Syntheso

I trialed Tianeptine 12.5mg three times daily for 18 days (2 weeks 4 days). I had planned to trial further than three weeks, but I could continue no further due to the lack of symptom relief/possibility of Tianeptine causing me to become really depressed.

At first, it seemed to work well, but in retrospect, this was probably the effects of my Sinemet trial still lingering. It seemed to make a useful anxiolytic when taken just before an event, though later on in the trial, there were no consistent effect to determine this. Throughout the trial I had days where felt moderate, great, and awful; the latter particularly towards the end. My visuals appeared the same/worse. There was no consistent effect I could determine from the trial. I must admit there were instances of heavy drinking in the trial which could have been a large influence (although, I have trialed other things with instances of heavy drinking and still found efficacy in a medication).

My conclusion; possible antidepressant / anxiolytic qualities when used acutely. Some apparent immediate positive effects, but not entirely consistent. Chronic use (up to 18 days); negative/inconclusive.

 

http://www.psychologytoday.com/blog/brain-myths/201302/read-paying-100s-neurofeedback-therapy-0

The studies noted at the end are concerning.

I'm going to project this on my wall when I get a chance.

This is incredible. It is promising to see a similar strategy for tinnitus that works too.

I am curious.. people with DP - does this alleviate your symptoms at all?

Also.. does anyone with HPPD not experience visual snow? 

It is interesting how staring at the static produces acid-like visuals, and, the colours green/yellow + blue/purple. Does anyone else see that? Are they actually in the video?

This is really interesting - yes it does seem to remove the visual snow from my vision temporarily.

I wonder if this could have permanent effects if done routinely?

It does look very useful and worth investigating, but I feel it is a little off-topic as it is not specific to the thalamus (which is what links David's theory and the study cited above).

It's entirely up to you. I consider the HPPD Stack thread as largely an orthomolecular approach. The idea of that thread is to explore non-pharmacuticals, starting with nutritional supplements and working up to suitable nootropics. I suppose what you are saying is that you see this thread as being more of a discussion of theories. But surely it's all the same in the end - we discuss theories and whatnot, presumably with one thing in mind; treatment prospects. So, it doesn't make a lot of sense to me to defer theoretical discussion from the HPPD Stack thread, and also I do not see how this thread would end up without treatment prospects being considered after drawing conclusions i.e surely they are one and the same? IMO, it would be helpful collate information from around the board to make it more accessible, concise and in one place; because there are lots of 'what supplements...' threads that have no organisation or description behind them. Another thread like this kind of confuses things further, I think.. 

To iterate, the HPPD Stack thread is intended to have a quick-fire, concise set of ideas that people can give a try immediately, with anecdotes in the second post. It is absolutely fine if we have discussions pages later, but the idea is to end up with some actual suggestions for treatments in the first post. The point being, things you can buy, do, utilise yourself.. whilst you are waiting for a doc/if your doc isn't helping etc.

I am skeptical that is is possible to reduce blood flow in certain parts of the brain as opposed to others. I wouldn't be interested in globally lowering the blood pressure in my head unless there was indication that it would be useful. I would be interested in exploring the idea of an op to lower the blood pressure in the thalamus.

What is the distinction from the concept of the HPPD Stack thread? Seems to just add more confusion rather than centralising all sorts of nutritional/supplemental approaches.

Have been drinking tonic water whenever the chance arises. It makes for an enjoyable drink (esp. with the gin!). 

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?

(1) a SPECT Scan (blood flow to different brain regions)

I have had a CT scan that apparently didn't show anything abnormal (wasn't actually done for HPPD though, but to rule out the shunt in my head and hydrocephalus as causes for HPPD symptomatology), I wonder if a SPECT scan would be more telling.

With regards to David's proposed theory (which implicates thalamocortical networks and feedback loops), see;
 

Activation of Thalamo-Cortical Systems in Post-Traumatic Flashbacks: A Positron Emission Tomography Study

 

Abstract

Trauma victims with post-traumatic stress disorder (PTSD) often experience ‘flashbacks’ that are described as being different from memories of other fearful biographic situations. We used Positron Emission Tomography and Statistical Parametric Mapping to compare in the same subject brain activation patterns during induced flashbacks with recall of fearful non-traumatic situations. During fearful recall there were significant activations of right precuneus. When traumatic memories were compared to neutral, right lingual gyrus, right thalamus / mamillary bodies, and right cerebellum were significantly activated. When brain activation during flashbacks was compared to simple fear, right mediodorsal thalamus (MD), right precuneus, and right cerebellum were significantly more active. With respect to recent experimental evidence concerning the function of thalamo-cortical systems, we hypothesize that post-traumatic flashback experiences are based on hyperactive thalamo-cortical ‘closed loop’ networks.

This study suggests that decreasing cerebral blood flow in the thalamus of PTSD patients can reduce 're-experience' symptoms. Perhaps this has some relevance for us.

 NaturalStacks has released a new Creatine product which is a combo with added Fenugreek and Himalayan Pink Salt. These potentiate Creatine.

Hmm.. do you know exactly what kind of each you've been taking? I only ask because I always stress when I speak to people that the smallest difference in quality can change everything. Not all CoQ10's are the same. I'm getting some pure powdered CoQ10 but I've also recently found some apparently extremely efficiently absorbed CoQ10's (and of course, more expensive  ) that I'll try next.

 

Try taking creatine on an empty stomach, preferably with any of the following: salt, baking soda, fenugreek, russian tarragon, or ALA (or a combination thereof). Each of those things (including taking it on an empty stomach) have been shown to either increase the absorption of creatine or have some synergy with it. 

