledge, as the New York Time health section has followed that epidemic research with How Doctors Helped Drive the Addiction Crisis.

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Where is the data that we must limit the dose to 100 mg per day morphine equivalent?

.    .

 

Someone must advocate for change. It’s not just pills, it’s not just opioids.

.

We are all at risk from disabling pain, loss of jobs and suicide

—yes, doctors too become disabled—

because of substandard education in pain management in this country

focused almost universally

on opioid treatment of pain.

..

Lack of funding killed the university interdisciplinary pain management centers in 1991

 

AND we need access to compounded drugs, herbs & supplements in our hospitals.

If Memorial Sloan Kettering Cancer Center can do it, why can’t my hospital?  

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Expect 100 mg oral morphine or equivalent maximum dose per day to rapidly become the standard nationwide. Insurers are refusing to cover the cost of higher doses. Even if you can afford $17,000 out of pocket each month for pain relief, your doctor will be shouldering liability if outside these rapidly evolving guidelines. Insurers rule – and they deny coverage of inexpensive compounded drugs that work better than opioids for my patients who have failed all known treatment. That’s why we need better education and more clinically focused research.

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Those who blame Obamacare for high insurance costs and business-wide practices need look no further than the price of medications, especially opioids.

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It seems everyone breezes over where Washington State came up with a maximum of 100 mg morphine (or equivalent) as a maximum daily dose of opioid. 

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This 100 mg maximum daily morphine dose became law in Washington State many years ago, initially for Workers Compensation, and will soon be adopted by Oregon.

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Of course we are all concerned about the shocking rise in deaths from prescription opioids that are occurring since opioids began to be used after Russell Portnoy published its use for chronic pain in 1991. We just didn’t know that they work for cancer pain that is usually acute pain, not for what is now tens of millions with chronic pain who are on opioids

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But opioids are still necessary for some. Those of my patients who take opioids will have a very hard time with the 100 mg morphine (or equivalent) maximum daily guideline. Informed consent is out the window. We all recognize the practice of medicine has been done by insurance companies since the late 1980’s when managed care took over. This will not change. Now insurers require the ICD10 diagnosis code before they will allow the pharmacist to refill an antidepressant that the patient has been taking for one year with much needed relief. This will give them more tools to deny paying.

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It would appear that those who govern our medication use (insurers and DEA) — and who deny coverage of even more useful, inexpensive medication –  feel that 100 mg morphine equivalent is the maximum dose that should be prescribed.   

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100 mg oral morphine is equivalent to:

~

66 mg Oxycodone

~

25 mg/hr Fentanyl Patch

~

25 mg hydromophone (Dilaudid)

~

120 mg hydrocodone (12 of the Vicodin, Norco, Lorcet 10 mg tablets)

~

30 mg Oxymorphone (Opana) use not recommended

~

Morphine               to                Methadone      

30-90 mg                                   One fourth the morphine dose

90-300 mg                                 One eighth (200 mg/day morphine = 25 mg methadone)

300-500 mg                               One twelfth the morphine dose

>500 mg                                    One twentieth the morphine dose

 ~

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Methadone conversion is far more complex than this guideline from University of Michigan

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Only 3% of medical schools teach pain management. That ignorance is costing us trillions in insurance and pharmaceutical fees, and right now the latter two are making war on each other by taking it out on you, the patient who is getting substandard care. They’re taking care of their financial needs that show us the symptoms of disease, pain, suffering, disability, loss of job, and the just published this week, the epidemic of suicide. We need to treat the cause, not just the symptoms. Medical education, injury prevention and treatment needs to be taught starting K-12. The cost would pay for itself but the Insurance Industry needs to pay for it there and in University Medical Schools because Congress will not pay for it. It would be a cost saving investment that would pay itself off in care for seniors when grandchildren have to spot mom and dad in the 24 hour, extended family care that strains budgets. We cannot afford not to teach trigger point basics to each kid and each physical therapist and MD. That alone could save tons of opioids and monthly visits for what never works for muscle strain that no one has found.

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I’m tired of seeing how degraded it has become. To fail to treat the cause of disability and suffering is far more in our hands now, it could happen if people were taught basics instead of opioids, K through medical school. Are we teaching only opioids? yes, it seems so. I am advocating for everything I have written about in this blog since 2009. Glial modulators, mechanical approaches, but compounded medications, in particular, are sadly becoming unaffordable because insurers have stopped coverage for them. Then we all lose one of the most important tools, the only tool, that my patients and millions of others have in treating intractable pain or treatment resistant Major Depressive Disorder, Bipolar Depression. Compounded medications often work after everything else has failed. The lives of my patients have usually either returned back to normal or  improved in ability to function. That has never been shown with opioids for chronic pain.

