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Sinemet: 5-10% improvement


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Visual, are you not concerned about long term usage? I know you are a fair bit older than me - I am 21, do you not think I should avoid long term Sinemet usage? My reading suggests this to me. Of course, I am not asking you to make a decision for me, but I want to understand your take on it.

There are various things I have read that suggest in the long run Sinemet will worsen PD and I presume all dopamine disorders. One such explanation is here.

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There should be concern about long term usage of anything.  I try to manage this by having washouts periods which also help to reevaluate where things are.  And by using low doses.

 

The problem with PD isn't levodopa as it is with dopamine itself.  Note in the article that DOPAL is made from dopamine, not levodopa.  Any med that increases dopamine will increase DOPAL.  Meds that make the dopamine more effective without making more of it would be ideal, but nothing helps PD people as well as levodopa.

 

One factor affecting studies is that for over 40 years now, people with PD are treated - there aren't brains available to study of non-treated PD because it is considered cruel to not treat the person.  This makes it difficult to draw accurate conclusions.

 

There is a debate between dopamine being neurotoxic verses neuroprotective.  Again, levodopa is in the lime light but the issue is with all dopamine meds.  It seems agreed upon that the earlier the diagnosis, the earlier the treatment, then the disease progresses slower (protective).  The problem is that by the time the first symptoms show, about 80% of the neurons are damages, they're working with only 20% and thus are overloaded and subject to more damage (toxic).

 

To illustrate.  If you had a car that had only 1 or 2 functioning pistons, what would you do?  It would run terrible, have little power, and you'd stop using it and get fixed.  In the days of V8 engines, sometimes a damaged piston was bypassed by removing the rocker arms ... 7 was almost as good as 8 and this was a cheap fix.  But 1 of 4 or 2 of 6 won't hack it.  With brains we don't have the option to park it or replace it.

 

So it comes down to balancing function and risk.  And thus the importance of finding the minimum effective dose.

 

Doctors are divided with this just as they are with benzos or pain relief.  Some say, "no problem" and others scream, "worst thing you can do".

 

While not concerned with short term trials, long term was a concern.  I don't want more trouble.  Also don't like to lose, lol.  However, we all gradually lose to aging ... mortality is real and sobering and unpleasant to think about.

 

So as you do your evaluation, layout the benefits.  If, for example, the only benefit was you can now play the sax better, then maybe that isn't enough justification for it.  But it improves your studies, etc.  Now if it takes 300mg or more a day, that would be a concern.  But if you can get most of the benefit from 100, then it becomes a better equation.

 

Since you know of having a COMT polymorph, then something there would be great.  However at this time COMT inhibitors are great for the executive center but terrible for the liver - the risk/benefit ratio comes down to 'no' for continued use.

 

 

Other useful things are ignored by 99.99% of doctors.  Nutrition for the brain, particularly detox things like NAC and glutathione are helpful.  Low glutathione causes PD damage just as it causes cataracts.  Then there is stress, both emotional and environmental.  PD is heavily connected to environmental exposures.  The more load on the brain, the intermediate metabolites (such as DOPAL) build up and cause damage.

 

So clean air, water, food, and sleep.  Learn to control emotional stress response.  A little stress is fine but chronic stress is like acid on the brain, slowly etching away (chronic anxiety/depression eventually causes 12% loss of neurons).  Often a person can't make a lot of change with their situation, but we can change how we feel and react.  If you like to read, a very good book on stress physiology is Why Zebras Don't Get Ulcers.

 

 

Hope this is helpful for you ...

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Thank you! A very balanced and thorough assessment.

To be honest - if I do not feel healthy enough to put hours into playing saxophone a day, then I am not really that happy; it is my life, and it's pretty much what's kept me through, and I have to obtain a certain degree of proficiency at this point to continue. Thus, my personal conclusion is to work with what I have and improve the now- but cautiously with regards to dose. So, I will proceed with Sinemet at a low dose, using as and when - when the battery feels a bit trickled out, and perhaps move into a more regular dosing pattern. I will do some experimentation and see what works for me. Before I proceed down that path I am going to lay off of it for a little bit and trial Tianeptine, as I have some sitting around, so I'll do that and make a report. At least I know Sinemet works for me.

Not sure if you have seen in the other thread on Methylation.. but my COMT polymorph suggests I already have lower COMT activity. So it seems I do not have an issue with COMT breaking down catecholamines. COMT inhibition is probably not the best treatment target for me? Not saying further COMT inhibition wouldn't help.

It's interesting that Gabapentin is your other choice of med. I feel like something GABA-involved is the last piece of my pie and I was considering looking into Gabapentin. 

