FDA-approved naltrexone, in a low dose, can normalize the immune system — helping those with
autoimmune diseases, and central nervous system disorders.
Welcome to the Low Dose Naltrexone (LDN) Home Page
Updated: June 15, 2016
The authors of this website do not profit from the sale of low-dose naltrexone or from website traffic, and are in no way associated with any pharmaceutical manufacturer or pharmacy.
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“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.
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.”
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.
First Study of LDN Published in US Medical Journal
Dr. Jill Smith’s original article, "Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease," in the January issue of the American Journal of Gastroenterology (2007;102:1–9), officially presents LDN to the world of scientific medicine. Smith, Professor of Gastroenterology at Pennsylvania State University's College of Medicine, found that two-thirds of the patients in her pilot study went into remission and fully 89% of the group responded to treatment to some degree. She concluded that “LDN therapy appears effective and safe in subjects with active Crohn’s disease.” (For further information on Smith's study, please see the linked Clinical Trials page.)
Endoscopic Improvement in Crohn’s Colitis with Naltrexone Figure A: Shown is the rectum of a subject with active Crohn’s
Disease before starting therapy with naltrexone 4.5 mg/day.
The mucosa is ulcerated, edematous, and inflamed. Figure B: Shows the same area of the rectum in the same patient
four weeks after naltrexone therapy. The lining is now healed, ulcers
resolved, and the mucosa is healthy. Copyrights: do not reproduce the above images and captions without written permission from
Jill P. Smith, MD, Professor of Medicine, H-045 GI Division,
Penn State College of Medicine, 500 University Drive, Hershey,
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.
CBS News Reports: "Wonder drug" LDN Could Help Treat Cancer, Multiple Sclerosis
JACKSONVILLE, FLA (CBS) — February, 2008 — This report features an interview with Lori Miles, an MS sufferer who can now walk again, thanks to LDN. Also quoted in the piece is Dr. Daniel Kantor, neurologist and director of the Comprehensive Multiple Sclerosis Program at the Shands Jacksonville Neuroscience Institute: "I would like all of us to write to our congressmen, ask the FDA and NIH—National Institutes of Health—to fund more research about LDN."
What diseases has it been useful for and how effective is it?
> Bernard Bihari, MD, as well as other physicians and researchers,
have described beneficial effects of LDN on a variety of diseases:
> 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
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)
Head and neck squamous cell carcinoma
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 manufacturer.
> LDN is not expensive.
One of the first pharmacies to compound LDN was Irmat Pharmacy in Manhattan. Their current price for a one month supply (30 capsules) of LDN is $45 dollars (for 4.0mg and greater; $37.50 for less than 4.0mg). Irmat does monthly quality control testing on its LDN, and will accept prescriptions from any licensed practitioner. No insurance is accepted. It can ship to the majority of states in the United States, but not internationally.
> Pharmacies that are known to be reliable compounders of LDN:
The Pharmacy Shop and Compounding Center, Canandaigua, NY
(585) 396-9970 (800) 396-9970
McGuff Compounding Pharmacy, Santa Ana, CA
(714) 438-0536 (877) 444-1133
Skip's Pharmacy, Boca Raton, FL
(561) 218-0111 (800) 553-7429
The Medicine Store Pharmacy,
(603) 225-2747 (877) 926-7637
Smith's Pharmacy, Toronto, Canada
(416) 488-2600 (800) 361-6624
Dickson Chemist, Glasgow, Scotland
IMPORTANT: Make sure to specify that you do NOT want LDN in a slow-release
Reports have been received from patients that their pharmacies have
been supplying a slow-release form of naltrexone. Pharmacies
should be instructed NOT to provide LDN in an "SR" or slow-release
or timed-release form. Unless the low dose of naltrexone is in an unaltered
form, which permits it to reach a prompt "spike" in the blood stream,
its therapeutic effects may be inhibited.
Fillers. Capsules of LDN necessarily contain a substantial percentage of neutral inactive filler. Experiments by the compounding pharmacist, Dr. Skip Lenz, have demonstrated that 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. He recommends either Avicel, lactose (if lactose intolerance is not a problem), or sucrose fillers as useful fast-release fillers.
> IMPORTANT: Make sure to fill your Rx at a compounding pharmacy that has a reputation for consistent reliability in the quality of the LDN it delivers.
The FDA has found a significant error rate in compounded prescriptions produced at randomly selected pharmacies. Dr. Bihari has reported seeing adverse effects from this problem. Please see our report, Reliability Problem With Compounding Pharmacies. Please see the above list of recommended pharmacies for some suggested sources.
What dosage and frequency should my physician prescribe?
The usual adult dosage is 4.5mg taken once daily at night. Because of
the rhythms of the body's production of master hormones, LDN is best
taken between 9pm and 3am. Most patients take it at bedtime.
People who have multiple sclerosis that has led to muscle spasms are advised to use only 3mg daily and to maintain that dosage.
For intial dosage of LDN in those patients who have Hashimoto’s thyroiditis with hypothyroidism and who are taking thyroid hormone replacement medication, please read Cautionary Warnings, below.
