Low dose naltrexone (LDN) - an overview

I am a 29-year old CFS/ME patient, medical writer and author. I was a speaker at the 2nd European LDN conference in Glasgow in April 2010, talking about my, my doctor's and some other Finns' experience with LDN in CFS/ME, see photos. I was also a speaker at the Birmingham LDN conference in October 2010, see photos. I have also collected huge page of scientific references related to LDN, which could previously only be found on my Finnish LDN site. In March 2013 I was a guest at a major Finnish TV show discussing CFS/ME with a doctor who prescribes LDN and another patient who uses LDN.


Low dose naltrexone was pioneered by the neurologist Bernard Bihari in the early 1980s, when he was studying medications used for drug and alcohol withdrawal. Naltrexone is an opiate antagonist, which means that it blocks opioid receptors in the brain and thus eliminates the feeling of pleasure caused by e.g. drinking alcohol. Because endogenous opioids (opioids produced by own our bodies, such as endorphines) are important for our well-being, such blockage often causes very bothersome side effects and patient compliance is difficult to achieve, even though naltrexone as such is an extremely safe drug.

Bihari noticed that very small doses of naltrexone (initially 3 mg, a fraction of the normal dose of at least 50 mg) taken at bedtime only blocked the opioid receptors transiently, which stimulated the body to produce more of its endogenous opioids and produced no significant side effects. He tried it as a treatment for HIV/AIDS and multiple sclerosis, two conditions that have been shown to be associated with low levels of beta endorphin, one of the most important endogenous opioids. In some of his AIDS patients the blood levels of beta endorphin as much as tripled when using low dose naltrexone.

The patients with MS and HIV/AIDS also experienced marked clinical improvement. The MS symptoms (especially fatigue) were relieved and the illness progression seemed to halt. Most patients never experienced a single MS attack after the initiation of low dose naltrexone. Patients infected with HIV had their viral counts drop radically, sometimes to undetectable levels. Their CD4 counts subsequently went up. As a result they were much less likely to get opportunistic infections and AIDS related malignancies.

Later development

Encouraged by his success Bihari also started experimenting with other conditions, such as other autoimmune illnesses and cancer, often with great results. Many other well-respected doctors have helped him in this revolutionary research, such as Ian S. Zagon, a distinguished professor and a member of the department of neural and behavioral sciences at the Penn State University, who specializes in opioid peptide research. The support from the patient community has also been overwhelming. Patients with MS have collected money for clinical trials and there have even been three conferences on LDN, the fourth one being held in October in 2008.

A study published early 2007 in the American Journal of Gastroenterology found that 89% of patients with Crohn's disease were improved on LDN and 67% achieved a full remission (P < 0.001). There are clinical trials currently running, about to start soon or already finished with results pending for at least the following conditions: multiple sclerosis, Crohn's disease (also in children), autism, fibromyalgia (in children), pancreatic cancer and squamous cell carcinoma of the head and neck.

A HIV/AIDS study is running in Mali, West Africa. Because LDN is extremely cheap to manufacture, even developing countries can afford to buy it. We are talking about a real revolution in the treatment of HIV/AIDS, something everyone can afford to take (manufactured in a third-world country LDN would cost about $10 a year) and which is very low on side effects.

Illnesses that can be treated with LDN

LDN has been succesfully used to treat the following conditions

Autoimmune diseases

  • multiple sclerosis
  • systemic lupus erythematosus (SLE/LED)
  • rheumatoid arthritis
  • ankylosing spondylitis
  • pemphigoid
  • sarcoidosis
  • scleroderma
  • Crohn's disease
  • ulcerative colitis aka colitis ulcerosa
  • Celiac disease
  • psoriasis
  • Wegener's granulomatosis
  • transverse myelitis
  • Hashimoto's thyroiditis, Graves' disease and other autoimmune forms of hypothyroidism and hyperthyroidism


  • bladder cancer
  • breast cancer
  • carcinoid tumor
  • colorectal cancer
  • glioblastoma
  • liver cancer
  • non-small cell lung cancer (NSLC)
  • chronic lymphocytic leukemia
  • lymphoma (both Hodgkin's and non-Hodgkin's)
  • melanoma
  • multiple myeloma
  • neuroblastoma
  • ovarian cancer
  • pancreatic cancer
  • prostate cancer
  • renal cell carcinoma
  • throat cancer
  • thyroid cancer
  • uterine cancer

