Hi Everett,
I also make an attempt to self treat, as in my use of LDN. But when we are also taking some powerful Rx drugs, I think we can get into trouble. Without going back to dredge out all my saved stuff, I'm going to try and present some of this things I seem to recall.
1. I believe significant doses of DXM are contraindicated on many PD meds like Sinemet or Mirapex. Also, back in the 90's there was a clinical trial using DXM at a good dose but for some reason nothing came of it.
2. In the Indian paper and their experiments with rats and DXM, the DXM dosages seem very large. So if a rat weighs 1lb (big rat) and they are giving it 15 to 75 mg/kg a day, that would be an equivalent dose of 1100mg for a 160 lb human (1kg=2.2lbs) based on the 15mg dose.
3. I am a hopeful believer in Dr. Hongs work at the NIH concerning low doses of naloxon, LDN, DXM and others. I believe their research shows that overactivated microglia (killer cells) cause neuroinflammation and diseases like PD. One of his points was that while overactivated microglia are bad and can be reduced by opioid blockers like LDN and DXM, it was also risky to cause a total blockade (high dose). A total microglial blockade could lead to other problems like cancer? Dr. Zagon, a pioneer in LDN, also believes in the low dose theory although he differs on how it works.
Don't know if any of this helps or makes sense, but that's it off the top of my head.
Ashley

I was hoping you were still monitoring this place. You have raised some interesting points and I will comment as best I can.
1- DXM is contraindicated for MAOIs and SSRIs, I know, but I haven't run across any claims of problems with sinemet, etc.

The studies in the 90s were inconclusive with good reason. They did not realize that they were dealing with a "bi-phasic" drug which had different effects at different dosages.

2- The relevance of the Indian paper is not the dosages per se, but rather the bi-phasic nature of its action. Without knowing that it is going to be very hard to make sense of any data, particularly when the variance of metabolic rate is factored in. One person takes "X" mg and does great. A second PWP takes the same dose and slips into a major Off as it slips into the serotonin phase.

3- I am familiar with Dr. Hong's work and, in fact, he is one of my "gurus". I particularly subscribe to the neuroinflammatory hypothesis and microglial activation' role. In this case, however, I think we are looking at a different effect of DXM. The LDN approach is based on the interaction with opioid receptors. The blocking of microglial action comes from a second action. Boosting BBB integrity probably comes from a third. And this experience that I am having comes from a fourth as described in the Indian paper and presumably involves the NMDA receptor antagonism.

In my case, I am well within the Low Dose range (about 4 mg per day) but that is due to my slow metabolism's special requirements. Someone else will have to determine the parameters of a normal PWP.

I am sure there are problems. I have already solved a few. But I have experienced a TEN-FOLD improvement. I don't mean to shout, but I am frankly staggered by this.

Now, a quick update, after deciing that the theanine alone was not working for me, I returned to DXM this morning with a single 4 mg dose with my first meds. Two weeks ago I would have been on a two-hour leash. Today the leash ran out at five and one-half hours.

A great site
http://www.ionchannels.org/showcitat...xtromethorphan

Rick,

This is all great stuff; thanks so much for sharing As for me, I look forward to the beginning of my 'weekend' on Thursday...I'm going to begin trying DXM as well. I have no idea what my metabolic rate is for this kind of things, so I'll start out slowly. Hopefully, I have closer to what you call a 'normal' metabolism, and I can offer a different dosing perspective.

It's interesting to think that something as ubiquitous as cough syrup may actually be one of those neuroprotective breakthroughs that researchers supposedly clamor over. Too bad that it can't be patented and re-imaged as a legit therapy for those of us who need it.

Sending long "on" vibes your way...

Laura

Thanks Laura. Be sure your meds don't conflict (no MAOIs, SSRIs, etc

I will suggest a way to begin based on what I've done so far. I would start with a quarter teaspoon in the morning with my first meds and take another quarter with each round afer that. When and if I reached the point of thinking "Hm, there might be something to this stuff..." I would stop for the day. Even so, one might still go into Off if the lagging dose is enough to push one over the hump into serotonin phase, so don't be discouraged if it happens. Now you have a better idea how to start tomorrow. Whatever the total taken the first day, I would start the second with half of it and see how my morning went.

In theory-
If you are a normal metabolzer, most DXM will clear out by the six hour mark and you will be back to baseline by evening. If you are a little slow then the DXM and its benefit will linger a little. If you are really slow and repeat the dose the next day, somewhere along the lne you will go off and it will be really off for a while. I had two hours when I couldn't stand up. It was a little scary because I hadn't figured this out at the time.

Good luck.

Mov Disord. 1998 May;13(3):414-7.
A trial of dextromethorphan in parkinsonian patients with motor response complications.

Verhagen Metman L, Blanchet PJ, van den Munckhof P, Del Dotto P, Natté R, Chase TN.

Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA.

The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications.

PMID: 9613730 [PubMed - indexed for MEDLINE]

Consider this 1998 study a minute knowing of the variation in metabolisms and the two-step nature of DXM. You begin with 18 PWP and give them a dose that would boost all but the fastest metabolizers out of the beneficial zone. Those "fast" guys would be the group of six that made the first cut. The other 12 experienced "decreased l-dopa efficacy". I bet they did at those dosages.
But the six who were able to metabolize fast enough to stay ahead of the wave did have positive results.

I'm not sure how useful my reporting will be...I'm awful when it comes to measuring, recording, etc. Just to give you an idea, my hs chemistry teacher actually took cover across the room when he realized I wasn't exactly scientific in mixing chemicals for a slightly volatile reaction.

I went back to read earlier threads on DM and ended up:

1) trying a low dose last evening before bed (1/2 teaspoon)
2) taking a morning dose eight hours later (1 teaspoon)

this is what I've noted thus far:

- immediate 'on' sensation when taking it at bedtime though I was not taking any Sinemet at that time. It definitely seems to stimulate dopa and my body noticed right away- faster, fluid gross motor movement, and I could knit at what seemed like warp speed. Overall, I slept much better; sounder (no need for benadryl as sleep aid), and woke up less stiff- I especially have problems with stiffness in my fingers and feet. Not so bad this morning.

-while more fluid when I awoke, I felt internally sluggish, a little uncoordinated and slow. I did take the morning DM dose with my meds both Mirapex and Sinemet. I had a much more fluid, less noticeable transition to 'on'. However, I did get a minor case of curly toes. Not sure if that was too many meds going on at once?

In general, I feel more 'normal'. In taking the DM, my meds have lasted 1-1.5 hours longer per dose, and I don't have a harsh wearing off sensation. I do notice meds start to diminish but it is much gentler; my body doesn't protest as much, and everything just feels more fluid. I haven't taken another dose of the DM as I want to see how long it lasts in my system for the day (so far I've gone 8 hours).

Of special note:

-No dyskinesias! I'm very sensitive to having too much dopamine in my system and have had mild dyskinesia early on. With the DM, less need to jump start my Sinemet CR with regular tabs and less unwanted movement.

-I feel normal! Fluid- I feel like I did before I started down the slippery slope of medication. More like myself than I have in over a year.

I want to be able to better pinpoint where my metabolism is to help out anyone else who wants to try this. I thought I was a quick metabolizer but I'm beginning to think that I may be in the 6-8 hour window of efficacy for DM- in the normal range, I'd say.

Laura

I have a few questions for those of you experimenting with DM:


-We're dosing based on finding that window for good symptom control- does this equate to or relate at all to the levels needed for neuroprotection?

In other words, neuroprotective benefit was found at femtomolar but not at picomolar levels. How in the world do we factor in this when dosing with a little plastic cup?

-I take it if the DM has guiafenesin or any other ingredient, it's not as efficacious? (I could initially only find DM with this additive)

-How does taking a supplement that has bioperine factor in? It's known to amp up meds in our system, I wonder if taking supplements might 'wash out' the potential neuroprotective benefit of DM?

Thank you so much for sharing your experiences and expertise!

Laura

You did a good job of describing my experience as well. The only exception would be that, despite everything I read, I did have some dyskinesia but I think that has eased now.

I don't think I would add bioperine in right now. Too many variables. I have quit everything but sinemet and requip until I get a handle on it. However, for the sake of my liver I added silymarin back in yesterday.

Currently I am trying a qtr tsp in the morning and again in th afternoon.

I have noticed a subtle difference when I go Off from too little vs too much. In the former case, movement is hard for me and requires that I overcome resistence from opposing muscles. With the latter it is more a matter of my limbs becoming very heavy and just not worth the effort. Also, this extends to my eyelids which is unusual. I suspect that this is a glimpse of what is called a disociative state by the anesthesiologists. This family of chemicals which includes DXM is used for pain control.

One of the others family members is PCP and is used for the purpose by veternarians. In my youth it was also sold for recreational use but under other names. I remember a time that a friend of mine convinced himself that he had od'd on it and that he was going to die. He didn't but he did spend the evening on my sofa very calmly and contentedly awaiting his death. Now that is disassociation!

In case anyone gets a bright idea to test PCP, btw, don't. It is some evil stuff. Stick to the cough syrup.

Regarding the neuroprotection, RLSmi correct me if I am wrong, but my understanding is that the low dose approach needs it to be there at the critical time in the early morning. That does not necessarily mean that its absence is required at other times. Also, a second protective action occurs in the damping down of the microglia which should be independent.

I'm avoiding the other ingredients to ward off unwanted effects. The plainer the better right now.

As for my "expertise".....