ULDN Inverse Titration Protocol FINAL

Using Ultra Low Dose Naltrexone to reduce opiate use and transition to LDN.
A novel approach for patients with Chronic Immune Neurological Diseases * to move away from opiate use to manage symptoms of pain and fatigue.
Ultra-Low-Dose Opioid Antagonists Enhance Opioid Analgesia and Reduce Tolerance

Lindsay H. Burns, Todd W. Vanderah, Hoau-Yan Wang
12/2008; DOI:10.1007/978-1-59745197-0_1 ABSTRACT
Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and attenuate the tolerance to analgesic effects normally seen with
* Chronic Immune Neurological Diseases of "C.I.N.D. is a term that covers a wide range of diseases affecting both the immune and neurological systems. These include Lyme disease, ME, CFS, CRPS, Fibromyalgia (FMS) and MS.
chronic opioid administration.

Source
http://www.researchgate.net/publication/226837972 _Ultra-LowDose_Opioid_Antagonists_Enhance_Opioid_Analg esia_and_Reduce_Tolerance
Michael Robinson
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Nov 2013
Acknowledgements
There are many people I need to acknowledge and thank for assisting with the compilation of this information. I cannot thank them all but they all have one thing in common. They advocate for their own health and they; advocate for the health and well being of others; demanding better treatments against misinformation and apathy. I also acknowledge the late Thomas Michael Hennessy, Jr. who passed away on September 9, 2013 in Florida USA after 25 years of living with the debilitating symptoms of a Chronic Immune Neurological Disease. Thomas knew more than most about the politics and problems getting an accurate diagnostic definition as well as focusing the medical community on the multiple causes and effective treatments. see Remembering Thomas Hennessy Jr. on Pg 50
Disclaimer
This information herein is not medical advice, it does not and should not replace medical advice. It has been compiled and been made available in the hope that patients and medical professionals will become aware of the research and opinions that exists on the use and benefits of ULDN and LDN, the increasing use of ULDN and LDN.
Creative Commons Use / CCL Statement
Share and share alike .... http://en.wikipedia.org/wiki/Share-alike
Michael Robinson
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Contents
Acknowledgements ................................................................................................... 2 Disclaimer ................................................................................................................. 2 Creative Commons Use / CCL Statement ................................................................. 2 Open Letter ........................................................................................................... 5 Aims and benefits of the ULDN Approach: ................................................................ 6 Protocol Overview ..................................................................................................... 8 A novel role for agonists ...................................................................................... 12 Additional Reading .................................................................................................. 17 Treating the cause not just masking symptoms................................................ 18 ULDN .................................................................................................................. 20 Observations by Dr Boris Gimbarzevsky .......................................................... 20 A selection of studies and published works ...................................................... 21 Studied, Recommended, Prescribed & Advocated by... ................................... 29 LDN - Extract from article by Dr Mercola .......................................................... 34 Doses and dilutions for ULDN and LDN ........................................................... 37 A DIY guide to diluting a 50mg tablet for ULDN and LDN liquid. ...................... 38 An important note Re Fillers............................................................................. 40 An important note if you change methods or dispensing pharmacy.................. 40 Pharmacist Dr Skip Lenz comments ................................................................ 41 Improving your capacity for activity - What really does help? .................................. 42 Remembering Thomas Hennessy Jr. ...................................................................... 50
Michael Robinson
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Clinical Success
ULDN reduces Opioid Tolerance."
"....primary goals I had in using Naltrexone in my patients was to see if I could slow the rate of development of opiate tolerance in patients on chronic opiate therapy ...."
".... patients have been using range from 10 micrograms to 100-200 micrograms 2-4 times daily.
Dr Boris Gimarzevsky
Source and further information:
http://drgimbarzevsky.com/Naltrexone/Lo w_Dose_Naltrexone_Observations1.html
Michael Robinson
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Open Letter
Friday 29th November 2013 To whom it may concern: The following information introduces a safe and effective approach to supporting the reduction of opiate use for those patients with ME, CFS, FMS who due to post exertion malaise have difficulty boosting the production of dopamine through vigorous exercise. With medical guidance and support the use of ULDN has been shown to: - reduce opioid tolerance - assist with the reduction of opioid medications use With persistence and support to find the individually suitable doses the patient over time seeks to move from using opioid medication to LDN. The following information is a compilation of research, online articles and discussions from doctors, researchers and patients. It is not intended to replace medical advice but instead to raise awareness of the use of ultra low dose naltrexone and low dose naltrexone as a safe, cheap and effective option. References and sources are included as hyperlinks through the document not as they would usually be references or tabled in an academic paper. This is document is not intended to be an academic paper or replace professional medical advice but as a compilation of some of the information readily available. Yours Sincerely Michael D. Robinson Sydney, NSW, Australia. turnitupmike@gmail.com
NOTE ULDN and ULDTX have been used interchangeably in some online discussions. ULDN = ULTRA Low Dose Naltrexone (ie micrograms usually between 10mcg and 200mcg) LDN = Low Dose Naltrexone (ie mg usually between 0.5mg and 5mg)
For the purpose of simplicity and clarity for all readers 'mcg' has been used in this document for 'micrograms' instead of the usual ' g '.
Michael Robinson
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Nov 2013
Aims and benefits of the ULDN Approach:

The aim of this approach is to:
- reduce opiate tolerance; - repair of the dopamine system affected by long term opiate medication; - reduce opiate use - taper opiate use to zero - begin using LDN long term
ULDN assists both reducing opioid tolerance and also in chronic pain and auto immune conditions like ME, Chronic Fatigue Syndrome and Fibromyalgia.
Studies and use of doses as small as nano and pico doses of Naltrexone have been shown to also benefit. Studies and clinical experience of doctors and patients using ULDN & LDN for this application show that there is a parabolic response to ultra low doses. It is therefore more desirable for patients to be able to titrate the dose to find the optimal dose.
Introducing ULDN assists the patient's recovery from the effects of long term opioid use. As that recovery improves it may be possible to reduce opioid use with a goal of tapering opioid use down, to zero use if possible.
Tailoring the treatment and inverse titration of opiate and ULDN medications allows the patient to take the dose of each medication that maximises their progress towards LDN use.
This "swap over" needs to be undertaken in a methodical, slow and steady manner to first support the recovery of the dopamine receptors and production to support the aim of moving towards replacing opiate use with LDN. NOTE : This approach is intended as part of an overall comprehensive approach to regaining health and well being.
Michael Robinson
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Nov 2013
Clinical Success
More effective long term treatment with LDN.
" (for)...... individuals suffering from neuropathic pain, this regime worked quite impressive in our hands." August 2010, Jan M. Keppel Hesselink, MD, PhD
Source and further information:
http://www.neuropathie.nu/treatme nt/low-dose-naltrexone-forneuropathic-pain.html
See clinical review of evidence
http://pain-topics.org/pdf/OpioidAntagonistsForPain.pdf
Michael Robinson
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Nov 2013
Protocol Overview
Inverse titration of ULTRA LOW DOSE NALTREXONE and opioid medication undertaken with physicians and patients working together is for the long term benefit of the patient's well being. While some patients may find benefit in the first few weeks, it may take other patients a few months to find a dose where the benefits of ULDN begin to be noticed.
The short acting immediate release ULDN is taken once daily around 10pm. This is when the body normally starts producing more dopamine and dopamine receptors. As ULDN only stays in the body for about 4 hours the "rebound" from even the smallest short acting doses of ULDN causes the body produce more dopamine and dopamine receptors.
NOTE : The graphic below is an approximation for illustrative purposes only. It is not to scale and individual decisions should be made with medical advice considering individual situations.
--- Opiate titration ----ULDN (ug / mcg) to LDN (mg) titration
1. Approx 3 months after starting ULDN begin slow reduction of opiates
2. After ULDN
starts to support dopamine then reduce opioid use, gradually increasing ULDN as able.
3. shows gradual increases of ULDN doses
4. 14 days after Opioid zero use taper ULDN to LDN
5. gradual & patient increases to LDN as appropriate.
Michael Robinson
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ULDN used in this way supports the repair of problems caused by long term opioid medication use. This problem is commonly referred to as " post opioid withdrawal syndrome". Doctors commonly recommend patients re invigorate the dopamine system through vigorous exercise but due to the complications such as "post exertion malaise", POTS or Postural Orthostatic Tachycardia Syndrome and Orthostatic Dysautonomia in patients with ME/CFS/FMS, this type of exercise is not possible and causes serious worsening of their condition.
ULDN allows for a more controlled way to support recovery and reduce opioid use without the unnecessary complications of rapidly withdrawing opioid medications until the patient requires less medication. As the ULDN supports the "repair" of the patient's dopamine receptors and production the opioid medication can be gradually reduced. It should be kept in mind that patients that have persisting pain may struggle to achieve the goal of zero opioid use. LDN has been shown to reduce pain in patients however the transition may be more challenging than both physician and patient hopes and require patience. . With patience and an experienced multi-disciplinary the aim is to completely swap the patient over from the ULDN + opiate mix and onto LDN as a long term beneficial medication. Although ULDN assists to repair the dopamine system it is a slow process and requires patience the long term goal is to begin LDN without opiate use. See also
Michael Robinson
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Nov 2013
ULDN dose requires individual titration
"The dose/response curve of naltrexone potentiation of analgesia appears to be parabolic; no response at too low a dose, a maximum response at a higher dose and then decreasing effectiveness as one continues to increase naltrexone dose. At some point, the dose of naltrexone will be high enough and it will be algesic; ie increase pain as it assumes its expected opiate receptor blocking role. The dose of naltrexone that will antagonize exogenous opiates and increase pain is quite variable among individuals. The lowest dose I've seen put a chronic opiate user into withdrawal has been 1 mg; naltrexone is a competative opiate antagonist and so to treat this withdrawal one needs to merely take more opiates." Source: http://drgimbarzevsky.com/Naltrexone/Low_Dose_Naltrexone_Observations1.html see also Observations by Dr Boris Gimbarzevsky p 20
Michael Robinson
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Increases to ULDN dose should be made slowly and as a general guide various discussions seem to indicate that after 3 or more months it will be much easier to reduce opioid use reduced by 10% every 1 to 3 months. This is a general guide for illustrative purposes only and individual approaches should be guided by the ability of the patient to sustain a reduction in opioid use in consultation with their treating doctors. The longer the patient has been on opioid medications the more difficult it will be to reduce the dose. As a general guide it should be noted that the smaller the doses become it may become harder to reduce opiate use however with ULDN these difficulties are lessened.
It should be kept in mind that the dopamine system being repaired has been altered by the introduction of prescribed opioid medications taken long term and so and will take time to repair. While all other multidisciplinary approaches to support this protocol should be encouraged it does need to be kept in mind that it will be a process that will happen at the patient's individual pace.
Patience and persistence will increase success as this may take many, and in fact should, be undertaken over months or even years rather than days or weeks. After 10 - 14 days of no opioid use the dose of ULDN can be gradually increased to 0.5mg (LDN levels for immune support) per day as either a single daily dose or split dose and increased thereafter according to LDN protocols .
Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and attenuate the tolerance to analgesic effects normally seen with chronic opioid administration. (Lindsay H. Burns, Todd W.
Vanderah, Hoau-Yan Wang)

