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

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Ketamine & Opioids Stop Working – TOLERANCE – the body no longer responds no matter how high the dose


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The comments below on ketamine tolerance apply to its use either for intractable pain or major depressive disorder. I have written about ketamine several times since April 2009. Tolerance means the medication no longer has an effect. If ketamine is to be needed for decades to come, we don’t have more than 10 years experience with repeated use to understand if and when it will stop working for our patients.

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Tolerance to ketamine is a growing potential as more infusion centers open each year.

Infusions are being used at fixed dosages

that are often too high or toxic

and predispose to tolerance and loss of efficacy.

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I’ve seen two cases of ketamine tolerance since about 2009 among persons with Complex Regional Pain Syndrome (CRPS). And the neuropathic pain of CRPS responds differently than other pain syndromes. We are all snowflakes, not one of us is alike another. But CRPS is unpredictable in many ways, and very predictable in others. It is also more dynamic and capable of being reversed in many who have it.

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Ketamine is given usually IV in a few centers in the country for CRPS and for Major Depressive Disorder. I prescribe it either via nasal spray or under tongue. I may, later this year, offer IV infusions to a small number of my patients who need both.

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If tolerance develops, would drug holidays work?

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Some people develop tolerance to their medication. In the old days, when I was training in the 1970’s, Parkinsons medication over time would stop working. Our only recourse was to do an inpatient drug holiday for weeks. We had to stop the drug. The resting tremor, the constant flailing, was exhausting and life threatening, especially if you had a heart condition. Newer Parkinson’s drugs completely circumvent this.

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Would drug holidays work if tolerance develops for ketamine or is it a goner forever?

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Opioids can cause tolerance through a known mechanism. They produce inflammation that causes more pain. Higher and higher doses fail to help pain. Addicts seek the high they once felt but cannot capture. This is why addicts die, chasing the impossible. Detox. Drug holiday. In the case of addiction, many are placed on Subutex, an opioid that acts on two opioid receptors and seems to prevent craving, in part at least because it has such a long half life that the blood level never dips.

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Ketamine infusions centers springing up.

Is that all they do?

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NIH and Yale began to test IV ketamine infusions in the 1990’s for major depressive disorder, and Robert Schwartzman, MD, at Hahneman in Philadelphia was one of the early ones to infuse ketamine for CRPS and contribute a large body of research on this pain.

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But in the last 2 or 3 years I receive a growing number of mailings advertising ketamine infusion centers. Just that, nothing more. Ketamine infusion centers, not pain specialists. All these young anesthesiologists popping out of training every year have a cash pay business; insurance doesn’t cover.

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Will ketamine stop working for patients who need to use it regularly for decades and decades? We don’t know. It should be studied.

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The first patient I saw with ketamine tolerance, I referred from San Diego to Professor Schwartzman in Philadelphia. She received inpatient IV around the clock for one week, then outpatient IV boosters every month. After eight months, she stopped responding. That’s when I called him to ask what to do? He did not know. So I used glial modulators. I posted her case years ago. She is in her 70’s, pain free since 2010, and two weeks ago, as a volunteer for the Red Cross, she supervised RN’s and evacuees from the flooding at Oroville dam. Tens of thousands of people, emergency care for families and homeless.

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A recent patient has had more than 20 surgeries in her hand that has CRPS. She has failed  IV ketamine, opioids, propofol given together in ICU for weeks and weeks. Surgery triggers the glia to produce neuro-inflammation.

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Another case though unusual, also posted years ago, a young male athlete, bedridden with CRPS affecting almost entire body. Flew to Professor Schwartzman 9 times and each time, the relief was gone by the time they reached the airport. He was taking opioid medication that may have been impossible to offset.

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This is what I advise when I prescribe ketamine for my patients to use at home as a nasal spray or sublingual:

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  1. Do not use it with opioids.Opioids cause inflammation, ketamine does the opposite. It modulates (reduces) inflammation.

  2. Never use it alone. It is a glial modulator, it is not only an NMDA receptor inhibitor.

  3. For intractable, treatment resistant cases, use as many glial modulators as you can.

  4. Ultra low dose naltrexone (20 micrograms TID) can profoundly reduce tolerance in patients on opioids: they may now need 1/2 to 1/8th the dose of opioid that simply had never quite done enough. Naltrexone not only relieves pain, it may profoundly improve function.

  5. Opioids stimulate glia to produce pro-inflammatory cytokines -> pain. Stop opioids if you can. You are likely to get far better results with glial modulators, especially if you have CRPS.

  6. Pain specialists should be offering a trial of glial modulators before they choose opioids for life.

  7. Use glial modulators as needed: ketamine, oxytocin (a hormone), tricyclic antidepressants (weaker than the others but can be profound for some), metformin.

  8. Metformin, a glial modulator!  for pain! in people who do not have diabetes. I will be posting on it this coming week — inshallah

  9.  Use it sparingly. Whether ketamine or opioids, use sparingly because of tolerance.

  10. If it is a good day, use less and use sparingly. If pain spikes, use higher dose, use sparingly.

  11.  When tolerance develops to ketamine, what then?

  12. Is it possible that a drug holiday would work? Should that be in months or years? we may never find out.

  13. Use ketamine and/or opioids sparingly. Prevent tolerance. You may not always need the same dose on a good day or when pain spikes.

  14. Make sure you are doing other things to relieve pain, not just ketamine or opioids.

  15.  Dextromethorphan helps, a sigma I receptor antagonist that reduces the excitotoxic glutamate

  16. Try as much as you can to exercise.

  17. Lift the mind to positive things. Learn to block thoughts of pain, dissociate from that. Choose life and doing and being.

  18. Develop momentum. Try never to judge; that includes being hard on yourself and others.

  19. Expand your spiritual life. Find your path if you don’t already have one. It may begin for all sorts of reasons, but figure it out. It’s real. Spiritual giants from all paths have had direct perception of the infinite in many ways and forms. Direct perception.

  20. S-ketamine clinical trials are now ongoing in the US. I was very disturbed to hear the side effects of S-ketamine infusion related last week. S-ketamine deeply disturbing. It is wrong to give everyone the same dose of ketamine. Not once have I ever heard anyone recount similar side effects from ketamine infusions. I got the impression from her they were not inclined to attribute it to S-ketamine, but it would be disturbing if they did not. Ketamine’s dose no matter how you give it is idiosyncratic, meaning some respond to 2 mg, some to 400 mg. It is wrong and should be unethical to subject someone to doses 200 times the dose they may need. It is dangerous and promotes tolerance.

  21.  If you’ve been stuck in bed, branch out and vary the things you do. Find music and poetry and literature. Maya Angelou suffered yet her words make you soar. Check out James Baldwin in the Oscar-nominated documentary “I Am Not Your Negro.” Baldwin’s immensely powerful analysis deconstructs movies, not as a mirror, but as a window into the imaginary; and how movies shape our thinking. As a movie critic, his writing is about poverty, class and “not everything that is faced can be changed, but nothing can be changed if it is not faced.” …  “There are days — this is one of them — when I wonder, how precisely are you going to reconcile yourself to your situation here…” So many writers fail to teach us how to analyze and think with such clarity. Something we don’t always do. We need to train ourselves to become critical thinkers. Baldwin brilliant mind demonstrates critical thinking at its best.

    Critical thinking is not a partisan issue. Tens of millions will lose jobs as robots rapidly take over in the next 3 years. Industry will reap more than ever in history. We all need to rethink our lives at some point.

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    Dylan’s song is about “the possibility that the most important (and least articulated) political issue of our times is that we are all being fed a false picture of reality, and it’s coming at us from every direction.”[10]

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    “Propaganda, all is phoney,” Dylan says in “It’s Alright, Ma (I’m Only Bleeding).”

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    Advertising signs that con you
    Into thinking you’re the one
    That can do what’s never been done
    That can win what’s never been won
    Meantime life outside goes on
    All around you.

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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 ketamine is FDA approved for another purpose, decades ago it was approved for anesthesia. In qualified hands, ketamine is one of the safest medications we have in our formulary.

