Low-dose Naltrexone

“Low Dose Naltrexone (LDN) may well be the most important therapeutic breakthrough in over fifty years. It provides a new, safe and inexpensive method of medical treatment by mobilizing the natural defenses of one’s own immune system.

I good start would be to look at this site:

Click to access LDN%202015%20Fact%20Sheet.pdf

LDN substantially reduces health care costs and improves treatment of a wide array of diseases. Unfortunately, because naltrexone has been without patent protection for many years, no pharmaceutical company will bear the expense of the large clinical trials necessary for FDA approval of LDN’s new special uses. It is now up to public institutions to seize the opportunity that LDN offers.”

To watch a short video explaining how LDN works, click here

An Eloquent Video, A Must See — April 2015

Norwegian, with English subtitles

At long last, a most professional, most persuasive video concerning LDN!

It was made in Norway in 2013, with English subtitles. Far from a sales pitch, it tries to tell an evenhanded story. Its sole omission, which one often finds in Europe, is the total disregard for the role of the late Bernard Bihari, M.D., who discovered the human uses of LDN in 1985. Other than that, it is nearly perfect and a joy to watch. It has led to an avalanche of LDN sales in that country (from a mere 300 users beforehand, it is now used by some 15,000 patients in Norway).

Please do not miss watching: http://www.tv2.no/a/5316228

Enjoy it!

Also watch  https://www.youtube.com/watch?v=z0p0ykSzy9o to see how it actually works.

  — David Gluck, MD

What is low-dose naltrexone and why is it important?

-Low-dose naltrexone holds great promise for the millions of people worldwide with autoimmune diseases or central nervous system disorders or who face a deadly cancer.

– In the developing world, LDN could provide the first low-cost, easy to administer, and side-effect-free therapy for HIV/AIDS.

Naltrexone itself was approved by the FDA in 1984 in a 50mg dose for the purpose of helping heroin or opium addicts, by blocking the effect of such drugs. By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones that our brain and adrenal glands produce: beta-endorphin and metenkephalin. Many body tissues have receptors for these endorphins and enkephalins, including virtually every cell of the body’s immune system.

In 1985, Bernard Bihari, MD, a physician with a clinical practice in New York City, discovered the effects of a much smaller dose of naltrexone (approximately 3mg once a day) on the body’s immune system. He found that this low dose, taken at bedtime, was able to enhance a patient’s response to infection by HIV, the virus that causes AIDS. [Note: Subsequently, the optimal adult dosage of LDN has been found to be 4.5mg.]

In the mid-1990’s, Dr. Bihari found that patients in his practice with cancer (such as lymphoma or pancreatic cancer) could benefit, in some cases dramatically, from LDN. In addition, people who had an autoimmune disease (such as lupus) often showed prompt control of disease activity while taking LDN.

How does LDN work?

> LDN boosts the immune system, activating the body’s own natural defenses.

Up to the present time, the question of “What controls the immune system?” has not been present in the curricula of medical colleges and the issue has not formed a part of the received wisdom of practicing physicians. Nonetheless, a body of research over the past two decades has pointed repeatedly to one’s own endorphin secretions (our internal opioids) as playing the central role in the beneficial orchestration of the immune system, and recognition of the facts is growing.

Witness these statements from a review article of medical progress in the November 13, 2003 issue of the prestigious New England Journal of Medicine: “Opioid-Induced Immune Modulation: …. Preclinical evidence indicates overwhelmingly that opioids alter the development, differentiation, and function of immune cells, and that both innate and adaptive systems are affected.1,2 Bone marrow progenitor cells, macrophages, natural killer cells, immature thymocytes and T cells, and B cells are all involved. The relatively recent identification of opioid-related receptors on immune cells makes it even more likely that opioids have direct effects on the immune system.3

The brief blockade of opioid receptors between 2 a.m. and 4 a.m. that is caused by taking LDN at bedtime each night is believed to produce a prolonged up-regulation of vital elements of the immune system by causing an increase in endorphin and enkephalin production. Normal volunteers who have taken LDN in this fashion have been found to have much higher levels of beta-endorphins circulating in their blood in the following days. Animal research by I. Zagon, PhD, and his colleagues has shown a marked increase in metenkephalin levels as well. [Note: Additional information for Dr. Zagon can be found at the end of this page.]

Bihari says that his patients with HIV/AIDS who regularly took LDN before the availability of HAART were generally spared any deterioration of their important helper T cells (CD4+).

In human cancer, research by Zagon over many years has demonstrated inhibition of a number of different human tumors in laboratory studies by using endorphins and low dose naltrexone. It is suggested that the increased endorphin and enkephalin levels, induced by LDN, work directly on the tumors’ opioid receptors — and, perhaps, induce cancer cell death (apoptosis). In addition, it is believed that they act to increase natural killer cells and other healthy immune defenses against cancer.

In general, in people with diseases that are partially or largely triggered by a deficiency of endorphins (including cancer and autoimmune diseases), or are accelerated by a deficiency of endorphins (such as HIV/AIDS), restoration of the body’s normal production of endorphins is the major therapeutic action of LDN.

> LDN has demonstrated efficacy in thousands of cases.

Cancer. As of mid-2004, Dr. Bihari reported having treated over 300 patients who had a cancer that had failed to respond to standard treatments. Of that group, some 50%, after four to six months treatment with LDN, began to demonstrate a halt in cancer growth and, of those, over one-third have shown objective signs of tumor shrinkage.

Autoimmune diseases. Within the group of patients who presented with an autoimmune disease (see above list), none have failed to respond to LDN; all have experienced a halt in progression of their illness. In many patients there was a marked remission in signs and symptoms of the disease. The greatest number of patients within the autoimmune group are people with multiple sclerosis, of whom there were some 400 in Dr. Bihari’s practice. Less than 1% of these patients has ever experienced a fresh attack of MS while they maintained their regular LDN nightly therapy.

HIV/AIDS. As of September 2003, Dr. Bihari had been treating 350 AIDS patients using LDN in conjunction with accepted AIDS therapies. Over the prior 7 years over 85% of these patients showed no detectable levels of the HIV virus — a much higher success rate than most current AIDS treatments, and with no significant side effects. It is also worth noting that many HIV/AIDS patients have been living symptom-free for years taking only LDN with no other medications.

Central Nervous System disorders. Anecdotal reports continue to be received concerning beneficial effects of LDN on the course of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS—Lou Gehrig’s disease), and primary lateral sclerosis. Dr. Jaquelyn McCandless has found a very positive effect of LDN, in appropriately reduced dosage and applied as a transdermal cream, in children with autism.

> How is it possible that one medication can impact such a wide range of disorders?

The disorders listed above all share a particular feature: in all of them, the immune system plays a central role. Low blood levels of endorphins are generally present, contributing to the disease-associated immune deficiencies.

Research by others — on neuropeptide receptors expressed by various human tumors — has found opioid receptors in many types of cancer:

  • Brain tumors (both astrocytoma and glioblastoma)
  • Breast cancer
  • Endometrial cancer
  • Head and neck squamous cell carcinoma
  • Myeloid leukemia
  • Lung cancer (both small cell and non-small cell)
  • Neuroblastoma and others…

These findings suggest the possibility for a beneficial LDN effect in a wide variety of common cancers.

How can I obtain LDN and what will it cost?

> LDN can be prescribed by your doctor, and should be prepared by a reliable compounding pharmacy.

Naltrexone is a prescription drug, so your physician would have to give you a prescription after deciding that LDN appears appropriate for you.

Naltrexone in the large 50mg size, originally manufactured by DuPont under the brand name ReVia, is now sold by Mallinckrodt as Depade and by Barr Laboratories under the generic name naltrexone.

LDN prescriptions are now being filled by hundreds of local pharmacies, as well as by some mail-order pharmacies, around the US. Some pharmacists have been grinding up the 50mg tablets of naltrexone to prepare the 4.5mg capsules of LDN; others use naltrexone, purchased as a pure powder, from a primary manufacture

How does LDN work?

Endorphins (feel-good molecules) are produced in most cells in the body, and are important regulators of cell growth and the immune system. Disorders of the immune system can occur with unusually low levels of these endorphins.

Naltrexone is a drug that binds to opioid (including endorphin) receptors. The body, feeling starved of natural endorphins (opiates), is now tricked to significantly increase its production of endorphins. Once the low dose naltrexone stops blocking the opioid receptors (usually in 2- 3 hours), the body is then able to benefit from the hugely increased levels of endorphins circulating in the blood stream. This is known as “the rebound effect”.

The benefits of the rebound effect can only be utilized by taking a low dose of regular naltrexone. Taking a high dose of naltrexone or using a timed-release formulation will continue to block the opioid receptors and no benefit will be achieved from the elevated endorphin levels.

Individuals vary in their metabolic speed and this will result in variations of the speed at which LDN is eliminated from the body, as well as the length of the rebound effect. A single daily dose of between 3mg and 4.5mg works well for most people, however some people benefit from building up their dose slowly.

How quickly does LDN work?

Some patients experience a very fast response to LDN – within days of taking it. In many cases the response can become evident after about two weeks of use. In some cases, especially those of long standing chronic conditions, it has taken up to two months for benefit to accrue. LDN doesn’t work for everyone and it is reasonable to expect that if it will work for you, the benefit will become apparent quickly and no later than 2 months from start of use.

Which dose do I need?

The standard dose used in clinical trials for adults has been 4.5mg. Some people, especially those with lower body weights or liver conditions, benefit from a lower dose such as 3mg or even less. Sometimes it is best to build up the dose in 0.5mg increments until the optimal dose is achieved. For children, the dose is always adjusted according to body weight. For pets, the dose is also adjusted according to body weight.

When should LDN be taken?

Although many people take LDN in the evening or before sleep, scientific studies have shown that it is equally effective if taken during the day. This is important for people who experience sleep disturbances as result of LDN.

Which medications must be avoided when using LDN?

LDN should not be combined with any opiate-based drugs as LDN will cancel their effects. Many painkillers are opiate based. Drugs such as Imodium® are also opiate based and LDN will neutralize its effect.

What side effects does LDN cause?

Side effects from LDN are unusual. Sleep disturbances tend to happen during the first few days of use, if taken at night. This can be avoided by taking it earlier in the day. Vivid dreams have been reported.

An interesting site for LDN users opinions and views about LDN is : http://www.ldndatabase.com

Post Traumatic Stress Disorder (PTSD)

PTSD Found to be Significantly Improved With LDN.  A recently published report from Germany details important success in the use of low dose naltrexone (LDN) for treating Post-traumatic Stress Disorder (PTSD). The illness involves prolonged severe anxiety following a painful ordeal and is associated with repeated re-experiencing of such events as well as general avoidance along with gloomy thoughts and feelings. This problem has affected large numbers of troops returning from wars in Iraq and Afghanistan. An abstract of the published paper can be found here.

