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Crohn's Disease Forum » Treatment » Low Dose Naltrexone » LDN AM or PM...some info...


03-10-2013, 01:59 PM   #1
JoyceF
 
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LDN AM or PM...some info...

This was posted by one of the people in our MS support group....
"Many cannot take LDN in the morning and keep their immune disease progression halted. I put this to the test 3 years into taking LDN for chronic progressive MS. On daytime dosing I came out of remission within 5 days and was headed back to needing a mobility scooter again and being totally exhausted. I immediately returned to my 10pm dosing and within a few days headed back into remission.

You should adjust your dose time to the country you are in. If you took it at 10pm in the US, take LDN at 10pm wherever you are. According to Dr. Bihari and wife Jacky, LDN works on the Biorhythm of the earth.

Off Daylight Saving Time do not take LDN any earlier than 9pm. On DST, do not take LDN any earlier than 10pm if you want the full endorphin boost. You do not have to go to sleep when you take LDN.....Most studies have shown that low dose naltrexone induces a two to three-fold increase in production of metenkephalin overnight. The low dose of naltrexone, which in higher doses would block endorphin and metenkephalin action on the receptor, is gone from the body in about three or four hours, whereas the elevated levels of endorphins and metenkephalins persist all day.

When 3.0mg or 4.5mg of LDN is taken late at night(between 9pm-3am) it induces a sharp increase in pituitary and adrenal production of beta-endorphin and metenkephalin, respectively, in the pre-dawn hours, when 90% of the day's manufacture of these hormones occur. Most studies have shown that low dose naltrexone induces a two to three-fold increase in production of metenkephalin overnight.

Naltrexone, when given to mice and people at high doses, raises endorphin levels in the body's effort to overcome the naltrexone blockade. This drug became the focus of Dr. Bihari's research group. When the group discovered that endorphins are almost all produced in the middle of the night, between 2 AM and 4 AM, the studies focused on small doses (1.5-4.5 mg at bedtime) with the hope that a brief period of endorphin blockade before 2 AM might induce an increase in the body's endorphin production. In fact, the drug did so in this dosage range. It had no effect below 1.5 mg and too much endorphin blockade at doses over 5 mg. A placebo-controlled trial in AIDS patients showed a markedly better outcome in patients on the drug as compared with those on placebo...

Here is a comment on the day/night LDN dosing by a very credible LDN Pharmacist, Skip Lenz...please read the entire comment as the two cycles he mentions pack different punch levels.

I really hate to get involved with this question, and the he said,he said responses. Who is right, Zagon or Bihari, well they both are right. One has to look at the diurnal nature of endorphin secretion to understand HOW they are both right. You get your zenith peak during your normal sleep cycle. You get your penultimate peak during your wake cycle. Taking LDN prior to your zenith peak will give you more bang for your buck than prior to your wake cycle peak. Therefore you will get some increase taking LDN at times other than prior to bedtime but they will not be the most you can get. Now if you take it indiscriminately temporally, then depending of which peak is next in the cycle, you will get a fraction of the response you would get if taken at an appropriate time frame. This explains why both docs are right, for those taking it in the am, you get the PM peak to skew upwards, those taking the PM dose gets the am peak to skew upwards. Dr.Skip

By Dr. Bihari,
Except with exercise, most endorphins are made between two and four in the morning. The brain sends a message out to the adrenal and pituitary glands and tells them to make endorphins. Giving a dose three, four, five hours before that, at bedtime 9pm, is enough to make that message from the brain much stronger.

The mechanisms involved in the beneficial effect of LDN on cancer and autoimmunity have three main elements. When 3.0mg or 4.5mg of LDN is taken late at night(between 9pm-3am) it induces a sharp increase in pituitary and adrenal production of beta-endorphin and metenkephalin, respectively, in the pre-dawn hours, when 90% of the day's manufacture of these hormones occur. Most studies have shown that low dose naltrexone induces a two to three-fold increase in production of metenkephalin overnight. The low dose of naltrexone, which in higher doses would block endorphin and metenkephalin action on the receptor, is gone from the body in about three or four hours, whereas the elevated levels of endorphins and metenkephalins persist all day. =============

Naltrexone, when given to mice and people at high doses, raises endorphin levels in the body's effort to overcome the naltrexone blockade. This drug became the focus of Dr. Bihari's research group. When the group discovered that endorphins are almost all produced in the middle of the night, between 2 AM and 4 AM, the studies focused on small doses (1.5-4.5 mg at bedtime) with the hope that a brief period of endorphin blockade before 2 AM might induce an increase in the body's endorphin production. In fact, the drug did so in this dosage range. It had no effect below 1.5 mg and too much endorphin blockade at doses over 5 mg. A placebo-controlled trial in AIDS patients showed a markedly better outcome in patients on the drug as compared with those on placebo...

http://www.lowdosenaltrexone.org/ldn_and_ai.htm

============

Quoting Dr. J. McCandless here...."We know LDN increases output of endorphins, which helps mood and immune function. Pituitary controls this output, but pineal obviously plays an important role here also." Dr. Jaquelyn McCandless

A study done that may help explain the human body, genes, etc....