See: http://www.researchgate.net/publication/226837972_Ultra-LowDose_Opioid_Antagonists_Enhance_Opioid_Analgesia_and_Reduce_Tolerance.
Michael Robinson
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A novel role for agonists

Naloxone Naltrexone and Naloxone (see p. 13) are commonly confused though have similar pharmaceutical uses in some oral medications included for their anti injecting abuse blockade role. Naloxone's two main uses are in anti injection abuse inclusion in combination opioid medications with Naloxone combined and as a emergency overdose reversal treatment. See MIMS or http://en.wikipedia.org/wiki/Naloxone for more information. Some studies of the use of ultra low dose naloxone alone have been undertaken, (mostly IV infusions) more common use of Naloxone is in combination medications mentioned above such as Targin, Suboxone or Buprenorphine. See clinical review of evidence
Targin (combination of Oxycontin and Naloxone) is often used by doctors for its decreased opioid effect on the bowel but ULDN has a greater beneficial effect than Naltrexone has. Other combined medications include Suboxone but these combinations do not allow for individual titration of either Naloxone (similar to naltrexone) or of the opiate dose. In recent years the price of Naloxone has increased significatly internationally in stark contrast to the low cost of Naltrexone. Suboxone and Buprenorphine are both relatively new medications compared to Naltrexone neither reduce tolerance and weaning of either medication is known to be extremely difficult. Current approx costs (in Australia) depending on dose for Targin, Suboxone or Buprenorphine is around $ 1 .56 / day e.g. Buprenorphine
(oxycodone hydrochloride 20 mg + naloxone hydrochloride 10 mg tablet: modified release)
http://www.pbs.gov.au/medicine/item/8935G though some options are significantly more expensive even on the PBS schedule.
Note the dose of Naloxone included in these medications is generally considered to be for anti injection abuse purposes combination medications and has not been extensively studied or used for the purposes of this protocol to support the dopamine system, immune system and move the patient off opiates and onto LDN.
Michael Robinson
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Naltrexone 50mg extended release

Used at 50mg and 300mg doses Naltrexone is commonly as an opioid blockade medication for heroin and alcohol addicts. At these doses is acts as an agonist to block opiates and also reducing cravings for intoxicating substances.
Low Dose Naltrexone immediate release

At 0.025 to 5mg LDN has a beneficial effect on the immune and dopamine system. Immediate release LDN has a half life of 4 hours. LDN's role in this protocol is the repair of the opioid growth factor, dopamine and immune systems. At doses under 1mg has been shown to not have a blockade effect that could precipitate withdrawals in patients using opioid medications. After patients have stopped using opiates for 14 days they can start on LDN. Generally starting at 0.5mg and working up to 1.5mg and then even slower to around 4.5mg/ day either as a single or split dose. Where patients may need to take both LDN and pain medications more information is available on the LDN information sites regarding the use of Tramadol with LDN. Dr Chris Steele, MBE, speaks about using LDN as a first choice as it effective, does no harm and is a safe drug. http://www.youtube.com/watch?v=CVpjsDK0LPA
See clinical review of evidence Additional Reading
A e-book of resources and cases of LDN use for the First International LDN Awareness Week 2009 by Julia Schopick see: http://preventionx.com/The-Faces-of-Low-DoseNaltrexone---HONEST-MEDICINE-My-Dream-for-download-w5661.html
Low dose naltrexone for neuropathic pain

http://www.neuropathie.nu/treatment/low-dose-naltrexone-for-neuropathic-pain.html The Fibromyalgia drugs your doctor (probably) knows nothing about. This article by Cort Johnson http://www.cortjohnson.org/ one of the leading advocates for CFS and Fibromyalgia research, awareness and improved treatments explains this opioid antagonist .
..."Opioid Antagonists More extensive use of opioid antagonists as well as the introduction of novel microglial activation inhibitors (miRNA) pose exciting new possibilities for the treatment of FMS. Ablin and Buskila
It may seem strange to target drugs that knock down one of the main pain inhibiting systems in the body but the opioid receptors in many FM patients appear to filled and elevated opioid activity in the brain can cause increased, not decreased pain sensitivity.
Low Dose Naltrexone (LDN) An opioid antagonist long used by people with fibromyalgia for relief, LDN finally got a clinical trial and it was successful. At the low doses used in the trial, Ablin and Busklin suggested LDNs effectiveness in FM may have been more due to anti-inflammatory effects than to opioid antagonism....."
see http://www.prohealth.com/library/showarticle.cfm?libid=18225 see also http://ldninfo.org/others.htm http://www.bwmbagus.demon.co.uk/BobsDocs/0-LDN-Side-effects.pdf
Michael Robinson
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Ultra Low Dose Naltrexone immediate release ULDN (1microgram - 500micrograms) Even at pico, nano and ultra low doses naltrexone has beneficial effects on the immune and dopamine systems. The dose requires titration for individual patients as at these low doses the beneficial dose can be parabolic and requires individual titration to find the dose that best suits. As patients improve the dose can be increased accordingly. It is important that in prescribing and dispensing ULDN fillers used in tablets and capsules not interfere with the immediate release. An experienced LDN compounding pharmacy be used or a suitable 50mg tablet be dissolved in distilled water by the patient and the appropriate liquid dose be measured.
ULDN has been studied and shown to: - prevent injection abuse (like Naloxone) in oral medications without affecting the opioid effect. - reduce opioid tolerance, - improves immune support function. - is not sufficiently large enough dose to cause blockade (ie does not cause withdrawals)
Current approximate costs of LDN and ULDN in Australia For Australian purposes and using one 50mg Naltrexone tablet per month diluted in distilled water to measure out liquid dose of LDN or ULDN the cost is approx 9c /day. ie $136 for 30 x 50mg tablets = $2.72 per month = 9 cents per day Source: http://www.pbs.gov.au/medicine/item/8370M
" (for)...... individuals suffering from neuropathic pain, this regime worked quite impressive in our hands." August 2010, Jan M. Keppel Hesselink, MD, PhD
http://www.neuropathie.nu/treatment/low-dose-naltrexone-for-neuropathic-pain.html
Michael Robinson
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Opioid Antagonists in Pain Management
Available evidence suggests that the opioid antagonists naloxone and naltrexone offer potential benefits for enhancing opioid analgesia as well as monotherapy for managing certain challenging pain conditions.
By Stewart B. Leavitt, MA, PhD
ULDN science published studies http://www.science.gov/topicpages/u/ultralow+dose+naltrexone.html
Michael Robinson
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Leading doctors advocate LDN as a medication of choice for Fibromyalgia.
Dr Sean Mackey, MD, PhD

speaks about improving treatments for chronic pain, Fibromyalgia and the use of LDN on this Research Channel Update on Fibromyalgia
Uploaded to You Tube on 1 May 2009

Redlich Professor, Stanford Division of Pain Medicine President-elect, American Academy of Pain Medicine Assistant professor of anaesthesia at the Stanford University Medical Centre
Source: https://www.youtube.com/watch?v=jtc2JARVpPw see also http://www.painmattersfilm.com/
More effective long term treatment.

Fibromyalgia is a mysterious disorder of unknown cause characterized by widespread pain, abnormal pain processing, sleep disturbance, fatigue and often psychological distress. According to the CDC, fibromyalgia affects an estimated 5 million adults. Dr. Sean Mackey, assistant professor of anesthesia at the Stanford University Medical Center, discusses our current understanding of this cryptic disorder: its pathology, diagnosis and treatment.
@36 - 39 minutes Dr Mackey discusses long term use of opiates.. can cause more pain than less.. healthy people feel good after working out.. fibro patients feel worse @ 42 minutes discusses LDN Source: https://www.youtube.com/wat ch?v=jtc2JARVpPw
Michael Robinson
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Additional Reading
Standford Researchers get to the root of stopping the pain rather than masking it . http://alumni.stanford.edu/get/page/magazine/article/?article_id=66226 ....."In a 2013 study by Younger's team, 31 fibromyalgia patients treated with low doses of a drug called Naltrexone that inhibits microglial cells in the CNS reported significantly less daily pain on average compared with a placebo pill. The link between the immune system and chronic pain is an unfolding story that encompasses other types of chronic pain, including complex regional pain syndrome. David Clark, a professor of anesthesia who studies the condition, notes that some of its features" .... "the development of neurological problemsare reminiscent of autoimmune disorders." * * (i.e. ULDN and LDN helps the improvement of such autoimmune disorders)
For more information on this study see http://updates.pain-topics.org/2012/03/low-dose-naltrexone-eases-fibromyalgia.html
ULDN and LDN Naltrexone offers many benefits over Naloxone - as Naltrexone benefits neuropathic pain conditions, "rests" the opioid receptor system, enhancing analgesia while overcoming prior opioid tolerance or hyperanalgesia. See Error! Reference source not found. http://preventionx.com/download.php?id=5675
Michael Robinson
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Treating the cause not just masking symptoms

