Re: Dosing of LDN twice a day at 4.5mg - Response to Jayne Crocker

[Guest guest]

Hi Jayne,

This topic is really about how the 'immune system' and its various processes and

outcomes are

variously described and defined:

If we accept that...

(a) An immune system is a system of biological structures and processes within

an organism that

protects against disease by identifying and killing pathogens and tumor cells.

http://en.wikipedia.org/wiki/Immune_system

then we must also accept that to kill pathogens, the immune system must rally

the troops (boost

production) in order to mount an attack, and suppressed/reduced numbers of

pathogens (in this

example) is not a mechanism, process, or action but an 'outcome'.

From what we know so far, our immune systems are beneficially influenced by

?-endorphins and

increases in ?-endorphins.

What we don't know, so far, is the extent of ?-endorphin's overall physiological

importance or in

other words, the full extent of what is an extensive range of processes and

interactions influenced

by ?-endorphin, and increases in ?-endorphin, in the body.

If we accept the definition of 'immunosuppressant' as any substance (endogenous

or exogenous) that

performs immunosuppression of the immune system...

( An immunosuppressant is any substance that performs immunosuppression of the

immune system.

http://en.wikipedia.org/wiki/Immunosuppressant

© Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit

or prevent activity

of the immune system.

http://en.wikipedia.org/wiki/Immunosuppressive_drug

then logically, ?-endorphins or increases in ?-endorphins, as a catalyst for

various immune system

processes and interactions within the body cannot be collectively defined

'immunosuppressant'.

Dr Zagon has researched extensively, and in recent years has focussed his

research on Opioid Growth

Factor (OGF), also known as Met-enkephalin, one of two endogenous opioid

peptides.

(d) Met-enkephalin ... is one of the two forms of enkephalin; the other is

leu-enkephalin. ... ' '

.... Leu-enkephalin is an endogenous opioid peptide neurotransmitter found

naturally in the brains of

many animals, including humans. ... '

http://en.wikipedia.org/wiki/Met-enkephalin

http://en.wikipedia.org/wiki/Leu-enkephalin

OGF alone at specific doses may effect 'suppression' as an outcome or may

'suppress' certain immune

system chemicals.

But Dr Bihari measured increases of up to 200% in endorphins following

administration of LDN and the

subsequent brief blockade of opioid receptors.

Increases in ?-endorphins have been associated with beneficial increases in

other body chemicals

(and the scientific community admits the full extent and functions of

?-endorphins in the body is

still unknown).

For these reasons my view remains unchanged about LDN and OGF not being

transposable as one and the

same.

LDN & OGF are two entirely different chemical compositions and propositions.

They will interact

differently when introduced to our body's complex chemical processes. And, each

individual chemical

composition will interact differently again on introduction depending on the

wide range of variables

associated with each individual patient's past and present health status and

past and present

treatment and lifestyle.

I have no scientific qualifications just a humble, unqualified opinion... and

from my perspective

LDN cannot be described as 'an immunosuppressant' as to date, I haven't seen any

research to support

that statement.

LDN is a catalyst that increases endorphins and endogenous OGF (and other immune

system co-factors).

Increased endogenous OGF is only one outcome from taking LDN.

So LDN and OGF cannot be transposed as being one and the same (which I noticed

the ldnscience.org

video also proposes).

And... trialling OGF is not the same as trialling LDN.

As I said, just my unqualified perspective, that I may very well have to change

in light of unknown

or future research.

All my best,

Cris

PS My sincere apologies to all for this lengthy response.

(1) Endorphin

' ... ?-endorphin is released into blood from the pituitary gland and into the

spinal cord and brain

from hypothalamic neurons. The ?-endorphin that is released into the blood

cannot enter the brain in

large quantities because of the blood-brain barrier so the physiological

importance of the

?-endorphin that can be measured in the blood is far from clear. ... '

http://en.wikipedia.org/wiki/Endorphin

(2) beta-Endorphin-induced stimulation of central sympathetic outflow:

beta-endorphin increases

plasma concentrations of epinephrine, norepinephrine, and dopamine in rats., Van

Loon GR, Appel NM,

Ho D. Endocrinology. 1981 Jul;109(1):46-53:

' ... Intracisternal administration of synthetic human beta-endorphin

(0.058-7.25 nmol) in

chronically cannulated, conscious, freely moving, adult male rats increased

plasma concentrations of

epinephrine, norepinephrine, and dopamine in a dose-related manner. ... '

PMID: 6263592 PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/6263592

(3) Beta-endorphin-induced increases in plasma epinephrine, norepinephrine and

dopamine in rats:

inhibition of adrenomedullary response by intracerebral somatostatin.

