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Low-Dose Naltrexone: Medical Revolution Or Pseudoscience?




Background on Naltrexone

Naltrexone is an FDA-approved drug that binds to and inhibits opiate receptors -– whose primary known function is to bind endogenous opiates (endorphins and enkephalins) and reduce pain. These are the same receptors that morphine, heroine, and other opiate drugs bind to. The primary use of naltrexone is to rapidly reverse opiate toxicity, or in the chronic treatment of opiate addiction.

But biology is always more complex than our initial understanding of any system. Evolution has a tendency to use what is at hand, and so receptors and hormones have been frequently co-opted for other uses over evolutionary history. This is partly why medications often have side effects –- the target of the drug is used for more than just the desired effect.

There is also evidence that opiate receptors exist on other cell types, including cells involved in immune function, and activating or inhibiting these receptors may therefore modulate immune function or other biological functions. So far so good –- all interesting and fairly standard basic science.

Translational Research

In the case of LDN the major problem comes at the level of translational research –- taking what we are learning from basic science and applying it to specific clinical applications. It should be noted that this type of research is very unpredictable. Most of the promising leads provided by basic science do not lead to effective treatments. There are many possible reasons for such failure to translate to clinical outcomes. It is possible that the basic science picture is still significantly incomplete, and the piece or pieces that are missing alter the ultimate clinical effect of the intervention. It is also possible that the basic science is simply wrong in one or more of its conclusions. Further, the basic science may be correct, and the predicted outcome legitimate, but the size of the effect clinically insignificant, and therefore not seen in clinical trials.

Or, the basic science may be looking at markers that are associated with the biological or disease process they are interested in, but are not causally related (just downstream effects), and therefore manipulating the markers has no effect. Or the markers may be very nonspecific and completely incidental. For example, many things will activate the immune system incidentally, resulting in elevated markers for immune activity. But modifying these markers, or even immune activity may do nothing for the underlying disease or process you want to treat.

There are therefore many blind alleys. The basic science should therefore be used cautiously, to point in the direction of potential translational research –- but not to justify clinical treatments.

Translational and other clinical research then proceeds to preliminary pilot studies. These types of studies are generally small and either open (not blinded) or with some blinding. They are not large, rigorous, and reliable clinical trials. The purpose of pilot studies is to see if a new treatment or approach is basically safe, and if it has any potential. You want to make sure that patients do not do clearly worse on the treatment. The point of preliminary research is to justify larger clinical trials –- not to support clinical claims.

I have discussed previously the work of John Ioannidis that indicates that most published research is wrong. Don’t take this the wrong way –- on scientific questions the research eventually works itself out. But when you take any question that has been fairly definitively answers, and then look back through the literature, many if not most of the preliminary studies published on the question turn out to have been wrong in retrospect. The take home lesson for this is that, when you are at the pilot study stage most positive studies will not pan out when more rigorous studies are done.

This should not be surprising. There are multiple factors that are known to bias small or poorly controlled studies toward the positive –- placebo effects, experimenter bias, and publication bias just being the most obvious.

If you read the conclusions to even very positive pilot studies you will find, “This study indicates that treatment X is well-tolerated by patients with disease Y,” or “This study indicates that larger clinical studies are warranted.” When researchers have to couch their conclusions in terms that will get past peer-review, that is all they can say. Problems arise, however, when proponents (whether or not they are the researchers) begin to make clinical claims that go beyond such caution.

Low-Dose Naltrexone (LDN)

So what is the current state of the science of LDN? At this point the basic science shows that opiate receptors, as I indicated, do more than modulate pain. This means they are a potential target for the development of new drugs, or new applications of existing drugs. While naltrexone is an antagonist –- it inhibits opiate receptors –- LDN causes a compensatory upregulation of native endorphins and enkephalins, which last beyond the effects of the naltrexone itself. This means, paradoxically, that a daily dose of LDN can be used to chronically increase endorphin and enkephalin levels.

This is all perfectly reasonable, but still a bit preliminary, basic science. It indicates the potential for translational research –- nothing more.


One study on fibromyaligia found symptomatic relief and reduced pain and tenderness. Beyond being preliminary, such effects could simply be due to increased endorphins (natural pain reducers), without having to invoke any other mechanism.There are also a few studies looking at Crohn’s disease and experimental allergic encephalitis (EAE –- a rat model of multiple sclerosis) with some  positive effects. The EAE study adds the further element of extrapolating from an animal model to a human disease.

There is also a pilot study of LDN in autism. While one outcome measure was positive, the rest were negative –- which to me is a negative study.  At the very least, LDN looks less promising for autism than for either painful or autoimmune diseases, which does make sense given that autism is a very different and complex disorder.

