Mine, at least. This is not a full report, but the effect warrants an interim one. Remember- no MAOIs nor SSRIs.
This is not Robert's bedtime program btw. I took two drops, yes, drops. Dks are gone in 30 min.

Rick,
If you are using a 15mg per teaspoon (5ml) preparation, 2 drops (approx 0.1ml) calculates to 0.3mg of DXM, less than one-tenth of what I take each night.

I find it ironic that MJFF just announced a $1 mil grant to scientists working to come up with a uniform way of standardizing the measurement of dyskinesias for biotechs and pharmas to use in evaluating new (patentable) drugs' anti-dyskinesia potential!

Keep us posted on how things continue in this trial.

Robert

Robert-
I shall but I am working with the handicap of being a slow metabolizer. The microdosing is beginning to give me some control but it is still a balancing act. However, I can tell you that there is a lot more to be gained here. Assuming you are a normal metabolism then your bedtime dose has cleared by the time you wake up. You're sleeping through the best part! See my blog post if you haven't already,

Rick,

Are you currently taking any agonist? I feel that the DM synthesizes really well with levodopa but doesn't touch the Mirapex. I really wonder how the DM works when one is on a monotherapy, either an agonist or dopa, I'm curious to see if it's in tandem with really only one drug, and to then see if there is an even increased benefit to it when isolated. Unfortunately, I'm on Mirapex but seeing the neuro tomorrow about a change to Requip. I do take DM sometimes during the day but I don't note any sort of toning down of the dysk. or any marked increased on time. I think for me the best effect was an evening out or more fluid effect of meds. Seems I had a short honeymoon, or daresay, placebo effect with daytime dosing, or maybe I'm not taking enough? I take 3.5 mg in morning with meds and every 4-5 hours therafter.

Last thing, are you taking any supplements. I stopped all mine when initially trying the DM, but I would like to reintroduce two of them. However, I'm afraid that they will negate or dampen any potential neuroprotective effect.

Thanks!

Laura

This is one thread I will be stalking.

Laura-
The rate of processing varies with individuals based on their liver enzymes. Some of us are as much as ten per cent of normal and levels build quickly at normal doses.

The DXM is bi-phasic. A little works. A little more not only doesn't but actually has an opposite effect.

If I followed your pattern, I would freeze by the second day because my liver couldn't keep up as levels rose.

I'm currently taking a day off to clear and will next test a larger dose but just every other day.

Our recent awards are focused on validating dyskinesia scales, as Robert mentioned. We believe this to be critical and timely given there are ~ 6 phase II trials underway (some of which we supported in their pre-clinical stages) and yet we lack a validated scale.

Lack of validated scales can translate into a non-starter from a regulatory perspective. Our goal is to provide clarity by assessing the various informal measures used today and then drive the effort validate the most informative one. If successful, this would not only pave the way for drugs currently approaching regulatory approval, but hopefully encourage companies with pipeline compounds that havent' sought approval due to lack of a clear regulatory pathway. This kind of practical investment (led by a "neutral" party in the eyes of regulators -- like MJFF rather than a pharma company) facilitates real progress. A robust pipeliine of potentially exciting new symptomatic drugs can actually get to patients rather than languish in the clinical/regulatory malaise.

Read more here: http://michaeljfox.org/research_MJFF...s_3.cfm?ID=600

Debi

There are several scales out there for rating dyskinesias. Will inclusion criteria require that the scales have been field tested (Piloted)?

Another question: almost every patient diary or anecdotal noteso that Ive seen in clinical trial study rates dyskinnesia presence.

for example, many patient diaries are stated like this:
ON/with dyskinesia
ON/without dyskinesia
OFF/with dyskinesia
OFF/without dyskinesia

I suppose this has been included to sort of report whether not new treatments show side effects of dyskinesias.

Final question: Patient diaries are usually completed by (surprise!) patients. Wouldn't there be a lot of subjective data if what the doctor sees as dyskinesia, the patient does not?

Peggy

None of these existing scales have been scientifically validated. You likely see information collected via diaries that might contribute to side-effect profiles for various treatments being investigated.

The problem we are addressing is the lack of validated clinical endpoints for trials of dyskinesias therapeutics themselves. Without the validated end points, the regulatory pathway is unknown.

Our effort was undertaken at the urging of several companies with potential compounds that could improve our ability to treat dyskinesias (which of course would be huge!).

d

Laura-
I forgot to answer you about agonists etc.
I take Requip 24 mg daily and Sinemet CR 600 mg daily and Sinemet standard 100 mg to start the day.

I, too, stoped supplements at the start.Once I was convinced that the effect was real, I added back in creatine a few days ago and yesterday restarted a multivitamin.

Debi-
Since you are reading this thread, let me add some info here in hopes that you can pass it on to someone who might make something out of it. Medline pulls up 30 hits on DXM with PD going back to 1991. There were even limited human trials. There is much more than control of dyskinesia, too.

But they missed something critical in those earlier studies, namely the fact that a little bit of DXM has a totally different effect than a lot. That seems to be well known in the drug culture, but the study below from 2007 is the first hint of it in the literature.

"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.

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

Dextromethorphan, a noncompetitive blocker of N-methyl-D- aspartate (NMDA) type of glutamate receptor, at 7.5-75 mg/kg, ip did not induce oral stereotypies or catalepsy and did not antagonize apomorphine stereotypy in rats. These results indicate that dextromethorphan at 7.5-75 mg/kg does not stimulate or block postsynaptic striatal D2 and D1 dopamine (DA) receptors. Pretreatment with 15 and 30 mg/kg dextromethorphan potentiated dexamphetamine stereotypy and antagonised haloperidol catalepsy. Pretreatment with 45, 60 and 75 mg/kg dextromethorphan, which release 5-hydroxytryptamine (5-HT), however, antagonised dexamphetamine stereotypy and potentiated haloperidol catalepsy. Apomorphine stereotypy was not potentiated or antagonised by pretreatment with 7.5-75 mg/kg dextromethorphan. This respectively indicates that at 7.5-75 mg/kg dextromethorphan does not exert facilitatory or inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptors. 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.

PMID: 17877148 [PubMed - indexed for MEDLINE]"

In the above "catalepsy" translates into "OFFS" and "potentiates stereotypy" to "ON". And activating dopaminergic neurons does a lot more than dampen dyskinesia, at least for me, But that dosage stepdown is easy to fall over.

See if someone can get it into a low-dose, time release form. Send me a sample and I'll let you know.