Rarely, the naltrexone may need to be purchased as a solution — in distilled water — with 1mg per ml dispensed with a 5ml medicine dropper. If LDN is used in a liquid form, it is important to keep it refrigerated.
The therapeutic dosage range for LDN is from 1.5mg to 4.5mg every night. Dosages below this range are likely to have no effect at all, and dosages above this range are likely to block endorphins for too long a period of time and interfere with its effectiveness.
> IMPORTANT: Make sure to specify that you do NOT
want LDN in a slow-release form (see above).
Are there any side effects or cautionary warnings?
> Side effects:
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.
Because LDN blocks opioid receptors throughout the body for three or four hours, people using medicine that is an opioid agonist, i.e. narcotic medication — such as Ultram (tramadol), morphine, Percocet, Duragesic patch or codeine-containing medication — should not take LDN until such medicine is completely out of one's system. Patients who have become dependant on daily use of narcotic-containing pain medication may require 10 days to 2 weeks of slowly weaning off of such drugs entirely (while first substituting full doses of non-narcotic pain medications) before being able to begin LDN safely.
Those patients who are taking thyroid hormone replacement for a diagnosis of Hashimoto’s thyroiditis with hypothyroidism ought to begin LDN at the lowest range (1.5mg for an adult). Be aware that LDN may lead to a prompt decrease in the autoimmune disorder, which then may require a rapid reduction in the dose of thyroid hormone replacement in order to avoid symptoms of hyperthyroidism.
Full-dose naltrexone (50mg) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300mg daily. The 50mg dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3mg and 4.5mg doses.
People who have received organ transplants and who therefore are taking immunosuppressive medication on a permanent basis are cautioned against the use of LDN because it may act to counter the effect of those medications.
When will the low-dose use of naltrexone become FDA approved?
> Although naltrexone itself is an FDA-approved drug, the varied uses of LDN still await application to the FDA after related scientific clinical trials.
The FDA approved naltrexone at the 50mg dosage in 1984. LDN (in the
3mg or 4.5mg dosage) has not yet been submitted for approval because the
prospective clinical trials that are required for FDA approval need to
be funded at the cost of many millions of dollars.
The successful results of the first US medical center research on LDN, an open-label trial that tested the use of LDN in Crohn’s disease (details here), was presented in May 2006 by Professor Jill Smith of the Pennsylvania State University College of Medicine. The National Institutes of Health has granted $500,000 for Dr. Smith's group to continue the study as a larger placebo-controlled scientific trial of LDN in Crohn's disease.
All physicians understand that appropriate off-label use of an already
FDA-approved medication such as naltrexone is perfectly ethical and
legal. Because naltrexone itself has already passed animal toxicity
studies, one could expect that once testing is able to begin, LDN could
complete its clinical trials in humans and receive FDA approval for one or more uses within two to four years.
What You Can Do
> Talk to your doctor.
If you are suffering from HIV/AIDS, cancer, or an autoimmune disease,
LDN could help. In AIDS and cancer therapy, LDN is often used in conjunction
with other medications.
Anyone with cancer or a pre-cancerous condition should consider LDN.
Many use LDN as a preventive treatment. Post-treatment, others have
been using LDN to prevent a recurrence of their cancer. LDN has been
shown in many cases to work with virtually incurable cancers such as
neuroblastoma, multiple myeloma, and pancreatic cancer.
As an AIDS drug, LDN leads to far fewer side effects than the standard "AIDS cocktail." When used in conjunction with HAART therapies, LDN
can boost T-cell populations, prevent disfiguring lipodystrophy, and
lower rates of treatment failure.
Do not be afraid to approach your doctors — physicians today are increasingly
open to learning about new therapies in development. Tell your doctors
about this website, or print out and hand them the information,
and let them weigh the evidence.
> Tell others.
If someone you know has HIV/AIDS, cancer, an autoimmune disease, or one of the aforementioned central nervous system disorders, LDN could save them from a great deal of suffering. If they use e-mail,
send them the address of this website (www.lowdosenaltrexone.org). Or,
print out the site and mail them the information.
> Help spread the word to the media, the medical
community, and to developing countries.
Low-dose naltrexone has the potential to reduce the terrible human loss now taking place throughout the globe. It is a drug that could prevent
millions of children from becoming AIDS orphans. It is a drug that could be a powerful ally in the war against cancer.
If you or someone you know has connections in the media, the medical
community, or to those in developing countries involved in AIDS policy
or treatment, please let them know about LDN.
About This Website
> This is a not-for-profit website.
This website is sponsored by Advocates For Therapeutic Immunology.
The purpose of this website is to provide information to patients and
physicians about important therapeutic breakthroughs in advanced medical
immunology. The authors of this site do not profit from the sale of low-dose
naltrexone or from website traffic, and are in no way associated with
any pharmaceutical manufacturer or pharmacy.
> Consult your doctor.
This website is not intended as a substitute for professional medical
help or advice. A physician should always be consulted for any medical
> Contact us.
For information on how to contact us with questions or comments, click here.
Please note that no response can be given to individual questions concerning medical symptoms or treatment.
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.
David Gluck, MD (NY Lic. #083512), is the editor of this website, ldninfo.org. He is a Board-certified 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.]
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: email@example.com; website.