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If LDN shows out to be a successful treatment option to MS I think it is interesting to think a little about how LDN might work. As far as I'm concerned todays view of LDN action is a bit weak.

The way in which LDN is doing good to people with MS is described on the internet as " by boosting the immune system".
What kind of research has resulted in these conclusions?
Among many anecdotal reports people report almost immediate relief. Would an altered immune system result in changes of symptoms that fast?

LDN is thought to make concentrations of endorphines higher. A very large number of scientific reports have described how beta-endorphine has a very potent vasodilative effect on microvascular vessels. Vasodilation, by the way, means relaxation of smooth muscles of the blood vessels. Altered cerebellar blood flow in MS has been reported in several reports. If this is primary or secondary to MS is unclear. If it is shown to be primary it is very interesting, especially if the blood flow locally is so restricted so it might cause hypoxic damage to nerve cells.

So my suggestion is that LDN works by affecting blood flow. Better blood flow -> immediate relief of symptoms. So you people on LDN: Have you noticed if your hands and feet have become warmer while on LDN ?

-MacGyver

Mac,

I think the term "boosting the immune system" when it comes to LDN has been a bit misunderstood. It would probably be better to say that LDN "regulates" the patient's immune system so that it can function in a more normal manner. I don't think anyone really knows how LDN is having such a positive effect on MS patients but the same situation exists for the CRAB drugs....the researchers simply don't know how these drugs have the effect they do on some MS people.

As for the increased circulation creating warmer hands or feet...my wife has been on LDN for almost 6 months and hasn't noticed this change at all. Then again, she is on Prokarin at the same time and Prokarin has the ability to regulate body temperature fluctuations.

Harry

PHARMACOLOGY

From : http://www.maripoisoncenter.com/ctr/9612naltrexone.html

Below info is per opioid detoxification

Naltrexone
Naltrexone is approved by the FDA for use in opioid detoxification, and alcohol detoxification programs in known substance abusers. Naltrexone is available only in the oral form. It is a modification of naloxone made by adding a carbonyl group to C-6. Naltrexone competes with the opioid agonists for the mu, delta, and kappa receptor sites in the central nervous system(3,8. It has an elimination half-life of 3.9-10.3 hours. Once taken, absorption is rapid and almost complete. However naltrexone has an extensive first pass hepatic metabolism so that bioavailability is poor. Only 5-20% of the drug enters the serum. It is metabolized to 6-beta-naltrexol which is a less potent but active opioid antagonist. Only 2% is excreted in the urine unchanged, while the remainder is processed in the liver to naltrexone-glucuronide and 6-beta-naltrexol and then excreted by the kidneys.
For ethanol detoxification, naltrexone doses are given at 50 mg per day, or 100 mg every other day, or 150 mg three times per week. In opioid dependence, a 25 mg test dose is given. If there are no signs of withdrawal, an additional 25 mg is given, then maintenance naltrexone therapy is set at 50-100 mg per day.

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Naloxone : Brand Name, Narcan

From: http://opioids.com/naloxone/

ABSTRACT
Background: There is evidence that the endogenous opioid system (EOS) is involved in the modulation of mood and neuroendocrine function. Furthermore, the possible involvement of the EOS in major depression has been postulated, although a clear role has not been established. Methods: The affective and endocrine responses to naloxone administration in seven female depressives and in seven matched controls and their diurnal variations were investigated. Subjects had an i.v. bolus of either 0.2 mg/kg naloxone or saline at two time points (09:00 or 18:00 h) and for 2 days in a single-blind, cross-over design. Results: The basal cortisol plasma levels, both in the morning and in the afternoon, showed higher values (P<0.05) in the depressives. There was a naloxone-induced increase in the adrenocorticotrophic hormone (ACTH), cortisol, and luteinizing hormone (LH) plasma levels, plus a subjective dysphoric effect in both groups. The depressives showed a greater dysphoric effect both in the morning and afternoon (P<0.05), and a blunted cortisol response in the afternoon (P<0.05). There were no differences between groups or time of day in the ACTH or LH responses. Limitations: The sample size was small, but by studying each patient as their own control, plus a matched control for every patient, softens this effect. Finding patients with a major depressive episode free of medication is difficult, and this aspect contributes to the size of the sample. Conclusions: These results suggest that opioid mechanisms may be involved in the HPA axis changes and possibly in mood changes found in depression. The discrepancy between increased sensitivity in depression to mood changes and decreased change in cortisol may indicate a ceiling effect for the latter.

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From : http://www.yourencyclopedia.net/Naloxone

Naloxone (trade name Narcan) is a drug used to counter the effects of overdosing on opiates such as heroin or morphine.

The drug has an extremely high affinity for the opiate receptors on nerve cells in the brain, and blocks those receptors quickly, often throwing addicts into immediate withdrawal symptoms.

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Carbonyl Group

From:http://www.thefreedictionary.com/carbonyl%20group

Noun 1. carbonyl group - the bivalent radical CO
chemical group, radical, group - (chemistry) two or more atoms bound together as a single unit and forming part of a molecule
carbonyl - a compound containing metal combined with carbon monoxide
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Mu, delta, and kappa receptor.

From : http://www.thebrain.mcgill.ca/flash/i/i ... roine.html

There are three kinds of receptors widely distributed throughout the brain: mu, delta, and kappa receptors.

These receptors, through second messengers, influence the likelihood that ion channels will open, which in certain cases reduces the excitability of neurons. This reduced excitability is the likely source of the euphoric effect of opiates and appears to be mediated by the mu and delta receptors.

The pharmacology that you posted about Naltrexone was obviously what is known about it in high dosage as applied to drug addicts.

LDN is less than 1/10 of this dosage and to date, I don't know of any data that exists to compare it to the high dosage levels. Perhaps if and when some clincial trials take place, we may get the proper answers.

Harry

Hi Harry, yes the info is for opioid detoxification, however the reason I posted is to look at the specifics of Naltrexone, MacGyver asked very good questions concerning the info available for Naltrexone.

As per what it is, the reference as it being modification of naloxone and what naloxone does, the compound used to modify and the areas specific as per receptors..

I am very curious myself for specifics, and they are hard to find, but I thought by first finding specific definitions of the base ingredients and the terminology assocciated with the definitions, perhaps it would be helpful to those who can understand these terms better than myself..

One thing I noticed is until a medical person who works in the neurological areas talks about Naltrexone, I could find no mention of it anywhere in any way connected to nuerological problems, other than the term "neuroendocrine"--http://cellbio.utmb.edu/neuroend.htm--from the abstract definition of Naloxone, perhaps this is where the relationship with Naltrexone and the neurological areas of MS meet?

Philip

Philip,

You make some excellent points here about the general lack of data available on LDN when it comes to the neurological situation.

I guess until someone, somewhere does some clinical trials on LDN, we really won't get to the bottom of all this. Hopefully by the end of this year something might happen in this area.

Take care.

Harry

My immediate response to LDN was better bladder control and less constipation. I do take Detrol XL, but the improvement in bladder control is even better with the LDN. Since it is summer, I haven't really paid attention to my hands and feet being warmer.

This study cites: "results relating to the effect of several opioid-related agents on microglial activation and neuroprotection. Among these agents, the opioid receptor antagonist naloxone...promises to be of potential therapeutic value for the treatment of inflammation-related diseases."

Role of nitric oxide in inflammation-mediated neurodegeneration
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
PubMed ID 12076984

SammyJo
LDN Survey http://home.earthlink.net/~dflomer/LDN/