Question about Sinemet and the HPPD dopamine hypothesis

[Mushubeans]

Studies have shown that Sinemet can improve symptoms of HPPD and I know some of the members on the forum have found this to be true in their own experiences. This poses a question.. All along, antipsychotics have been cautioned against when it comes to treating HPPD because of their antagonization of the 5-HT2a receptor. Could this be totally wrong? Could the reason antipsychotics worsen HPPD have to do with their lowering of dopamine? It would seem a likely possibility considering that by raising dopamine, Sinemet ameliorates many of the symptoms, including depersonalization which antipsychotics also tend to exacerbate. I'd love some input on this!

[Syntheso]

I personally feel that Sinemet might even exert some of its effects through lowering serotonin. SSRI's make HPPD worse. It seems illogical that 5-HT2a antagonists would do the same. But then again it just goes to show that this is not as simple as a polar neurochemical imbalance.

[VisualDude]

'Original' antipsychotics work with suppressing D2, not serotonin.  Modern 'atypical' antipsychotics reduce D2 less strongly and increase serotonin - and according to current understanding, shouldn't actually work at all for delusions (just another we-don't-know-what-is-going-on).

 

Levodopa (Sinemet) has no direct effect on serotonin.  That being said, nudge one transmitter and it will affect another to some degree.

 

I'm a 'Sinemetty' ... it is very helpful for me.

 

 

Dr A's dopamine hypothesis is based on COMT metabolism so, technically, his point of view is that Sinemet would have little response.  His Tolcapone + Sinemet trial had about 1/3 of people with good response.  And there was a clear distinction with non-responders.  Therefore only some of HPPDers have a frank dopamine problem.  5HT2a is an inverse receptor in the visual system (inhibitor), and it is the 'active-point' for most hallucinogens, therefore it is implicated besides dopamine.

 

There have been no studies on Sinemet alone ... and I may be part to blame because of my promoting that people try it or other dopamine enhancing meds ... it's just that when the shoe fits it is extremely comfortable! ... and it is also an avenue that all doctors ignore.

[Mushubeans]

So in your case, sinemet alone reduced your HPPD and DP? What mechanism would underlie that?

[VisualDude]

Never had actual DP, so can't speak for that one.  Though Merkan got relieve from DP with Sinemet.

 

However, it has done a lot for my visuals.  Before, I had a 'motion-blindness' ... slow frame rate like a poor web connection ... about 1 second between frames.  Also, poor contrast, night vision, dull colors, flat depth perception, fuzzy/blurry vision, lingering negative afterimages.  These are fully addressed.  There are things that are not addressed fully which include DR, starbursts, halos.  Other things too but it gets tiring to remember and think about them all.

 

Dopaminergic neurons often are in small regulating circuits.  They use the term 'signal-to-noise ratio' in the same sense as with sound/electronics.  These mini-circuit choose/fine-tune actions.  For example, behind each photoreceptor in the eye is a dopamine neuron that 'decides' how much signal to pass on, thus spot adjusting contrast.  They even link up groups affecting how much signaling goes to detail (focal visual processing) and how much shunts to movement (ambient visual processing).

 

When these neurons run out of fuel (in the form of dopamine), they get stuck in whatever state they were in.  Levodopa provides raw material to make dopamine.

 

While there are interrelations, such as my halos are better because vision is sharper (so less blur to mush around into the halo problem), it seems that each HPPD symptom has is own circuit/set-of-circuits involved.  So the mechanism is slightly different.  But if the defect involves micro-managing, there is a good possibility dopamine is involved. 

 

If scientists ever get interested in us, they would have a whole lot of fun.  Great job if they were paid by the hour.

 

Would that it be so simple that we could just take a pill and make it all go away ...