Also, I must reiterate from my other post 'opting for the med-free route' [well, I am not so sure I am going to go down that route entirely, not right now with my final uni assessments].. that I do feel like I would benefit from some CBT to help with my relationship to the visuals and also motivation. Despite having so more more ability than say 1-2 years ago, I still struggle to psychologically get up and get on with things; I have got used to not doing as much due to not being able to when my HPPD was aggressive.

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To be honest - if I do not feel healthy enough to put hours into playing saxophone a day, then I am not really that happy; it is my life, and it's pretty much what's kept me ...

 

That is quite understandable.  I tend to feel that way about guitar ... except I have no skill [yet].

 

 

Not sure if you have seen in the other thread on Methylation.. but my COMT polymorph suggests I already have lower COMT activity. So it seems I do not have an issue with COMT breaking down catecholamines. COMT inhibition is probably not the best treatment target for me? Not saying further COMT inhibition wouldn't help.

 

Saw your post and haven't processed it yet.  Here is the issue.  COMT does a lot of stuff. 

 

[ Note to everyone: This COMT gene stuff is difficult to grasp so this is an open invitation to get these concepts correct.  So please contribute and correct as this goes ]

 

Terms:

 

A gene is said to be polymorphic if more than one allele occupies that gene’s locus within a population

 

An allele, is one of a number of alternative forms of the same gene or same genetic locus.

 

COMT is located on chromosome 22.  It has 6 exons, spans 27 kb and encodes a protein of 271 amino acids.  There is a singe functonal nucleotide polymorphism (SNP) on exon 4 of the COMT gene: rs4680.  These are: AA, AG, and GG.  A=Valine.  G=Methionine.  [ So sometimes written as Val/Val (AA), Val/Met (AG), and Met/Met (GG) ]

 

As to what is "normal", that is a misunderstanding.  If I understand this correct, http://snpedia.com/index.php/Rs4680 , then ~45% of people are Met/Met, ~40% of people are Val/Met, and ~15% are Val/Val.

 

While the effects of these variations are broad, with regards dopamine, it is just this: Valine breaks down dopamine about 4 times faster than Methionine.  So if you are Met/Met, dopamine in the prefrontal cortex will hang around longer thus 'signaling' longer.  Val/Val will 'eat' dopamine fast and 'signal' short.  Val/Met is inbetween.

 

Dopamine's relationship with COMT is 'felt' the most in the prefrontal cortex because that is almost the only what dopamine is 'cleared'.  Whereas other parts of the brain have other mechanisms involved.

 

In relationship to HPPD, "Inhibition of catechol-Omethyl transferase (COMT) increases inhibition of sensory input in humans carrying the G/G polymorphism. Accordingly, I hypothesized that inhibition of COMT would reduce symptoms in HPPD." - Dr Abraham.

 

 

As for methylization, we will have to look that up to document the effects.  Again COMT does lots of stuff.  Most is found in the liver which does not have neurons.  So you are Val/Met so have less dopamine in the prefrontal cortex than 45% of the population and, perhaps, respond more to levodopa ???

 

Here is a side point of whether cannabis is "safe" regarding schizophrinia and COMT polymophisms http://www.nature.com/nrn/journal/v7/n7/box/nrn1925_BX1.html

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That is quite understandable.  I tend to feel that way about guitar ... except I have no skill [yet].

 

'All' it requires is time :P

Cheers for the info.

I have the G:G polymorphism.. which means for me COMT inhibition would, in theory, be quite effective for my HPPD, correct?

I am a bit confused about the link between COMT inhibition and methylation though. I will try and work it out.

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Practice, practice, practice.  It is cool to see how the brain learns coordination to play.

 

So having G:G means your dopamine naturally hangs around (and least likely to have psychosis from weed?). is used the quickest.

 

At this point there are more answers then questions.  Dr A mentions G:G but does he do so because he thinks they might be most responsive to tolcapone?  Or is it mentioned more as a 'knowledge quote' about G:G and sensory input?  He does in the end suggest gene testing might reveal something ... and elsewhere suggest that the graph of trips-per-getting-HPPD show 2 thresholds that typically implicate genes.

 

Then there is this to consider: since all our brains must do the same functions regardless of polymorphism, would the neuron/synaptic structures compensate (in their formation) to whatever COMT type a person is?  Remember, not all synapsis are equal.  Bigger ones have more 'signal' as do those that are closer to the axion.  If dopamine is rarer/shorter then bigger/closer synapsis might compensate.  Also, there could be more generation of dopamine in the first place to compensate for the 'rarification' by COMT.  Would those who generate more dopamine mean that they are more likely to get damage from dopamine itself or environmental toxins?

