...I am sleepy? I'm not even going to try to edit that one.

We could see if there was a common thread.We would have to discount the placebo effect.Here goes:
Curcumin
Concentrated Omega 3
True food Natural VitaminE
Acetyl Lcarnitine&alpha lipoic acid marketed as Alpha(It is important to take these together...synergy)
True Food Maxi Q10 Only 120 mg(Only just started this because of expense)
Super antioxidant
Suitable cough medicine .
True food indicates it has been treated to maximise its potential
Amount taken is manufacturers maximum recommended dose except for cough syrup
All this costs a fortune but we think it worth a go. We will not really know if it is worth it for years
PLUS
40 minutes in gym doing running(yes running) cross trainer and now cycling.This is done on about 4 or 5 days a week.On at least one of the days he does not go to the gym he Morris Dances(The bells and hankies and stick variety)

It's been just over 36 months since I started taking 4.5 mg of naltrexone, LDN. At that time they said my increasingly worse tremor was MS but 4 months later I started Sinemet which worked and so I now have PD. Since that time Mirapex was added to my PD and Sinemet was reduced somewhat. I still take relatively low amounts of both drugs maybe because I'm still early onset?. I also take 400 mg of Q10 and some magnesium daily. I'm now 58 and my first tremor symptoms began maybe 5 years ago. My tremor is gone for now and outside of the drug side effects and poor sleep and low blood pressure, I manage quite well. I think I can say my PD has not progressed but it's hard to say. I hope it's because of the LDN. I've read a lot on what to expect about PD progression when beginning Sinemet and I am still not clear where I should be along the curve. I still wait for the other shoe to drop on progression but taking LDN gives me some hope for now that maybe I'll be ok. Note: I base most of my believe in LDN on the work done by Dr. Hongs group at the NIH. They have shown that low doses of opioid receptor antagonists like naloxone, naltrexone and dextromethorphan can slow or halt simulated PD in rodents.
http://www.ncbi.nlm.nih.gov/sites/en...&dopt=Abstract

I was quite excited by this thread, because as people were taking LDN and DM back in 2006, then by now, over 5 years later, enough time has passed to get hopefully some feeling for whether there is a neuro-protective effect.

My suggestion is that it would be really helpful if someone who has taken LDN or DM could post something like the following.

A rough description of their condition (including drug doses needed) when they started taking LDN or DM and how long that was after diagnosis, how long they have taken LDN or DM for, and a rough description of their condition (including drug doses) now (or when they stopped taking LDN or DM as some seem to have done).

If enough people who have been taking DM and LDN could do this we could perhaps begin to get a picture of how their progression compares with the typical progression of someone not taking these.

Of course anecdotal evidence will never be as good as a double-blinded placebo-controlled trial but, in the absence of any such trial, this is all we have. It seems to me to be valuable. And it's valuable even if it shows that these things do not work. At least we would know.

Anyway thank you everyone who has shared knowledge on these topics

I posted similar to a more recent thread specifically in reply to Ashleyk, but this original thread seems more appropriate for asking everyone who may have been doing this.

David

I began posting on this subject back in 2005 on the old braintalk forum. As described in my posts earlier on this long thread, I have been faithfully taking 3.5-5mg of DM in pediatric cough syrup each night at bedtime since sometime in 2005. Therefore, I think that makes me the longest-term user of this approach to attempt neuro protection for PD.

The result has been that I feel that I have experienced quite significant slowing of progression of my Parkinson's disease symptoms. However there has been a slow, steady increase in the doses of sinemet required to allow me to maintain good control of my symptoms, bradykinesia, balance difficulties, shuffling gait, and some postural instability. I have increased from 100mg of IR carbi/levo 3X daily in 2001 when diagnosed, to one each of 100mg IR and 200mg of CR 3X daily, at 5 hour intervals. I occasionally forget to take the second or third dose. If more than a couple of hours late, my symptoms faithfully remind me of the error. Once "off", however, it is difficult to get back truly "on" after taking the skipped dose.
I have never had significant tremor. When I am "on", which is about 90% of my waking hours, my gait is essentially normal, and I am not seriously limited in endurance. Until the last few weeks I have also taken 900-1200 mg of CoQ12 daily. I plan to resume the CoQ10 because I sense that my symptoms have begun to be more apparent.

I would, like staurus/David, also like to hear from as many of you as are willing to share your experience with dextromethorphan in attempting to slow progression of Parkinson's disease.

Robert

[I couldn't post links to studies. I might have put them without tags but would that have been against the forum's principles?]

This has been interesting thread, thanx!

I apologize if my writing has errors as english isn't my native language.

Despite I don't have PD I decided to register and post my experiences with DXM because I have been interested about it and have been suspecting it might have had positive effect on my dopamine system and mental health. I have used it a lot but for different purpose what has been discussed here. I'm 29 years old male from Europe.