So far this would all be just an obscure corner of medical research, hardly worth the public’s attention and of use only to medical researchers looking for promising leads to follow up. But here is where the pseudoscience comes in –- some advocates are promoting LDN as a breakthrough medical treatment for a long list of diseases and disorder, going well beyond the research.

The website,, embellishes the preliminary research and presents LDN as an effective treatment. They list that it is effective for:


* Bladder Cancer
* Breast Cancer
* Carcinoid
* Colon & Rectal Cancer
* Glioblastoma
* Liver Cancer
* Lung Cancer (Non-Small Cell)
* Lymphocytic Leukemia (chronic)
* Lymphoma (Hodgkin’s and Non-Hodgkin’s)
* Malignant Melanoma
* Multiple Myeloma
* Neuroblastoma
* Ovarian Cancer
* Pancreatic Cancer
* Prostate Cancer (untreated)
* Renal Cell Carcinoma
* Throat Cancer
* Uterine Cancer

Other Diseases:

* ALS (Lou Gehrig’s Disease)
* Alzheimer’s Disease
* Ankylosing Spondylitis
* Autism Spectrum Disorders
* Behcet’s Disease
* Celiac Disease
* Chronic Fatigue Syndrome
* CREST syndrome
* Crohn’s Disease
* Emphysema (COPD)
* Endometriosis
* Fibromyalgia
* Irritable Bowel Syndrome (IBS)
* Multiple Sclerosis (MS)
* Parkinson’s Disease
* Pemphigoid
* Primary Lateral Sclerosis (PLS)
* Psoriasis
* Rheumatoid Arthritis
* Sarcoidosis
* Scleroderma
* Stiff Person Syndrome (SPS)
* Systemic Lupus (SLE)
* Transverse Myelitis
* Ulcerative Colitis
* Wegener’s Granulomatosis

Right there we have a huge red flag –- a treatment that works for a long list of diseases with different etiologies. Many of the diseases on the list are autoimmune, and therefore an immunosuppresant could theoretically be applied to many autoimmune diseases. But many of the diseases on the list are not autoimmune.

Treating a long list of cancers is another red flag, as well as HIV/AIDS. The justification for this is that LDS “boosts the immune system,” this phrase alone also being another indication of a dubious treatment. Scientists do not talk of “boosting” the immune system because this concept is too vague to be of any use. The immune system in healthy individuals is probably already operating within optimal parameters, especially since immune activity is a trade off between fighting off invaders while not causing too much damage to the host. Increasing immune activity, therefore, does not always equal improving immune function. In individuals who have a weakened immune system because of chronic disease, poor nutrition, or toxicity their immune systems can be restored to more normal function with treatment -– but these are often specific treatments that address an underlying cause.

Further, there is an inherent contradiction in simultaneously treating diseases that are autoimmune (the immune system attacking the host), and immunodeficiency diseases (like AIDS) and claiming to treat cancer by “boosting” immune activity. Increasing immune activity actually worsens autoimmune diseases, and suppressing the immune system would worsen AIDS. This is a difficult contradiction to resolve.

The end result is just another bogus treatment with claims that are literally too good to be true, based upon pre-clinical or preliminary evidence only. Proponents have turned into proselytizers –- saying on their website:


Truly promising and science-based treatments do not need an organization to promote them. The science will speak for itself.


The opiate system and drugs to manipulate it are standard biomedicine, and we may see an expansion of the indications for naltrexone as the clinical research progresses. I would also not be surprised at all if this line of research does not pan out –- we simply cannot tell at this stage.

Meanwhile, the LDN community are turning a promising if preliminary treatment into essentially what is snake oil by promoting it for an implausibly long and contradictory list of indications. They are making the classic mistake of extrapolating prematurely from preliminary evidence, and relying heavily on anecdotes. Anecdotes are just another form of preliminary evidence (a particularly weak form at that)  that should only be used to indicate promising new research, but not as a basis for clinical claims.

Ironically, LDN promoters may in fact harm research into LDN by giving it a bad name. Researchers may be reluctant to hitch their careers, or funding agencies commit resources, to a treatment that has a dubious reputation. If the research is promising it will still get done, but if anything it’s likely to be slowed by the efforts of the LDN promoters.

This is just one of the many ways in which pseudoscience poisons the system.


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14 Responses to “Low-Dose Naltrexone: Medical Revolution Or Pseudoscience?”

  1. David Johnson says:

    This article is fundamentally in denial about how trials of new drugs are funded and why LDN has been so widely adopted by patients. I should know because my autoimmune disease is in complete remission thanks to LDN and my wife is a molecular biologist who works at a large biotech in highly regulated areas of medicine.