 

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I’m too exhausted to be in a position to edit what I’ve written just now, or write adequately. I am just furious at the direction our country for decades has pushed into opioid treatment rather than pain management. This has reached peak brewing since the DEA conference yesterday, dictated by the FDA funded by opioid manufacturers.

~

It is a hope that Insurers could fund an analysis of the billions that could be saved and suicides prevented if they funded pain management. What is there to live for than a life free of pain and disability?

.

The analysis could show how much is saved when training begins with the young, how to prevent and treat injury. How helpful a child can be to aging grandparents or parents when illness strikes the family. We always turn to family first, as we should. Why is something of the field of pain management not taught in K-12?

 

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The FDA just authorized two opioids for children this last week. I have a vague memory one was oxycontin in children. I do not argue against opioids, I have given opioids to tiny children when I worked in hospice. Children have crippling arthritis too and other medical needs for opioids.

.

I am not arguing against opioids. I am saying that what is taught is zero pain management. The focus on drugs is completely unbalanced.

 

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If Sloan Kettering can teach herbal and supplementary medicine to cancer patients, why not begin the study of herbal medicine at K-12 since a lot of parents are taking it instead of using common sense such as exercise, weight loss, family time, relaxation. And herbal and supplementary medicine is what these young ones will teach their children when they grow up. Hopefully prevent some of the toxicity from swallowing all sorts of useless and dangerous things on the shelves.

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Rational health care must begin young in the schools. .

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Stephen Colbert: “I love the thing that I most wish had not happened.”


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Excerpt from a recent interview of Stephen Colbert by Joel Lovell:

.

“…he is the youngest of eleven kids and … his father and two of his brothers, Peter and Paul, the two closest to him in age, were killed in a plane crash when he was 10.”

..

The interview ends with the realization he had of their deaths.

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..

.

….I love the thing that I most wish had not happened.

.

I asked him if he could help me understand that better, and he described a letter from Tolkien in response to a priest who had questioned whether Tolkien’s mythos was sufficiently doctrinaire, since it treated death not as a punishment for the sin of the fall but as a gift. “Tolkien says, in a letter back: ‘What punishments of God are not gifts?’ ” Colbert knocked his knuckles on the table. “ ‘What punishments of God are not gifts?’ ” he said again. His eyes were filled with tears. “So it would be ungrateful not to take everything with gratitude. It doesn’t mean you want it. I can hold both of those ideas in my head.”

.

He was 35, he said, before he could really feel the truth of that. He was walking down the street, and it “stopped me dead. I went, ‘Oh, I’m grateful. Oh, I feel terrible.’ I felt so guilty to be grateful. But I knew it was true.

.
“It’s not the same thing as wanting it to have happened,” he said. “But you can’t change everything about the world. You certainly can’t change things that have already happened.”

.

Consider that this is coming from a man who millions of people will soon watch on their televisions every night—if only there were a way to measure the virality of this, which he’ll never say on TV, I imagine, but which, as far as I can tell, he practices every waking minute of his life.

.

The next thing he said I wrote on a slip of paper in his office and have carried it around with me since. It’s our choice, whether to hate something in our lives or to love every moment of them, even the parts that bring us pain. “At every moment, we are volunteers.”

..

.

 

~~~~~~~~~~~~~~

.

 

‘What punishments of God are not gifts?’ Tolkien

.

~~~~~~~~~~~~~~

.

“So it would be ungrateful not to take everything with gratitude. It doesn’t mean you want it.

I can hold both of those ideas in my head.”

.

~~~~~~~~~~~~~~

.

 It’s our choice, whether to hate something in our lives or to love every moment of them,

even the parts that bring us pain. “At every moment, we are volunteers.”

.

~~~~~~~~~~~~~~

.

 

.

 

.

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.

.

..

.

.

.

.

.

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

.
This material 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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Analgesic Response to Ketamine Linked to Circulating microRNA in Complex Regional Pain Syndrome


.

.

Analgesic Response to Intravenous Ketamine

Is Linked to a Circulating microRNA Signature

in Female Patients

With Complex Regional Pain Syndrome

.

.


The ability to measure Micro RNS’s (miRNA) in blood looks like it may become an important tool someday once it is available for the clinic. It could be used to predict if your condition will respond to various medications.