A presentation about the history and need for improvements to treating chronic pain. http://www.janussc.org/downloads/Opioids_and_Post_Op_Pain_Management.pdf
There are many other links and attachments referred to throughout the rest of this document that address ULDN more specifically however it is prudent to put this discussion in context. Throughout this document are references to the need to improve treatment of Chronic Pain. This presentation explains the importance of a new approach. Traditionally anyone with chronic pain has been prescribed pain masking medication, the long term use of which does not improve their chronic pain nor their health. For those with chronic immune neurological diseases including Lyme, ME, CFS and Fibromyalgia as too often when their treating doctors have not had a test result to point to as a cause of the pain start to blame the patient and suggest the pain is imaginary. Thankfully as more studies give more doctors information they can understand about what the disease is doing to their patient they can better provide treatments more specific to the causes rather than simply guessing at treatments and prescribing symptom masking pain medications. Pages 1 - 15 of the document outlines historical use of opioids. This information is covered in many places but for the purposes of this document it is at least worth mentioning in passing. http://www.janussc.org/downloads/Opioids_and_Post_Op_Pain_Management.pdf
The historical context explains the history of the old approach for chronic pain conditions including Fibromyalgia. (Note there is extensive published material about the difficulties of treating Fibromyalgia, tolerance and poor response to opioids as well as the need to consider Lyme, mold and other causes in order to address the cause rather than simply make the condition worse by exacerbating a chronic pain condition with long term opioid use problems. These include effects on hormones, the dopamine system as well as hyper analgesia.)
In this regard the chart on page 15 of
The Journal of Pain Volume 9, Issue 8 , Pages 700-713, August 2008 Oxycodone Plus Ultra-Low-Dose Naltrexone Attenuates Neuropathic Pain and Associated -Opioid ReceptorGs Coupling Tally M. Largent-Milnes, Wenhong Guo, Hoau-Yan Wang, Lindsay H. Burns Todd W. Vanderah
http://www.janussc.org/downloads/Opioids_and_Post_Op_Pain_Management.pdf also discusses Magnesium use to reduce pain. Addressing the issue of supplements (including magnesium and Vitamin D3 as well as tailoring dietary approaches to eliminate food intolerances and addressing issues as far ranging as muscle and joint injuries to viral, mold and chemical exposure are also necessary).
Michael Robinson
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Pain Management programs need to be updated to address the new information that is available that can assist patients. Pp 16-17 reference the progress of new and better approaches to pain management for the Fibromyalgia patient, and also in this document the post operative patient in preventing a well known cause of post operative complex regional pain syndrome (not unlike Fibromyalgia) While the discussion of the use of injected Naloxone and oral doses of Naltrexone in some cases could be interchangeable it is important in this instance to consider that the management plan is for the purpose of tapering down the dose of opioid medication to as low as is practically possible without increasing unmanaged pain while also reducing tolerance. However the key interest in trialling the ULDN nightly dose is to assist in boosting the dopamine production and dopamine receptors for which ULDN seems to be the safest and only option available considering the CFS problems. At these mcg levels ULDN is only in the body for about 4 hours and causes the body to produce more dopamine and create more dopamine receptors and this overcome the post withdrawal syndrome issues that complicate reduction of opioid doses especially with CFS patients. It is clear that the old approach to treating chronic pain in ME, CFS and Fibromyalgia patients did not work and a new approach must be implemented. http://www.janussc.org/downloads/Opioids_and_Post_Op_Pain_Management.pdf for more contacts and information about this topic see also http://www.nfra.net/NewFuture.htm
Michael Robinson
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ULDN
Observations by Dr Boris Gimbarzevsky

Selected extracts ".... Even though the doses of naltrexone may seem miniscule, there are some very interesting things that seem to happen with endogenous opiate systems when one uses naltrexone in conjunction with opiates.
Dr. Boris Gimbarzevsky 20/4/2004 Source: http://drgimbarzevsky.com/Naltrexone/Low_Dose_Naltrexone_Observations1.html
"...One of the primary goals .... slow the rate of development of opiate tolerance in patients on chronic opiate therapy."
"....If the result was due to placebo effect, then one would expect pain relief at the 1 microgram dose. This dose did absolutely nothing for her and once she hit 10 micrograms good analgesia resulted. Now the placebo effect is thought to be mediated by endorphins as placebo analgesia can be blocked with intravenous naloxone and it could be that my action of giving her the naltrexone resulted in increased endorphin release and the ULDNTX potentiated these endorphin effects. She continued to use the naltrexone with good ..."
Generally I suggest to patients that they experiment with combining microgram doses of naltrexone with opiate analgesics and I have seen reductions ...... in opiate analgesic doses when this approach has been used. One indication that a drug is doing something is when patients ask for more of it. I've had patients use opiates and naltrexone in combination and then come back asking for more naltrexone as it seemed to be helping with analgesia.
Dr. Boris Gimbarzevsky 20/4/2004 Source: http://drgimbarzevsky.com/Naltrexone/Low_Dose_Naltrexone_Observations1.html More at http://drgimbarzevsky.com/Naltrexone/Low_Dose_Naltrexone_Observations1.html and http://drgimbarzevsky.com/Naltrexone/
Michael Robinson
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A selection of studies and published works

The following few pages are just a selection of the published studies listed on Sciece.gov into the use of Ultra Low Dose Naltrexone For more see http://ldninfo.org/ldn_trials.htm http://www.science.gov/topicpages/u/ultra-low+dose+naltrexone.html
Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats
Microsoft Academic Search Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and alleviate opioid tolerance and dependence. ............ potential of oxycodone+ultra-lowdose naltrexone(NTX) versus oxycodone alone. ..........
Francesco Leri; Lindsay H. Burns 2005-01-01
http://www.science.gov/topicpages/u/ultra-low+dose+naltrexone.html
Human abuse liability assessment of oxycodone combined with ultralow-dosenaltrexone

Microsoft Academic Search ......" Preclinical and clinical studies have shown that opioids combined withultra-lowdose naltrexone (NTX) may have increased\\u000a analgesic potency and have suggested reduced abuse or dependence liability. ....."
David Andrew Tompkins; Ryan K. Lanier; Joseph A. Harrison; Eric C. Strain; George E. Bigelow 2010-01-01
Ultra-low-dose naltrexone suppresses rewarding effects of opiates and aversive effects of opiate withdrawal in rats
Microsoft Academic Search Rationale Ultra-low-dose opioid antagonists enhance opiate analgesia and attenuate tolerance and withdrawal........ Objectives To determine whether ultra-lowdosenaltrexone (NTX) coadministration alters the rewarding effects of opiates or the aversive\\u000a effects of opiate withdrawal.\\u000a \\u000a \\u000a \\u000a Methods We used the conditioned place preference (CPP) and conditioned place aversion (CPA) paradigms to assess whether ultra-low-dose\\u000a NTX alters the acute rewarding effects of oxycodone or morphine, or the
Mary C. Olmstead; Lindsay H. Burns 2005-01-01
Michael Robinson
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Oxycodone Plus Ultra-Low-DoseNaltrexone Attenuates Neuropathic Pain and Associated ?-Opioid ReceptorG s Coupling
Microsoft Academic Search Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in ?-opioid receptor (MOR)G protein coupling from Gi\\/o to Gs that can be prevented by cotreatment with an ultra-lowdose opioid antagonist. In this study, using lumbar spinal cord tissue
Tally M. Largent-Milnes; Wenhong Guo; Hoau-Yan Wang; Lindsay H. Burns; Todd W. Vanderah 2008-01-01
http://www.science.gov/topicpages/u/ultra-low+dose+naltrexone.html http://www.jpain.org/article/S1526-5900(08)00480-X/abstract
Enhancing acupuncture by low dosenaltrexone.

PubMed To find appropriate and effective treatment options for chronic pain syndromes is a challenging task. Multimodal treatment approach has been gaining acceptance for chronic pain. However, combining treatments, such as acupuncture, with rational pharmacology is still in its infancy. Acupuncture influences the opioid and cannabinoid system through releasing endogenous receptor ligands. Low dosenaltrexone also acts on both these systems, and upregulates the opioid and cannabinoid receptors. The authors hypothesise that low dose naltrexone could enhance the pain-relieving effect of acupuncture. PMID:21415049
Hesselink, Jan M Keppel; Kopsky, David J 2011-03-17
Michael Robinson
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http://www.researchgate.net/publication/226113151_Ultra-LowDose_Naltrexone_Decreases_Dependence_and_Addictive_Properties_of_Opioids
Book extract - Chapter 13

Ultra-Low-Dose Naltrexone Decreases Dependence and Addictive Properties of Opioids
Lindsay H. Burns, Francesco Leri, Mary C. Olmstead 12/2008; DOI:10.1007/978-1-59745-197-0_13