    The FDA funds its review of clinical trials of drugs using funds paid to it by pharmaceutical companies. As far as getting new drugs approved, we have a pay-to-play system which is basically an implementation of the conservative assumption that everything which is good for you will be profitable. An immortality potion could be discovered in clinical practice and no trials would be conducted on it and no FDA approval would be obtained in the absence of trials if it could not be patented. Without a patent, there would be no private sector funding for the immortality potion, and without funding, there would be no trials. Without trials, the immortality potion could no receive FDA approval. And probably Dr. Steve Novella would let his patients die rather than prescribe it. The main idea here is that economic conservatives have long ago remade our government’s regulation of medicines in a form which excludes trials of really promising non-patentable medicines. Doctors have largely accepted this system without discussing its limitations and problems with their patients.

    The last paragraph of the article shows how completely the author has failed to recognize this reality (a not uncommon problem, even amongst pharmaceutical and medical professionals). LDN has been used clinically with amazing results for 25 years, and no one funded trials during this long period because of the before mentioned defects in way drugs are trialed and regulated. So you can’t blame the lack of trials on the recent attention which naltrexone has received from the “LDN community”, which only exists recently thanks to the Internet. And in fact the potential of LDN has proven to be so great that academics have finally started to conduct studies on many aspects of its use. Of course the extent of their studies are limited by their funding, which is negligible. The kinds of study the author proposes have been prevented because of the cost, and it is a serious sin of omission to not acknowledge this. In some countries like the UK the LDN patients are finally making progress in getting bills passed to force the government to study this drug. If pharma companies could charge people like me $500 per month for naltrexone, they would get trials done ASAP, and I would pay up considering the miracle that naltrexone has proven in my case.

    There is absolutely no chance of LDN getting a bad name with patients, because if you are completely and miraculously relieved of all the symptoms of one of these nightmarish autoimmune diseases your experience is not going to be ignored by other patients. I heard about LDN from someone on a chat board who had complete remission from taking it. I had complete remission taking it. I have now told 4 other patients about it, and they have all had complete remissions. Probably most people who had their autoimmune disease put into remission by naltrexone were saved by an anecdote. If it wasn’t for these anecdotes and the Internet’s ability to spread them, none of these people would have been saved from the progression of their disease.

    It is doctors who are getting a bad name thanks to LDN. Most of us on LDN saw our diseases progress for years before we started the drug, producing irreversible damage (irreversible even by LDN) during which time our neurologists or other doctors pushed the latest pharma experiments with their awful side effects and dismal results. When we finally found out about LDN from other patients and asked these doctors to prescribe it, we got a short rude answer which followed the same logic expounded by Dr. Novella. Then we got rid of these doctors and had complete or partial remission in many cases once we started naltrexone. If it wasn’t for anecdotes we would still be guinea pigs for big pharma.

    These are the ways in which conservative free-market philosophy has poisoned our health. Truly promising and science-based treatments DO need an organization (i.e. a profitable corporation) to fund and promote them in our system. LDN is proof of that. Anyone who fails to understand or acknowledge why is either basically uninformed, a victim of delusional free-market capitalism, or a shill for pharmaceutical companies who are profiting from the failure to trial, develop, and use promising therapies. In the case of LDN, this has been killing and injuring people with autoimmunity every day for 25 years.

    There is a lot that isn’t known about LDN, that is for sure. And according to many doctors who prescribe it, there are some people who can’t tolerate it or don’t respond for some unknown reason. About 20% of people who try it is the number I have heard. As Dr. Novella mentions, naltrexone’s mechanism of action is really not fully or well understood. Of course in the past this was true of most other drugs discovered in clinical practice, back when doctors were capable of thinking for themselves rather than being sock puppets for big pharma. Back then doctors would prescribe apparently miraculous medicines which had been proven safe even if they hadn’t been approved for a specific use by the FDA. But if you are interested in a really comprehensive discussion of the questions and uncertainties concerning naltrexone’s mechanism of action, you should read “The Promise of Low-Dose Naltrexone Therapy”, not the fairly superficial discussion found here.

    Big pharma has invested billions in treatments for the diseases which are often put into complete remission by naltrexone. Most of this investment has produced little or nothing of value, at least from the perspective of the quality of life of someone sick with Lupus, Multiple Sclerosis, or the other diseases where naltrexone is often effective. Big pharma better hope that patients with autoimmunity stop sharing anecdotes and listen instead to Dr. Novella’s non-evidence based defense of a system corrupted at its core by free-market delusions.