.

MicroRNAs are emerging as important modulators of various psychiatric (schizophrenia, bipolar disorder) and neurological conditions including pain, epilepsy, cognitive dysfunction, neuronal development, structure and function. “MicroRNAs are small, non-coding RNAs that act as post-transcriptional regulators of gene expression.  miRNA’s can be affected by morphine and affected by other drugs. It is hoped that complex clinical phenotypes may be profiled in assays of peripheral blood and may predict response to treatment such as in this study. Ketamine is given for selected patients that have failed to respond to standard treatment.

.

This research was published in Pain, June 2015, by Professor Schwartzman’s group at Drexel University. Seven of his patients with Complex Regional Pain Syndrome were ketamine responders and 6 were poor responders. They note that, “Although [ketamine] treatment is generally effective, approximately 30% of patients have an inadequate response to ketamine.”

.

“Stability in circulation and dysregulation in disease state are 2 features making extracellular miRNAs useful candidates for biomarker discovery. Alterations in miRNA profiles have been reported for rheumatoid arthritis and systemic lupus erythematosus as well as for painful conditions such as irritable bowel syndrome, chronic bladder syndrome, endometriosis, and migraine. Cerebrospinal fluid from patients with fibromyalgia showed differential expression of 9 miRNAs.”

.

Quoting directly from the article:

.

Highlights

.
•We studied ketamine treatment–induced miRNA alterations in blood from patients with CRPS.
•Differential miRNA expression was observed in whole blood before and after treatment.
•Before therapy, 33 miRNAs differed between responders and poor responders.
•Lower pretreatment levels of miR-548d-5p may contribute to higher UDP-GT activity.
•Circulating miRNAs can be potential biomarkers in predicting treatment response.

.

From the Abstract

.

Investigation of the mechanistic significance of hsa-miR-548d-5p downregulation in poor responders showed that this miRNA can downregulate UDP-glucuronosyltransferase UGT1A1 mRNA. Poor responders had a higher conjugated/unconjugated bilirubin ratio, indicating increased UGT1A1 activity. We propose that lower pretreatment levels of miR-548d-5p may result in higher UDP-GT activity, leading to higher levels of inactive glucuronide conjugates, thereby minimizing the therapeutic efficacy of ketamine in poor responders.

.

Perspective

.
This study suggests the usefulness of circulating miRNAs as potential biomarkers. Assessing miRNA signatures before and after treatment demonstrated miRNA alterations from therapy; differences in miRNA signature in responders and poor responders before therapy indicate prognostic value. Mechanistic studies on altered miRNAs can provide new insights on disease.

 

.

 

From the Discussion

.

Ketamine is also considered to be the prototype for a new generation of glutamate- based antidepressants that can alleviate depression within hours of treatment. Several biological measures have been explored to characterize treatment response and to gain insight into mechanisms underlying the rapid antidepressant effects of ketamine. A plasma metabolomics study in patients with bipolar depression suggested that the basal mitochondrial b-oxidation of fatty acids differed between responders and nonresponders to ketamine. Other studies have shown differences in baseline plasma concentrations of D-serine, serum levels of interleukin 6, and plasma levels of Shank3, a postsynaptic density protein involved in NMDA receptor tethering and dendritic spine rearrangement.

.

.

Differences in the ability to metabolize ketamine because of interindividual differences and pharmacogenetic factors have been proposed to contribute to the varied responses to ketamine therapy and its clinical outcome. Similar conclusions have been drawn for patients with depression; plasma from patients with treatment- resistant bipolar depression who had undergone a single 40-minute infusion of a subanesthetic dose of ketamine showed that although NK is an initial metabolite, it is not the major circulating metabolite. This again suggests that other downstream metabolites of ketamine may play a role in the pharmacological effects of the drug. It is also known that (2S,6S)-hydroxynorketamine is an active and selective inhibitor of the a7 subtype of the nicotinic acetylcholine receptor; this activity was shown to contribute to the pharmacological responses associated with the antidepressant activity of (R,S)-ketamine. We postulate that in patients with CRPS, 1 factor contributing to resistance is an altered pharmacokinetic profile produced by enhanced elimination of active metabolites downstream of NK, which is mediated by hsa-miR-548d-5p. However, because we have relied on indirect evidence of a higher percentage of direct/indirect bilirubin in poor responders, indicating increased UDP-GT enzyme activity, additional studies investigating hydroxynorketamine and its downstream metabolites along with their glucuronide conjugates in plasma and urine will provide direct evidence for the role of miR-548d-5p in mediating response to ketamine therapy in responders and poor responders.