Other illnesses

  • hepatitis C
  • amyotrophic lateral sclerosis (ALS)/primary lateral sclerosis (PLS)
  • autism
  • Alzheimer's disease
  • Parkinson's disease
  • Behcet's disease
  • chronic obstructive pulmonary disease (COPD, emphysema)
  • endometriosis
  • fibromyalgia
  • chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)
  • irritable bowel syndrome (IBS)
  • chronic Lyme disease/post Lyme syndrome
  • polycystic ovary syndrome (PCOS)
  • neuropathic pain
  • complex regional pain syndrome (CRPS)

Possible indications

Some of the following are or have been suspected to be autoimmune diseases, but LDN may not have been tried for them yet. Other indications on the list are suggested by clinical studies showing an endorphin deficiency, or by patients who have taken LDN for other conditions and also experienced relief in these symptoms.

  • myasthenia gravis
  • eczema
  • asthma
  • allergies
  • narcolepsy
  • acne
  • rosacea
  • insomnia and some other sleep disorders
  • migraine
  • trigeminal neuralgia
  • restless legs syndrome (RLS)
  • depression
  • chronic urticaria (hives)
  • interstitial cystitis
  • obsessive compulsive disorder (OCD)
  • type I diabetes
  • type II diabetes
  • dementia
  • post-traumatic stress disorder (PTSD)
  • schizophrenia

It should be noted while this is definitely not a conclusive list of illnesses that can be treated with LDN, it is not (nor has it been claimed to be) a treatment for everything (you may think that these lists included "every possible illness on the face of earth", but in reality there are tens of thousands of medical conditions). There are other drugs that can be used to treat as many or almost as many conditions. One of them is medical marijuana. Peculiarly cannabis can be used to treat most of the illnesses on these lists, especially the first three lists. Unfortunately this effective and low-risk treatment is still illegal in most countries, while LDN is available just about everywhere - and carries no stigma of drug use.

Mode of action

Endorphins are often associated with the pleasant feeling we (or most of us) get from e.g. exercise. But endorphins are much more than that. Beta endorphin and met enkephalin, another opioid peptide produced by the body are now known to have profound effects on the immune system. Numerous animal studies have demonstrated that met enkephalin acts as an anti-cancer agent. Beta endorphin levels have shown to be low in HIV/AIDS, many autoimmune conditions and e.g. migraine.

Low dose naltrexone acts as an immunostimulant, which may seem like a weird choice to use as a treatment in autoimmune illnesses, as they have been generally seen as manifestations of an overactive immune system and are usually treated with immunosuppressants. However more and more data is emerging that suggests that autoimmune conditions may in fact be forms of immunedeficiency. That may explain why LDN works so well for them. It may well be that underactive/overactive are oversimplifications for defining something as complex as the immune system.

LDN is also thought to block activation of microglia, a type of white blood cells found in the central nervous system (brain and the spinal cord). Activation of microglia causes so-called "sickness behaviour", e.g. fatigue, fever, pain and other bothersome symptoms.

What does it actually do

What LDN does depends on the illness being treated. In most autoimmune diseases the disease progression halts and symptoms, especially fatigue but also pain, muscle weakness and cognitive problems are alleviated. People with MS often note relief in their bladder problems. The lipodystrophy caused by antiretroviral (HIV) drugs usually improves significantly. Most patients with MS never experience another attack of the disease. Some patients report up to 90% improvement in their symptoms. In patients with degenerative illnesses like ALS and Alzheimer's the illness progression is slowed down. People with ALS may even regain already lost function, but this apparently does not happen in AD, so it is crucial to begin the treatment as early as possible.

LDN does not work for everyone, but it is extremely effective in autoimmune disease and HIV/AIDS. It is somewhat less effective for chronic Lyme and Bihari has reported that some 50% of patients with CFS/ME are helped by the drug (the number appears to be bigger for fibromyalgia). I do not have any numbers for other conditions. I have inspired many others to try LDN and only one did not notice any improvement in her condition (she has CFS/ME).

Bihari reports that a halt in cancer growth occurs in about 50% of the cancer patients he treats. Some of these patients show objective signs of tumor shrinkage. Some patients who have been deemed terminal with a little time left are still alive and doing well years later, such as a patient with pancreatic cancer (one of the deadliest cancers) whose case was published in Integrative Cancer Therapies. According to Bihari LDN works best for the following cancers: multiple myeloma, Hodgkin's disease, breast cancer, cancers of the gastrointestinal tract (including the pancreas) and non-small cell lung cancer. That isn't to say that cancer patients should ditch their existing treatments, but LDN can be taken with chemotherapy and radiotherapy - not to mention that some patients only have surgery for their cancer and others are sent to hospice when all treatment has failed (or considered to not be of help).