Van Loon GR, Appel NM, Ho D.

' ... Synthetic human beta-endorphin, 7.25 nmol intracisternally, in

unanesthetized, freely moving,

chronically cannulated, adult male rats increased plasma concentrations of all 3

catecholamines:

epinephrine, norepinephrine and dopamine, for the 2 h period studied. ... '

PMID: 6112047 PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/6112047

(4) Lancet. 1980 Nov 1;2(8201):946-9.

Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal

fluid after

acupuncture for recurrent pain; Clement- V, McLoughlin L, Tomlin S, Besser

GM, Rees LH, Wen HL.

Abstract

Low-frequency electroacupuncture effectively alleviated recurrent pain in 10

patients. Basal levels

of beta-endorphin and met-enkephalin in the lumbar cerebrospinal fluid (CSF) of

these patients were

not different from those in pain-free control subjects. After electroacupuncture

in the patients wit

h pain CSF beta-endorphin levels rose significantly in all subjects, but

met-enkephalin levels were

unchanged. These results suggest that the analgesia observed after

electroacupuncture in patients

with recurrent pain may be mediated by the release into the CSF of the

endogenous opiate,

beta-endorphin.

PMID: 6107591 PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/6107591

(5) Clin Endocrinol Metab. 1983 Mar;12(1):31-56.

Opiate receptors: enkephalins and endorphins.

Grossman A, Clement- V.

' ... Classical mu-receptors probably have beta-endorphin as an endogenous

ligand, and seem to be

involved in the modulation of pain perception, low-frequency acupuncture

analgesia, and the

stimulation of prolactin, growth hormone and thyroid-stimulating hormone

release. ... '

' ... In the periphery, beta-endorphin is concentrated in the corticotrophs of

the anterior

pituitary, and is cosecreted with ACTH and related peptides. Circulating

Met-enkephalin originates

in the gut, sympathetic nervous system and adrenal medulla. ... '

Abstract

Opiate receptors in the central nervous system may be classified according to

pharmacological,

behavioural, or binding studies. Classical mu-receptors probably have

beta-endorphin as an

endogenous ligand, and seem to be involved in the modulation of pain perception,

low-frequency

acupuncture analgesia, and the stimulation of prolactin, growth hormone and

thyroid-stimulating

hormone release. Met-enkephalin is likely to be an endogenous ligand for the

delta-receptors, which

predominate in the basal ganglia and limbic systems; such receptors may

tonically inhibit the

release of corticotrophin-releasing factor. It has been suggested that the

newly-described

kappa-receptors may inhibit the release of vasopressin and

gonadotrophin-releasing factor; dynorphin

may be their endogenous ligand. Endogenous opiates controlling cardiovascular

and respiratory

reflexes are likely to activate mu-receptors, while high-frequency acupuncture

may alleviate the

symptoms of opiate withdrawal by allowing an increase in Met-enkephalin to

activate delta-receptors.

In the periphery, beta-endorphin is concentrated in the corticotrophs of the

anterior pituitary, and

is cosecreted with ACTH and related peptides. Circulating Met-enkephalin

originates in the gut,

sympathetic nervous system and adrenal medulla. Met-enkephalin may also be

extracted from carcinoid

tumours and phaeochromocytomas. Elevations in circulating Met-enkephalin may

occur in certain

disease states with cardiovascular and psychiatric manifestations. However,

manipulation of

endogenous or exogenous opiates has as yet no certain place in any clinical

situation.

PMID: 6303648 PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/6303648

Cris Kerr

'Advocate for the value of patient testimony'

Freely Shared LDN Resource Book: 'Those Who Suffer Much, Know Much'

http://www.ldnresearchtrustfiles.co.uk/docs/2009.pdf

Ex Administrator - 'Case Health - Health Success Stories' website

(May 2001 to May 2009 - casehealth.com.au & casehealth.com)

" The good we secure for ourselves is precarious and uncertain

until it is secured for all of us and incorporated into our common life. "

Jane Addams

______________________________________________________

11. FW: Dosing of LDN twice a day at 4.5mg

Posted by: " jaynelcrocker " jaynelcrocker@... jaynecrocker64

Date: Tue Jun 15, 2010 9:03 pm ((PDT))

Further to my earlier email from Dr Zagon, I questioned LDN being an

immunosuppressant - please see

his response below and articles attached.