ABSTRACT Ultra-low-dose opioid antagonist cotreatment was first shown parad oxically to enhance opioid analgesia and to reduce analgesic tolerance and physical dependence. In this chapter, we review data demonstrating that ultra-low-dose naloxone or naltrexone reduces several components of opioid dependence and addiction. While the reduction in opioid dependence, first demonstrated as a reduction in somatic withdrawal signs, might seem merely a correlate of the attenuation in tolerance, the data reviewed here show that ultra-low-dose naltrexone also reduces the psychological or negative affective aspect of acute opioid withdrawal. In addition, the acute rewarding properties of opioids are reduced by ultra-low-dose naltrexone. The attenuation of rewarding effects occurs in the same ultra-low dose ranges shown to enhance analgesia, thus dissociating the rewarding or addictive effects of opioids from their analgesic properties. Furthermore, in intravenous self-administration procedures in rats, ultra-low-dose opioid antagonists coadmin-istered with opioids reduced their rewarding potency, reduced motivation to obtain the drug, and reduced drug-seeking in the absence of drug availability. Finally, in a Phase III clinical trial, the ultra-low-dose naltrexone component of Oxytrex significantly reduced physical signs of opioid dependence after abrupt cessation of treatment, compared to withdrawal from oxycodone alone. Together, the data reviewed in this chapter suggest a reduced potential for opioid dependence and addiction by certain ultra-low-dose opioid antagonists combined with opioids, concurrent with the enhanced analgesia from these opioid agonist/antagonist cotreatments.
Source
http://www.researchgate.net/publication/226113151_Ultra-LowDose_Naltrexone_Decreases_Dependence_and_Addictive_Properties_of_Opioids
This book chapter details a journal article about the opioid + ultra low dose antagonist combination approach http://www.paintrials.com/publications/pti609_JournalArticle.pdf
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Recent Patents on CNS Drug Discovery, 2010, 5, 210-220 PTI-609: A Novel Analgesic that Binds Filamin A to Control Opioid Signaling Lindsay H. Burns,and Hoau-Yan Wang Pain Therapeutics Inc., San Mateo, CA, Dept. of Pharmacology and Physiology, CUNY Medical School, New York, NY, USA
Received: June 4, 2010; Accepted: August 9, 2010; Revised: August 13, 2010
http://www.paintrials.com/publications/pti609_JournalArticle.pdf ..." Combined with opiates, ultra-low-dose naloxone or naltrexone can enhance and prolong the analgesia of the opiate alone and prevent or attenuate opioid ..."
Opiate Receptors and Antagonists: From Bench to Clinic

edited by Reginald L. Dean, Edward J. Bilsky, S. Stevens Negus source
http://books.google.com.au/books?id=zqj2vy6VFUcC&pg=PA9&lpg=PA9&dq=Opioid%22ultra+low+dose+naltrexone%22&sour ce=bl&ots=z2opOl_e2&sig=7WkwQykEY5uH15J6cSrftqDcxZY&hl=en&sa=X&ei=Wm2PUvzZIq3xiAfsoYDACw&ved=0CHIQ6AEwCA#v=onepag e&q=Opioid%22ultra%20low%20dose%20naltrexone%22&f=false
see p 9 for more information about the benefits of the combination of opioids with ULDN
For more scholarly discussion of the workings of Naltrexone see Antidotes: Advances in Research and Application: 2011 Edition: Scholarly Brief
Ch 2 pp 28...
http://books.google.com.au/books?id=JG64gRbV3DYC&pg=PA28&lpg=PA28&dq=:+A+Novel+Analgesic+that+Binds+Filamin+ A+to+Control+Opioid+Signaling&source=bl&ots=5Vj2XBc6s3&sig=DNyQxUHFauxDTtD6F1lApullUGM&hl=en&sa=X&ei=0qCfU ueNNeayiQfe2ID4DA&ved=0CEoQ6AEwAw#v=onepage&q=%3A%20A%20Novel%20Analgesic%20that%20Binds%20Filamin %20A%20to%20Control%20Opioid%20Signaling&f=false
Michael Robinson
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Why so much excitement about LDN if my doctor doesn't know about it? LDN "Easily compoundable at local pharmacies LDN will never get financial support from drug companies for drug trials but studies are being done. (The FM trials, below, were sponsored by the American Fibromyalgia Association.) In 2013, 23 LDN trials (underway or completed) on disorders ranging from fibromyalgia to alcoholism abuse to multiple sclerosis to narcotics withdrawal ...."
http://www.cortjohnson.org/blog/2013/08/28/mecfs-doc-asserts-low-dose-naltrexone-becomingstandard-treatment-chronic-fatigue-syndrome-fibromyalgia/
Read more: Low Dose Naltrexone Becoming Standard Treatment for Chronic Fatigue Syndrome and Fibromyalgia http://www.cortjohnson.org/blog/2013/08/28/mecfsdoc-asserts-low-dose-naltrexone-becoming-standard-treatment-chronic-fatigue-syndromefibromyalgia/
De Meirleir begins this latest video talk by referring to the exciting but small LDN/Fibromyalgia study at Stanford. (Stanfords 2009 study found that LDN significantly reduced pain, fatigue, and stress, and helped to improve sleep and reduce gut issues and headaches. De Meirleir explained that LDN is an opiate receptor blocker and is used in very small doses (0.5-5.5 mg/day) relative to its normal dosing (5 grams, which is 5000 mg). It turns out that the partial blockage of the opioid receptors tricks the brain into producing more of its own opiates, thus reducing pain and improving sleep (but not generally reducing fatigue). Read more: Low Dose Naltrexone Becoming Standard Treatment for Chronic Fatigue Syndrome and Fibromyalgia more at
I want to make a plug for Low Dose Naltrexone Dr. Nancy Klimas Simmaron Roundtable Meeting: Read more: Low Dose Naltrexone Becoming Standard Treatment for Chronic Fatigue Syndrome and Fibromyalgia
See more at The Doctor's Medical Library : Low Dose Naltrexone by Ron Kennedy M.D. http://www.medical-library.net/content/view/533/41/ http://www.cortjohnson.org/treating-chronic-fatigue-syndrome-mecfs/drugs-forchronic-fatigue-syndrome-mecfs-treatment/low-dose-naltrexone-ldn-fibromyalgiachronic-fatigue-syndrom/ See clinical review of evidence
Michael Robinson
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More books are being published like this one below - see the description for more information about the history and uses of LDN
The Promise Of Low Dose Naltrexone Therapy: Potential Benefits in Cancer, Autoimmune, Neurological and Infectious Disorders [Paperback]
Elaine A. Moore (Author), Dr. Yash P. Agrawal (Foreword),Samantha Wilkinson (Collaborator)
http://www.amazon.com/Promise-Low-Dose-NaltrexoneTherapy/dp/0786437154/ref=sr_1_1?s=books&ie=UTF8&qid=1360756230 &sr=1-1&keywords=low+dose+naltrexone
Publication Date: December 1, 2008 | ISBN10: 0786437154 | ISBN-13: 978-0786437153
Naltrexone is an opiate antagonist drug developed in the 1970s and approved by the FDA in 1984 for opiate and drug abuse treatment. When used at much lower doses in an off-label protocol referred to as low dose naltrexone (LDN), the drug has been shown to halt disease progression in Crohn's disease and certain cancers, to reduce symptoms in multiple sclerosis and autism, and to improve numerous autoimmune and neurodegenerative conditions, including Parkinson's disease and amyotrophic lateral sclerosis (ALS). Grounded in clinical and scientific research, this book describes the history of naltrexone, its potential therapeutic uses, its effects on the immune system, its pharmacological properties, and how the drug is administered. It also lists fillers and compounding pharmacies, doctors who prescribe LDN, and patient resources, and includes interviews with LDN patients and researchers.
Michael Robinson
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Oxytrex Studies highlight need for inverse titration of doses. The study and patent of a combination drug called "Oxytrex" (Oxycontin plus Ultra-low dose Naltrexone) as single medication has made some progress into this area of combining ultra low dose natrexone with opioid use. It also has application as an abuse resistant prescription medication. see p.4. of Pharma Note Jan 2013
http://copnt13.cop.ufl.edu/doty/pep/pharmanote/January2013.pdf
Clinical Medicine Insights: Therapeutics

R e v i ew
Clinical Medicine Insights: Therapeutics 2010:2 857
Ultra-Low-Dose Naloxone or Naltrexone to Improve Opioid Analgesia: The History, the Mystery and a Novel Approach
Lindsay H. Burns1 and Hoau-Yan Wang2
1Pain Therapeutics Inc., San Mateo, CA, USA. 2Deparment of Pharmacology and Physiology, CUNY Medical School,
There is enthusiasm for a combination medication such as Oxytrex based on both the abuse resistant concerns as well as the opioid tolerance prevention. FDA approval of Oxytrex is still undetermined. The Oxytrex concept has exciting possibilities in the application of managing pain and reducing opioid tolerance if the medication were to be available. However for those seeking to reduce opioid medication and move onto LDN taking ULDN and opioid doses as individual medications and titrating the doses inversely allows for a dose by dose tailoring of each medication.
see also http://opioids.com/tolerance/oxytrex.htm and Journal : Clinical Medicine Insights: Therapeutics Ultra-Low-Dose Naloxone or Naltrexone to Improve Opioid Analgesia: The History, the Mystery and a Novel Approach http://www.la-press.com/ultra-low-dose-naloxone-ornaltrexone-to-improve-opioid-analgesia-the--articlea2351
Abstract: Combining opioid agonists with ultra-low (typically pgng/kg) doses of the opioid antagonists naloxone or naltrexone can enhance analgesic efficacy and decrease certain side effects. Such combinations have also been shown to decrease tolerance, dependence and addictive potential in animals. We now know that ultra-low-dose naloxone/naltrexone effects occur by preventing a G protein coupling switch (Gi/o to Gs) of the mu opioid receptor (MOR) that occurs briefly after acute administration or persistently after chronic administration of opioids. The picomolar binding site for naloxone or naltrexone in these effects is on the scaffolding protein filamin A (FLNA), rather than on opioid receptors. Interestingly, a second, nanomolar binding site on FLNA may disrupt the benefits of binding the picomolar site, perhaps explaining why ultra-low-dose naloxone/naltrexone effects vanish at just slightly higher doses. A novel analgesic drug candidate aims to avoid this issue by binding only the high-affinity FLNA site, while simultaneously activating MOR. Binding this single site on FLNA also provides anti-inflammatory activity.
Keywords: signaling, filamin A, naloxone, naltrexone, conditioned place preference, anti-inflammatory
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More information about the studies and development of Oxytrex
Oxycodone Plus Ultra-Low-Dose Naltrexone Attenuates Neuropathic Pain and Associated -Opioid ReceptorGs Coupling