It may take anywhere between a day and a few months to experience relief from LDN. Cancer obviously takes a longer time to respond than some other illnesses. I recommend that the treatment be evaluated for at least three months. There is nothing to lose if it does not work in the end, but there is much to gain.

You can also watch this interesting documentary film about LDN I found on the LDN website and uploaded on Google Video.

How is it used

There are usually no side effects to the treatment. Some people experience problems with sleeping during the first week. Nausea, feeling "high", gas and bloating, hunger pangs and increased spasticity may occur in the beginning and usually go away in a few days. LDN is normally taken every night between 9 PM and 3 AM, as the body produces most of its endorphins between 2 AM and 5 AM. Sometimes it is taken in the morning if there are significant sleep disturbances, especially in CFS/ME. Finnish doctor Olli Polo has even prescribed it to be taken several times a day (in CFS/ME) with good results.

LDN can safely be taken with almost all medications, foods or supplements, but because it is an opiate antagonist it cannot be taken with any narcotic painkillers (opiates), including tramadol and taking it with immunosupressive drugs (like corticosteroids) may cause the drugs to "cancel out" each other's effects, as LDN is an immunostimulant. However, some doctors believe LDN can be taken with some opioids and some immunosuppressants. There are reports of incompatability with ketamine and Roaccutane. The only absolute contraindication is a past organ transplant, because that requires immunosuppressive medication for life, and thus taking an immunostimulant might cause graft rejection.

Any doctor can prescribe LDN as an "ex tempore" prescription, which must be filled by a compounding pharmacy. Some people use foreign pharmacies, as it is legal in most countries to order medications from abroad with a valid prescription. LDN may be formulated as capsules or liquid, but the liquid has to be refrigerated and is less convenient when traveling. It is recommended that calcium carbonate is not used as a filler for tablets. The recommended dose is 4.5 mg, but some people, especially those with severe MS, only take 3 mg. Often prescriptions are written for 1.5 mg capsules so that the patient can try taking either two or three at once. LDN is also relatively inexpensive, usually costing between $15 and $40 a month.

My own perspective

I am a sufferer of the neurological illness CFS/ME, which in my case has been progressive since I got sick on the 28th of August 2000. I first heard of LDN in 2004, but it took until early 2007 before I was able to obtain a prescription, thanks to the brilliant professor I have as a doctor. I have been using LDN since March 2007. I could already notice benefits the very next day after I started taking it. My fatigue and muscle weakness are a lot better, I don't "crash" nearly as easily as I used to and the crashes are significantly milder (I used to get bedbound from very mild effort, like stirring a soup!). My cognitive problems have improved though not as much as my fatigue. My chronic fever and chronic urticaria, both among my most bothersome symptoms are 90-95% gone. My asthma is also a lot better. Most importantly, LDN seems to have stabilized my condition. I believe I would be in wheelchair, probably even nursing home, now if it wasn't for LDN. While I'm far from a cure my quality of life is very much improved.

Many people I personally know have also benefited from LDN, including literally dozens of CFS/ME and fibromyalgia patients, several people with multiple sclerosis, several people with Crohn's disease and several people with multiple autoimmune diseases.

Please, if you think LDN might help you or someone you know, don't pass up this chance. It could change your/their life like it changed mine and thousands of others'.

My articles about LDN

My LDN articles are currently offline due to reasons beyond my control. I have them on my computer, but because I'm over 2,000 hours backlogged with work I haven't got them back online yet. Hopefully soon.

My medical textbook, Reviving the Broken Marionette: Treatments for CFS/ME and Fibromyalgia also features LDN among more than 250 other medications for these illnesses. I do make a point to stress that LDN is the treatment I recommend most. The new Finnish version, out from Finn Lectura in May 2010, has a foreword from professor Olli Polo, who prescribes LDN for CFS/ME and fibromyalgia in Finland. My other Finnish medical books Hankala potilas vai hankala sairaus (Finn Lectura 2011) and Uusia hoitoja autoimmuunisairauksiin (New Treatments for Autoimmune Diseases) (Finn Lectura 2013) also feature LDN.

I have also written a chapter for a book about low dose naltrexone which will be out in 2014.

For more information

The Low Dose Naltrexone Homepage
LDN_Users Yahoo! group
LDN World Database

Patients have ranked LDN as the most effective treatment for the following conditions:

Rheumatoid artritis
Parkinsonin's disease
Crohn's disease (I)
Crohn's disease(II)