Excerpt: The low dose treatment with naltrexone proved to be effective whereby 11 out of 15 patients reported immediate positive effects and 7 described a lasting helpful effect. The majority of patients who felt positive effects reported a clearer perception of both their surroundings and their inner life. Assessment of reality and dealing with it improved as did the perception of their own body and affects as well as self-regulation. The treatment was very low in side effects….Treatment with low-dose naltrexone may be a helpful element in the treatment of patients with complex posttraumatic stress disorder.

[Editor’s Note: Because there has been no specific pharmacotherapy available for PTSD, treatment has focused on psychotherapeutic approaches, and this, in turn, has been hampered by the lack of availability of qualified therapists—which makes this report on the effectiveness of LDN, a simple medication, all the more exciting.]

Some of the Research into LDN:

Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15.

The use of lowdose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain.


Lowdose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone‘s better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.

Arthritis Rheum. 2013 Feb;65(2):529-38. doi: 10.1002/art.37734.

Low Dose Naltrexone in the Treatment of Fibromyalgia.

Lowdose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.



To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of lowdose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue.


Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain.


When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking lowdose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Lowdose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during lowdose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Lowdose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported.


The preliminary evidence continues to show that lowdose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication.

Copyright © 2013 by the American College of Rheumatology.

Low Dose Naltrexone LDN by Jeffrey Dach MD
Low Dose Naltrexone (LDN)

by Jeffrey Dach MD

A Drug to Reverse Narcotics Overdose

Imagine a drug addict slumped over from a lethal heroin overdose. He has shallow breathing and will die unless he receives prompt medical care in the emergency room. If he is lucky enough to make the trip to the ER, the doctors will give him an IV injection of Narcan (Naloxone), the drug of choice to reverse narcotics overdose, waking the victim and snatching him from the jaws of death.Left Image: Duane Hanson’s sculpture “Drug Addict” from 1974, Courtesy of wikipedia.  The addict sitting the floor is a sculpture in a musem.  The man standing is an anonymous museum visitor. (18)

A close cousin of Naloxone is Naltrexone, another opioid antagonist used as treatment for for narcotics and alcohol addiction.

Chemical Structures of Naloxone, Naltrexone and Morphine are similar (see above three diagrams).

 Naloxone (Narcan)    Naltrexone          Morphine


Naltrexone: FDA approved since 1984

First etherized patient Jeffrey Dach MD

Narcan is available in the hospital operating room where anesthesiologists use it to wake up the patient after the operation. (image at left: first use of anesthesia).  Opiate antagonists such as Narcan reverse the sedating effect of opiates by binding to the opioid receptors in the brain.

Left Image: First operation under ether anesthesia on October 16, 1846 (21) Courtesy Library of Congress.

Naltrexone was synthesized in 1963 and FDA approved since 1984.  Naltrexone is a close chemical cousin to Narcan with very similar chemical structure, and is used to treat narcotics and alcohol addiction. (see chemical structure diagrams above).  It was a surprise for me to find out that Naltrexone has other very important uses at a much lower dosage as an oral capsule.  Medical scientists have been carefully studying its effect of Naltrexone on the immune system, and its clinical benefits for a host of disease states for the past 20 years.

Low Dose Naltrexone, (LDN), How Does it Work?

The beneficial effect of low dose naltrexone, LDN, was discovered by Bernard Bihari, MD (1)(1A), a physician in New York City who found that a small dose (3 mg) of naltrexone taken as a capsule at bedtime blocks the opiate receptors in the brain for a few hours during sleep, which then stimulates the brain to increase production of endorphins over the next 24 hours. These endorphins then stimulate the immune system. Although Bihari did much of the early clinical work, Zagon did much of the groundwork with animal research studies at Pennsylvania State University (3-17).

LDN Cures Crohn’s Disease

crohns sb barium jeffrey dach md A recent publication in the Jan 2007 Journal of Gasteroenterology on the use of LDN in Crohn’s Disease, was the first breakthrough publication to appear entitled, Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease by Jill Smith MD.

Left Image: Typical appearance of Crohn’s disease involving terminal ilem with ulcerations noted on barium small bowel examination (red arrows) . Courtesy of Jeffrey Dach MD, private collection.

Crohn’s disease is a severe inflammatory condition of the small bowel which can be difficult to treat. Not difficult for LDN however. Jill Smith, M.D. reported that two-thirds of her 17 Crohn’s patients went into remission, and 90% of the group had some benefit. Her article showed impressive colonoscopy photos before and after LDN treatment with complete clearing of the inflammatory changes in the bowel mucosa. Dr. Smith concluded that “LDN therapy appears effective and safe in subjects with active Crohn’s disease.”(2)

Other Conditions Which Benefit from LDN

The major therapeutic action of LDN is the restoration of normal endorphin production by the brain. This is beneficial for any condition in which there is a deficiency in endorphin production, such as autoimmune disease, cancer and HIV/AIDS. Bernard Bihari, MD, who discovered the LDN protocol has used it in hundred of patients in the following categories:

LDN for Cancer

LDN is useful for cancers of the Bladder, Breast, Colon & Rectal Cancer , Glioblastoma, Lung Cancer (Non-Small Cell), Lymphocytic Leukemia (chronic), Lymphoma Hodgkin’s and Non-Hodgkin’s) Malignant Melanoma, Multiple Myeloma , Ovarian Cancer, Pancreatic Cancer, Prostate Cancer (untreated), Renal Cell Carcinoma, Uterine Cancer,

LDN is useful for Autoimmune and other Diseases:

MRI of Multiple Sclerosis Jeffrey Dach MD

Image: Monthly MRI Scans of Multiple Sclerosis, small bright spots come and go, courtesy wikipedia.