Tally M. Largent-Milnes, Wenhong Guo, Hoau-Yan Wang, Lindsay H. Burns, Todd W. Vanderah Received 14 August 2007; received in revised form 4 February 2008; accepted 7 March 2008. published online 12 May 2008. see http://www.jpain.org/article/S1526-5900(08)00480-X/abstract
An Extract from "High-Affinity Naloxone Binding to Filamin A Prevents Mu Opioid ReceptorGs Coupling Underlying Opioid Tolerance and Dependence" ...." Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and attenuate tolerance and dependence, with a mechanism long hypothesized as a blockade of excitatory signaling opioid receptors [1][4]. Ultralow-dose opioid antagonists can also reverse hyperalgesia caused by acute, lowdose opioids to produce analgesia [5]. Additionally, ultra-low-dose naltrexone has recently been shown to attenuate opioid reward or addictive properties ...." ..."....... This high-affinity binding site in c-terminal FLNA therefore appears to underlie the paradoxical enhancement of opioid analgesia and prevention of analgesic tolerance and dependence by ultra-low-dose opioid antagonists. In identifying the binding site though which ultra-low-dose opioid antagonists prevent MORGs coupling, our data also reveal an important regulation of MOR G protein coupling by filamin A...." Source: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001554
see also http://www.researchgate.net/publication/226837972_Ultra-LowDose_Opioid_Antagonists_Enhance_Opioid_Analgesia_and_Reduce_Tolerance
Pharma Note newsletter Vol 28 Issue 4 Jan 2013 discusses the various combination medications, their developments effects, doses and uses.
pp 1-2 Pharmacology of narcotics (opioids) Pp. 2 and 4 Mechanisms of Abuse resistance and deterrence & opioid receptor effects p 3 list of FDA approved combination opioid and abuse deterrent combination medications. p. 4 Novel abuse resistent narcotics under review - includes Oxytrex and safety of oral combination doses of opioid medications with naloxone and naltrexone combinations. See http://copnt13.cop.ufl.edu/doty/pep/pharmanote/January2013.pdf
Michael Robinson
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Studied, Recommended, Prescribed & Advocated by...

The following list of some of the Professors, doctors and researchers who have published studies, peer review articles and online discussions of ULDN and LDN. It is by no means an exhaustive list but is indicative of the expertise and experience of those professionals advocating on behalf of the well being of patients that this cheap, safe and effective medication be seriously considered and tried.
This list includes;

Redlich Professor, Stanford Division of Pain Medicine President-elect, American Academy of Pain Medicine Assistant professor of anaesthesia at the Stanford University Medical Center Research Channel update on Fibromyalgia and pain treatments see https://www.youtube.com/watch?v=jtc2JARVpPw
Video Uploaded to You Tube on 1 May 2009 Fibromyalgia is a mysterious disorder of unknown cause characterized by widespread pain, abnormal pain processing, sleep disturbance, fatigue and often psychological distress. According to the CDC, fibromyalgia affects an estimated 5 million adults. Dr. Sean Mackey, assistant professor of anesthesia at the Stanford University Medical Center, discusses our current understanding of this cryptic disorder: its pathology, diagnosis and treatment.
@36 - 39 minutes Dr Mackey discusses long term use of opiates.. can cause more pain than less.. healthy people feel good after working out.. fibro patients feel worse @ 42 minutes discusses LDN
Source: https://www.youtube.com/watch?v=jtc2JARVpPw
Stanford School of Medicine - Systems Neuroscience and Pain Lab
Fibromyalgia Symptoms are reduced by low-dose naltrexone: A pilot study. Pain Medicine (2009) Jarred W. Younger and Sean C. Mackey
http://med.stanford.edu/snapl/research/ldn.html
see also http://www.painmattersfilm.com/
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Catherine Cahill, PhD

University of California Associate Professor http://www.anesthesiology.uci.edu/index.shtml http://www.anesthesiology.uci.edu/research_faculty_cahill.shtml
Dr. Tom Gilhooly MBChB MRCGP (Glasgow )

One of the keynote speakers and author of many articles for the LDN Research Trust Dr Tom G talks about LDN at world conference
Dr Tom Gilhooly is a 46-year-old General Practitioner who has worked in the East End of Glasgow for the past 16 years. He is a nationally-recognised expert on addiction, and advises both the Scottish Parliament and the UK Government on drug strategy. Tom is married with three children, and he also has two dogs. He has a long-term interest in nutrition, and founded The Centre for Nutritional Studies (CNS) Ltd in 2002, with the aim of carrying out nutritional research. In the past two years he has become aware of LDN, and is an enthusiastic supporter of this treatment (as well as natural treatments) for MS. He now runs an MS clinic in Glasgow.
http://www.ldnresearchtrust.org/node/3 http://www.youtube.com/watch?v=fWrG_UQtbsU eg See page 3 of: http://www.ldnresearchtrustfiles.co.uk/docs/May%20-%20Newsletter.pdf and http://www.skipspharmacy.com/wplog/pharmacy-news/ldn-2008-videos-here/
Michael Robinson
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Dr. Tim Gerstmar

https://www.facebook.com/AspireNaturalHealth/posts/10151779725083469
Aspire Natural Health 704 like this.
10 August at 15:00
We are experts at treating:
G - Can ultra-low dose naltrexone remove some of the side effects of opioid painkillers? In the comments section of the same post, George Henderson and Peter D (a vet anesthesiologist) discuss some preliminary research about how ultra-low dose naltrexone (a fraction of LDN) can be given along with opioid painkillers (like morphine), don't interfere with the painkilling aspect, but do block some of the negative effects of the drugs. If you're on opioids for chronic pain, this is definitely something to look into, although (unfortunately) good luck finding an MD to prescribe it to you, still you might consider finding an alternative provider.
Dr. Boris Gimbarzevsky (Kamploons, British Columbia) - see his easy to read observations Observations by Dr Boris Gimbarzevsky page 20 Jan M. Keppel Hesselink, MD, PhD
http://www.neuropathie.nu/treatment/low-dose-naltrexone-for-neuropathic-pain.html
Dr Nancy Sajben
Pain Management Specialist in San Diego writes about using ULDN and LDN since 2004 and explains the benefits of ULDN and LDN on the central pain processing neurochemistry for chronic pain, chronic depression and post traumatic stress disorders. Many links to studies and publications - see: http://painsandiego.com/2009/05/26/low-dose-naltrexone-ldn/
Dr Chris Steele, MBE, talks about LDN

http://www.youtube.com/watch?v=CVpjsDK0LPA
Michael Robinson
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http://www.ldnscience.org/low-dose-naltrexone/ldn-researchers Ian S. Zagon Ph.D. Distinguished Professor, Distinguished Educator, and Director of the Program on Education in Human Structure Hershey Medical Center, Penn State University College of Medicine http://www.ldnnow.co.uk/1431.html https://profiles.psu.edu/profiles/display/113208 Patricia J. McLaughlin Ph.D. Professor of Neural and Behavioral Sciences and Director of the Graduate Program in Anatomy Hershey Medical Center, Penn State University College of Medicine http://www.ldnnow.co.uk/1431.html https://profiles.psu.edu/profiles/display/111836 Jill P. Smith M.D. Professor of Medicine Hershey Medical Center, Penn State University College of Medicine Moshe Rogosnitzky Director of Research MedInsight Research Institute Dr. Jarred Younger Instructor in Pain Management, Department of Anesthesia Stanford University School of Medicine Sean Mackey M.D., Ph.D. Chief, Pain Management Division Stanford University School of Medicine Maira Gironi M.D. Institute of Experimental Neurology (INSPE) and Department of Neurology San Raffaele Scientific Institute, Milan, Italy
Michael Robinson
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Other doctors and LDN

http://lowdosenaltrexone.org/ Bernard Bihari, MD, was the discoverer of the major clinical effects of low dose naltrexone. A private practitioner in Manhattan, Dr. Bihari was a Board-certified specialist in Psychiatry and Neurology. Dr. Bihari's curriculum vitae.
Chronic Fatigue / Fibromyalgia Syndrome According to Dr. Bahari, people with fibromyalgia and chronic fatigue syndrome have had marked improvement using LDN, suggesting that these entities probably have an important autoimmune dynamic as well. Many have reported improvement - some noticing an immediate difference and others only after a prolonged period of use.
Source : http://www.digitalnaturopath.com/treat/T74481.html David Gluck, MD (NY Lic. #083512), is the editor of this website, ldninfo.org. He is a Boardcertified specialist in both Internal Medicine and Preventive Medicine. Dr. Gluck has served as medical director for JCPenney and MetLife, and is now semi-retired, living and working in New York City. [Ed. Note: Please do not confuse David Gluck, MD with an unrelated doctor of similar name in New York, David A. Gluck, who is a specialist in Obstetrics and Gynecology.] See also http://www.youtube.com/watch?v=ONVebX1sMHk http://www.skipspharmacy.com/wplog/pharmacy-news/3rd-low-dose-naltrexone-ldn-conferencevideos-here/ http://www.lowdosenaltrexone.org/conf2008.htm
Dr Ian Zagon
Distinguished Professor, Distinguished Educator, and Director of the Program on Education in Human Structure Hershey Medical Center, Penn State University College of Medicine Extensively published see:
https://profiles.psu.edu/profiles/display/113208 (Dr Ian Zagon from Penn State University, the worlds foremost authority on the endorphin and OGF effect of LDN)
Ian S. Zagon, PhD, has spent over two decades in doing basic research concerning endorphins. He is Professor of Neural and Behavioral Sciences, Pennsylvania State University, Dept. of Neural and Behavioral Sciences, H-109, Hershey Medical Center, Hershey, PA 17033; office phone: (717) 531-6409; email: isz1@psu.edu ---------------------------------------------------------------------------------------------------A quick overview of LDN from http://www.lowdosenaltrexone.org/ at http://www.youtube.com/watch?v=NgfxWGrL4T8
Michael Robinson
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LDN - Extract from article by Dr Mercola