.

They noted a significant difference in body weight between responders and nonresponders (heavier), but not in duration of disease and analgesic response to ketamine. Toward that end, they will publish separately upon

.

… investigating the link between miR-34a, which showed 28-fold reduction in poor responders relative to responders (Table 2), and the neuroendocrine system….

.

From the Conclusion

.

Our studies showed that miR-548d-5p can regulate UDP-GT but not CYP3A4, suggesting that UDP-GT activity in responders and poor responders may be mediated by differences in the level of circulating miR-548d-5p. Lower levels of miR-548d-5p in poor responders before treatment could result in higher UDP-GT activity, leading to the production of more inactive glucuronide conjugates and faster elimination of active ketamine metabolites downstream of NK. Thus, the levels of hsa-miR-548d-5p could minimize the therapeutic efficacy of ketamine and pain relief. Differences in miRNA signature can thus provide molecular insights distinguishing responders from poor responders. High failure rates of drugs targeted to treat neuropathic pain warrant changes in approaches. Studies targeting well-defined patient populations for clinical trials will play a crucial in developing drugs that may be efficacious in a subset of patients. Extending this approach to other treatment and outcome assessments might permit stratification of patients for maximal therapeutic outcome.

.

.

How frustrating it is for patients and family who must cope with an intractable condition such as pain or Bipolar Disorder or treatment resistant Major Depression that has failed all commonly prescribed medications. For all of them, we need changes in approach.

.

“High failure rates of drugs targeted

to treat neuropathic pain

warrant changes in approaches.”

.

Perhaps scientists reading this would comment upon how it may relate to tolerance as it differentially occurs in those receiving intermittent ketamine vs continuous intravenous infusion.

.

Dysregulation of miRNA’s has been shown in psychiatric disorders including depression and schozophrenia, neurodevelopmental disorders, cognitive dysfunction,  epilepsy, chronic pain states with implication for the cause and treatment of these disorders.

.

Research targeting miRNA’s as novel treatment for depression has shown that chronic fluoxetine, repeated electroconvulsive shock therapy, and acute ketamine have the capacity to alter hippocampal miRNA levels.

.

It is hoped these tests may be available someday clinically as the cost of off-label treatment not covered by insurance is a great burden for those already disabled by intractable pain or treatment resistant depression.

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PUBLIC WARNING

warning reprinted with permission of Demitri Papolos, MD
.
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.

.

.

.

.

.

.

.

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

.
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!

.

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

.

.

.

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.

.

S-Ketamine for Patients with Neurological Injury – Revising a Dogma


.

.

Continueing on yesterday’s discussion of S-Ketamine, here, there is an interesting Anesthesia & Analgesia review article 2005, entitled:

.

Revising a Dogma: Ketamine for Patients with Neurological Injury?

.

Money quote:

.

“In the laboratory, ketamine has neuroprotective, and S(+)-ketamine additional neuroregenerative effects, even when administered after onset of a cerebral insult. However, improved outcomes were only reported in studies with brief recovery observation intervals. In developing animals, and in certain brain areas of adult rats without cerebral injury, neurotoxic effects were noted after large-dose ketamine. These were prevented by coadministration of GABA receptor agonists.”

.

~

.

If we are to use ketamine in the setting of intractable conditions, because nothing else works at all or works better, we must begin to have more data. Its effects on the brain seen in animals has specifically never been proven to occur in humans. We need more data in humans after chronic use.

..

Those who are disabled, deserve the choice to continue what works for desperate situations. At the same time, much needed research should be done on both racemic and S-ketamine. The affordable racemic ketamine, generic, off patent, and the S-Ketamine yet to be on market. S-Ketamine may be so strictly defined by FDA indications as to restrict its use considerably.

.

And for chronic depression, outside of emergency, insurers may not  cover without step therapy and prior authorization. That and cost will severely limit its use.

.

 .
..

.

.

.

.
PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
.
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.

.

.

.

.

.

.

.

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

.
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!

.

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

.

.

.

.

S-Ketamine – What’s That?


 

.

W-H-A-T’s  T-H-A-T?

.

..

S-Ketamine nasal spray is undergoing clinical trials in a few countries in Europe for treatment of Major Depressive Disorder. It may have fewer side effects and be effective at a lower dose than the FDA approved racemic ketamine we now have in the U.S.

.

