What do the white rats think of LDN? (and anyone else of course )

there are many members of the ms forum here that are on ldn.

LDDM, that is low-dose dextromethorphan. This drug is in the same class as naltrexone; dextrorotatory morphinans, along with naloxone and the metabolic product of dextromethorphan, hydroxy-dextromethorphan. All of these, along with the endogenous opioids dynorphin and methionine enkephalin, have the property of somehow diminishing the activation of microglial cells in the brain by aggregated proteins or some other unknown substance(s). It is thought that microglial activation, with their production of ROS (reactive oxygen species) and certain cytokines like TNF-alpha start a vicious cycle of injuring neurons which, in turn, secrete other substances which further activate the microglial cells. This general process is now thought to contribute to the progressive nature of several neurodegenerative diseases such as PD, MS, AD, ALS and ?? Recently, LDN has also been shown to effectively control Crohns' disease, another inflammatory condition, by a group at Penn State Med Center.

The really weird property of these microglial-calming substances is that they are apparently effective at impossibly low concentrations, femto-molar. Also, the most effective way to take them (at least naltrexone and dextromethorphan) is once a day, preferably at bedtime. Whatever receptors respond to them apparently require a short "spike" of the drug, after which the effect (still not fully understood) occurs.

This is how I understand it, anyhow. Literature links to the scientific work that has been done can be found on the web at LDN.org, or on postings on this forum by AshleyK or myself.

Robert

If Dextromethorphan is in the same class as Naltrexone, I wonder if Naltrexone would not get along with Azilect. On the other hand if only a a small dose is required it may not cause any noticeable side effects. Who knows about long term use though...

Thanks for the info, interesting.

One thing about the DM is that it has been around for a long time, has been used extensively by all ages, has been abused at huge doses, etc. It has had every opportunity to reveal any problems and yet they are almost nonexistent. In fact, if one compares it to other PD drugs it wins hands down in this department.

The only negatives I have been able to find are the theoretical problems with requip in the liver and the slow metabolism issue for 20% of the population. The first may not be a problem and the second may just require a dosage correction.

I take DM, so I cant speak much about LDN, except that AshleyK has been taking it for 3 years or better, and not only hasnt progressed, but was able to cut her med regimen down as well

As Curious mentioned, there are some folks on the MS forum who have been using it with positive results..From what I understand, it has been used to treat HIV and Cronins Disease as well..I think it was initially used to treat HIV

i'll post the link tomorrow...

but check out the ms forum. larryldn posted a youtube video about ldn.

http://neurotalk.psychcentral.com/thread38929.html

Hi, below is a collection of info on low dose naltrexone and dextromethrophan. I would also like to say that I have been on LDN now for 42 months along with my PD meds and I seem to be holding my own.
Ashley

Study of LDN in Primary Progressive MS to be Presented at AAN. Dr. Maira Gironi and colleagues of Milan, Italy have been invited to announce the results of their recently completed pilot study to the American Academy of Neurology in April in Chicago. The six-month, multi-center trial was carried out in 40 patients, all of whom had primary progressive multiple sclerosis. Safety and efficacy of LDN on spasticity, pain and fatigue were the major outcome measures of the study, which has especial importance because reliably measured endorphin levels were documented throughout.
In October 2007, much of the data were presented at the European Congress of MS in Prague:

We have approached a 6-months, pilot, multicentric, open-label, therapeutic study with LDN aimed at evaluating its safety and efficacy on spasticity, pain and fatigue occurring in 40 pts with PPMS.
Clinical and biochemical evaluations are performed at different time points during the study. Appropriate scale for testing spasticity, pain and fatigue (e.g. Ashworth, Fatigue Severity Scale, Visual Analogue Scale) are used as an integral part of the periodical neurological examination. Beta-Endorphin levels in peripheral blood mononuclear cells are also measured by radioimmunoassay.
So far, 40 pts with a diagnosis of PPMS, according to McDonald criteria, have been enrolled in the study (19 males, 21 females, mean age 53.4 years, mean age at onset 41.2, mean Expanded Disability Status Scale 5.5). Optimization of [gabaergic and/or serotoninergic] drugs has been performed in all pts before the enrollment. Opioid-containing-drugs, immunosuppressive or immunomodulator drugs were considered as a contraindication to study enrollment.
Transitory haematological abnormalities (increase of liver enzymes, hypercholesterolemia), mild agitation and sleep disturbance were the commonest adverse events. Only two drop-outs occurred (one for protocol violation and one for severe increase of hypertonia). In conclusion, LDN has shown, so far, to be a safe treatment in PPMS. We are now collecting and analysing efficacy results.
Dr. Gironi’s general impression of how the trial is proceeding thus far was as follows: "LDN could be useful for a quite good number of MS patients affected with spasticity, fatigue, and pain. A subjective improvement on fatigue has been [experienced] overall".

And, this is an email that I sent to the MJF concerning their award of $3M to Industry for research. Never received a reply from them. I suspect it's all about Big Drugs making Big Bucks.



January 31, 2008
Michael J. Fox Foundation Awards up to $3 Million to Industry Teams to Jumpstart Promising PD Drug Development
Hello Research Staff,
I read your news release at NeuroTalk Parkinson's of which I am a member. I would like to make you aware that there has been a lot of research done on neuroinflammatory disease protection at the Neuropharmacology Group of the NIH under the leadership of Dr. John Hong. They have produced many research papers on opioid compounds (naloxone, naltrexone (LDN), dextromethornphan etc) at very low doses that show significant neuroprotection in PD induced rodents.
There is also a large user group of LDN that take Low Dose Naltrexone (4.5mg naltrexone) to hopefully stop the progression of many neuro diseases. Others at NeuroTalk take 5mg of dextromethorphan at night. I was dx'ed with PD about five years ago and have been taking 4.5mg of naltrexone for 41 months. I have not had to increase my mix of Sinemet and Mirapex over that time and my symptoms are mostly gone for now.
I would think, since MJF is funding the above research, they would have a say in what drug compounds are studied. I am wary of any "Industry Team" doing drug research. It is not in the financial interest of the Drug Industry to market old drugs for new uses. Both naltrexone and dextromethorphan have been around for a long time and are very cheap. I would be much more confident of a positive outcome if you directed more of your funding towards independent universities that work in this field .
Sincerely, Ashley

Research papers on opioids and neuroprotection
http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract
http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract
http://www.aapsj.org/view.asp?art=aapsj080369
http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract
http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract
http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract

Articles on Low Dose Naltrexone, LDN (note, naloxone is similar to naltrxone) in the treatment of disease including pancreatic cancer.
http://www.lowdosenaltrexone.org/others.htm (see pdf attach. Berkson-Presentation)
http://www.lowdosenaltrexone.org/index.htm

http://health.groups.yahoo.com/group...r/messages?o=1

The authors describe the long-term survival of a patient with pancreatic cancer without any toxic adverse effects. The treatment regimen includes the intravenous alpha-lipoic acid and low-dose naltrexone (ALA-N) protocol and a healthy lifestyle program. The patient was told by a reputable university oncology center in October 2002 that there was little hope for his survival. Today, January 2006, however, he is back at work, free from symptoms, and without appreciable progression of his malignancy. The integrative protocol described in this article may have the possibility of extending the life of a patient who would be customarily considered to be terminal. The authors believe that life scientists will one day develop a cure for metastatic pancreatic cancer, perhaps via gene therapy or another biological platform. But until such protocols come to market, the ALA-N protocol should be studied and considered, given its lack of toxicity at levels reported. Several other patients are on this treatment protocol and appear to be doing well at this time.

PMID: 16484716 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/sites/en...=pubmed_docsum

Naloxone = Naltrexone
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus
http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus

http://www.fred.psu.edu/ds/retrieve/...estigator/isz1
http://www.fred.psu.edu/ds/retrieve/...z1/completepub

http://skipspharmacy.com/ldn.php

Wow, thanks for the gathered info Ashley!

Did the MJF foundation respond?

Hi, from the poll here, I guess I'm the only one taking LDN (44 months on LDN and still not much has changed). No one else on LDN?
Below is a news article on a man who has been on LDN since 2004.
Regards, Ashley

http://www.mailtribune.com/apps/pbcs...100308/-1/LIFE

"Marquez said her father started taking 3 mg a day late in 2004, far less than the 50 mg that's prescribed for addiction treatment.
"It was like a miracle," she recalled.
Marquez said the spasticity in her father's left leg disappeared over several days, and his caregiver said he stopped complaining about back pain.
Speech is difficult for Bentley, 78, a former Marine and marathon runner who worked as a forester and wrote two mystery novels, but he said LDN "stopped the progression" of his symptoms. Naltrexone apparently works by stimulating the body's own immune system, said Dr. Ian Zagon, a professor of neural and behavioral sciences at Pennsylvania State University."