Like Rick I must disavow any claim to expertise with the DXM approach in attempting to delay/arrest neurodegeneration. All I can claim is some familiarity with the literature and my own subjective experience, along with brief conversations with Dr. Hong in 2006 at the World Parkinson's Congress and by phone. When I told him that I was taking DXM in cough syrup using the single low dose at bedtime protocol recommended by the low-dose naltrexone people, his main concern seemed to be that the preparation contain only DXM as the active ingredient, and to particularly avoid any which contain polystyril which is added to slow down the release of the DXM into the circulation. He seemed to be subscribing to the idea put forth by Zagon that the drug should only briefly bind cell surface receptors proir to the natural early morning time of optimal release of endogenous opioids by the cells.

The pharmacokinetics of DXM (rates of its tissue transport, metabolism and excretion) would certainly have substantial effects on body levels of the drug following its administration. About all I know about these processes is that DXM is very rapidly absorbed, that it readily crosses the blood-brain barrier, and that one of its main metabolites is a hydroxy derivative which Hong has previously shown to be equal to the parent drug in supressing microglial activation.

As Rick has already mentioned, DXM interacts with MDMA receptors, which are known to have effects on the release of dopamine and other neurotransmitters. His suggestion that the apparent on-extending effects that he and Laura have experienced are related to these receptors certainly seems plausible to me.

I presently restrict my use of DXM to the bedtime routine. Although I currently do not experience well-defined "offs", I would be open to experimenting with additional daytime dosing if they were to develop, especially if you, Rick and Laura, continue to see definite benefit in it.

Robert

Well, to me you are all experts given that I'm still just trying to make sense of it all I'm just trying to do the opposite of robotrippin'...what could we call it for PWP? robodribblin'

I found the main thread on DXM started in 2007. Rick, you tried it back then; any reason that you feel comfortable sharing why you stopped? Also, AshleyK asked if using an agonist like Mirapex actually countered the effect of the DXM, but I didn't see anyone answer this- does anyone know?

Also, is it a no-no to drink and then take the DXM? I have a glass of red wine at night sometimes.
It would be great to hear from other brave white rats who tried this starting two years ago. Have you remained on it, and how goes it now?

Laura

Lauea-
I began having blood pressure problems which I finally realized were seemingly coming from several natural MAOIs that I was unwittingly taking (green tea, turmeric, etc). I also had realized that I was a slow metabolizer and getting mild (but pleasant) hallucinations as a result. With other things to deal with. it went on the shelf for a while.

There is an interesting paper at http://www.braintechllc.com/Dextromethorphan.aspx

"What makes DXM so interesting is that the behavioral changes caused by varying doses of the drug can be traced directly to proportional amounts of receptor occupation. In this way, effects of DXM can be separated into three different behavioral and experiential “plateaus”. These plateaus directly correlate with various dosages at which certain receptors become saturated. In this way, DXM offers a unique glimpse at how neuropharmacological action is directly related to drug experience and behavioral changes (White, 2001, Section 9). Throughout the following sections, please refer to figure 1 for a graph approximating the receptor binding (and saturation) as a function of DXM dose.

At a low dose (1.5 to 2.5 mg/kg), or “level 1”, the effects of DXM are mainly determined by its PCP2 receptor binding profile (see figure 1). When DXM binds to the PCP2 binding site (which is located in the dopamine reuptake complex), dopamine reuptake is inhibited (Akunne et al., 1992). This has the effect of raising synaptic dopamine levels, which has a similar end-effect (but of different magnitude) as the antidepressant Bupropion or the recreational drug cocaine (Witkin et al, 1993). The PCP2-related increase in dopamine levels may be related to the reports of euphoria at this first “dose level.” These reports often link a feeling of euphoria to auditory stimulation (music) and motor stimulation (motion). Prolonged use of DXM can lead to addiction in some individuals because of its dopaminergic activity (especially in the nucleus accumbens). Although there are no dangerous physical withdrawal symptoms, psychological dependency (and withdrawal-related depression) can occur with regular use (McElwee, 1990). Fortunately, it is reported (but has not yet been scientifically verified) that many users find significant negative effects also accompany the DXM experience. These negative side effects may explain why so few people choose to use DXM regularly. Acting counter to this dopamine increase, activation of sigma1 receptors, located on dopaminergic nerve terminals, reduces normal NMDA-stimulated dopamine release (Gonzales et al., 1995). At low doses, binding to sigma1 is relatively low. However, at higher doses, PCP2 receptors become saturated and sigma1 activity continues to increase. For this reason, synaptic dopamine increase is most dramatic at this low dose level and diminishes at higher doses. This dopamine regulation at higher doses may also help explain why DXM is not more commonly abused."

Rick,

So I think I read above that you stopped almost all of your other supplements to get a clear reading on the DXM. Does that mean that you've stopped all the items listed in your "Current Blend"?
Katherine

Yes, with the exception of silymarin for my liver, I stopped everything. Getting the dosing right is a real challenge because of my metabolic rate and I needed as few variables as possible. Having said that, however, today I am skipping the DXM to give my system a chance to clear it out. I have been having some bloating that concerns me. Nothing that I have read indicates that hepatic concerns come with DXM, but we "slow" metabolizers worry. In lieu of the DXM, I am taking a ginger capsule which at least one study indicates falls in the same family of NMDA antagonists. Sorry to complicate things, but if a "slow" guy like me can get a handle on this then it should be easy for normal folk.

In general, I still consider the DXM to be a big success. The metabolic problem is a real pain in the butt with the gradual "OD" effect being so hard to anticipate. I am thinking about going even lower on the dosing to maintain a constant level with a weekly "flushing" day to reset the system. One wants a happy liver to take that approach, however.

The important thing, to me, is the realization of the potential of these NMDA antagonists. DXM and ecstasy clearly improve symptoms. Theanine and ginger should, but the jury is still out. Another exists called mematine. I'm sure there are others, but the research hasn't been done.

I almostforgot. Magnesium is another. Mrs. D, if you see this, what is the most efficient of the many options on Mg?

How about an update, Rick? And anyone else who's trying the DXM.

Did you see the W5 show on MS and poor venous return? (Dr. Zamboni in Italy). There were studies on this years ago that no one picked up on. I figure it's people who have a very personal interest and know how to research who are going to find an answer for us.

Wendy,

I obviously can't speak to the neuroprotective properties as I only started this therapy, but I will say that symptomatically I really do notice a difference. My med "on" window has widened a bit (I'd say it started more dramatically with an hour longer of "on" time but has leveled off to more like 30 min.), but the dramatic change has been there's more 'communication' between the meds and my system. Much less dyskinesia, and I feel like I do much better under stress with it. The most dramatic change is in the morning dose of DXM- it really kick drives my other meds into working right away. I am currently taking a scant 1/2 teaspoon at night before bed and another 1/2 tspn in the morning before work. I hope there is a long term benefit

Laura

The DXM has great potential and, if not for my "slow" metabolism, I'd have a glowing report on it. Unfortunately I am forced to spend time experimenting with various dosing strategies.

If I take a qtr tsp I do very well the first, not so well the second, and have problems the third day as system levels increase. So I am trying different schedules as well as alternating with mucuna and ginger which seem to have similar effects in small doses.

More on my blog.