     

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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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Spinal Cord Stimulators – comment on RSD


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Spinal Cord Stimulators 

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 Craig’s comment

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By no means do I mean to say that I or anyone else has better insight into how to treat pain, but I am against spinal cord stimulators [SCS’s] for treatment of pain due to CRPS, and possibly against use in other situations. I demand that the billions in profit they made be put into a retrospective and prospective study of damage caused by them in order for them to give full informed consent.

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I have 3 goals writing this.

  1. SCS’s

  2. Craig’s experience

  3. The Only Real Answer for severe pain, not damaging the system with opioids

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Informed consent is never given for spinal cord stimulators because it requires truth telling, something our corporations have been reluctant to do. Business ethics are not medical ethics, as we keep being reminded daily in the headlines.

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I enclose, below, a generously expressed and detailed comment by a man who had the patience to sit down and  write the painfully gory details so you can weigh-in on your decision whether to follow your pain specialist’s opinion to give you one. I don’t want anyone to feel suckered into choosing them and if I had pain I’ll admit I’d crave relief too. Anything. I’d be in line before the doors open.

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But if you have CRPS, spinal cord stimulators will create more pain. CRPS evolves unpredictably, by a will of its own. I know some very desperate patients with CRPS everywhere including face, mouth, gums, tongue, organs, trunk, limbs. Spinal cord stimulators will create more pain. Keep in mind, I don’t see the 5 year success stories even for lumbar disc pain. They don’t need me if they are pain free.

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But if you have CRPS and desperate need for pain relief because all else has failed — every known drug in highest possible doses of ketamine, propofol, opioids for weeks in ICU fail to even touch pain— there is one thing, and only one thing to do and I will set it out below. I just sent my recommendation to a patient with CRPS in extreme pain.

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My recommendation, below, is for patients who have nowhere else to turn.

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First I’ll mention the problems Craig encountered with SCS’s. He sent his comment to the opening page of this blog, so I will reproduce below. 

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I am currently undergoing a trial Medtronic SCS. I have had to have it reprogrammed 3 times since it was installed 5 days ago. I have had sensations and issues that I have addressed with my rep and my neurosurgeon. I get a severe headache when the unit is turned on. I get the constant feeling of having to urinate. I have current running through my testicles which they can not seem to program out and I am getting little pain relief. I have had to failed back surgeries, many failed injections and I have CRPS. The leads that were inserted when I was in the table covered my mid back and both legs. After I got to my feet and waited while they programmed the unit in another room. They came in and plugged it in and I no longer had coverage on the right side. My crps is in both legs, my hands, arms and face. The lyrica helped to tamp down some of the burning but I am in pain 24/7 and this was my last resort. I have scar tissue completely surrounding my S1 nerve. By the grace of God, I am on my feet, on crutches. I seem to get a look of disbelief when I tell them the unit is causing these issues or it’s not giving me the relief I was counting on. Relief, only to cause greater issues and pain. Is not relief to me. I can not wait to get this trial out of my back. I believe the leads slipped and that is why I am not getting the full coverage I had on the table. The issues I have had are as follows: severe headache, constant feeling of having to urinate, extreme joint pain, abdominal pain, sleeplessness, involuntary jerking, surges in current even when sitting still. Intense pain around the lead insertion site. Current uncomfortably running through my testicles, regardless of setting. It is my opinion there is still not a lot known about crps and I have read evidence of people have great success with these units. Everyone reacts differently. My body obviously creates a lot of scar tissue and my orthopedic surgeon created a fair amount herself. I can’t imagine even more or being forced into a chair for yet another unlucky decision. The medication helps and I have lived this far without the optimism that it would end soon. I had high hoed for this device but I don’t think it is right for me.

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One of my patients with CRPS was hospitalized for weeks with recurring unusual abscesses and required repeated surgery of hand and forearm. Even before surgery, she had failed opioids, failed ketamine, and was in ICU for weeks and weeks while the same medications were still given along with Propofol and IV Tylenol. Nothing helps her extreme pain.