LDN treatment has benefited these diseases: ALS (Lou Gehrig’s Disease), Autism Spectrum Disorders, Chronic Fatigue Syndrome, Crohn’s Disease, Fibromyalgia, HIV/AIDS, Multiple Sclerosis (MS), Parkinson’s Disease, Psoriasis, Rheumatoid Arthritis, Scleroderma, Systemic Lupus (SLE), Ulcerative Colitis, Wegener’s Granulomatosis.

LDN Has Virtually No Side Effects:

Occasionally, during the first week’s use of LDN, patients may complain of some difficulty sleeping. This rarely persists after the first week. Should it do so, dosage can be reduced from 4.5mg to 3mg nightly.

Caution About Narcotics Withdrawal

Because LDN blocks opioid receptors throughout the body for three or four hours, people using narcotics pain pills such as Ultram (tramadol), morphine, Percocet, Duragesic, Oxycontin or codeine, should not take LDN until after complete withdrawal from their narcotic drugs. The use of LDN may induce narcotics withdrawal.

Although naltrexone is FDA approved, the LDN protocol is what is called “off-label use”, and it is unlikely that any company will spend the millions needed to fund studies for FDA approval of the LDN protocol. However, off-label use of an FDA approved drug such as naltrexone is commonplace and widely accepted. The naltrexone capsules are inexpensive, about 20 dollars a month. The treatment is safe, with no adverse side effects.

Pharmacies that offer compounded LDN capsules:

The Compounder Pharmacy 340 Marshall Ave Unit 100, Aurora, IL 60506-2956 Phone: 630-859-0333 Fax: 630-859-0114.  (22)

Skip’s Pharmacy 21000 Boca Rio Rd Suite A-29 Boca Raton, Florida 33433, telephone 561-218-0111 800-553-7429 Fax: 561-218-8873 (24)

Thanks to Larry Frieders, the Compounder for bringing LDN to my attention, and for making low cost LDN capsules available to the public. (22)

Articles with related Content:

LDN Part Two   (second part to this article)

Jeffrey Dach MD

7450 Griffin Rd Suite 180/190

Davie, FL 33314

Phone: 954-792-4663



References: (1) http://www.ldninfo.org/index.htm

Web site for low dose nalotrexone information.

(1A) http://www.ldninfo.org/bbihari_cv.htm

Curriculum Vitae, BERNARD BIHARI, M.D. 29 West 15th Street New York, N.Y. 10011, (212) 929-4196 retired as of March 2007.

(2) http://www.ncbi.nlm.nih.gov/pubmed/17222320

Low-dose naltrexone therapy improves active Crohn’s disease.Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Am J Gastroenterol. 2007 Apr;102(4):820-8. Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.

OBJECTIVES: Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues. In an open-labeled pilot prospective trial, the safety and efficacy of low-dose naltrexone (LDN), an opioid antagonist, were tested in patients with active Crohn’s disease. METHODS: Eligible subjects with histologically and endoscopically confirmed active Crohn’s disease activity index (CDAI) score of 220-450 were enrolled in a study using 4.5 mg naltrexone/day. Infliximab was not allowed for a minimum of 8 wk prior to study initiation. Other therapy for Crohn’s disease that was at a stable dose for 4 wk prior to enrollment was continued at the same doses. Patients completed the inflammatory bowel disease questionnaire (IBDQ) and the short-form (SF-36) quality of life surveys and CDAI scores were assessed pretreatment, every 4 wk on therapy and 4 wk after completion of the study drug. Drug was administered by mouth each evening for a 12-wk period. RESULTS: Seventeen patients with a mean CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased significantly (P= 0.01) with LDN, and remained lower than baseline 4 wk after completing therapy. Eighty-nine percent of patients exhibited a response to therapy and 67% achieved a remission (P < 0.001). Improvement was recorded in both quality of life surveys with LDN compared with baseline. No laboratory abnormalities were noted. The most common side effect was sleep disturbances, occurring in seven patients. CONCLUSIONS: LDN therapy appears effective and safe in subjects with active Crohn’s disease. Further studies are needed to explore the use of this compound.

(3) http://www.ncbi.nlm.nih.gov/pubmed/6640516

Cancer Lett. 1983 Nov;21(1):89-94. Opioid antagonists inhibit the growth of metastatic murine neuroblastoma.Zagon IS, McLaughlin PJ.

Naltrexone (NTX), an opiate antagonist, had an inhibitory effect on the growth of S20 Y neuroblastoma in A/Jax mice. Daily injections of 0.1 mg/kg NTX resulted in a 69% tumor take, 70% delay in time prior to tumor appearance, and a 60% increase in median survival time. Inoculation of NB in control mice resulted in 100% tumor take within 15 days. The pattern and incidence of metastases of NTX and control mice were similar. These results show that NTX has antineoplastic activity, and suggests a role for the endogenous opioid system in neuro-oncogenic events.

(4) http://www.ncbi.nlm.nih.gov/pubmed/6316064

Life Sci. 1983 Dec 12;33(24):2449-54.