Jayne Crocker

Dear Jayne:

We have a paper in press - Immunobiology - that B lymphocytes are

suppressed in cell proliferation by the OGF-OGFr axis - this is how LDN does its

job. When the

paper comes out I will send it to you. We have another paper submitted showing

that T lymphocytes

are also suppressed in cell proliferation by OGF. Our studies under in vivo

conditions are underway

and stand in agreement with our other results.

I have spent considerable time in these studies reviewing much of the flawed

investigations from

past researchers giving the false impression that LDN is an immunostimulant.

There are papers

suggesting otherwise - we have nailed it down to the molecular level. Knockdown

OGFr and OGF does

not work!!! Now, use your head - would you want more immune response if you

have MS or arthritis or

lupus. No. This would make autoimmune diseases worse. If I did not do so

earlier, I will attach 2

papers on MS.

Dr. Zagon

2 of 2 File(s)

low dose naltrexone/attachments/folder/688545640/ite\

m/listv1310_154_161_2010OGFMS.pdfLDNMS.pdf

4a. Dosing Twice a Day - From Dr Ian Zagon

Posted by: " jaynelcrocker " jaynelcrocker@... jaynecrocker64

Date: Tue Jun 15, 2010 9:17 am ((PDT))

To put this matter to rest, I contacted Dr Zagon for his views on dosing

4.5mg x 2/day and the below is his response:-

Dear Jayne:

First, LDN is an immunosuppressant - not an immunostimulant (as thought -

wrongly - by many).

Second, we recommended a dosage of 3 - 10 mg/day based on pharmacokinetics. 9

mg/day - getting to

the edge but should be okay - this person may not be optimizing her dosage

however. Remember - you

only want the LDN working for 4-6 hr/day - the higher the dosage the longer it

hangs around and the

shorter the time for your endorphins to work.

Third, stress has nothing to do with LDN.

Fourth, I am seeing some people who become tolerant to LDN and need to take it

once every 2 and some

every 3 days. I can tell you that LDN can work even as long as once every 4 or 5

days.

Dr. Zagon

[Guest guest]

Apology... I work in plain text and my email prog decided in its infinite wisdom

to replace what it

didn't recognize with ?. (Maybe it's smarter than I give it credit for?)

'?-endorphin' has been replaced with 'b-endorphin' in this copy.

Hi Jayne,

This topic is really about how the 'immune system' and its various processes and

outcomes are

variously described and defined:

If we accept that...

(a) An immune system is a system of biological structures and processes within

an organism that

protects against disease by identifying and killing pathogens and tumor cells.

http://en.wikipedia.org/wiki/Immune_system

then we must also accept that to kill pathogens, the immune system must rally

the troops (boost

production) in order to mount an attack, and suppressed/reduced numbers of

pathogens (in this

example) is not a mechanism, process, or action but an 'outcome'.

From what we know so far, our immune systems are beneficially influenced by

b-endorphins and

increases in b-endorphins.

What we don't know, so far, is the extent of b-endorphin's overall physiological

importance or in

other words, the full extent of what is an extensive range of processes and

interactions influenced

by b-endorphin, and increases in b-endorphin, in the body.

If we accept the definition of 'immunosuppressant' as any substance (endogenous

or exogenous) that

performs immunosuppression of the immune system...

( An immunosuppressant is any substance that performs immunosuppression of the

immune system.

http://en.wikipedia.org/wiki/Immunosuppressant

© Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit

or prevent activity

of the immune system.

http://en.wikipedia.org/wiki/Immunosuppressive_drug

then logically, b-endorphins or increases in b-endorphins, as a catalyst for

various immune system

processes and interactions within the body cannot be collectively defined

'immunosuppressant'.

Dr Zagon has researched extensively, and in recent years has focussed his

research on Opioid Growth

Factor (OGF), also known as Met-enkephalin, one of two endogenous opioid

peptides.

(d) Met-enkephalin ... is one of the two forms of enkephalin; the other is

leu-enkephalin. ... ' '

.... Leu-enkephalin is an endogenous opioid peptide neurotransmitter found

naturally in the brains of

many animals, including humans. ... '

http://en.wikipedia.org/wiki/Met-enkephalin

http://en.wikipedia.org/wiki/Leu-enkephalin

OGF alone at specific doses may effect 'suppression' as an outcome or may

'suppress' certain immune

system chemicals.