Original reason for my DXM use was to assist with my drug withdrawal and tolerance issues (benzodiazepine etc.) and to help with depression and anxiety associated with that process. I explored DXM and believed it would do more good than harm for the situation I had. I had had previous experience with benzodiazepine addiction and withdrawal at 2008 and after that process I was about 2 years very depressed, anxious and kind of disabled mentally to do anything which only led me to using benzos again. So I wanted to avoid that happening.

My thoughts of its dopaminergic effects:

First is that after 2008 withdrawal I had lot of 'extrapyramidal symptoms' with drugs like amitriptyline or even small doses of antipsychotis like quetiapine (25-50mg).

In case if it isn't familiar..

" Extrapyramidal syndrome (EPS) is due to the blockade of dopamine receptors in the basal ganglia, leading to Parkinson-like symptoms such as slow movement (bradykinesia), stiffness, and tremor." - Wikipedia

Second is that even with small doses of those kind of drugs my depression, apathetic and unmotivated feeling, social isolation all got worse. That implied to me that I had insufficient dopamine levels many years after benzodiazepine withdrawal. Maybe because of long and continuous stress and pain, inflammation and their negative effects on gaba- and opioidergic systems. I wanted to avoid that and so from different drugs I had studied and dealt with DXM with its dopamine boosting, SNRI, NMDA- and Voltage Gated Calcium Channel antagonist properties fitted perfectly to that situation.

Now, when over year has passed I'm quite positive DXM has indeed had a positive effect on my condition. Reasons:

1) No EPS of any kind even with large doses of antipsychotics (using sometimes to get sleep) or trisyclic antidepressants.

2) No anxiety, depression or other ill feelings after withdrawals - which were very present at 2008.

3) I don't have any PAWS symptoms after withdrawals.

And it seems that my dopamine is now going pretty good without DXM because I haven't use it over two weeks and I don't still have signs of dopamine deficiency.

My DXM doses were much larger than has been here discussed. At first I used medium doses (60-120mg/d) and progressed to bigger amounts at max. about 600-800mg/d with grapefruit juice which supposedly improves it absorption and extends half-life.

What I found also was that DXM indeed seems to inhibit tolerance to at least benzodiazepines. It was easier for me to taper benzo dose with DXM than without it.

But few points has come to my mind about DXM supposed opioid antagonist properties. I must say that at least it feels it has rather opioid agonist than antagonist properties. Its hard for me to believe that its immediate 'opioid like effects' comes from endogenous opioids through antagonism because opioid effect can be felt under its influence but not after it wears of. With naltrexone its different. If you use it enough (equivalent doses like 500mg) you get bad feelings, nausea, insomnia etc. from blocking opioid receptors and a positive rebound or "withdrawals" after it wears off or with stable dose after few days when body compensates.

Also, differences are according to studies I've read that:

1) Naltrexone attenuates opioids effects if used simoultaneously
2) DXM enchances opioid effects when used simoultaneously

Both even have positive correlation with dose but to different directions. How do you explain that difference if both are antagonist to opioid receptors? I admit that DXM's NMDA - and Voltage gated calcium channel antagonism definately and possible Sigma agonism plays a role there but hard to believe they could alone cause those differences.

So that is some kind of puzzle to me.

Sorry if I have missed something but at least these studies indicate it might affect through different mechanism or are these effects maybe secondary from its opioidergic effects?:

[B]Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation.[B]

"Pretreatment (30 min) of rat mesencephalic neuron-glia cultures with DM (1-10 micro M) reduced, in a dose-dependent manner, the microglia-mediated degeneration of dopaminergic neurons induced by lipopolysaccharide (LPS, 10 ng/ml)."

[B]Pubmed: 12649371[B]

This is also interesting new study from 2013:

[B]Dextromethorphan Protects Cells in the Oligodendroglial Lineage and Stimulates Glial Proliferation (P05.164)[B]

"DM at 100 nM-20 microM was not toxic to OL at 1 day, with increasing toxic
ity at 50-100 microM. Glutamate (100 microM) killed 70% of OL; DM protected, reducing OL death to 55% at 100 nM DM and 30% at 20 microM DM, a concentration similar to that found in rat brain after oral administration of 30 mg/kg DM + quinidin"

This study was on this side but I didn't see much comments about it:

[B]Thomas, D.M., and Kuhn, D.M. MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity.*Brain Research*1050(1-2):190-198, 2005.

This is also interesting study:

[B]Effects of*dextromethorphan*on glial cell function: Proliferation, maturation, and protection from cytotoxic molecules.[B]

"These agents and DM were not toxic to AS or MG at the concentrations used. Thus, DM stimulates proliferation of OPC, and protects both OL and OPC against excitotoxic and inflammatory insults. GLIA 2014."