Naltrexone modulates growth in infant rats.Zagon IS, McLaughlin PJ.

Naltrexone, a potent opiate antagonist, had both stimulatory and inhibitory effects on somatic growth in preweaning rats depending on dose. Daily injections of 50 mg/kg naltrexone, which blocked morphine-induced analgesia for 24 hr/day, resulted in increased body and organ weights, and acceleration in the appearance of physical characteristics and maturation of spontaneous motor activity. Naltrexone in a dosage of 1 mg/kg, which blocked morphine-induced analgesia for 4 hr/day, had the opposite effects. These results show that naltrexone can modulate growth, and suggest a role for the endorphins and opiate receptors in developmental events.

(5) http://www.ncbi.nlm.nih.gov/pubmed/10592296

Brain Res. 1999 Dec 4;849(1-2):147-54. Cloning, sequencing, expression and function of a cDNA encoding a receptor for the opioid growth factor, [Met(5)]enkephalin.

Zagon IS, Verderame MF, Allen SS, McLaughlin PJ. Department of Neuroscience, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA, USA.

The native opioid growth factor (OGF), [Met(5)]enkephalin, is a tonic inhibitory peptide that modulates cell proliferation and tissue organization during development, cancer, cellular renewal, wound healing and angiogenesis. OGF action is mediated by a receptor mechanism. We have cloned and sequenced a 2.1-kilobase (kb) cDNA for a receptor to OGF (OGFr). The open reading frame was found to encode a protein of 580 amino acids, and eight imperfect repeats of nine amino acids each were a prominent feature. The protein encoded by this cDNA exhibited the pharmacological, temporal and spatial characteristics of the OGFr. Functional studies using antisense technology demonstrated an enhancement in cell growth. The molecular organization of the OGFr has no homology to classical opioid receptors. These results provide molecular validity for the interaction of OGF and OGFr in the regulation of growth processes.

(6) http://www.ncbi.nlm.nih.gov/pubmed/11029512

Opioid growth factor regulates the cell cycle of human neoplasias.Zagon IS, Roesener CD, Verderame MF, Ohlsson-Wilhelm BM, Levin RJ, McLaughlin PJ.

Department of Neuroscience and Anatomy, H-109, The Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA.

The native opioid growth factor (OGF), [Met5]-enkephalin, is a tonic inhibitory peptide that modulates cell proliferation and migration, as well as tissue organization, during development, cancer, homeostatic cellular renewal, wound healing, and angiogenesis. OGF action is mediated by the OGF receptor (OGFr). To investigate the target of OGF as to cell proliferation, the effects of excess OGF, and a deprivation of OGF-OGFr interaction by an opioid antagonist, naltrexone (NTX), were examined in 3 human cancer cell lines: pancreatic (BxPC-3), colon (HT-29), and head and neck (CAL-27). OGF exposure decreased growth, DNA synthesis, and mitosis, and increased the doubling time from control levels. FACS analysis revealed a marked increase in cells in the G0/G1 phase and compensatory reduction in cells in S and G2/M phases. Consistent with this observation, the percentage of labeled mitosis (PLM) analysis showed a notable increase in the time of the G0/G1 phase. Receptor blockade with NTX increased the rate of growth, length of DNA synthesis and mitotic phases, and decreased doubling time from control values. FACS analysis indicated an increase in the proportion of cells in S and G2/M phases, and a decrease in the number of cells in the G0/G1 phase. PLM evaluation demonstrated a shortening of the length of the S and G2 phases in the 3 cell lines, and decreases in the M and G0/G1 phases in some cancers. These results indicate that OGF action is directed at the G0/G1 phase, but interruption of OGF-OGFr interfacing has widespread repercussions on the cell cycle. The data on blockade of OGF-OGFr during log phase growth suggest a requisite escorting of the growth peptide and its receptor through the cell cycle.

(7) http://www.ncbi.nlm.nih.gov/pubmed/8620464

Cancer Lett. 1996 Mar 29;101(2):159-64.

Inhibition of human colon cancer by intermittent opioid receptor blockade with naltrexone.Hytrek SD, McLaughlin PJ, Lang CM, Zagon IS.

Nude mice inoculated with human colon cancer (HT-29) and receiving 0.1 mg/kg naltrexone (NTX) beginning immediately after tumor cell injection exhibited a marked retardation in tumorigenicity. This dosage of NTX, which blocked opioid receptors for 6-8 h/day, resulted in a delay of 2.4-fold in tumor appearance compared to control subjects. At the time (10 days) when all control mice had tumors, 80% of the mice in the 0.1 mg/kg NTX group had no signs of neoplasia. Binding capacity, but not affinity, of [3H][Met5]-enkephalin was reduced 85% of control levels in tumor tissue from mice of the 0.1 NTX group. Plasma, but not tumor tissue levels of [Met5]-enkephalin were elevated (2.5-fold) in contrast to control values. These results suggest that daily intermittent opioid receptor blockade with NTX provokes the interaction of opioids and receptors in the interval following drug availability, with opioids serving to inhibit tumorigenicity of human colon cancer.

(8) http://www.ncbi.nlm.nih.gov/pubmed/9066724

Cancer Lett. 1997 Jan 30;112(2):167-75. Opioid growth factor (OGF) inhibits human pancreatic cancer transplanted into nude mice.Zagon IS, Hytrek SD, Smith JP, McLaughlin PJ.

