Rheumatoid Arthritis Support

It has been theorized that LDN works in multiple modalities. It's known mechanism of action is in binding the opioid receptor and blocking binding at this site. Opioid receptors affect reward and various psychoactive functions of behavior and emotion.

The evidence of an interaction of endorphins to the immune system is limited and it is likely that endorphins are only a minor player in the immune system. The most cited literature is indeed not how endorphins modify the immune system, but rather the reverse. Specifically, during infection, when the immune system is elevated endorphins may be released, not to affect the immune system but to modulate feelings of pain and discomfort. Rather than endorphins modifying the immune system the major effects are in the opposite direction and well known in common experience: the immune system can make us feel better or worse. However, perhaps implicated in the connection between stress and immune function, there is some evidence that opioids may cause some immunosuppression at high doses.

Although opioids are widely used for the treatment of severe pain it is also known that opioids, in particular morphine, cause immunosuppression. Therefore, their use may complicate treatment of persons with an already impaired immune system, e.g., patients suffering from cancer or AIDS. However, there is no evidence that doing the opposite, blocking opioid receptors, has any effect on the immune system

Although in vitro endorphins increase the effects of the immune system, in vivo, they are immunosuppressive. This apparent contradiction can be explained, because, at least in the case of morphine, the site of opiate action appears to be in the central nervous system (CNS). Moreover, the effects appear to be mediated by the adrenal gland, most probably by catecholamines. Much of the debate regarding LDN seems to confuse the results in vitro with those of in vivo work where opioids are immunosuppressive

It is unlikely that opioid blockade with naltrexone has any effect on the immune system, as none has been demonstrated in the scientific literature in vivo or in live patients. The proposed mechanisms of LDN on the immune system are self contradictory indicating that it is immunomodulatory when no such evidence exists. Opioids are immunosuppressive and there is no known effect of lose dose blockade of opioids, nor is there any evidence in the literature that low dose blockade with LDN results in a release of opioids at some later time, not just at a therapeutic dose but also not at any detectable dose at all.

Despite scientific evidence to the contrary alternate theories have been posited originally by Dr. Bihari is as follows (It should be noted that Dr. Bihari is neither a pharmacologist nor a biochemist, but a psychiatrist).

Naltrexone, which is a pure antagonist to opiates, causes an artificial blockade of the endorphin/opioid receptors in the brain. Dr. Bihari proposes that unlike the normal (~50& mg) dose of naltrexone used to treat drug addiction, which maintains this blockade continuously for 24 hours (preventing any derived pleasure from taking the forbidden drugs), low dose naltrexone (~3& mg to 4.5& mg) may block the endorphin receptors for only a couple of hours. During that time, endorphins may fail to attach to the receptors and the body compensates by creating more endorphins. (Note that Dr. Bihari prescribes LDN to be taken at bedtime to take advantage of the body's pre-dawn boost in endorphin production.) Once the low dose naltrexone dose has been metabolized, Dr. Bihari conjectures that the body is left with a "normal" amount of endorphins as compared to healthy controls, which consequently "normalizes" the immune function. The link between endorphins and immune system regulation is a good candidate for more research.

There is no published scientific evidence that the mechanism of action proposed by Dr. Bihari actually occurs. Additionally, any change in endogenous endorphin levels theorized does not explain how they would simultaneously increase immune function in HIV as well as decrease it in multiple sclerosis.

Since 2005, at least 3 separate scientific reports have described an underlying immunodeficiency as being characteristic of four different autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, Crohn's disease and chronic fatigue syndrome. In addition, recent scientific research has demonstrated abnormally low beta-endorphins in all forms of multiple sclerosis.


Adapted from the Wikipedia article Low dose naltrexone, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki