A lot of new faces here, but you will get used to me.

I think that I have found something valuable and want to pass it on. It has, thus far, done more for me than anything I have found. Dextromethorphan (DXM) is the ingredient in the most widely used cough syrups in the US. It is a cousin to the chemical used in the LDN protocol and has long been used by a few on this board in that capacity.

However, in reading the literature, I realized that it was capable of much more. In fact, if I can sustain the effect, I will have to call it equal to either sinemet or requip, the two drugs that I am most familiar with. I realize that that is a rather bold statement. But I am beginning to believe it.

I will go into more detail later, but to give you an idea of the potential, I am going to paste in an excert from a message to a friend this morning:

<<Begin quote>>
I began anew yesterday and took a quarter tsp of DXM in the morning and have done so again this morning. (A moment to clarify. Cough syrup is standardized at 15 mg per tsp and the suggested dose for cough is 30 mg every six hours with a max of 120 mg per 24 hrs. I am taking a single 4 mg dose each morning at present. One-thirtieth of the label max. Even if my metabolism is slow (which I suspect that it is) that leaves a good safety margin.) I am going to start talking in terms of "mg" rather than "tsp" so remember that one tsp equals 15 mg.


So, having taken 4 mg yesterday morning, I had a pretty good day. No particularly bad periods until evening and they were better than a couple of weeks ago. In fact, I am going to invent a unit of measurement for my overall condition. I will call it the Misery Index and define it at 100 two weeks ago and ten yesterday. At 100 I was taking large amounts of medication on a two hour schedule and getting poor results. I was regularly going Off at the end of the two hour window with Freezing. It was common for it to require two hours or more to get back On so I would "lose" an entire cycle. This was typically the state of affairs in the afternoon. Mornings were better and evenings worse. It was not unusual to be forced to crawl to bed at least once a week. Similarly, it was not unusual to go Off with Freezing in public as morning turned into afternoon. On one occasin I was forced to crawl out of my bank. Loss of bladder control via urge incontinence happened as much as twice a week. Sleep was around four hours nightly with early awakening disrupting my med schedule. It was common to find myself cutting my day short to "rush" home as I felt the first signs of approaching Off. In short, I was a sad puppy and that state is an MI of 100.

Yesterday, however, was an entirely different matter. No true Off until 10:00 PM. Medications on a 3 to 4 hour cycle. No other problems. I even did some yard work. That's an MI of 10.

Sorry to go on so, but as I did it I realized that it was an opportunity to bring some order to the mess and was writing it for me as much as for anyone.

I slept well (7 hours), awakened at 6:00 AM and was On in 45 minutes (was 1 to 2 hours). BP = 136/87. Took 4 mg DXM with a 10/100 sinemet plus a 50/200 sinemet CR plus 8 mg requip. It is now 9:30 AM and still fully On.

<<<End quote>>>

I will elaborate on this later today....

Don't jump ahead and try anything until I can finish. In particular, do not do anything if you take an MAO inhibitor as it could cause serious problems. Selegeline, deprynl, etc. Also, there is a wide range of metabolic rates to be taken into account.

J.S. Hong has made a good case for the neuroprotective effects of DXM. Among other things, it blocks the runaway microglial reaction to LPS.

A more recent paper is what caught my eye, however-

1. Indian J Exp Biol. 2007 Aug;45(8):712-9.

Effects of dextromethorphan on dopamine dependent behaviours in rats.

Gaikwad RV, Gaonkar RK, Jadhav SA, Thorat VM, Jadhav JH, Balsara JJ.

Using rats, it was found that a low dose of DXM :
"The results are explained on the basis of dextromethorphan
(15-75 mg/kg)-induced blockade of NMDA receptors in striatum and substantia nigra
pars compacta. Dextromethorphan at 15 and 30 mg/kg, by blocking NMDA receptors,
activates nigrostriatal dopaminergic neurons and thereby potentiates
dexampetamine stereotypy and antagonizes haloperidol catalepsy. Dextromethorphan
at 45, 60 and 75 mg/kg, by blocking NMDA receptors, releases 5-HT and through the
released 5-HT exerts an inhibitory influence on the nigrostriatal dopaminergic
neurons with resultant antagonism of dexampetamine stereotypy and potentiation of
haloperidol catalepsy."
My translation is that low doses act on NMDA receptors to increase dopamine but as doses increase the effect tips over into production of serotonin. The former makes us On and the latter makes us Off.

The trick is to get enough to trigger the former without slipping into the latter and that's what I have been working on.

More later.
Department of Pharmacology, Krishna Institute of Medical Sciences, Karad 415 110,
India.

Would you mind sharing which brand you use?

So far, I have gone through a bottle of CVS generic "Maximum Strength Tussin" and am presently using Robitussin PM. The only critical thing is to avoid the ones that have added active ingredients. The active ingredients shold be only "Devtromethorphan HBr".

Now, as to dosing. It is a little complicated due to two things:
1) there is a "narrow therapeutic window"and while a little is enough, a little more is too much, and
2) there is a wide range of metabolic rates among individuals.

The latter is especially important. Roughly ten percent of the population are "slow metabolizers" and I seem to belong to that group. A dose that would normally be gone in four hours might take four days for me. If I am taking it as per the bottle, the levels in my blood are going to go up pretty quickly and tip me into a major Off. that is going to be true of everyone, though. The variable will be how quickly your own liver breaks it down balanced against how often you take it and how much. The only way to handle this is trial and error.

In my own case, I began about a week and a half ago taking about 4 mg 4x per day. Note that this is about what i suggested for a single dose. Day One was great but by Day Three things were falling apart. Further research turned up the paper in my first post and things made sense again. So I laid off it for a couple of days and have started again with 4 mg each morning. My goal is to find the "sweet spot" for my particular metabolism. Every individual will have to do something similar, but it should be easier with a normal metabolism.

those who have been taking a single dose at bedtime would not notice the effect since a normal metabolism clears it in about four hours. So, if anyone tries this, I sure would like to know.

Thank you. You saved me a lot of eye squinting reading labels.

This really is something special. I will keep at it and bump this up from time to time.

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