Racemic means it has equal amounts of left-and right-handed enantiomers of a chiral molecule. Google those words if you wish, or just look at your left and right hand. They are not the same. That’s the point, and that’s why FDA must approve new clinical studies on S-Ketamine nasal spray which, I understand, is being fast-tracked by the FDA for Treatment Resistant Depression.

.

S-ketamine has twice the affinity for the NMDA receptor (compared to racemic), it’s a 4-times more potent dopamine re-uptake inhibitor, and there’s quicker elimination from body too. However, it still may have a hallucinogenic effect related to enhanced glucose metabolism in prefrontal cortex . . . . But not due to effect on sigma receptors, because it doesn’t have much affinity for those; and it may still elevate liver enzymes.

.

I will be very interested if that’s true of liver enzymes. It is extremely rare in my experience.

.

I am told that Thomas Insel, MD, the Director of the National Institute of Mental Health, NIMH, says ketamine is the most important new drug in psychiatry.

.

I hope my patients could feel that level of support from their local treating doctors. In my experience it is one of the safest medications I have prescribed in 40 years of medicine. I saw patients with intractable status epilepticus, chronic pain, cancer pain and treatment resistant depression. There is simply nothing comparable to ketamine. These conditions can be highly refractory.

.

Further, Dr. Insel “Acknowledges That Antipsychotics May Worsen Long-Term Outcomes.” I have seen psychiatrists who prescribe antipsychotics all their lives, now discharge patients now normal on ketamine at long last after decades of treatment resistant depression that has ruined their lives, their finances and their families.

.

Why? Because it works? Because it’s generic and there are no drug representatives who come every week to offer free dinners? I hate to think that but the wall of resistance is awful for these patients.

.

..

I am deeply concerned that S-ketamine nasal spray

may be allowed only

for use in Emergency Departments.

.

~

.

That means the dose will

likely not be individualized.

.

.

It should be made available not just for Emergency Departments but also for outpatient use to physicians specially trained in the simple technique of how to start low, go slow, as we do in medicine to find an effective dose with fewest side effects. We have taught that at UCLA Epilepsy Center since the early 1980’s. And we use ketamine IV for Status Epilepticus – it works in emergency when nothing else works, and it’s a lot safer than many other drugs that induce coma: No effect on breathing. Of course, we are not inducing coma for depression or pain. We only use high-dose ketamine to do that for anesthesia in the Operating Room or for Status Epilepticus in the ICU. It is wonderful for pain when all else fails, including continuous infusion for cancer pain or Complex Regional Pain Syndrome.

.

Outside of emergencies, start low, go slow works for ketamine as well as it does for epilepsy medication and for strong opioids like fentanyl spray for rapid changes in cancer pain.

.

Going fast in high dose increases the potential for injury, even dreaded side effects or death. Yes, in an emergency we may consider the use if benefit exceeds the risk. That is best done in special facilities or ICU. The Benefit: Ketamine may allow suicidal ideation to resolve in ten minutes. But if the untrained ER doctor gives a high dose in a big man who needs a tiny dose – and yes, I have large male patients who respond to tiny doses – why give an unnecessarily high-dose to a person who has already suffered black suicidal thoughts that very night and almost killed him or herself?

.

When you start low, go slow, one does not need to rush for suicidality to be gone in minutes. We can wait 1 or 2 days if need be. But it can still resolve in 10 minutes in some, and at most one or two days in almost everyone. Breathe . . . . . . . easy. . . . . . like new life, a return of life, dawning.

.

I’ve seen cancer patients who had such severe hallucinations from Narcan that instantly reversed their opioid, slamming their body into acute withdrawal, that they literally saw the devil. They would never go near drug that again if in their power. Trembling fear. That could potentially happen with ketamine when given in a dose too high, the “one formula fits all.”

.

Hallucinations: The other day I saw a patient who had a history of hallucinations with Lyrica, Cymbalta, and now with ketamine after he slowly increased the dose to a non-effective low dose of 20 mg. He vividly remembers the hallucination. But his neuropathic pain is so extreme, and he had failed everything else, he was willing to try it again after specific instructions. Hallucinations did not recur. Yes, there is a method: Teach the body how to develop tolerance to the drug and the side effect will not continue; now you are able to push the dose to the effective level for depression or, in far higher doses, for neuropathic pain.

.

.

Persons with Major Depressive Disorder

respond to

far lower doses of ketamine

than persons with severe neuropathic pain.

.

.

