LDN dosing times

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Below is an email from Norman Brown, Ph.D., Ph.D. LMFT, Assoc. Prof.

Humanities & Psychology,Embry-Riddle Aeronautical University, Daytona

Beach, FL. I contacted him for information when the subject of dosing

time first came up. He is currently writing a Medical Hypotheses

article with a coauthor. Dr. Brown's daughter is on LDN and his

coauthor is as well. They have a more direct connection to Dr. Zagon

and knowledge of trials and studies pertaining to LDN, so I asked him

if he could give us his insight.

............

I got the light, from Jill , whose Crohn's Disease trial with

LDN encountered the sleep disturbance problem. Here is what she

wrote about it.

Dear Dr. Brown;

Thank you for writing. I was in Boston at the Liver meetings and I

leave today fgor Chicago for the Pancreas meetings.

As far as taking the naltrexone at night versus the day: Dr Zagon has

done some basic science research showing that enkephalins and

endorphins are secreted in a diurnal fashion with most being at

night. Since one of the hypothesis regarding the mechanism of action

of

low dose naltrexone is that it temporarily blocks the receptor

causing an elevation in these opioids...he proposed that the best

time to get the most effects would be at bedtime.

In our Crohn's trial sleep disturbances however occurred in about 1/3

of those and some had to change the naltrexone to the morning because

of side effects. Naltrexone still had an effective response in these

patients regardless of the tming. So obviously we need more research

in the area and controlled trials.

Now I would add that numerous research studies dating back to the

1980s have shown in animals that chronic use of NTX, including low

doses (in much rarer studies, because only Zagon had discovered the

value of LDN in the 80s) for as little as 1 week (and 2 weeks in

Sarkar's 2004 published study on HDN) raises the number of endorphin

RECEPTORS in brain, spleen, spinal column at least, and 4 different

types of such receptors were increased. So it's not just an increase

in circulating endorphins ,which Jill could not measure in her

study, because metenkephalin (the only one she tried to measure)

decays too quickly in the blood serum. Only Dr. Sacerdote in Milan

measures beta-endorphin in the blood cells themselves, where BE

doesn't decay, so its concentration really does increase, as my

daughter's blood showed, and her forthcoming MS blood data will

show.

The temporary increase in BE & ME might be greater when LDN is taken

at night, but there is no research evidence among the 250 articles I

have reviewed that implies that taking LDN at any time of day or

night wouldn't be just as likely as any other time to cause the body

to produce more endorphin receptors, of all four types--since NONE of

those animal studies that found those increases involved

administering the naltrexone at the animals' bed time. The general

agreement among studies was for a 60% increase in Mu receptors, the

most important for LDN, and less, perhaps 40% for Delta receptors,

and Kappa and Epsilon increases much less clear. The important part

is CHRONIC USE, DAILY FOR AT LEAST 2 WEEKS. After that beginning, I

think it's quite possible (tho I have no evidence for or against that

being a good strategy) to skip a dose or two every week, because the

increase in receptors does not decay very quickly at all--since

's Crohn's study showed gains in disease symptoms were

maintained 4 weeks after discontinuing LDN.

and Zagon have not studied receptor proliferation themselves,

and apparently they have not looked at Sacerdote's or Sarkar's

studies (and many others) that link endorphins to immune system

changes. I will be bringing all these together in my Medical

Hypotheses article on LDN for autoimmune & cancer treatment, but I

can't get to it till Christmas Vacation.

You are free to forward any of this to group if you want--since

it's important to allow LDN dosing at different times for those with

sleep disturbance. Since LDN speeds up one's metabolism somewhat, it

could be useful for people who tend to feel groggy and slow at

particular times each day--it could conceivably turn that experience

around, as well as maintain the " supersized endorphin system " that

LDN prompts the body to develop within a few weeks of beginning to

use it.

Sacerdote's blood and immune system data will show how quickly the

growth in endorphin system begins to improve the capability of the

immune system to cope with MS (and other " incidental " diseases) by

increasing Natural Killer cells and other immune factors.

Norman Brown, Ph.D.