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Anesthesiologists on staff in ICU threw everything they had at the pain for weeks. Most anesthesia pain doctors would have probably done what they did because that is the limit of tools we have.

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When you have hit the limit of benefit from opioids, ketamine, propofol, we have nothing else that treats pain with one exception: drug holiday.

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Stop all analgesics including Tylenol that destroys the liver as severely as cancer, the severity of which was newly discovered and published yesterday.

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The receptors for these analgesic drugs have up-regulated to such an extent they have caused the situation. Again, I stress, everything that was done during the ICU admissions would be done by any anesthesiology pain specialist. Those are the only tools. They cause the problem. The same for opioid induced hyperalgesia. We used to do it with Parkinson’s drugs in the 80’s.

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The only way to rehabilitate the up-regulation of all those receptors that have now exploded in numbers, immune to anything you throw at them, is stop the drugs.  Stop all of them for weeks, maybe months, years, no one knows, you are all the human guinea pig waiting to happen. But if we restart them, how long do we wait, how quickly will it again lead to this massive hyper-excitable state of pro-inflammatory cytokines that we know have gone wild, flooding the CNS. A flooded engine will not restart.

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Ketamine at least is known to reduce pro-inflammatory cytokines, but the system is too busy exploding, birthing new receptors that take over, and you’ve got a 55 car pile up. Well, more like millions I’d guess. No scientist here. Clnically, when can we resume something after a drug holiday, how soon and which drug? I’d avoid opioids because they create more pro-inflammatory cytokines. Choose ketamine, because they reduce pro-inflammatory cytokines, but if it works at all, stop it at first sign of tolerance, which is the need for increased dose. It becomes less effective. Walk a fine line, endure more pain because unless you do, it will no longer help. Opioids, analgesics of many kinds. 

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How do we get you through a drug holiday because we know withdrawing these drugs will trigger even more pain for possibly weeks until the system settles down?

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Pain storms, hurricanes

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This is complex regional pain syndrome where we see this insanity of pain storms. There is no other condition, unless several neuropathic pains in people with cancer, nowhere I have seen this type of pain in decades except CRPS – comparable to pain of subarrachnoid hemorrhage, blinding pain.

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No one has answers. None. One university does outpatient infusions of ketamine six hours daily for 8 to 12 weeks. Does it help? A small percentage. Outpatient, 6 hours daily, 5 days a week, staying at a hotel, 8 weeks.

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This is CRPS/RSD. No one has answers. It is futile to throw more of the drug in the system. That is my opinion. You have a choice and may choose otherwise. It is your body. You may stay on monthly opioids for decades, until you finally admit how poorly they work. A drug holiday is what we did in the 70s during my ancient training with Parkinson’s patients. They needed full 24-hour support. The American medical system has changed since then and those are not options currently available—cost.

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You need full psychological and psychiatric support.

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The Only Real Answer

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The country needs to invest $10 million to complete the clinical trials needed for an injectable, long-lasting interleukin 10 [IL-10], the anti-inflammatory cytokine. It already has full scientific and animal studies performed by and with the world’s foremost glial scientist at University of Colorado Boulder. Professor Linda Watkins has won awards from many countries. She has been the keynote speaker at the annual academy pain meetings for years. IL-10 can relieve pain for three months in animals that have intractable chronic neuropathic pain. This is not new —–NIH I’m looking at you to fund clinical trials. And those of you who care, do a Kickstarter to fund the clinical trials.

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This is the power of the innate immune system. NIH would rather fund research on the unknowns like stem cells rather than the known. It’s known for decades, NIH does not like to fund pain research. Glia are not all about pain. They are the innate immune system, the key to Alzheimer’s, neurodegenerative diseases, almost all known disease including atherosclerosis. It’s all about inflammation. We need the trials to stop giving drugs that cause inflammation, opioids —–CDC fiats are not as good as a drug that relieves pain, a drug that really works on mechanism. Where will the addicts go if the ER only has IL-10 for pain? That is one way to overspend on ER visits.  And NIH, please get us some real clinical research funding on how to use glia for our benefit. Get us some research on the entourage effect, combining medications to achieve relief especially for neuropathic pain.

Then bring on some crack negotiating teams from insurers to do some negotiation about pharmaceutical prices. Our new president has mentioned that.

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Please bring this to everyone’s attention. One way to get a grip on pain and/or depression is to build hope, help others, and energize behind a goal.

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Kickstarters work to raise tens of millions overnight. 

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IL-10 – animals have been shown to be pain free for three months, already proven in animal studies, by one of the world’s most widely acknowledged pain specialists Professor Linda Watkins, PhD. We need the final steps to fund the clinical trials in humans.

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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 Consensus Statement for Mood Disorders Needed


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I just had a call from a student writing a paper on ketamine. Question #1: What % respond to ketamine.

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Why are we still asking this rather than treating with ketamine?

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3.7% of Americans are disabled with Major Depression, many for decades, or entire lives. Antidepressants may work on only 30%. It’s time we had a consensus statement on use and training of ketamine.

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Read Cornel West: Pity the sad legacy of Obama, before you read on.

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Pity the sad legacy of psychiatry. Even neoliberals fail to speak up, stuck in the dictates of the few. We’ve known for decades that ketamine is effective treatment. It can work in hours. IV ketamine clinics are popping up like Jack in the Boxes and will continue to increase in number.

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It is time to ask: Is IV the only way to administer? Is it cost effective? Do these doctors have the right training?

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We need a consensus statement from psychiatrists and from the American Academy of Psychiatry and Neurology on training in inflammation, the innate immune system and treatment with ketamine.

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Every psychiatrist and mental health specialist should be instructed in rationale, the innate immune system, glia, inflammation, addiction medicine, glial modulators (ketamine is only one), and how to look at the whole system, holistically, not just one more drug. Inflammation, diet, exercise, among these.

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A focus on Ketamine alone in treating a complex organ like the brain is incomplete. Think inflammation, brain, spinal cord, glial modulators, not just drugs, not just ketamine. Ketamine is potentially addicting, a schedule III drug. Evaluate a patient just as you do when prescribing opioids.

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Then we need consensus on its use for intractable chronic pain including RSD/CRPS.

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Why don’t schools teach anything on the human body and the immune systems rather than biology and cutting up frogs?

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 Data below is from National Institute of Mental Health:

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Major Depression Among Adults.

  • Major depression is one of the most common mental disorders in the United States.

  • The 12-month prevalence data for major depressive episode presented here are from the National Survey on Drug Use and Health  (NSDUH). Based mainly on the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), in the NSDUH study a major depressive episode is defined as:

    • A period of two weeks or longer during which there is either depressed mood or loss of interest or pleasure, and at least four other symptoms that reflect a change in functioning, such as problems with sleep, eating, energy, concentration, and self-image.

    • Unlike the definition in the DSM-IV, no exclusions were made for a major depressive episode caused by medical illness, bereavement, or substance use disorders.

  • In 2015, an estimated 16.1 million adults aged 18 or older in the United States had at least one major depressive episode in the past year. This number represented 6.7% of all U.S. adults.

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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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Glia regulate glucose & metabolism – diabetes, obesity, Alzheimers – will change treatment


 

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Sugar has a stronger effect on our brains than we even realised, study finds

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The complete opposite of what scientists thought.

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From publication today in Cell

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Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability

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Quoting from the Sciencealert report:

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“German scientists have discovered that our brains are actively taking in sugar from the blood stream, overturning the long-held assumption that this was a purely passive process.

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Even more surprising, they also found that it’s not our neurons that are responsible for absorbing all that sugar – it’s our glial cells, which make up 90 percent of the brain’s total cells, and . . .

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Not only does the find go against conventional wisdom on how our brains respond to sugar intake, it also shows how cells other than our neurons can actively play a role in controlling our behaviour.

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Astrocytes – which are a specialised form of glial cell that outnumber neurons more than fivefold – have long been thought of as little more than ‘support cells’, helping to maintain the blood-brain barrier, carry nutrients to the nervous tissue, and play a role in brain and spinal cord repair.