Ketamine is unique for its rapid onset relief, and, when it is administered in an individualized way, it has fewer side effects. Many physicians and lay persons are likely afraid of rare side effects, and they may shun this valuable drug. Even now, everyone is started with the same sudden high IV dose: BHAM a big dose! Thus, when S-ketamine is FDA approved for use in a nasal spray the need to limit that method to emergency settings is very reasonable: the high dose BHAM! for S-ketamine spray in Emergency. Ketamine can be rapidly effective.

.

But for chronic severe forms of Major Depressive Disorder when there is no sudden emergency, I know of no better way to teach the use of ketamine nasal spray than we do now when we teach the use of rapid onset fentanyl spray under tongue. Simply teach how to begin treatment, slowly, at home, to reach the effect in one or two days.

.

I urge the FDA approve home use of S-ketamine for chronic conditions. There is very little difference between the use of rapid onset fentanyl spray under tongue for severe cancer pain and the use of ketamine nasal spray. I teach that to patients and doctors. It is humane and easily within our reach to address intolerable suffering.

.

With use of medication at home rather than Emergency Room, the patient is given control of a chronic intractable condition that fails to respond to other remedies. As always, physicians must assess past records and the entire history, the risk of addiction and drug abuse, and follow the patient at reasonable intervals for potential toxicity.

.

The main difference between ketamine and high dose opioids is that ketamine does not affect breathing, whereas we know what does, and its making headlines: death from prescription opioids. Any drug could potentially cause death, that’s why we use utmost caution and best judgement. Read about all the street addicts you want, and the sad thing is ketamine is now the #1 drug of abuse in China, but how different is that from opioids even on our streets? Yet, if you had an intractable condition, name the top drugs you would want to take home with you.

.

Here I discussed more about my experience with the drug for Treatment Resistant Depression.

 

.

.
PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
.
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.
.

.

.

.

.

.

.

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

.
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!

.

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

.

.

.For

Intranasal Ketamine in Major Depressive Disorder


.

.

Physicians at Icahn School of Medicine at Mount Sinai, New York, studied intranasal ketamine in 18 patients with Major Depressive Disorder, published in 2014:

.

A Randomized Controlled Trial of

Intranasal Ketamine in Major Depressive Disorder

.


Conclusions

.

“This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.”

.

I have previously posted more detail on this study. They report a significant antidepressant effect occurred as early as 40 minutes in some. I have seen some respond in seconds. But the dose is unique and specific to each person and there is no response until that dose is reached.