Source : http://articles.mercola.com/sites/articles/archive/2011/09/19/one-of-the-rare-drugs-that-actually-helpsyour-body-to-heal-itself.aspx
It is not often that I advocate the use of prescription drugs, but low-dose naltrexone (LDN) is one of those rare exceptions that may hold the promise of helping millions of people with cancer and autoimmune disease. As a pharmacologically active opioid antagonist, LDN works by blocking opioid receptors, which in turn helps ... your body's immune system. How LDN Harnesses Your Own Body's Chemistry to Fight Disease The latest research in Experimental Biology and Medicine just confirmed that LDN does in fact target the opioid growth factor (OGF)/opioid growth factor receptor (OGFr) pathway to inhibit cell proliferation. Previous research by professor Ian S. Zagon of The Pennsylvania State University, who also conducted the Experimental Biology and Medicine study, found that OGF regulates the growth of cancer cells, and all cancer cells use the OGF-OGFr pathway in growth regulation. It is through this mechanism that LDN is thought to exert its profound inhibitory effect on cancer growth. Further, LDN also works with your body's immune system through its interactions with your body's endorphins. Though most commonly referenced in relation to your mood, endorphins also play a role in pain relief, immune system regulation, growth of cells and angiogenesis (the growth of blood vessels that feed a tumor). Typically, LDN is taken at bedtime, which blocks your opioid receptors, as well as the reception of endorphins, for a few hours in the middle of the night. This is believed to up-regulate vital elements of your immune system by increasing your body's production of metenkephalin and endorphins (your natural opioids), hence improving your immune function. ......edited....... How can one substance impact so many different diseases? As written on the nonprofit Web site LowDoseNaltrexone.org, which is an excellent resource for more information: ......edited.......
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......edited....... Your Doctor Probably Doesn't Know About Low-Dose Naltrexone LDN has been an FDA-approved drug for over two decades, conventionally used to treat drug- and alcohol addiction at doses of 50mg to 300mg. Much lower doses (3 to 4.5 mg) are used for LDN's immunomodulating properties as discussed above, .......... ........ None of the pharmaceutical giants back it, as at an average price of $15 to $40 for a month's supply, the income potential isn't very promising. This means there are no friendly sales reps visiting your doctor talking about the potential benefits of this drug in very low doses, and as a result very few physicians are aware of LDN. So, if your physician is not familiar with LDN, you will need to bring it up to him or her, or, alternatively, seek a health care provider who is already knowledgeable at using LDN as a form of treatment. There are a number of pharmacies and compounding pharmacies in the United States and Canada that are reliable sources of the compound in low-dose form. CAUTION: Important LDN Points to Consider if You Use It Avoid slow-release (SR) or timed-release naltrexone. You want to be sure the LDN you receive is in unaltered form that allows you to receive the full dose quickly. Slow-release formulas may not give you the full therapeutic effects.
Be aware of inactive fillers. Part of the LDN capsule will contain a "neutral" filler material, however there is some evidence to suggest that calcium carbonate as a filler could interfere with the absorption of LDN. So to be on the safe side, avoid LDN capsules that contain calcium carbonate fillers.
Ideally, if you are interested in using LDN as a potential treatment consult with a knowledgeable health care practitioner who can guide your therapy and also help you find a reliable compounding pharmacy.
Source: http://articles.mercola.com/sites/articles/archive/2011/09/19/one-of-the-rare-drugsthat-actually-helps-your-body-to-heal-itself.aspx
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"Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and attenuate tolerance and dependence, with a mechanism long hypothesized as a blockade of excitatory signaling opioid receptors [1][4]. Ultra-low-dose opioid antagonists can also reverse hyperalgesia caused by acute, lowdose opioids to produce analgesia [5]. Additionally, ultra-low-dose naltrexone has recently been shown to attenuate opioid reward or addictive properties ..."
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001554
see also
http://www.researchgate.net/publication/226837972_Ultra-LowDose_Opioid_Antagonists_Enhance_Opioid_Analgesia_and_Reduce_Tolerance
Michael Robinson
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Doses and dilutions for ULDN and LDN

The following five pages are included for illustrative purposes only. Patients can dilute 50mg in 500mls of distilled water and measure out the required dose of mcg per ml See A DIY guide to diluting a 50mg tablet for ULDN and LDN liquid. on Pg 38 If desired a second step can be added to decant a small amount of the concentrated solution off into a second bottle and top it up with distilled water for a lower dilution rate to make it easier to measure the desired mls Alternatives include obtaining their prescription from a compounding pharmacy as a capsule or liquid and should discuss this with both their physician and the pharmacy. see An important note if you change methods or dispensing pharmacy. on Pg 40 If using a compounding pharmacy it is important to use a reliable and experienced compounding pharmacy who understands the prescribing of ULDN and LDN. In dispensing capsules or liquid on prescription some fillers used can interfere and it is important that the capsules be immediate release with inactive fillers. eg Dr Skip Lenz from Skip's Pharmacy ships internationally and is widely recommended as the most experienced pharmacist globally on this topic see also Pharmacist Dr Skip Lenz comments on Pg 41 http://www.skipspharmacy.com/wplog/services/low-dose-naltrexone/ http://www.skipspharmacy.com/wplog/home-2/contact/ General info:info@skipspharmacy.com Clinical Questions:skipthepharm@aol.com
Opioid Antagonists in Pain Management
..."Available evidence suggests that the opioid antagonists naloxone and naltrexone offer potential benefits for enhancing opioid analgesia as well as monotherapy for managing certain challenging pain conditions...."
By Stewart B. Leavitt, MA, PhD
Source http://www.practicalpainmanagement.com/treatment s/pharmacological/opioids/opioid-antagonists-painmanagement
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A DIY guide to diluting a 50mg tablet for ULDN and LDN liquid.
Start small, increase slowly! Be patient! see also http://ldninfo.org/index.htm#How_can_I_obtain_LDN If patients are experiencing side effects * these tend to pass after a week or two but many patients reduce the dose for a few days to a week to find a dose that lessens these early minor symptoms. This is a significant benefit of liquid doses and individual titration. * See Side effects reported from LDN clinic trials at http://www.ldnnow.co.uk/55401.html If diluting a 50mg tablet in a sterile bottle using distilled water - filler from the tablet (depending on brand of tablet used) stays in the bottom of the bottle this is to be poured out at the end of the month and a new batch prepared each month. Let the tablet dissolve in the distilled water without agitating the mixture.
Alternative 1 - 50mg tablet in 500mls distilled water To dilute a 50mg Naltrexone tablet in 500mls distilled water for ULDN or LDN doses NOTE 1mg = 1000mcg and 50mg = 50, 000mcg This method adds a 50mg tablet to 500mls distilled water (do not agitate just let it dissolve) The concentration will therefore be 50,000 mcg per 500 mls = 100mcg per ml or 20mcg per 0.2ml 0.5mg dose would require 5mls, 1mg dose require 10mls of this dilution and so on 10mls = 1mg 20mls = 2mg 25mls = 2.5mg Alternative 1 option B - If even smaller doses of ULDN are required as an easier to measure liquid amount First a 50mg Naltrexone tablet in 500mls distilled water as per alternative 1 ie 50,000 mcg per 500 mls and then take 50 mls of that dilution and add 450 mls of distilled water to it In this second bottle the concentration will be 10mcg per ml or 2mcg per 0.2ml
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The concentrate and diluted bottles should be clearly marked and both stored in the fridge. Some discussions suggest they may last longer than 30 days but generally it is recommended to make a new batch each month in a sterilised bottle(s).
If you prefer to dissolve the 50mg tablet in 1L (note the previous page was for 500mls) the example below is for 1,000mls or 1L of distilled water the following calculations would be applicable.
Alternative 2 - a 50 mg tablet in 1L distilled water 50mg tablet it 1L thus 50, 000mcg in 1,000mls of distilled water making a dilution of thus 50mcg per 1ml of liquid for ULDN if you wish to start with very small amounts 0.2mls of this dilution = 10mcg 0.2mls of this dilution = 10mcg 1mls = 50mcg 2mls = 100mcg 5 mls - 250mcg 10 mls 500mcg = 0.5mg for LDN 10 mls 500mcg = 0.5mg 20mls = 1mg 25mls = 2.25mg
If a LDN or ULDN is obtained from a compounding pharmacy it will be dispense at the dose prescribed by the doctor. See also An important note if you change methods or dispensing pharmacy. Pg 40 See also
http://davidnixon.over-blog.com/measuring-low-dose-naltrexone-from-a-50mg-tab http://www.rivernewsdesk.com/ldn-central/how-to-prepare-ldn/
A guide to some dose related terminology
http://www.shelbycountykentucky.com/EMS/Pharmacology%20Drug%20Dosage%2 0Calculations.pdf
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Nov 2013
An important note Re Fillers

It is important the doctor, patient and pharmacist all understand the effect of the different fillers used in both 50mg tablets and in compounded smaller dose capsules. While some doctors recommend one filler for consistency of their studies for the patient it is preferable to obtain a prescription where the filler used is inactive and not going to interfere with the immediate release of the dose taken. The ideal situation for ULDN is to have a compounding pharmacy dispense pure Naltrexone dissolved in distilled water at the required dose. This may not always be possible so dissolving 50mg tablets in distilled water or emptying LDN 5mg compounded capsules into distilled water are acceptable and widely used alternatives. For more information about fillers see Source: http://www.lowdosenaltrexone.org/gazorpa/LDNFillers.html
" The use of calcium carbonate as a filler will interfere with absorption of the LDN capsule. Therefore, it is suggested that calcium carbonate filler not be employed in compounding LDN capsules. Either Avicel, lactose (if lactose intolerance is not a problem), or sucrose fillers as useful fast-release fillers can be used."
Source http://www.medical-library.net/content/view/533/41/
An important note if you change methods or dispensing pharmacy.