But Dr Bihari measured increases of up to 200% in endorphins following

administration of LDN and the

subsequent brief blockade of opioid receptors.

Increases in b-endorphins have been associated with beneficial increases in

other body chemicals

(and the scientific community admits the full extent and functions of

b-endorphins in the body is

still unknown).

For these reasons my view remains unchanged about LDN and OGF not being

transposable as one and the

same.

LDN & OGF are two entirely different chemical compositions and propositions.

They will interact

differently when introduced to our body's complex chemical processes. And, each

individual chemical

composition will interact differently again on introduction depending on the

wide range of variables

associated with each individual patient's past and present health status and

past and present

treatment and lifestyle.

I have no scientific qualifications just a humble, unqualified opinion... and

from my perspective

LDN cannot be described as 'an immunosuppressant' as to date, I haven't seen any

research to support

that statement.

LDN is a catalyst that increases endorphins and endogenous OGF (and other immune

system co-factors).

Increased endogenous OGF is only one outcome from taking LDN.

So LDN and OGF cannot be transposed as being one and the same (which I noticed

the ldnscience.org

video also proposes).

And... trialling OGF is not the same as trialling LDN.

As I said, just my unqualified perspective, that I may very well have to change

in light of unknown

or future research.

All my best,

Cris

PS My sincere apologies to all for this lengthy response.

(1) Endorphin

' ... b-endorphin is released into blood from the pituitary gland and into the

spinal cord and brain

from hypothalamic neurons. The b-endorphin that is released into the blood

cannot enter the brain in

large quantities because of the blood-brain barrier so the physiological

importance of the

b-endorphin that can be measured in the blood is far from clear. ... '

http://en.wikipedia.org/wiki/Endorphin

(2) beta-Endorphin-induced stimulation of central sympathetic outflow:

beta-endorphin increases

plasma concentrations of epinephrine, norepinephrine, and dopamine in rats., Van

Loon GR, Appel NM,

Ho D. Endocrinology. 1981 Jul;109(1):46-53:

' ... Intracisternal administration of synthetic human beta-endorphin

(0.058-7.25 nmol) in

chronically cannulated, conscious, freely moving, adult male rats increased

plasma concentrations of

epinephrine, norepinephrine, and dopamine in a dose-related manner. ... '

PMID: 6263592 PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/6263592

(3) Beta-endorphin-induced increases in plasma epinephrine, norepinephrine and

dopamine in rats:

inhibition of adrenomedullary response by intracerebral somatostatin.

Van Loon GR, Appel NM, Ho D.

' ... Synthetic human beta-endorphin, 7.25 nmol intracisternally, in

unanesthetized, freely moving,

chronically cannulated, adult male rats increased plasma concentrations of all 3

catecholamines:

epinephrine, norepinephrine and dopamine, for the 2 h period studied. ... '

PMID: 6112047 PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/6112047

(4) Lancet. 1980 Nov 1;2(8201):946-9.

Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal

fluid after

acupuncture for recurrent pain; Clement- V, McLoughlin L, Tomlin S, Besser

GM, Rees LH, Wen HL.

Abstract

Low-frequency electroacupuncture effectively alleviated recurrent pain in 10

patients. Basal levels

of beta-endorphin and met-enkephalin in the lumbar cerebrospinal fluid (CSF) of

these patients were

not different from those in pain-free control subjects. After electroacupuncture

in the patients wit

h pain CSF beta-endorphin levels rose significantly in all subjects, but

met-enkephalin levels were

unchanged. These results suggest that the analgesia observed after

electroacupuncture in patients

with recurrent pain may be mediated by the release into the CSF of the

endogenous opiate,

beta-endorphin.

PMID: 6107591 PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/6107591

(5) Clin Endocrinol Metab. 1983 Mar;12(1):31-56.

Opiate receptors: enkephalins and endorphins.

Grossman A, Clement- V.

