Syntheso

'All' it requires is time 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.

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.

Cheers for keeping a diary mate, I will be following with interest. Your experience with Z-health sounds promising. I hope there is continued progress.

I've read people contest over it. Of course, the best thing to do would be to get your histamine levels tested, but this can be a hassle. It served for my purpose (I flushed at a low dose); it seemed to corroborate with my suspected histadelia, subsequent response to SAMe and DNA testing. I have always thought of it as something to take with a pinch of salt, but that will probably steer you in the right direction.

I was reading this explanation by a Longecity member on COMT and methylation. Irrespective of HPPD, I started supplementing SAMe (for those that don't know, a methyl donor) a while back, as I suspected myself to be moderately histadelic (high histamine); I have symptoms and a niacin flush test suggested so too. I am quite convinced that SAMe makes my overall feeling of well-being better, having had periods on and off taking it. Histamine imbalances produce psychiatric symptoms, such as depression and anxiety. I wondered if an underlying histamine imbalance could be producing symptoms that I assumed were to do with HPPD. SAMe does seem to have a positive effect on my well-being - it certainly does not make me feel bad, which suggests that I am an undermethylator. Reading the thread above was the first time I heard of a link between methylation and COMT activity. This suggests a target for preventing the breakdown of catecholamines. Correcting histamine imbalances, particularly (just?) histapenia, might in turn help HPPD. Derived from the thread; High COMT Activity - Histapenia (Low Histamine) - Overmethylation - Lower Catecholamine Levels [Low COMT Activity - Histadelia (High Histamine) - Undermethylation - Higher Catecholamine Levels] My own case doesn't suggest a link between methylation and HPPD, it in fact suggests I should be less susceptible to HPPD. I have the COMT polymorphism that suggests lower COMT activity i.e more dopamine. So, I benefit from a methyl donor, but this suggests I should have higher catecholamine/DA levels than usual.. it is strange then, that I have HPPD. Then again, perhaps not. I guess we can infer that for me, my DA issue does not lie with COMT activity? [That is not to say that my COMT activity has not been altered post-HPPD-onset. It could well have done. But it seems at least not at the level of genes, as I had the test done with HPPD.] However, if you are an overmethylator, this would presumably contribute to your HPPD. Perhaps it is an idea for people to get their histamine levels checked? If you were an overmethylator that would most definitely (I infer) contribute to HPPD. Also, if you had any significant histamine imbalances they would contribute to your sense of well-being anyway.

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.

Fantastic information, thank you very much. I am sure I will have some questions for you shortly.

Are you still on Sinemet, Visual? Have you experienced any side effects? My understanding is that Sinemet would only really feel noticeable to someone with low DA levels i.e someone with normal DA levels could take Sinemet and not feel an effect. Is this what you mean by battery charging, if you're full of charge, you don't feel the effects? Also, do you split your dose throughout the day? I get the impression that it wouldn't be so important for Sinemet. Lastly, from your reading. Does mid-long term Sinemet use have implications for the future, will your body get used to the exogenous source of DA and become dependent on it? I am having second thoughts about using Sinemet for more than a short period. Some stuff I have read worries me.

Yeah, I probably am getting a bit excited. You can get it done on 23andMe.

Sorry to hear your experience. But - whilst I have read reports of people finding immediate positive effects, I have read that the effects are really meant to take a couple of weeks. I think it works in a similar way to the antagonism - upregulation relationship, which might explain an initial worsening of well-being.

I didn't get on with Tofisopam, IIRC it made my visuals worse. I forgot/didn't realise that it was the 'only stimulant benzo', as they call it. I couldn't sleep after I took it, which was my purpose. Perhaps the stress of not being able to sleep caused the visuals to become worse. I could try it again and make another report.

I don't understand why some physicians struggle with the HPPD diagnosis and come up with all these other whacky ideas. Of course, it is important to look at different possible avenues, but if you start experiencing the very specific kind of symptoms associated with HPPD shortly after using hallucinogenic drugs.. why would you not be compelled to go with that diagnosis other than simply because you haven't heard of it before?!

Look forward to hearing your results so we can compare, Visual. I am up to 3 x 25/100 pills a day. There is definitely an improvement in my visuals, only in the dark though. There is now only quite gentle visual snow and very faint strobing. Still no fatigue. I feel very calm, a wonderful sense of calm, collected. Concentration is much better- practiced saxophone for around an hour today without having to fidget. I think I am going to stay on Sinemet till the end of May, as it is the last two months of my degree. I have a lot of lost time to make up for.

Thanks, Visual. So, there is not really much of a therapeutic value in tonic water alone?

I've had no complaints Okay, cheers Chris. Were the improvements permanent (IIRC you stopped)?

Etizolam has been opted for as an alternative benzo (analogue) by a few on here.. do a search and you should come up with some stuff.

Would love to see some visual improvements. After how long did you start upping your dose? A few days? How can you be sure the visual improvements weren't from Clonazepam? I'm not sure about %, I took the Swanson Full Spectrum.