When taking ULDN or LDN stick to the same method and / or the same compounding pharmacy and ensure that the prescriber and dispensing pharmacy use the same process or fillers. This is important because a 50mg Naltrexone tablet is in fact more filler than Naltrexone so the actual available ULDN in each DIY diluted dose may not be as high as the notional figures calculated. This is not a practical concern unless you change brands of tablets or change from one method such as changing from diluting your own 50mg tablets in distilled water to sourcing your ULDN or LDN already compounded. If you make changes discuss with your doctor about lowering the dose to 1/5th and titrating upwards again to check the actual strength of the new supply.
Michael Robinson
Page 40
Nov 2013
* Just one of the well known and experienced compounding pharmacists willing to assist patients and medical professionals understand the role and use of LDN is Dr Skip Lenz. 'Skip' provides a great deal of online and personal information to fellow professionals on ULDN and LDN. http://www.skipspharmacy.com/wplog/services/low-dose-naltrexone/
Pharmacist Dr Skip Lenz comments
From: Dr. Skip Subject: Naltrexone Date: October 23, 2003 As I have said before, if I had MS, the only drug that I would absolutely be taking is LDN..... In 4 years of dispensing LDN, with over 10,000 patient months, I have heard of only three cases of exacerbation... this is truly a nobrainer. I would find someone to prescribe it no matter the cost or effort. Skip Lenz, Pharm. D.
Source: http://crystalangel6267.webs.com/myresearchonldn.htm See also Best of Dr Skip and other LDN videos on Skip's pharmacy page http://www.skipspharmacy.com/wplog/category/low-dose-naltrexone/ http://www.skipspharmacy.com/wplog/pharmacy-news/ldn-2008-videos-here/ LDN Conference Nashville Part 1 http://www.youtube.com/watch?v=HuIQcm1Ixmg Part 2 http://www.youtube.com/watch?v=sJK8XKY2puA http://www.skipspharmacy.com/wplog/services/low-dose-naltrexone/ http://www.skipspharmacy.com/wplog/home-2/contact/
Michael Robinson
Page 41
Nov 2013
Improving your capacity for activity - What really does help?

Stopping the push hard crash hard cycle. This is a problem some doctors and academics still struggling to understand. The "PACE" or "GET" approach is usually combined with a multidisciplinary approach of CBT and GET (or PACE). (see links below) Original studies that promoted this approach failed to understand the challenge that Post Exertion Malaise (PEM) onset can be delayed by hours or even days after activity. It has since been shown that to push a patient to undertake increased levels of activity without a baseline of the individual's capacity to sustain that activity without adverse long term PEM was not considered in the original UK PACE study that is often used to justify this approach. Without realising that the indelicate approach of PACE or GET unsuitable for indiscriminate application CIND (such as ME, Lyme, MS, CFS or Fibromyalgia etc) are pushed beyond Although the Graduated Exercise Program promotes improved fitness and boosts the dopamine system in depressed patients helping them rebuild their dopamine system and capacity for activity it has a significant opposite effect on the patient with CIND (CFS, ME, Fibromyalgia etc).
Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
..."... Fifty-one percent. of respondents reported that ... GET worsened their health...."...
...."...healthcare professionals who strive to help their patients cannot do so without assessing risks versus benefits for each intervention they prescribe. To do this suitably, they need good data on harms. Greater vigilance for harms could restore patient trust and assist clinicians in adhering to the maxim, .... "Primum non nocere" (first, do no harm).
Source: http://iacfsme.org/BULLETINFALL2011/F all2011KindlonHarmsPaperABSTRACT/t abid/501/Default.aspx Full report as PDF file at
The goal of improving fitness, and capacity for http://iacfsme.org/LinkClick.aspx?fileticke t=mW6AiEZ5RVw%3d&tabid=501&force activity as well as boosting endorphins, download=true dopamine is a much longer one for this group of patients and requires careful monitoring of their capacity which can vary from day to day and even hour to hour. The role of ULDN can assist in many ways including "reset" of the opiate affected dopamine system as well as assisting reduce pain, inflammation, neuralgia etc. The complications of diseases like ME, Lyme, CFS and Fibromyalgia prevent the patient from making significant improvements without significant
Michael Robinson
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Nov 2013
challenges. If they are pushed to undertake any activity be it walking, sitting in class or physical therapy it is important to avoid the down side of 'post exertion malaise'.
Cognitive behaviour therapy for chronic fatigue syndrome in adults. AAuthors Price JR,et al. Show all Journal Cochrane Database Syst Rev. 2008 Jul 16;(3):CD001027. doi: 10.1002/14651858.CD001027.pub2. AAffiliation Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford, UK, OX3 7JX. jonathan.price@psych.ox.ac.uk Comment in Evid Based Ment Health. 2009 Feb;12(1):16. Update of Cochrane Database Syst Rev. 2000;(2):CD001027.
...." There is a lack of evidence on the comparative effectiveness of CBT alone or in combination with other treatments, and further studies are required to inform the development of effective treatment programmes for people with CFS...." Source http://www.ncbi.nlm.nih.gov/m/pubmed/18646067/
The "G.E.T. / PACE" approach of pushing patients to do more activity without first evaluating their real capacity or the harm of this approach is damaging to patients in both the short and long term. It pushes them beyond their capacity to do that activity causing the PEM crash and long term set-backs. Increased activity beyond the patient's capacity for activity tolerance causes increase "crashes" of Post Exercise Malaise. This crash cycle may not occur until hours or often days after the activity. Even if patients self report increased activity over the duration of the program the GET/PACE approach encourages them to press on doing increased harm. Even if increased bursts or intensity of activity are undertaken long term the insensitive GET / PACE approach is the proverbial sledge hammer to peel a grape.
Randomised controlled trial of CBT and GET intervention therapy with 1 year follow up
Patients receiving CBT, GET and conventional pharmacological treatment ......were worse than controls ..... bodily pain, strength and difficulties all worse...12 months after the intervention.
Source http://www.bamt.be/nieuwsbrief/01-2012/art5.pdf
Michael Robinson
Page 43
Nov 2013
Moving Beyond PACE & GET
The debate between pushing a failed PACE approach on unsuspecting patients and improving capacity for activity has been a long running one.
http://www.cortjohnson.org/blog/2013/03/01/not-keeping-pace-analysis-suggestscbtget-study-findings-in-chronic-fatigue-syndrome-mecfs-biased-and-overstated/ http://evaluatingpace.phoenixrising.me/homepageanim.html and finding an exercise approach that helps long term has led to more effective approaches than GET/PACE and it is these approaches that help us repair and rebuild our dopamine system as well as activity capacity. http://www.cortjohnson.org/exercise-resource-center-chronic-fatigue-syndromemecfs/ Understanding what is to be measured to know what improvement is essential see http://www.cortjohnson.org/blog/2013/09/17/foreign-illogical-result-keller-exercisetesting-chronic-fatigue-syndrome/ http://www.cortjohnson.org/blog/2013/08/04/treatable-chronic-fatigue-syndromesubset-if-doctors-will-just-look-for/
continues .....
Michael Robinson
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Nov 2013
Other references re CBT and GET