 

Yet 'time' is part of equation, not just amount.  Because neurons communicate by firing (ion discharge) and the pulses are always same strength (only time between pulses vary), then the time interval would be somewhat different between the polymorphism.  In the end, genetics do affect personality traits/tendencies just as hair or eye color.  The SNP mentions 'warrior' verses 'worrier' charateristics between val and met subtypes.

 

What does it all mean?  Are certain types more vulnerable to get HPPD?  Are certain types more responsive to dopamine?

 

So collection of data will be helpful.  And there are many other 'dopamine' polymorphisms to consider, not just COMT.

 

 

As for COMT inhibitors, then increase dopamine in prefrontal cortex.  But also decrease important liver functions such that liver enzymes rise and can be damaging to the liver.

 

 

So on the lighter side, what are some of your favorite saxophone pieces?

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  • 3 weeks later...

So how is your Sinemet trial/use going?  It been two weeks?

 

I ceased use entirely a couple of weeks ago, until yesterday. This was to give Tianeptine a trial, which I will write up about in a week's time when I have given it three weeks. I have taken Sinemet the last couple of days because my lethargy came back since discontinuing, also visuals worsened (perhaps due to Tianeptine) and in general the positive results above faded. Due to the busy time of year, I needed a little support. After Tianeptine I will be continuing with Sinemet with half pills as you suggested.

 

Practice, practice, practice.  It is cool to see how the brain learns coordination to play.

 

So having G:G means your dopamine naturally hangs around (and least likely to have psychosis from weed?).

 

At this point there are more answers then questions.  Dr A mentions G:G but does he do so because he thinks they might be most responsive to tolcapone?  Or is it mentioned more as a 'knowledge quote' about G:G and sensory input?  He does in the end suggest gene testing might reveal something ... and elsewhere suggest that the graph of trips-per-getting-HPPD show 2 thresholds that typically implicate genes.

 

Then there is this to consider: since all our brains must do the same functions regardless of polymorphism, would the neuron/synaptic structures compensate (in their formation) to whatever COMT type a person is?  Remember, not all synapsis are equal.  Bigger ones have more 'signal' as do those that are closer to the axion.  If dopamine is rarer/shorter then bigger/closer synapsis might compensate.  Also, there could be more generation of dopamine in the first place to compensate for the 'rarification' by COMT.  Would those who generate more dopamine mean that they are more likely to get damage from dopamine itself or environmental toxins?

 

Yet 'time' is part of equation, not just amount.  Because neurons communicate by firing (ion discharge) and the pulses are always same strength (only time between pulses vary), then the time interval would be somewhat different between the polymorphism.  In the end, genetics do affect personality traits/tendencies just as hair or eye color.  The SNP mentions 'warrior' verses 'worrier' charateristics between val and met subtypes.

 

What does it all mean?  Are certain types more vulnerable to get HPPD?  Are certain types more responsive to dopamine?

 

So collection of data will be helpful.  And there are many other 'dopamine' polymorphisms to consider, not just COMT.

 

 

As for COMT inhibitors, then increase dopamine in prefrontal cortex.  But also decrease important liver functions such that liver enzymes rise and can be damaging to the liver.

 

 

So on the lighter side, what are some of your favorite saxophone pieces?

Sorry I didn't respond to this. This is interesting; The Musician's Brain As A Model Of Neuroplasticity.

 

Have you got your DNA results back yet?

Interesting that I am supposedly least likely to have psychosis from weed. I have always had really bad reactions to weed, rendering quite schizophrenic symptoms in me (only whilst 'high').

With regards to Sinemet + HPPD, after reading about this study, the same thought occurred to me; perhaps dopamine dysfunction is not the main pathogenetic factor (in fact, as I write this, I think it probably isn't). Perhaps the COMT polymorphism is just one variable that could make one's HPPD better or worse. In which case, there is still high reason to target it for treatment, but, I still think 'the answer' (if there is one) lies elsewhere. It is noteworthy that visuals have been improved with Sinemet, which does suggest a pathogenetic involvement.

There have not been that many Sinemet triers, as you say, but in terms of some vague conclusions that can be drawn about user experiences;

- Upping/downing serotonin seems completely hit and miss, more negative (although the latter has not really be tried). Anecdotally, it seems like an unfavourable treatment target.

- Upping dopamine (Sinemet) seems to have positive/neutral results.

- Upping GABA seems to universally alleviate symptoms. With one exception I can think of; Puppeteer responding badly to Gabapentin, which does confuse the hell out of me. 

Upping GABA is the only thing that has ever made me temporarily visual-free.

I am not suggesting that there is GABA dysfunction in HPPD. It's something that roars though as a treatment target, it's just a shame how unsustainable it is.

Anyway, I digress, and I am not really sure where I was going with that.