  2. Nuno Zimas says:

    I can’t agree more with the previous comment. Purposefully or not, the author of this article completely bypasses the sinister role big pharma plays in selecting which substances are eligible for large clinical trials. If not patented or patentable, any active principle is ditched outright. LDN is based on sound science, as acknowledged by
    many of its critics. Why no sizable clinical trials are carried out? Ask an economist, not lab employees holding MD credentials.

  3. Greg says:

    You made an interesting, but naive, statement:


    To me, it seems that the pharmaceutical companies that have the resources to conduct the studies you mention are the very ones that would try to discredit any “cheap” drugs that could prove beneficial. The drug companies are out to make money; they are not truly out to help sick people. For example, the major MS medications have doubled in price in the past few years. Why? Mostly because their exclusive licenses to make the drugs are expiring, and they want all the profit they can get in the meantime (and hey, insurance pays for most of that cost, nevermind what that does to insurance costs).

    Why would a drug company commit possibly hundreds of thousands of dollars to test a drug that costs less than $30/month, when they can sell drugs that cost more than $30,000/month for the same disease? With those levels of profit, their best bet is to discredit the less-expensive drugs.

  4. Ben says:

    The comments above all add something, but the diatribe that leads this comment board seems to be a reaction to something other than Dr. Novella’s article. Yes, this drugs works for you and people you know, and yes, it should be receiving attention from the medical industry, but nothing Dr. Novella stated contradicts this notion. His critiques are completely sensible:

    1. This LDN has no class I studies associated with it, and much of the evidence that it works is generated by a group with a vested interest in its promotion. All he says here is that we should actually do a proper double-blind study to corroborate the existing evidence… if it’s as miraculous as the first comment makes it sound, it should sail through with flying colors.

    2. Assuming that it does relieve symptoms, the mechanism may be simple analgesia… i.e. it might be like reporting that morphine fixes broken bones because patients report that their symptoms are gone. If this is true it may still be viable as a drug for some conditions, but masking something like AIDS or cancer (which LDN purports to treat) would be harmful indeed.

    3. Past experience suggests that there are no panaceas, and we should be suspect of any substance that claims to fix all things. This has been claimed by a huge number of snake-oil salesmen in the past, and caution is prudent. This is especially true because – as Dr. Novella points out – some of the conditions LDN is being recommended for are apparent contradictions: it doesn’t seem likely that a drug can both suppress immune reactions (autoimmune disorders) and boost it (AIDS). Furthermore, the closest things to a “wonderdrug” we’ve made (prednisone comes to mind) have all had serious side effects when taken chronically. Ergo, more formal research is necessary.

    Yes, there are problems with the FDA’s procurement system, but nothing Dr. Novella asserts is anything but sensible (though the “science-based treatments do not need an organization to promote them” is a little naive). Feel free to tirade, but if you’re going to direct that tirade at the author of an article it should be more germane.

  5. Stirling Rand says:

    Naltrexone is off patent, the drug is cheap. What company will spend any amount of money to research a drug that can not make them money? You said :”but in a preliminary phase that does not justify clinical use.” 10,000 + people use LDN and claim that it works, the largest single group is people with MS and they claim that the disease progression has stopped. There is enough evidence that shows that the drug works to have the NHS or some other public entity to do the trial. In the mean time people who would benefit from the drug can still get it, cheaply. Once the pharma companies get hold of it the price will skyrocket, lots of evidence to prove that

  6. dAVId Hallgarth says:

    LDN has served me well over the last three years, it has kept my leukemia in remission, and my immune system
    stronger, and I have hard copies of lab work, CBC’s to support my position, since starting LDN, I no longer am bothered with skin cancer, whilst you sit comfy in your office and ponder which new auto you may purchase next year.
    We the LDN groups, are in the trenches, you may ponder your next family vacation whilst we
    suffer from many health issues, you may smugly think it must be proven a hundred times over before you do your duty and write a script, we must continue to stay alive. I can imagine you fitting in well on the Texas Medical Board that hunts, killers in the medical community, Dr. Burzinski down, deal or alive.
    And no, LDN does not help everyone, but it has not destroyed anyone either, ie like your profit motivated vaccines and chemo, get a real job, become socially responsible, not just profit motivated, and not align your sociopathic self with big pharma, david lubbock tx.

  7. Harry says:

    If you had a clue what you were talking about your comments might be worth considering.
    Try living with UC and finding that all the “accepted drugs” don’t work over a ten year period
    and the know-it-alls, like you, come up with removing my colon as a solution.

    After taking LDN for 6months and dropping all other meds my latest scope “shows no signs of
    active disease”.