Neuro Endocrinol Lett. 2009;30(3):284-99.
A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many
patients with ME/CFS. Twisk FN, Maes M. ME-de-patinten Foundation, Limmen, the Netherlands. frank.twisk@hetnet.nl
..."CBT/GET is not only hardly more effective than non-interventions or standard medical care, but many patients report that the therapy had affected them adversely, the majority of them even reporting substantial deterioration"... Source http://www.ncbi.nlm.nih.gov/pubmed/19855350
...."......combinations of treatments. ..... intervention ....... should also explore individual factors to identify which patient subgroups would be the most likely to respond to what particular treatment....." Source : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743408/
"...present treatments are not effective for a large group of patients...." Source https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1954607/
Possible Detrimental Effects of Cognitive Behaviour Therapy for Chronic Fatigue Syndrome Heins M.J. Knoop H. Prins J.B. Stulemeijer M. van der Meer J.W.M. Bleijenberg G. Psychother Psychosom 2010;79:249 256 (DOI: 10.1159/000315130) Source : http://www.karger.com/Article/Pdf/315130
continues .....
Michael Robinson
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Nov 2013
There is solid evidence that the PACE or GET approach advocated in the past is more damaging than many doctors were aware of. Improvement isn't just measuring how far or hard patients push themselves one time but what happens after that. http://www.cortjohnson.org/blog/2013/09/15/cdc-whiffs-opportunity-prove-reducedexercise-capacity-in-chronic-fatigue-syndrome/ More exercise resources see: http://www.cortjohnson.org/exercise-resource-center-chronic-fatigue-syndromemecfs/ http://www.cortjohnson.org/blog/2013/08/13/heart-rate-monitor-program-improvesheart-functioning-in-chronic-fatigue-syndrome-mecfs/
Learning to rest before the crash cycle or PEM takes its toll and understanding where the individual's limits are can assist the person to rest well before the PEM crash trigger is reached. In this way long term sustainable increases in activity are achieved. ULDN has a beneficial role in this process as do many nutritional supplements and a competent physical therapist working to ensure there are no physical issues like posture, foot support and so on that haven't been addressed before undertaking this next step. The use of ULDN to restore or repair the dopamine system not only helps reduce the reliance on pain masking medication but has many other beneficial and supportive effects for the patient's well being. See also http://evaluatingpace.phoenixrising.me/homepageanim.html
http://www.cortjohnson.org/blog/2013/03/01/not-keeping-pace-analysis-suggests-cbtget-studyfindings-in-chronic-fatigue-syndrome-mecfs-biased-and-overstated/ http://www.cortjohnson.org/blog/2013/05/17/coping-works-in-chronic-fatigue-syndrome-except-whenit-doesnt-study-suggests-large-group-gets-no-help/ http://www.cortjohnson.org/blog/2013/04/17/are-oxygen-starved-tissues-causing-pain-and-fatigue-infibromyalgia-and-chronic-fatigue-syndrome-mecfs/
continues .....
Michael Robinson
Page 46
Nov 2013
Beyond CBT Although many pain clinics introduce patients to CBT (Cognitive Behavioural Therapy), Mindfulness, Self hypnosis, Mediation and other similar "headspace" approaches a superficial understand and practice of these approaches has unfortunately left many patients wondering if anything can help them. If not well understood these approaches are often dismissed as irrelevant new age mumbo jumbo. However prayer, worship of God, a peaceful focussed and calm mind is as old as humanity. In our modern lifestyle we have replaced confidence with uncertainty and fear. Our minds become focussed on evaluating uncertainties. Instead of taking time for calm relaxation we are so hyper aware that even when resting our mind is so busy that it doesn't relax into the cycles that allow for restorative repair. Few fully appreciate the significant roles of the different brain cycles including how we can support our own healing in a way Dr Herbert Benson calls "remembering wellness". An important question to ask: "Are you thinking your mind or is your mind thinking you?" Often our brain processes focus our brain activity on the high alert status of "scenario evaluation" commonly called worry. IT is important to clearly and consciously consider if these evaluations of the past (recycling old experiences, feelings and reactions) and also potential future activities (ie worry) is literally "winding you up" into an increased stress alert state. The higher the alert status the more energy the body consumes preparing for the impending doom and the less resources and energy are available for rest, repair and restoration. We need a deep calm restful mind to repair our body and restore a healthy mind and body. Normally this would occur during restful sleep but can also be achieved with practice of self hypnosis and deep relaxation methods. Once learned we can take a calm focussed mind into our daily activities which also helps maintain a lowered stress demand on our body and reduces the fatigue and pain many experience from multiple factors including the heightened stress alert state that a mind in a heightened alert crisis state creates. CBT / Mindfulness and other relaxation methods practiced regularly (at least once a day) assist in helping us choose a calm restful mind over a hyper activated one. In combining the various approaches that the individual feels comfortable with we learn to choose our mental focus. Live a more thankful and appreciative lift. continues .....
Michael Robinson
Page 47
Nov 2013
In a calm state we are actually more aware and less distracted by internal worries less overwhelmed by external sensory inputs like noise. There are five different kinds of brainwaves Beta, Alpha, Theta, Delta and Gamma
Understanding Brainwaves to Expand our Consciousness (Scott Dro)
Source:
http://www.themindunleashed.org/2013/10/understanding-brainwaves-to-expandour.html https://fbcdn-sphotos-d-a.akamaihd.net/hphotos-akash4/q71/1378640_681524631865448_2113386869_n.jpg
continues .....
Michael Robinson
Page 48
Nov 2013
Mastering one or a few of these brain and mind thinking methods are known to be of great benefit for good health but they are of even greater benefit for those needing to restore health. Chinese traditional practices teach the more healing focussed Qigong and fitness and general health focused Tai Chi Some people begin with a standard relaxation approach be it prayer or simply learning to calm and relax both the mind and body. It takes persistence and patience and if benefits aren't seen immediately it is helpful to understand the importance of sticking with it. It is also important to understand how refocusing our thoughts, dealing with stress etc all affect our brain's chemistry. In order to rebuild and repair the damage of long term opioid use retraining the brain to not rely on opioid medications requires diligent persistence. Dr Herbert Benson from Harvard Medical School is one of many reputable medical researchers who have made available online an approach that helps in many ways. see http://www.relaxationresponse.org/steps/ This approach is also advocated by many including the late Dr Ainsle Meares who was a man ahead of his time. See http://www.goodreads.com/book/show/1373559.Relief_Without_Drugs Mindfulness or refocussing of the mind, taking time for restful relaxation that allows our body to enter the relaxed repair cycle is something that can be learned. Once you understand it's role it is important to persist and apply these methods regularly not occasionally. As Dr Herbert Benson puts it, the relaxation response is about your body remembering wellness to achieve wellness. Though seemingly simply the challenge is to apply this at least daily. Like breathing, eating or drinking, it is something that helps us more if we continue to do it. By combining these approaches with Qigong, or Tai Chi, focusing mental activity on present tasks, setting achievable goals and taking a positive thankful approach to life are all ways that help repair the thought process at physical brain and body.
Michael Robinson
Page 49
Nov 2013
Remembering Thomas Hennessy Jr.

Thomas Hennessy Jr. 's passing reminds us of the toll this diseases takes on people's lives. The vibrant life it steals from successful people and the terrible toll of ineffective treatments. I'm including this information here as a tribute to the life of a friend and for those readers who want to connect with the organisations that are campaigning for improvements in diagnosis and in treatment of the many "CIND's from Gulf War Syndrome, CFS, ME, Fibromyalgia to MS and Lyme disease. For too long we have suffered misunderstanding and trivialisation of pain and fatigue. The devastating impact on personal and family life as well as the economic losses of long term illnesses and inappropriate treatments has to stop, and can stop. As patients advocate for greater sharing of information and improvements in research and treatment no longer need anyone suffer for years or decades..
For 25 years Thomas Hennessey Jr. advocated for those who could not advocate for themselves despite the devastating toll this disease took on his own life. His death on September 9, 2013 in Florida USA is a condemnation on the lack of appropriate treatment and the real cost of chronic pain not properly treated.
The following links are to some of the organisations who paid tribute to the life and campaigning of TMH and is indicative of the impact he had. He founded May12.org launching the annual ME Day on Florence Nightingale's birthday, worked with many other people and organisations and now the baton passes on to us. May 12 Website
http://www.may12th.org/index.html
TMH Facebook Memorial Page
https://www.facebook.com/pages/Thomas-Hennessy-Jr-MemorialPage/424861217634688?fref=ts
Tributes to Thomas Hennessy, Jr., http://www.youtube.com/watch?v=7ea1GV0SZEg http://www.cortjohnson.org/blog/2013/09/28/my-brother-by-choice-goodbye-tomhennessy-fierce-advocate-memorial-tomorrow/ http://phoenixrising.me/interviews-3/10317-2 http://healthmattershow.com/me-cfs-mecfs-or-not-argument-by-tom-hennessy/
Michael Robinson
Page 50
Nov 2013

ULDN Inverse Titration Protocol FINAL

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Using Ultra Low Dose Naltrexone to reduce opiate use and transition to LDN.

Ultra-Low-Dose Opioid Antagonists Enhance Opioid Analgesia and Reduce Tolerance

chronic opioid administration.

Creative Commons Use / CCL Statement

Share and share alike .... http://en.wikipedia.org/wiki/Share-alike

ULDN reduces Opioid Tolerance."

Source and further information:

Aims and benefits of the ULDN Approach:

More effective long term treatment with LDN.

Source and further information:

See clinical review of evidence

--- Opiate titration ----ULDN (ug / mcg) to LDN (mg) titration

1. Approx 3 months after starting ULDN begin slow reduction of opiates

3. shows gradual increases of ULDN doses

4. 14 days after Opioid zero use taper ULDN to LDN

5. gradual & patient increases to LDN as appropriate.

See clinical review of evidence

ULDN dose requires individual titration

Vanderah, Hoau-Yan Wang)

A novel role for agonists

Naltrexone 50mg extended release

Low Dose Naltrexone immediate release

See clinical review of evidence Additional Reading

Low dose naltrexone for neuropathic pain

see http://www.prohealth.com/library/showarticle.cfm?libid=18225 see also http://ldninfo.org/others.htm http://www.bwmbagus.demon.co.uk/BobsDocs/0-LDN-Side-effects.pdf

Opioid Antagonists in Pain Management

By Stewart B. Leavitt, MA, PhD

ULDN science published studies http://www.science.gov/topicpages/u/ultralow+dose+naltrexone.html

Leading doctors advocate LDN as a medication of choice for Fibromyalgia.

Dr Sean Mackey, MD, PhD

Dr Sean Mackey, MD, PhD

Source: https://www.youtube.com/watch?v=jtc2JARVpPw see also http://www.painmattersfilm.com/

More effective long term treatment.

For more information on this study see http://updates.pain-topics.org/2012/03/low-dose-naltrexone-eases-fibromyalgia.html

Treating the cause not just masking symptoms

Observations by Dr Boris Gimbarzevsky

A selection of studies and published works

Human abuse liability assessment of oxycodone combined with ultralow-dosenaltrexone

Enhancing acupuncture by low dosenaltrexone.

Book extract - Chapter 13

Lindsay H. Burns, Francesco Leri, Mary C. Olmstead 12/2008; DOI:10.1007/978-1-59745-197-0_13

Opiate Receptors and Antagonists: From Bench to Clinic

Publication Date: December 1, 2008 | ISBN10: 0786437154 | ISBN-13: 978-0786437153

Clinical Medicine Insights: Therapeutics

More information about the studies and development of Oxytrex

see also http://www.researchgate.net/publication/226837972_Ultra-LowDose_Opioid_Antagonists_Enhance_Opioid_Analgesia_and_Reduce_Tolerance

Studied, Recommended, Prescribed & Advocated by...

Dr Sean Mackey, MD, PhD

see also http://www.painmattersfilm.com/

Catherine Cahill, PhD

Dr. Tom Gilhooly MBChB MRCGP (Glasgow )

http://www.ldnresearchtrust.org/node/3 http://www.youtube.com/watch?v=fWrG_UQtbsU eg See page 3 of: http://www.ldnresearchtrustfiles.co.uk/docs/May%20-%20Newsletter.pdf and http://www.skipspharmacy.com/wplog/pharmacy-news/ldn-2008-videos-here/

Dr. Tim Gerstmar

We are experts at treating:

Dr Chris Steele, MBE, talks about LDN

Other doctors and LDN

LDN - Extract from article by Dr Mercola

See clinical review of evidence

Doses and dilutions for ULDN and LDN

Opioid Antagonists in Pain Management

Source http://www.practicalpainmanagement.com/treatment s/pharmacological/opioids/opioid-antagonists-painmanagement

An important note Re Fillers

An important note if you change methods or dispensing pharmacy.