Oh yes - please note. 5-10% improvement might not sound that fantastic, but given how much I have already recovered, I actually think that is, and that there is much larger implications for people who are less recovered than me. I suggest...

I actually noticed it after the 'head nausea' had gone on the first day. In the evening I went to the philosophy reading group in the space that I run and was able to communicate and understand better than usual (still not that good though), I also felt anxiolysis. MP was my suggestion that Sinemet would be good for me. I took it for a few days and it really helped. I needed over 5g (full spectrum). Sometimes, it didn't really seem to help, though. This was possibly on days where I hadn't dosed the day or so before though, not too sure. I remember being able to concentrate for 5 hours (never happened before) on 6g. In those hours I did the same amount of work I would have done in 2-4 weeks. Not an exaggeration. I slept much much better on MP, and didn't wake up feeling groggy, but really cleared headed.

Yes, I do dose @ 25/100 once daily. You are right - that's exactly the difference. I honestly cannot believe that I do not feel any fatigue in me right now and haven't done for the last few days. Psychologically, my mind is saying, "uh, don't you wanna sleep.. probably about time you slept, right"? I really don't want/need to, at all. I do not have any recollection of my life with HPPD where this is the case - without having to force myself up or to stay awake.

Was considering posting this in another thread, but thought that the success story might get drowned out. I know I posted elsewhere that I was going to opt for a med-free route, but the opportunity to try Sinemet came up so I thought I would do so and report. Today is my fourth day taking Sinemet (25/100). Before starting I felt 80% back to normal, I now feel 85-90%. It has completely knocked out my lethargy.. the first days of my HPPD life I have not felt like I need to sleep at some point in the day, and I have been able to get out of bed in the morning, something I have really struggled with. Concentration is much better too, and general cognition and ability feels better. Nothing to notice on the visuals yet. As a side note; first dose made me feel very strange... a kind of nausea in the head; quite a horrible feeling (which was not good considering I was driving, but it was manageable, nonetheless). There was this great feeling though where it suddenly all just quickly went, like loads of pressure building up and releasing (dopamine hitting the brain?) Also, to further what we already know about the success of GABAergics in HPPD + relative success of Sinemet... as a one off occasion for what was to be a demanding evening of running a large event, I took 1mg etizolam in the evening before (having taken Sinemet for two days). I felt at 99% in that situation with the 1% being the visuals, or at least my relationship to them. I felt great, confident, I could have good long discussions, no anxiety, quicker witted.. compared to, in the last few months, running similar events and having tried 1mg and on a separate occasion 2mg of Etizolam alone, where I just felt a bit better and more comfortable (no anxiety), but not with the conversational and cognitive abilities that the Sinemet contributed (GABAergics alone do give me cognitive benefits though). Put simply: the best I have ever felt in my HPPD life. It is a shame I didn't try something cognitively demanding like reading or practicing an instrument. Though, running large events is a cognitively demanding, and normally something I don't feel quite comfortable with. It's still early days, I plan to take it for a while longer to see if I get any improvements. Any Sinemet success-storier's.. let me know how long it took you to reach the full efficacy. My reading suggests this should be around a week. Well wishes, S

Hm, I am not sure what got me so excited because I too freak out about the idea of downregulating GABAR's. This is what led me on a search to find substances that weren't GABA agonists (but that improve GABA).. I didn't think that because the compound itself isn't a GABA ligand, doesn't mean it cannot cause downregulation (that's a lot of negatives for you). Silly me! At the moment, the only things I am utilising to improve GABA are bacopa monneiri, taurine and theanine. I am looking for more. ODISA - oh wow, you just found me a site that is exactly what I have been looking for in my life!

Old AED. Looks good. Anyone tried it? Mechanism of action[edit]The mechanism of action of valproate is not fully understood.[35] Its anticonvulsant effect is attributed to the blockade of voltage-dependent sodium channels and increased brain levels of gamma-aminobutyric acid (GABA).[35] The GABAergic effect is also believed to contribute towards the anti-manic properties of valproate.[35] In animals, sodium valproate raises cerebral and cerebellar levels of the inhibitory synaptic transmitter, GABA, possibly by inhibiting GABA degradative enzymes, such asGABA transaminase, succinate-semialdehyde dehydrogenase and by inhibiting the re-uptake of GABA by neuronal cells.[35] It also possesses histone deacetylase-inhibiting effects.[54]

Have you tried bacopa monnieri and/or theanine? Would probably be good to supp them to aid your GABA receptors.

Antagonists tend to upregulate the receptors they bind to, whilst agonists downregulate them. Hence, benzo withdrawal, for example, occurs after GABA receptors have been agonised to the degree of downregulation, meaning, a decrease in the number of receptor cells and thus the effect of ligands is diminished. Antagonists, as you know, block the receptor from being 'activated' by receptor agonists. So MgT antagonises the NMDAR's, blocking agonists and calcium influx, but also has the action of increasing the receptor density. I think the brain does this to maintain homeostasis. Perhaps someone else can describe better.