' ... Classical mu-receptors probably have beta-endorphin as an endogenous

ligand, and seem to be

involved in the modulation of pain perception, low-frequency acupuncture

analgesia, and the

stimulation of prolactin, growth hormone and thyroid-stimulating hormone

release. ... '

' ... In the periphery, beta-endorphin is concentrated in the corticotrophs of

the anterior

pituitary, and is cosecreted with ACTH and related peptides. Circulating

Met-enkephalin originates

in the gut, sympathetic nervous system and adrenal medulla. ... '

Abstract

Opiate receptors in the central nervous system may be classified according to

pharmacological,

behavioural, or binding studies. Classical mu-receptors probably have

beta-endorphin as an

endogenous ligand, and seem to be involved in the modulation of pain perception,

low-frequency

acupuncture analgesia, and the stimulation of prolactin, growth hormone and

thyroid-stimulating

hormone release. Met-enkephalin is likely to be an endogenous ligand for the

delta-receptors, which

predominate in the basal ganglia and limbic systems; such receptors may

tonically inhibit the

release of corticotrophin-releasing factor. It has been suggested that the

newly-described

kappa-receptors may inhibit the release of vasopressin and

gonadotrophin-releasing factor; dynorphin

may be their endogenous ligand. Endogenous opiates controlling cardiovascular

and respiratory

reflexes are likely to activate mu-receptors, while high-frequency acupuncture

may alleviate the

symptoms of opiate withdrawal by allowing an increase in Met-enkephalin to

activate delta-receptors.

In the periphery, beta-endorphin is concentrated in the corticotrophs of the

anterior pituitary, and

is cosecreted with ACTH and related peptides. Circulating Met-enkephalin

originates in the gut,

sympathetic nervous system and adrenal medulla. Met-enkephalin may also be

extracted from carcinoid

tumours and phaeochromocytomas. Elevations in circulating Met-enkephalin may

occur in certain

disease states with cardiovascular and psychiatric manifestations. However,

manipulation of

endogenous or exogenous opiates has as yet no certain place in any clinical

situation.

PMID: 6303648 PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/6303648

Cris Kerr

'Advocate for the value of patient testimony'

Freely Shared LDN Resource Book: 'Those Who Suffer Much, Know Much'

http://www.ldnresearchtrustfiles.co.uk/docs/2009.pdf

Ex Administrator - 'Case Health - Health Success Stories' website

(May 2001 to May 2009 - casehealth.com.au & casehealth.com)

" The good we secure for ourselves is precarious and uncertain

until it is secured for all of us and incorporated into our common life. "

Jane Addams

______________________________________________________

11. FW: Dosing of LDN twice a day at 4.5mg

Posted by: " jaynelcrocker " jaynelcrocker@... jaynecrocker64

Date: Tue Jun 15, 2010 9:03 pm ((PDT))

Further to my earlier email from Dr Zagon, I questioned LDN being an

immunosuppressant - please see

his response below and articles attached.

Jayne Crocker

Dear Jayne:

We have a paper in press - Immunobiology - that B lymphocytes are

suppressed in cell proliferation by the OGF-OGFr axis - this is how LDN does its

job. When the

paper comes out I will send it to you. We have another paper submitted showing

that T lymphocytes

are also suppressed in cell proliferation by OGF. Our studies under in vivo

conditions are underway

and stand in agreement with our other results.

I have spent considerable time in these studies reviewing much of the flawed

investigations from

past researchers giving the false impression that LDN is an immunostimulant.

There are papers

suggesting otherwise - we have nailed it down to the molecular level. Knockdown

OGFr and OGF does

not work!!! Now, use your head - would you want more immune response if you

have MS or arthritis or

lupus. No. This would make autoimmune diseases worse. If I did not do so

earlier, I will attach 2

papers on MS.

Dr. Zagon

2 of 2 File(s)

low dose naltrexone/attachments/folder/688545640/ite\

m/listv1310_154_161_2010OGFMS.pdfLDNMS.pdf

4a. Dosing Twice a Day - From Dr Ian Zagon

Posted by: " jaynelcrocker " jaynelcrocker@... jaynecrocker64

Date: Tue Jun 15, 2010 9:17 am ((PDT))

To put this matter to rest, I contacted Dr Zagon for his views on dosing

4.5mg x 2/day and the below is his response:-

Dear Jayne:

First, LDN is an immunosuppressant - not an immunostimulant (as thought -

wrongly - by many).

Second, we recommended a dosage of 3 - 10 mg/day based on pharmacokinetics. 9

mg/day - getting to

the edge but should be okay - this person may not be optimizing her dosage

however. Remember - you

only want the LDN working for 4-6 hr/day - the higher the dosage the longer it

hangs around and the

shorter the time for your endorphins to work.

Third, stress has nothing to do with LDN.

Fourth, I am seeing some people who become tolerant to LDN and need to take it

once every 2 and some

every 3 days. I can tell you that LDN can work even as long as once every 4 or 5

days.

Dr. Zagon