"About 70 percent of the genes were found to increase activity at night, the remaining 30 percent during the day. The genes are involved in a variety of functions, and govern such processes as: inflammation (swelling), the immune response, cell adhesion (how cells bind, or join together), the cell cycle (the reproduction and death of cells), the cytoskeleton (the inner structural material of cells), calcium metabolism, cholesterol production, endothelial tissue (the tissue that lines many of the body's organs and structures), transcription (the process by which DNA sequences are eventually converted through RNA into proteins), effects of the thyroid gland on the pineal gland, cell signaling (the process through which hormones and other factors control cells), copper and zinc biology"

'Gene Scan Shows Body's Clock Influences Numerous Physical Functions From Immunity to Thyroid Hormones, Pineal Gland Exerts Effects on 600 Genes'

NIH NEWS NATIONAL INSTITUTES OF HEALTH

For Immediate Release Monday, March 30, 2009

Gene Scan Shows Body's Clock Influences Numerous Physical Functions From Immunity to Thyroid Hormones, Pineal Gland Exerts Effects on 600 Genes

The pineal gland - integral to setting the body's sleep and wake cycles -may be involved in a broad range of bodily functions, according to a study by researchers at the National Institutes of Health and other institutions.

Using a technology that scans for the activity of thousands of genes at a time, the researchers found that the activity of more than 600 genes in the pineal gland are synchronized in some way with the 24-hour sleep and wake cycle. The genes influence such diverse functions as inflammation and immunity.

Researchers have traditionally studied the gland in hopes of gaining insight into the health problems of shift workers and people who frequently travel between time zones. The pineal gland produces the hormone melatonin, which regulates the cycle of sleep and waking.

"The results of this study indicate that the pineal gland may be involved in a far greater range of physiological functions than we thought," said Duane Alexander, M.D., director of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development, where much of the research took place. "An understanding of how the pineal gland interacts with the genes that the researchers identified could provide insight into a broad range of disorders and conditions."

The study appears in the March 20, 2009 issue of The Journal of Biological Chemistry. The study's first author was Michael J. Bailey, of the NICHD Section on Neuroendocrinology. Other authors of the paper were from the NIH Center for Information Technology, NIH's National Institute of Mental Health, Cardiff University, Wales, the University of Copenhagen, Denmark, King's College of London, England, and The Genomics Institute of the Novartis Research Foundation, San Diego, Calif.

The pineal gland is located within the brain, explained the study's senior author, David Klein, Ph.D., Chief of the Section on Neuroendocrinology. To conduct the study, Dr. Klein and his colleagues analyzed rodent pineal glands with a gene chip, a device that can analyze the activity of thousands of genes at a time. The researchers found that the activity of 604 genes changed on a 24-hour schedule, more than has been reported to occur in any other tissue.

The researchers discovered that these genes increase their activity from 2-to 100-fold during a 24-hour cycle. About 70 percent of the genes were found to increase activity at night, the remaining 30 percent during the day. The genes are involved in a variety of functions, and govern such processes as:

inflammation (swelling) the immune response cell adhesion (how cells bind, or join together) the cell cycle (the reproduction and death of cells) the cytoskeleton (the inner structural material of cells) calcium metabolism cholesterol production endothelial tissue (the tissue that lines many of the body's organs and structures) transcription (the process by which DNA sequences are eventually converted through RNA into proteins) effects of the thyroid gland on the pineal gland cell signaling (the process through which hormones and other factors control cells) copper and zinc biology

"We were really surprised by what we found," Dr. Klein said. "We did not expect to find 24-hour rhythms in the functioning of so many genes."

Dr. Klein said that, as he and his coworkers expected, many of the genes active in the pineal gland are also active in the retina of the eye. The study authors cited this finding as highly compelling evidence that the pineal gland and the retina evolved from the same primitive light detecting structure. An earlier study on this possible evolutionary relationship is available at: http://www.nichd.nih.gov/news/releases/pinealgland.cfm

The pineal gland is controlled by a brain structure known as the suprachiasmic nucleus, located at the base of the brain, Dr. Klein said.