.

~~~

.

It is hoped that more studies will be funded, though that seems unlikely since congress slashed the NIH budget in 2010 by the unthinkable 30%, never done in history.

.

Entire generations of scientists are now lost forever.

.

Ketamine Safety

.

Ketamine is one of the safest medications I have prescribed in 40 years of medicine. And I meticulously obtain laboratory studies at least twice a year to verify any potential harm as it has been reported in addicts that it may affect bladder, kidney, liver or biliary system. I first prescribed ketamine about 14 years ago for intractable pain rated 10 on a scale of 10 for 30 years; and prescribed ketamine since Spring 2012 for Major Depression. For years I searched to find a spray with a metered dosing system. Thus since late 2011, intranasal has been the delivery I find most useful. When given as nasal spray or under the tongue, not swallowed, it goes straight to the bloodstream, bypassing the liver, and works for depression because the liver does not convert it to a different metabolite.

.

Nevertheless, it is important to stress that ketamine must be monitored for any possible adverse effects including toxicity and/or addiction. I require long distance patients to be followed by a psychiatrist or psychologist regularly while on ketamine. So far, my returning patients have been stable for years.

.

Further, when given by the nasal or sublingual route, I do not see the side effects that my anesthesiology colleagues see after I.V. infusion. I’ve been in board meetings with some of the finest anesthsiology pain specialists in the country sharing and comparing experience. I don’t see those complications. But that is what is published and I.V. is how it is given in the few centers where ketamine is used for treatment of Major Depression or Bipolar Depression.

.

Ketamine is a short acting medication whether it is given I.V. or nasally or under the tongue. But it is quite bitter and most prefer nasal delivery.  Review the case study of the professional who traveled out of state once or twice weekly for one year to receive I.V. ketamine. She had failed ECT 9 or 10 times – memory loss was so bad she got lost in her own neighborhood. She now does very well on a small dose every 48 hours given nasally. In the same post, I reported the patient with Juvenile Bipolar Disorder, Fear of Harm phenotype whose profound thermoregulatory abnormalities respond in seconds to ketamine, with a very small 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.

.

Unfortunately research protocols require the study of fixed dosages in order to be a cost effective study for one sample size at one dose to be even slightly meaningful, even then 18 patients studied at Mt. Sinai is a small study at the one dose they used.

.

The principle that I have always used is “start low, go slow.” That allows for the discovery that some large men may require the tiniest dose and some tiny 90 pound seniors may require some of the largest doses I’ve seen. It cannot be predicted by body weight. Anesthesiologists generally think in terms of mg/kg body weight, for example the 0.5 mg/kg I.V. generally used for depression. But ketamine’s dosage variance is unrelated to weight. That likely explains why some develop frightening symptoms when given IV, and others do not respond. One size does not fit all. That method either under-doses or overdoses.

.

There are case reports on this website giving examples of some individuals I have seen with Major Depressive Disorder. One man is unusual in needing a small dose only every 6 to 8 weeks, but most use the nasal spray daily or every second or third day. I suspect that after initially starting ketamine on a daily basis for one or two weeks, the frequency of dosing may be lowered to every two or three days. Less is more.

.

Professor David Feifel at UCSD guesstimates that ketamine helps 70% of persons with Major Depression. I think that’s a fair statement given that we are unlikely even to see the unknown number who remain at home, forever feeling they are unable to leave their confinement. We know that effects of ketamine are blocked in mice that are deficient in BDNF. We may speculate that when ketamine fails in persons with Major Depression, that may be due to lack of BDNF. We know exercise helps Major Depression and exercise increases BDNF. Much more research is needed.

.

The use of ketamine is essentially a first line drug for Complex Regional Pain Syndrome (CRPS). That may never be said in publications, but that has been the case for years in persons with CRPS who have failed all other medications. I specialize in CRPS, a form of neuropathic pain that leads to suicide more often than any other pain syndrome.

.

For pain, intranasal ketamine is far shorter lasting, typically three hours, rarely six. And requires doses far higher than for Major Depression or Bipolar Depression. Even then, when used for pain six times daily in very high doses, it has proven to be profoundly safe with few if any side effects that last less than half an hour, if present at all.

.

.

Inflammation

.

The role of inflammation and glia in the pathogenesis of depression has been well established since 2000, and discussed here. The study of ketamine has taken on new life with the discovery that it profoundly lowers pro-inflammatory cytokines produced by microglia. Inflammatory cytokines have been shown to be elevated in chronic pain and in Major Depression. That is why I feel it is important to prescribe adjuncts that also lower inflammatory cytokines. And patients with Major Depression and Bipolar Depression have reported the adjuncts make ketamine stronger and last longer. Some don’t even need ketamine after awhile, but remain on the adjuncts.

.

Ketamine is not a cure and I find it is best used with adjunct medication. In my experience, ketamine and adjunct medications are likely to help as long as prior to treatment, patients are still able to function, to work at least somewhat. I do have 4 patients in the last four years who have not left their home or their bed for many years, and they failed to respond. Sadly, one older woman had to be institutionalized for life, her melancholic depression was so deep. When ketamine is even partially effective, I have patients who had been too fatigued to work before treatment, yet who are able to return to graduate school for a PhD and do well for years on a stable dose. It is immensely rewarding to be a part of this unique therapy, to see them regain life and function after years of misery and disability.

 

.

.

Studies

.

S-Ketamine

.

It is my hope to be able to compare S-ketamine, that is not yet FDA approved, with the racemic* ketamine that we now have, that was FDA approved in 1970 in high dose as an anesthetic. Obviously we do not use high anesthetic doses for control of pain or Major Depression. I understand unfortunately that when clinical studies are completed, S-ketamine will be available only in emergency departments.

.

*Racemic means the molecule has equal amounts of left and right-handed enantiomers (mirror images) of a chiral molecule (meaning, you cannot superimpose the left hand with the right hand. They mirror but do not superimpose). Thus both left and right racemic ketamine mixture has been FDA approved, but the S-ketamine, the left sided molecule is considered a different drug, and must be FDA approved.

.

Without FDA approval, ketamine can be studied with FDA permission that provides an Investigational New Drug (IND) application.

.

Given the lack of funding for almost any research in this country, I would consider doing a patient-funded study if patients showed interest. It would be modeled on the intranasal study published in the Mt. Sinai study, above, i.e. short term, randomized, double blind, placebo controlled.

.

It is reported that S-ketamine may be more effective with fewer side effects. This must be proven and cannot be taken at face value without several studies. Shockingly, some publications in recent years have been fabricated and woven into mythology.

.

.

Finally, ketamine is off-label for pain and for major depression.

.

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

..

“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.”

.

 

.
PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
.
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.

.

.

.

.

.

.

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

.
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!

.

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

.

.

.

 

 

Ketamine – small doses work in depression and bipolar disorder


.

.

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.

.

Ketamine really does work

.

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

.

Two Cases

.

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.

.

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.

.

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.

.

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.

.

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.

.

**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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Do You Have Depression? Are you the one who runs into snow wearing shorts?


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Since you were a baby, thermoregulation may be the source of the problem

that triggers your depression or the depression of someone you know.

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You may be a candidate for a research study if you have other key characteristics.

Treatment may help.

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Contact the Juvenile Bipolar Research Foundation.

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OR

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Demitri Papolos, MD, is the psychiatrist who, in collaboration with many others, has discovered that body temperature appears to be at the origin of this condition:

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Juvenile Bipolar Disorder, Fear of Harm phenotype.

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Dr. Papolos has written many publications and has published a book, with Janice Papolos, describing this serious disorder. “The Papoloses were the first to sound a national alarm about the dangers of using antidepressant and stimulant drugs with this population of children.”

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Either the link to Dr. Papolos or the Research Foundation, above, can give you further information on treatment.

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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 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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I am not affiliated with Dr. Papolos, but wish to call attention to the dedicated academic work they have been doing for this devastating mood disorder. .

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Of interest, thermoregulation appears to be modulated by low dose naltrexone (LDN).

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It has been anecdotally reported to relieve heat intolerance in persons with Multiple Sclerosis.

I have seen a response with Juvenile Bipolar Disorder/Fear of Harm, and

severe postmenopausal hot flashes were completely reversed by LDN.

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Naltrexone blocks the TLR4 receptor. There is a strong literature on TLR4 and temperature regulation. This raises the interesting question whether anyone has done objective studies to show that low dose naltrexone may be modulating temperature in patients. If you have experience with this, please add your 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.