Nude mice inoculated with human pancreatic cancer (BxPC-3) cells and receiving 5 mg/kg of opioid growth factor ([Met5]enkephalin; OGF) three times daily exhibited a marked retardation in tumorigenicity compared to animals injected with sterile water (controls). OGF-treated animals had a delay of 43% in initial tumor appearance compared to control subjects (10.6 days). At the time when all of the control mice had tumors, 62% of the mice in the OGF group had no signs of neoplasia. Tumor tissue excised from mice after 30 days was assayed for levels of [Met5]enkephalin and zeta opioid receptors. Tumor tissue levels of [Met5]enkephalin were 24-fold greater in OGF-treated mice than controls, but plasma levels of OGF were 8.6-fold lower in animals receiving OGF. Specific and saturable binding of radiolabeled [Met5]enkephalin to nuclear homogenates of pancreatic tumor tissue was recorded, with a binding affinity (Kd) of 10 nM and a binding capacity (Bmax) of 46.8 fmol/mg protein. Binding capacity, but not affinity, of [3H-Met5]enkephalin was reduced by 58% of control levels in tumor tissue from mice of the OGF group. OGF and the zeta (zeta) opioid receptor were detected in human pancreatic tumor cells by immuno-cytochemistry. These results demonstrate that an endogenous opioid and its receptor are present in human pancreatic cancer, and act as a negative regulator of tumorigenesis in vivo.

(9) http://www.ncbi.nlm.nih.gov/pubmed/6867737

Science. 1983 Aug 12;221(4611):671-3. Naltrexone modulates tumor response in mice with neuroblastoma.Zagon IS, McLaughlin PJ.

(10) http://www.ncbi.nlm.nih.gov/pubmed/6300232

Matthew, PM, Froelich CJ, Sibbitt WL, Jr., Bankhurst AD, Enhancement of natural cytotoxicity by beta-endorphin, J Immunol 130, pp.1658-1662, Apr 1983.

(11) http://www.ncbi.nlm.nih.gov/pubmed/6867737

Zagon IS, McLaughlin PJ, Naltrexone modulates tumor response in mice with neuroblastoma, Science 221, pp.671-3, Aug 12, 1983.

(12) http://www.ncbi.nlm.nih.gov/pubmed/6867737

Hytrek SD, McLaughlin PJ, Lang CM, Zagon IS, Inhibition of human colon cancer by intermittent opioid receptor blockade with naltrexone, Cancer Lett 101(2), pp. 159-64, Mar 29, 1996.

(13) http://www.ncbi.nlm.nih.gov/pubmed/8853403

Zagon IS, Hytrek SD, Lang CM, Smith JP, McGarrity TJ, Wu Y, McLaughlin PJ, Opioid growth factor ([Met5]enkephalin) prevents the incidence and retards the growth of human colon cancer, Am J Physiol 271(3 Pt 2), pp.R780-R786, Sep 1996

(16) http://www.ncbi.nlm.nih.gov/pubmed/6087062

Zagon IS, McLaughlin PJ, Duration of opiate receptor blockade determines tumorigenic response in mice with neuroblastoma: a role for endogenous opioid systems in cancer, Life Sci 35, pp. 409-416, 1984.

(17) http://www.ncbi.nlm.nih.gov/pubmed/6087062

Zagon IS, McLaughlin PJ, Opioid antagonist modulation of murine neuroblastoma: A profile of cell proliferation and opioid peptides and receptors, Brain Res 480, pp. 16-28, 1989.

(18) http://commons.wikimedia.org/wiki/ImageDuane_Hanson_Drug_Addict_Louisiana_1975.jpg

Duane Hanson’s sculpture “Drug Addict” from 1974 (together with an unidentified museum guest). Picture taken at an exhibition at the Louisiana Museum of Modern Art, Denmark. Source Own work Date Spring 1975 Public domain.

(19) http://en.wikipedia.org/wiki/Naloxone

Wikipedia: “Naloxone is a drug used to counter the effects of opioid overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory system. It is marketed under various trademarks including Narcan, Nalone, and Narcanti, and has sometimes been mistakenly called “naltrexate.” It is not to be confused with Naltrexone, another opioid receptor antagonist with qualitatively different effects, used for dependence treatment rather than emergency overdose treatment.”

(20) http://en.wikipedia.org/wiki/Naltrexone

wikipedia:”Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade. In some countries including the United States, an extended-release formulation is marketed under the trade name Vivitrol. It should not be confused with naloxone, which is used in emergency cases of overdose rather than for longer-term dependence control.”

(21) http://commons.wikimedia.org/wiki/Image:Southworth_&_Hawes_-_First_etherized_operation_(re-enactment).jpg

Re-enactment of the first operation under anesthesia (ether). The actual operation took place on October 16, 1846; Daguerrotype TITLE: Operating room of the Massachusetts General Hospital, Boston.   Mr. Holman with surgeons: John Mason Warren, George Hayward, Solomon D. Townsend, John Collins Warren and James Johnson around man on operating table. Daguerreotype by Southworth & Hawes, ca. 1850. No known restrictions on publication.

(22) http://www.thecompounder.com/index.php

The Compounder Pharmacy 340 Marshall Ave Unit 100 ~ Aurora, IL 60506-2956

Phone: 630-859-0333 Fax: 630-859-0114

(23) http://wcbstv.com/topstories/lo.dose.naltrexone.2.732830.html

Drug Addiction Medication May Treat Other Diseases Dr. Max Gomez NEW YORK (CBS)

MAy 2008.