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But we now have evidence that they also play a role in human feeding behaviours, with researchers finding that their ability to sense and actively take in sugar is regulating the kinds of appetite-related signals that our neurons send out to the rest of the body. 

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And we’re not talking about a little bit of sugar here: the human brain experiences the highest level of sugar consumption out of every organ in the body. 

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“Our results showed for the first time that essential metabolic and behavioural processes are not regulated via neuronal cells alone, and that other cell types in the brain, such as astrocytes, play a crucial role,” explains study leader Matthias Tschöp from the Technical University of Munich.

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“This represents a paradigm shift and could help explain why it has been so difficult to find sufficiently efficient and safe medicines for diabetes and obesity until now.”

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Tschöp and his team decided to investigate how the brain decides to take in sugar from the blood – and how much – because this is directly related to our feelings of hunger.

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. . .The team used positron emission tomography (PET) scans to observe how insulin receptors act on the surface of the brain’s astrocytes. Insulin is a hormone produced by the pancreas to allow the body to use or store sugar (in the form of glucose) from carbohydrates in the food we eat.

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They found that if these receptors were missing on certain astrocytes, it would result in less activity in the neurons that are responsible for curbing food uptake, called proopiomelanocortin neurons. 

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Not only that, but they found that astrocytes missing insulin receptors actually became less efficient over time in transporting glucose into the brain – particularly in a region of the hypothalamus that sends out signals that you’re full, or satiated.

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So it looks like glial cells, not the neurons, are the true ‘gate-keepers’ for how much sugar our brains absorb, and we now know that sugar has such a powerful influence on them, they’re seeking out sugar, rather than just passively absorbing it.

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A better understanding of how this works could change everything about how we treat obesity in the future.”

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References to whet the appetite:

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Kleinridders, A., Ferris, H.A., Cai, W., and Kahn, C.R. Insulin action in brain regulates systemic metabolism and brain function. Diabetes. 2014; 63: 2232–2243

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De Felice, F.G. and Ferreira, S.T. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes. 2014; 63: 2262–2272

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Ferreira, S.T., Clarke, J.R., Bomfim, T.R., and De Felice, F.G. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement. 2014; 10: S76–S83

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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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Complex Regional Pain Syndrome in Remission 6 years


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 Complex Regional Pain Syndrome

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Celebrating six years of complete remission

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Why ketamine should never be used alone

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I first posted her case here. 

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For years, pain below both knees was 8 to 9 on scale of 10, “like I had swallowed a fire burning.”

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She was unable to stand or walk for more than 4 years before seeing me. This week, I again saw this very healthy athletic RN who at almost 70 of age is very youthful, very energetic. She failed IV ketamine given first by Dr. Schwartzman daily for one week, then boosters for 8 months.

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After 8 months of ketamine, then no response at all. None. 

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That’s when I prescribed other glial modulators and rational polypharmacy that brought CRPS into remission. Then very very slowly tapered off all but one, leaving only low dose naltrexone (LDN) for the last 8 years. Zero pain. None. Hiking, working, fully active.

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When used in conditions with known neuro-inflammation, rats or human, LDN is a one of the most powerful, most effective glial modulators I have ever seen clinically in my patients in the last 15 years.

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Until proven otherwise clinically, LDN should be taken lifelong in those cases.

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This website is not for email.

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The advertising is not approved by me and

unrelated to anything on these pages.

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

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Cannabis: CBD may help pain when rectal suppository morphine is a problem


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Marijuana, cannabis, is overlooked for pain control

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CBD – cannabidiol — is the immune/glial suppressor

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It is anti-inflammatory in brain and spinal cord

 

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Correction 3/28/16:

It is not legal to transport CBD to states where marijuana is illegal, though it has no psychoactive properties. This is explained in detail by two doctors who wrote in drugpolicy.org, March 2015. I recommend reading the article as it makes several important points.

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The cannabis plant, and everything in it, is illegal under federal law. And even in states where it is legal, it is not legal to ship cannabis products from state to state, or to leave the state with such a product.