[B]Pubmed:24526455[B]

What is really the main positive action of DXM regarding dopaminergic system? I list here positive actions I think of and would be glad if someone can correct them if they are wrong:

1) Direct increase in dopamine
2) Dopamine receptor density increasing effect
3) Inflammation reducing effect
4) Exitotoxicity preventing effect

[B]Is it possible DXM and LDN affect through different mechanisms to improving brain health?[B]

Would naltrexone have had same kind of positive effects as DXM in ex. those [U]in vitro[U] studies I posted?

Also that methamphetamine study if thinking LDN. If LDN stimulates immune function through OGF and opioidergic system would it then have lead to rather worse outcome by increasing microglial function..? Or would it have stabilazed and inhibit their function like DXM? With different or same mechanism?

Also I'm thinking about those doses. I believe that femtomolar doses could also help but at least usually studies have used larger doses and one pubmed review stated that when there isn't positive results with DXM its usually because of too small doses and they suggested quinine for preventing first pass metabolism. On the other hand, they have usually studied some protective effects from excitotoxicity like in ischemic strokes or something.

Correct if I'm wrong but when looking ex. these studies I referred here it seems doses are bigger than < 10mg. That methamphetamine study has a little vague statement about amount but if it was 5mg/kg (which was only number I found) it is kind of large amount to man.

Other study used molars but stated 30mg/kg + quinine which is extremely large dose.

That dopaminergic degeneration preventing study stated 1-10 micro M which might equal to 1.5-15mg/kg if comparing to that other studys comparison. So very big doses compared to 10mg or under.

What I'm going to try is using DXM and LDN together. I can report here what it does. I was thinking 60-120mg DXM and maybe 4.5mg naltrexone.

My reasons are mental (and overal) health and addiction prevention. There has been studies indicating DXM could be good antidepressant (it actually is best I have ever tried) and especially to people who have a family history of alcoholism/addiction. That has probably something to do with its NMDA antagonism. It has been previously noted that Ketamine causes rapid improvement in depression and it is a strong NMDA antagonist.

So one reason for that medium large dxm dose is depression treatment as I can same time reduce my tricyclic antidepressant allmost zero as they have some effects so similar (SNRI). I would maybe use even larger amount and drop off other AD:s completely but there comes too much side effects mainly NMDA antagonism which starts to affect memory a little bit. Also it is reasonable to think what long term causes could extensive NMDA antagonism have even though it has been noted that DXM doesn't cause any lesions to primates or even to rats (MK-801 is what Olney used). Also that is the good dose for me to optimum sleep quality as I have had deep and refreshing sleep with that dose of DXM and don't need to use GABAergics anymore.

Thanx

Hi and welcome
Sorry but yes, any attempts at linking by newly joined members get automatically blocked or flagged by our software.

Your quotes were approved without the links as PubMed is public domain ie no copyright. ( Usually we cannot allow copy/paste quotes from any site that has copyright, and so only the link is allowed.)

Hello,
I am posting for my wife who has had PD and was dx'd 12 years ago. All previous posts were made by me, John, and not Ashleyk. Going back, reading this thread on DXM or LDN, is a sad letdown on the hope I had for these opioids. I became a believer in these drugs especially after reading the NIH research papers by Dr. Hong et-al. Assuming that the LDN my wife was getting from Skip's Pharmacy for 8 years was real, I can say that her PD has progressed to the point where she needs a lot of attention and is probably at a stage in the disease that is typical for her type of PD. She faithfully took the capsules every night but stopped maybe 2-3 years ago believing she was progressing. I tried to get her to try DXM but she couldn't wouldn't do it. My recomendation would be to forget about LDN and try DXM 1/2 tsp.
Her condition now is poor. She is fragile, having lost 30 lbs, along with severe osteoporosis, 3 fractured vertebrae from many falls, very forgetful and now having hallucinations at times. She is not good at taking her meds. She is taking about 8x 100mg of Stalevol, maybe 2x levoc-dopa 100mg and 1x Neupro patch 4mg daily. She has a lot of off time, little good time and dyskinesia which effects her mind and is scary. I have asked her docs to hospitalize her for PD so someone can figure out a better treatment but I guess that won't happen until she goes to the ER. She will see a new neurologist in 2 weeks who I hope will send her to a PD specialist at Brigham and Woman's Hospital in Boston. I am very frustrated with everything especially the failure of everyone/anyone to come up with a much better treatment than L-dopa.
John

sorry about your wife and thanks for sharing.

John-
Sincere wishes and prayers for you. It is so heartbreaking to see hopes dashed. I have been getting glimpses of the future myself from time to time and don't like it a damn bit. One of the things that we don't like to do is to dredge into the archives of the oldtimers such as PIENO going back 20 years or so and realizing that those people said much the same things as we do or did. Sobering.

I am not going to hold out false hope for you. Sometimes even kindness is cruel. I just checked and the cupboard is low on things that may help particularly once the polypharms begin their dance. The cupboard may be low but there is always a place at the table. We share what we have.
-Rick