(24) http://www.skipspharmacy.com/sppress/?cat=8

Skip’s Pharmacy LDN PAGE 21000 Boca Rio Rd Suite A-29 Boca Raton, Florida 33433

561-218-0111 800-553-7429 Fax: 561-218-8873

Jeffrey Dach MD

7450 Griffin Road Suite 190

Davie, Florida 33314






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An LDN User Story: Mellisa Miller Shares Her Experience Using LDN for Fibromyalgia

Fibromyalgia is a disorder characterized by widespread pain, abnormal pain processing (strong reactions to things that other people would not find painful), fatigue, sleep disturbance, and often psychological distress. Other common symptoms are: headaches, irritable bowel syndrome, morning stiffness, tingling or numbness in hands/feet, problems with thinking and memory (sometimes called “fibro fog”), and other pain syndromes. According to the Centers for Disease Control website, the prevalence of fibromyalgia is estimated to be around 2% (around 5 million adults, in 2005), and affects more women than men (ratio 7:1). Adults with fibromyalgia are 3.4 times more likely to have major depression than those without. It has also been associated with lower levels of health-related quality-of-life and more loss of work productivity.

While certain differences in people with fibromyalgia have been discovered (e.g. elevated levels of a neurotransmitter called Substance P in the cerebrospinal fluid), the cause (or causes) of fibromyalgia are still unclear. People with fibromyalgia are typically treated with pain medicines, antidepressants, muscle relaxants, and sleep medicines. There are three medications approved for fibromyalgia in the United States, but many patients are not helped by them. Even with recommended aerobic exercise and muscle strengthening, relaxation and psychological therapies, the symptoms of the disorder are still hard for many patients to tolerate.

Melissa MillerMellisa Miller, who lives in Kentucky, USA, offered to share her story about her experience using LDN as a treatment for her fibromyalgia:

I became a nurse (LPN) in 1991 and I loved every minute of it. In 2002, while working as a dialysis nurse, I began having bilateral elbow pain and stiffness. I thought it was from the work I was doing at the time: lifting and transferring our patients, lifting and carrying supplies. I thought that I had just over-extended my arms/elbows. Then, before I knew it, I had pain and stiffness in just about every joint, also fatigue that was worsening each day. This had a major effect on me, my family, and my career. My husband was an active duty army helicopter pilot at the time, we were raising two daughters and I was working as a dialysis nurse. I cut my hours back at work, but that didn’t help, so I tried working at another nursing job. Things seemed to get worse with that– more pain and more fatigue. I was diagnosed with severe fibromyalgia in 2004 by the third rheumatologist I had seen within two years.

In the beginning I was started on nonsteroidal anti-inflammatories which did nothing, then everything from hydrocodone to Oxycontin to morphine-patches/lollipops which helped some with pain relief but mostly made me drowsy or feel “out of it”. I couldn’t take any of that while working because it definitely would have affected my thinking and my response time to any type of emergency or patient need. So, I’d be in constant pain all-over while at work, and only once I got home, after I made dinner and helped with the girls’ homework, I would take a pain pill. It did not make sense to me that there wasn’t something better I could take to give me a better way of life! I was miserable for many years, although the muscle relaxers did give me some relief and didn’t make me as groggy as the opiates would. At the time, the medical community knew or accepted very little information related to fibromyalgia as truly real or concrete, so it was a battle for a few years trying to convince some of my providers that fibromyalgia was real, that I was in constant moderate to severe pain, and the only time I wasn’t in pain was when I could finally sleep some.

By November 2006 my symptoms had continued to worsen, and major depression quickly set in. After 15 years of being a nurse, my pain and depression finally got the better of me and I decided to quit my nursing job and try to focus on getting better. It has been hard getting over not being able to work as a nurse, but I have come to terms with it. Now I know that “who I am” defines me and not “what I was.”

Then, about 7 years ago I went through a particularly severe depression due to the chronic pain. I had come to a point where I was so exhausted and still in unbelievable pain and I spent more hours of the day in the bed than out of it. Suddenly, it felt like my depression went from “zero to sixty” in no time at all. I finally realized, as my husband came into our bedroom and saw me in bed cradling my favorite family photo and crying like a baby, that I may be in need of help! All I wanted to do was to stop my pain, if only for a minute or a few seconds…because it was unbearable. I ended up admitting myself to a hospital for about 4-5 days; they said my medications were not the best ones for my chronic pain. After a few days of medications and doses being adjusted and group/individual therapy, I went home feeling less ‘cloudy’ but still in constant pain. About 3 months later, out of nowhere it seemed, with severe all-over fibro pain, fatigue, weakness, and feeling so hopeless and worthless, I decided I was ready to “end it.” I opened a bottle of sleep medication, poured what was left in it on the vanity and started taking two at a time. I felt like I was watching someone else do this, and I wanted to yell at them to stop! But nothing came out of my mouth. I felt as if someone was pushing me to do this, saying, “You’ll make life better for your family and you won’t feel pain anymore!!” But, by the Grace of G-d, my husband knocked on the bathroom door and asked if I was okay and I said, “Yes, everything will be okay now!” He didn’t buy it at all, and continued to knock until I finally opened the door. He saw the bottle and pills on the vanity and said, “Missy, what have you done?” When I told him, he just grabbed me, hugged me tight and rushed me to the emergency room. After that, I was admitted to the psychiatric unit for 5 days and after another rearrangement of my medications and some great counseling. I left there feeling much better mentally but still suffering with chronic pain.