~~~~~

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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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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Ketamine Nasal Spray for Major Depression – The First Randomized Controlled Trial


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A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

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Psychiatrists from Mt. Sinai in New York this month have published the first randomized controlled trial of intranasal ketamine showing it is safe, well tolerated, and rapidly effective in treating symptoms of depression in persons with Major Depressive Disorder.

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This is a small study of 18 patients with treatment resistant depression showing a significant antidepressant effect occurred as early as 40 minutes in some. 44% responded after 24 hours compared to 6% placebo. Ketamine was significantly different from placebo at 40 minutes, 240 minutes, and 48 hours, but not separable from placebo at 72 hours or 7 days thought they were still better. And ketamine was significant at improving anxiety symptoms at 24 hours. There were no clinically significant changes in heart rate or blood pressure and all changes resolved in four hours. “No serious adverse events occurred.”

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“Intranasal ketamine was well tolerated with only very minimal increases in dissociation, psychosis-like symptoms or hemodynamic parameters.” They felt these very minimal behavioral side effects and insignificant changes in blood pressure and pulse were consistent with the lower blood levels of ketamine compared to the higher doses used in studies of IV ketamine. Bioavailability via intranasal route is reported to range from 25% to 50%.

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Their sample had an average of 4.1 ± 3.9 treatment failures, compared to 5.7 and 5.1 in previous studies – those required a minimum of 2 to 3 treatment failures to enroll. Other clinical characteristics did not differ including “duration of illness, length of current depressive episode, and history of ECT.” They allowed ongoing treatment of psychotropic medication.

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They chose a 50 mg dose based on a previous study and on the dose used in persons with a chronic pain disorder (Daniel Carr, et al 2004). It is a lower dose than the 0.5 mg/kg dosage commonly given intravenously. They point out one limitation of the study was the use of the single dose and a standardized protocol, which did not allow them to study optimal dosing. Future study is needed to address optimal dosing, relapse prevention and scheduling of treatment.

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The minimal side effects shown in their study correlates well with my experience. I find the effective dose of ketamine is idiosyncratic. That means it is unpredictable and specific only to that individual. Large males may need only the smallest dose, and tiny elderly females may require far higher doses. That may account for the higher response rate that I believe I am seeing, however, I have not tracked percentage of responders. I have not seen toxicity in years of prescribing either for intractable pain or treatment resistant depression. Importantly, in my opinion, relapse prevention must address not only different neurotransmitters but also neuroinflammation, pro-inflammatory cytokines.

 

 

 

 

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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.

~~~~~

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.

.

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

.

.

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