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A recent study from Israel showed that CBD in its natural form as a whole plant extract is superior over a single, synthetic CBD compound for treating illness. The plant has continually outperformed synthetic versions in research studies.

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…There are many support groups for children with epilepsy whose parents are using medical cannabis, such as this forum run through the Epilepsy Foundation. Connecting with them can be a great resource for staying on top of the developments with CBD and the other therapeutic cannabinoids in the cannabis plant.

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Dr. Malik Burnett is a former surgeon and physician advocate. He also served as executive director of a medical marijuana nonprofit organization. Amanda Reiman, PhD, holds a doctorate in Social Welfare and teaches classes on drug policy at the University of California-Berkeley.

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Cannabis has been used for thousands of years. It has been in the U.S. pharmacopoeia since 1850. A medical textbook from the 1920’s lists medical uses for cannabis. A Mexican American grandfather on hospice in 1995, explained how cannabis had helped his arthritic joints decades before.

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When alcohol prohibition failed and was repealed in 1933, Harry J. Anslinger, head of the Federal Bureau of Narcotics from 1930 to 1962, created the word marihuana claiming it led to addiction, violence, overdosage. Anslinger used racist propaganda to instill fear in Americans that only Mexicans and Negros use cannabis which led to creation of the Marijuana Tax Act passed by congress in 1937. Not unlike the CDC Opioid Guideliness of March 2016, it was passed over the objections of the AMA.

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The American Medical Association (AMA) opposed the act because the tax was imposed on physicians prescribing cannabis, retail pharmacists selling cannabis, and medical cannabis cultivation/manufacturing. The AMA proposed that cannabis instead be added to the Harrison Narcotics Tax Act. The bill was passed over the last-minute objections of the American Medical Association. Dr. William Creighton Woodward, legislative counsel for the AMA objected to the bill on the grounds that the bill had been prepared in secret without giving proper time to prepare their opposition to the bill. He doubted their claims about marijuana addiction, violence, and overdosage; he further asserted that because the word Marijuana was largely unknown at the time, the medical profession did not realize they were losing cannabis. “Marijuana is not the correct term… Yet the burden of this bill is placed heavily on the doctors and pharmacists of this country.”

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Israel’s Professor Rafael Mechoulam is widely recognized for his work on cannabis over more than 40 years. He and his lab isolated and identified THC, CBD, cannabinoid receptors, endogenous cannabinoids – your brain makes two of them! Your body has more cannabinoid receptors than any other type. It was he who published 40 years ago that CBD controls certain types of epilepsy in children – and it was ignored until Dr. Sanjay Gupta publicized this in the last one or two years.

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Professor Mechoulam says CBD from the plant (the plant is illegal in the United States) outperforms synthetic CBD.

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However, standards for CBD products do not exist, assays may be unreliable, it may be extracted with harsh chemicals that are harmful to those who are ill, and FDA has warned against false claims of efficacy. 

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Nevertheless, there are indications CBD may help pain. It has no psychoactive properties. It does not cause intoxication. There is no THC in it.

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CBD, Cannabidiol, is one of the 86 known cannabinoids in the cannabis plant that has 400 chemicals. In addition, the plant has perhaps 100 or 200 unique terpenes, also said to help symptoms. 

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Topical CBD may help – keep that in mind when Blue Shield’s formulary offers only rectal suppository morphine (unless you wait days and hope they will approve a prior authorization).

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I received a note today about Colorado Hemp Farmers:

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a woman in her sixties suffering from sciatica who is having her nurse rub her back with a coconut oil extract of a specific strain of industrial hemp rich in CBD, but without significant THC. She reports that the pain alleviation is remarkable with the soothing extract, which she judged to be superior to when commercially available CBD oil was used. 

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Have any readers have tried CBD for pain?

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Your feedback would help to inform researchers to add an additional arm to the tests now being done in rats.

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I have heard from one man with severe pain today. He uses CBD in many forms. It helps pain a little, and also it is calming. He describes it like you know pain is better after you take ibuprofen. Similar with CBD. He does not feel at all drugged.

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This site is not for email.

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

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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.

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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 educational website is

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