It wasn’t until about a year later, in 2009, that my primary care physician finally realized that my pain still wasn’t under control, and referred me to an “interventional” pain clinic. They had open minds and were constantly researching new and older treatments for pain control. At my very first appointment, I was told almost immediately that there were not many options left for pain control that I had not already tried. The doctor excused himself for a moment during which time I felt so defeated and started to prepare myself for the typical “there’s nothing we can do–you will just need to learn how to deal with constant pain” answer. But a different doctor walked in and he described that there was an old medication that is being used in a different way than in the past, and explained how this new treatment called “low-dose-naltrexone” is showing a lot of promise in relieving chronic pain in a variety of conditions including cancer, MS, Crohn’s disease, and many others. He said there was evidence it provided pain relief in fibromyalgia and that it also had very few (if any) side effects. I was at the point of wondering if I was going to spend the rest of my life in constant pain. When the doctor told me about LDN I felt hopeful again. It had been a few years since I’d heard anything positive as far as pain relief. I knew I was ready to give it a try! I said to the doctor,“Sign me up!”

Before starting LDN, I did research online and found the “lowdosenaltrexone.org” website. They also had a page for users or those interested to discuss their experience with LDN, so I asked a few questions and got a lot of positive feedback. I then decided to give it a try.

I was very blessed with having a group of doctors who were open-minded. My pain doctors were (and are) still great about writing scripts for me monitoring my LDN therapy. With any new physician or healthcare provider that I see, I do have to explain what it is and how it works.

My initial physician prescribed liquid LDN for me. In order to obtain it, I had to find a compounding pharmacy (at the time there were only 3 pharmacists in town that did compounding). I would go every 9-10 days to pick up my 10-day supply of LDN around $12/100cc bottle. After about a year or so of getting my LDN this way, I had a discussion about the compounding process with my pain specialist’s physician assistant. That’s when I decided to start compounding it on my own–it was more cost efficient, convenient, and just easier to do myself. So now I can get the naltrexone from any pharmacy I choose, pay a small co-pay and compound it myself!

I started with getting a 50mg tab compounded in 100cc water, and was instructed to take 5cc (contains the equivalent of 2.5mg of naltrexone) every 12 hours. [The twice-a-day dosing schedule is what the initial physician prescribed for me. I’m not really sure how or why they started me on this particular regimen.] I began taking it in August 2009. I only experienced one side effect: “vivid” dreams, which only lasted for the first few days. It was during those same first few days, as I recall, that we began noticing that some of my symptoms were improving. My husband and daughters said there was almost an immediate improvement in me. My husband said, “It feels like I’m starting to get my wife back!” You can’t get much better than that 🙂

Since starting LDN, I feel more in control of my pain management and my health. I continue to have fibromyalgia pain constantly but the intensity has decreased. My “fibro-fog” (thinking/remembering problems associated with fibromyalgia) has improved some as well. While having fibromyalgia means having “fibro-flares” of increased pain and tenderness due to over-exertion, stress, weather, acute illness and other triggers–it’s much more tolerable for the most part while on LDN. I’ve been able to do more traveling since starting on LDN. I’ve been doing more of my favorite hobbies since I’ve been feeling better. I’ve also been able to (and felt like) doing more volunteer work, which I love! On the whole, I feel that my pain management from taking LDN has been extremely stable. I feel more in control of my pain and my life again.

Even after six years, I still feel I am continuing to do well on my LDN therapy. Surprisingly, the amount of LDN that I take has not changed over time; I still take the exact same dosage as when I started. So far, they haven’t suggested any changes to my dosing or timing, and I see no reason to make a change. This is what works great for me—though I acknowledge it is not the same for everyone.

I would love for every fibromyalgia sufferer and chronic pain sufferer out there to know the facts about low dose naltrexone and the possibilities it has for chronic pain relief. I cannot tell you how much this one medication has made a difference in my pain relief and my LIFE. I want to spread the word about LDN so that those who don’t know about it will learn from my experience. Believe me, it is so worth taking a chance!

Wishing you all the best, 

Mellisa Miller

More about Mellisa:

I am a loving wife of almost 30 years, the majority being while my wonderful husband was on active duty for 22 years, and we currently reside in Lexington, Kentucky, USA. We have two beautiful grown daughters who are amazing, and we just welcomed the arrival of our first grandbaby-girl!

I try to keep busy with volunteer work and hobbies. I have volunteered for the local Veteran’s Administration, helping with activities for those living in their Long-Term Care Unit such as Bingo Night & Super-Bowl parties. I’ve also volunteered for the non-profit charity for our troops called “Military Missions” where I helped with collecting and sorting needed items, filling boxes and mailing care packages for deployed troops. I also currently volunteer as an Alzheimer’s advocate for the Alzheimer’s Association. I mainly help with emailing our government leaders about important Alzheimer’s information and anything else they need me to do. This is a very important charity for me personally, as my Dad had an aggressive type of dementia that took his memory almost totally away within a year; he passed away shortly after that. Now my Mom has severe dementia and Alzheimer’s; I go as often as I can to see her and spend as much time as I can with her.

As far as hobbies, I enjoy baking, especially cupcakes: the best part for me is making the frosting and decorating them! I’m also learning a lot about photography right now, which is perfect because we just had our first grandchild and I plan on taking as many photos of her as I can!

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