The suprachiasmatic nucleus is known as The Mind's Clock, because it coordinates body rhythms in response to changes in lighting that are detected by the eyes. The suprachiasmatic nucleus is connected to the pineal gland by nerve cells. At night, a brain chemical called norepinephrine, which transmits information through nerve cell networks, is released in the pineal gland. Norepinephrine, in turn, stimulates the production of another compound within the cells of the pineal gland, known as cyclic adenosine monophosphate (cyclic AMP). Cyclic AMP causes the pineal gland to produce melatonin.

The researchers noted that the daily changes in gene activity observed in the study were controlled by the release of norepinephrine and the increase of cyclic AMP.

"This is surprising, because we did not anticipate that the release of one molecule -norepinephrine - would be found to control the activity of hundreds of genes," Dr. Klein said. "It appears that this one signal triggers a highly complex response that is necessary for normal rhythmic function of the pineal gland."

Dr. Klein added that he and his colleagues are planning future studies to discern both how the cells of the pineal gland are controlled and how they influence the genes controlling other cellular functions.

"We have a long way to go before we can fully understand the role of the pineal gland and what makes it tick," Dr. Klein said. "I suspect that the pineal gland plays a much broader role in human health than anyone has ever imagined."

This research was funded by the Intramural Research Program of the NICHD; the Center for Information Technology; The Wellcome Trust; the Biological Sciences Research Council; the Lundbeck Foundation; the Danish Medical Research Council; the Novo Nordisk Foundation; the Carlsberg Foundation; the Fonden til Lægevidenskabens Fremme; the Simon Fougner Hartmanns Familiefond; and Pennsylvania Commonwealth Health Research Formula Funds.

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute's Web site at http://www.nichd.nih.gov/

The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov

http://www.lowdosenaltrexone.org/ldn_and_ai.htm

This was posted by gretchen over on the Yahoo LDN forum.....

"Oh boy what a difference.........I have to go back on night time dosing....

I have been on day time for 4 days and what a difference. I am back to going to BR ALOT

feeling like flu, my euphoria got up and left..........SO tonight, I am back on night time, I will be able to deal with the sleepless nights alot better knowing that the nightime dosing DOES make a difference at least with this crohns patient.

I had 11 days of joy and high euphoria, 4 days into daytime dosing, I am back to where I was prior to LDN.

just a note to let others on crohns know how it worked for me

gretchen"
03-10-2013, 08:28 PM   #2
mnsun
Senior Member
 
Join Date: Nov 2011
Thanks, Joyce, that makes simple sense. On a related note, I feel the health of the pineal gland is of utmost importance. Its impairment could be another factor in autoimmune/hormonally complicated diseases.

Ensuring pitch black sleeping conditions, maybe investing in one of those gradual light emitting alarms, perhaps supplementing with melatonin every once in awhile, avoiding xeno(BPA)/phyto(soy, for one) estrogens or other exposure to hormones (rbgh), avoiding halogen intake (fluoride, bromine..in bread) except supplementing iodine (research nascent, lugols, atomic, diatomic, or kelp) every once in awhile (especially if you use sea salt) along with selenium/magnesium, seems to be ways to possibly help keep the pineal working. I've only vaguely researched this stuff, but D3 probably somehow stimulates the pineal gland and its hormonal dynamics.

I know family members who have had hormonal problems due to ?unnatrually?calcified pineal glands (sometimes due to fluoride--often in antidepressants) which may have also been complicated due to birth control pills.

Further possible considerations:
-Luke, Jennifer. "Fluoride Deposition in the Aged Human Pineal Gland". Caries Res 2991 (35): 125–28. Retrieved 2009-05-20.
-http://www.naturalnews.com/033875_iodone_deficiency.html
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Last edited by mnsun; 03-10-2013 at 09:54 PM.
03-10-2013, 08:32 PM   #3
Jmrogers4
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Jacqui

Mom to Jack (18) dx Crohn's 2/2010
Vitamin D -2000mg
Remicade - started 1/9/14; 7.5ml/kg every 6 weeks
Centrum for Him teen multivitamin
Past meds: Imuran/Azathioprine; allopurinol; methotrexate; LDN; Prednisone; Apriso; Pentasa; EEN

Husband dx Crohn's 3/1993
currently none due to liver issues
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