    All my GIs look at the test results, shake their heads and say it’s impossible.

    If you want further details including test results let me know. I’ll share.

    Yeah, right.

  8. Jay Zmudka says:

    There are 10 thousand members of the Yahoo LDN group who would disagree.
    In other words, we have a social network on the Internet for our clinical trial, we don’t need your big pharmy funded class 1 studies. Disruptive isn’t it?

  9. Ben says:

    @Jay – Seriously?…Seriously!? You want to use a Yahoo group as a legitimate measure of a drug’s effectiveness? There’s a LARGE Yahoo group for virtually every off-the-wall crank health claim (colloidal silver, anti-vaccine, homeopathy, and other demonstrably false treatments)… this lends NO legitimate support to your argument, and it’s precisely why we regulate drug claims so closely: Almost any substance that is tried by a large number of people is going to have large numbers of people who see “results”, but when you run these same populations through a double-blind trial you find that these “cures” were nothing but (a) random chance (a certain percentage of people will get better in any given time period) or (b) placebo. I’m not trying to claim that LDN wouldn’t succeed under such scrutiny, but citing a yahoo-group as evidence shows just how little you understand the scientific method.

  10. Dickheads says:

    you are all dickheads…

  11. Elisa Pretsky says:

    There is a happy medium between touting something as a cure- all and offering something that may/may not be helpful for certain conditions. The bigger question is why are people looking for alternatives to the science based, FDA approved medications offered for their conditions? My personal experience(and I am also a medical professional) has led me to try “snake oil”. The fact is that there are serious problems with the way medicine is practiced today. It is formulaic, non-holistic, and wrought with side effects. i was prescribed a medication that resulted in production of autoantibodies and have been sick for over a year with chronic muscle/joint pain, night sweats, and flu like symptoms(possibly a flare of my quiescent Crohn’s disease). Since my CRP and ANA were not significant noone has offered any treatment for me. Also, many doctors have been dismissive of my claims that these symptoms were a result of the medication. many MDs are ignorant about the unintended effects and pathways that are effected/ altered by certain drugs.Why do certain drugs cause joint pain, sore throat, flu-like symptoms, menstrual irregularities? These side effects will be listed but doctors don’t understand the mechanism by which they are caused. They don’t understand the connection between hormonal disruptions and immune function.They don’t check for liver enzyme deficiencies which can make a difference between therapeutic and toxic with some drugs. I know this because I will ask these questions and they look at me like I have 3 heads. They know as much about the drugs they prescribe as a lay person who can read a package insert published by the drug company whose primary purpose is profit.
    The fact is that LDN is inexpensive and safer than, say, steroids, methotrexate, TNF blockers, and antiretrovirals which all come with sometimes life-threatening side-effects. So if this drug MAY offer some quality of life to the sufferers who want to try it, than why not? No one will jump to fund research for this drug because it is cheap an unprofitable, not because it is dangerous. The worst that will probably happen is that people will be disappointed if it doesn’t work for them. I, myself, educate myself and am wary of sensational claims. I weigh costs/risks of alternative treatments.
    My personal experience on LDN is that within 1 1/2 weeks of taking it my pain was reduced by about 50% and my energy level went up by about the same %. Also, I have not had a low grade temp in months now and the frequent infections I was getting since taking a course of prednisone have resolved. The only side effect I’ve had is early morning waking which is controlled with occasional use of an antihistamine or Rozerem.
    If the public demand becomes great enough for this drug, I would not be surprised if some pharma lab starts working in their basement trying to alter some molecules but retain the same effect so that they can repatent a “new” dug with a fancy name full of X’s and Z’s and charge hundreds of dollars a month like Rozerem which doesn’t do much more than the unpatentable melatonin.

  12. mar says:

    I have intersttial cystitis and have lost my job becuase I was in so much pain..tryed Lyrica. Amitriptyline, Tramadol etc…and still had pain…
    Now on LDN all my pain is gone.

  13. Gwen wilson says:

    My sister has completely stopped a severe case of MS with LDN. I have also stopped a case of Ankylosing Spondylitis with LDN. What science cannot explain is why they are not offering this no side effect, low cost drug as a treatment option. It is easy for you to dismiss, but look on the internet and Yahoo. THERE IS SCIENTIFIC EVIDENCE, JUST NO MONEY TO PUT A FORMALIZED STUDY TOGETHER. The medical community is indeed scared of this revolutionary drug and your article put it into print. The idea that your article did not investigate and only condemned the drug is close to malpractice. If only one person stops the pursuit of this drug, then you will have a great deal of life-changing suffering on your hands.
    Gwen Wilson

  14. Embroidery Digitizing says:


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