Favourite saxophone pieces.. well, I spend most of my time working with improvised music, so anything that makes for an interesting springboard to improvise. I spend a lot of time working with the repertoire of jazz standards and other 'jazz' works up until the present day. Also my own compositions and those of musicians I play with. I do like playing the Bach Cello Suites on saxophone. For you, guitar pieces?

 

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  • 3 weeks later...

Well, for what it is worth, I have the A:A polymorphism - the valine aminos that eat up dopamine the quickest wherever COMT is active, such as the prefrontal cortex (an HPPD area).  This was suspected and supports the strong response with Sinemet.

 

One would posit that anyone with HPPD and the COMT A:A polymorphism would benefit with Sinemet or stronger.

 

 

Edit:  Correction: Am WRONG above

 

Am A:A polymorphism but that is the met/met and thus has the longest lasting dopamine.  Have tried COMT inhibitor with Sinemet but it didn't seem any different than taking Sinemet alone.

 

So ... am going to guess that my dopamine need may not be COMT related, but other genes.

 

Literature on genes is difficult to read, there are multiple symbols and text often assumes one knows what they are talking about.  It does seem, however, that personality traits and health traits tend to should up in studies with multiple gene combinations ... just to make it all the more difficult.

 

Further input from members to clarify this would be greatly appretiated.  Thanks...

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I don't tolerate Keppra very well.  At moderate amounts (1000mg / day -- the highest I could get to), mood swings are intolerable.  And at that amount it begins causing mild CEVs.

 

However, occasionally as small amount before bed helps to sleep without intolerable side effects.

 

As a child I always had very mild CEVs which seem to be completely gone by mid 40s.  Ironically they have not been part of my visual perception problems.

 

There may be some who got help for CEVs with Keppra ... don't remember but you could look up.  (Or they could volunteer that info if reading this post)

 

As far as Sinemet helping CEVs, don't remember anyone specifically report that.  Just that a few very happy with Sinemet.  The more specific members report symptom-to-med responses, the more helpful it can be.

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'All' it requires is time :P

Cheers for the info.

I have the G:G polymorphism.. which means for me COMT inhibition would, in theory, be quite effective for my HPPD, correct?

I am a bit confused about the link between COMT inhibition and methylation though. I will try and work it out.

 

You're right (I was wrong) you should benefit the most from COMT inhibition.

 

Did you learn more on the methylation stuff?

 

Some of the confusion with A,C,G,T,Val and Met may because research in COMT came early in gene studies so the used Val/Met instead of A/G.  And depending on how a gene strand is read, it T is A and C is G.  Wish they would have standardized a little better.

 

So we are opposits: AA verses GG.  I respond strongly to Sinemet and you respond less so.  Am suspecting that my problem is not COMT gene related, though there are several COMT genes.  Found a list of 80+ dopamine genes ... lots of homework now...

 

But the nature of your responces seems similar.

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You're right (I was wrong) you should benefit the most from COMT inhibition.

 

Did you learn more on the methylation stuff?

 

Some of the confusion with A,C,G,T,Val and Met may because research in COMT came early in gene studies so the used Val/Met instead of A/G.  And depending on how a gene strand is read, it T is A and C is G.  Wish they would have standardized a little better.

 

So we are opposits: AA verses GG.  I respond strongly to Sinemet and you respond less so.  Am suspecting that my problem is not COMT gene related, though there are several COMT genes.  Found a list of 80+ dopamine genes ... lots of homework now...

 

But the nature of your responces seems similar.

 

Visual, sorry I did not reply to your PM. I'll get back to you this evening.

Didn't look into that any more.. am reading about other things at the moment. I'll get around to it.

So it seems that the COMT gene is not a hugely determinative factor in HPPD...

Back to me and Sinemet.. have been on it at <2 pills/day for the last couple of weeks. Not really getting the success that I initially had, although things are okay. I am not getting consistent results. Some days I will drink a cup of coffee with the Sinemet and be good for the whole day. Other days, I am still fairly unmotivated.. which manifests itself in laziness (going to sleep.. although I am not sure I would call it lethargy, just anhedonia). I am going to try what you recommended to me privately. I added in Gabapentin 300mg before bed recently, just to take the edge off things. It's my last month of studies (exams etc.) so want to be on good form. Once completed I will do a washout, including supps, for 1-2 months, let the body do a bit of its own healing. Then I have plans to try some other things.

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  • 1 year later...

Its been a while since you've posted on this thread.  Was wondering ...

 

Do you still use Sinemet from time to time?

 

Or was the 5-10% not enough to justify it?

 

Am curious about whether 'dopamine' responders (strong or partial) have thiamine weakness.  If you are able, please give this a look and trial.  http://hppdonline.com/index.php?/topic/5027-thiamine-cocarboxylase/

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