 

The information on Aspirin as a supplement is vast; I haven't researched much on how it affects the mitochondria, but I know that it can cause mild mitochondrial uncoupling (thus heat production), and when this happens a lot of enzymes are activated downstream that are beneficial. This can decrease ATP a bit, but the heat production does a lot in and of itself. It also seems to stimulate T3, which I would hypothesize leads to mitochondrial biogenesis because T3 can achieve that; but I've never seen any direct studies on Aspirin-->mitochondriogenesis. I have seen studies indicating it aids in myelination of the brain, though. 

I take Holland and Barrett's CoQ10 brand, 60mg/day. I always take Creatine as soon as I get up (empty stomach), as do I with most supps, before I eat. The Creatine I use is from NaturalStacks, which is a combo with added Fenugreek and Himalayan Pink Salt. I'll post that in the HPPD Stack thread, actually.

I have been taking CoQ10 + Creatine for a while now. Non-surprisingly, can't say I feel much better, perhaps in a more general way. Creatine appears to have moderate noticeable benefits. Never heard of Aspirin for mitochondrial support. Will check it out.

Best,
S

BPC, could you organise what you believe to be important points under headings, kind of like I did in the first post, with links to studies. Keep it concise. Then I can put the suggestions in the main post.

Read in relation to this hypothesis.

Metabotropic glutamate receptors differentially regulate GABAergic inhibition in thalamus.

Abstract

Thalamic interneurons and thalamic reticular nucleus (TRN) neurons provide inhibitory innervation of thalamocortical cells that significantly influence thalamic gating. The local interneurons in the dorsal lateral geniculate nucleus (dLGN) give rise to two distinct synaptic outputs: classical axonal and dendrodendritic. Activation of metabotropic glutamate receptors (mGluRs) by agonists or optic tract stimulation increases the output of these presynaptic dendrites leading to increased inhibition of thalamocortical neurons. The present study was aimed to evaluate the actions of specific mGluRs on inhibitory GABA-mediated signaling. We found that the group I mGluR (mGluR(1,5)) agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) or optic tract stimulation produced a robust increase in spontaneous IPSCs (sIPSCs) in thalamocortical neurons that was attenuated by the selective mGluR(5) antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). In contrast, the group II mGluR (mGluR(2,3)) agonists (2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) or (2S,2'R,3'R)-2-(2'3'-dicarboxycyclopropyl)glycine (DCG-IV) suppressed the frequency of sIPSCs. In addition, mGluR(1,5) agonist DHPG produced depolarizations and mGluR(2/3) agonists APDC or L-CCG-I [(2S,1'S,2'S)-2-(carboxycyclopropyl)glycine] produced hyperpolarizations in dLGN interneurons. Furthermore, the enhanced sIPSC activity by optic tract stimulation was reduced when paired with corticothalamic fiber stimulation. The present data indicate that activation of specific mGluR subtypes differentially regulates inhibitory activity via different synaptic pathways. Our results suggest that activation of specific mGluR subtypes can upregulate or downregulate inhibitory activity in thalamic relay neurons, and these actions likely shape excitatory synaptic integration and thus regulate information transfer through thalamocortical circuits.

Prefrontal cortical network activity: Opposite effects of psychedelic hallucinogens and D1/D5 dopamine receptor activation.
 

Abstract

 

The fine-tuning of network activity provides a modulating influence on how information is processed and interpreted in the brain. Here, we use brain slices of rat prefrontal cortex to study how recurrent network activity is affected by neuromodulators known to alter normal cortical function. We previously determined that glutamate spillover and stimulation of extrasynaptic N-methyl-d-aspartic acid (NMDA) receptors are required to support hallucinogen-induced cortical network activity. Since microdialysis studies suggest that psychedelic hallucinogens and dopamine D1/D5 receptor agonists have opposite effects on extracellular glutamate in prefrontal cortex, we hypothesized that these two families of psychoactive drugs would have opposite effects on cortical network activity. We found that network activity can be enhanced by 2,5-dimethoxy-4-iodoamphetamine (DOI) (a psychedelic hallucinogen that is a partial agonist of 5-HT(2A/2C) receptors) and suppressed by the selective D1/D5 agonist SKF 38393. This suppression could be mimicked by direct activation of adenylyl cyclase with forskolin or by addition of a cAMP analog. These findings are consistent with previous work showing that activation of adenylyl cyclase can upregulate neuronal glutamate transporters, thereby decreasing synaptic spillover of glutamate. Consistent with this hypothesis, a low concentration of the glutamate transporter inhibitor threo-beta-benzoylaspartic acid (TBOA) restored electrically-evoked recurrent activity in the presence of a selective D1/D5 agonist, whereas recurrent activity in the presence of a low level of the GABA(A) antagonist bicuculline was not resistant to suppression by the D1/D5 agonist. The tempering of network UP states by D1/D5 receptor activation may have implications for the proposed use of D1/D5 agonists in the treatment of schizophrenia.


http://www.ncbi.nlm.nih.gov/pubmed/17293055

Re: MgT upregulating NR2B; from what I've found, this is what you don't want happening. NR2A is the one you want to upregulate.. But again; still have to look further in to it, but this is how it seems to me now.

Could you explain why?

I'd buy a new occipital lobe. Get tha shiii fitted.

That sounds like a hefty ol' trip!

Welcome to the board...

I don't see faces in the way you describe, but I quite frequently think I see faces/figures in my peripheral or when I turn quickly. Must be pretty freaky, so wishing you all the best.

You are referring to 'pseudohallucinations'.

The right eye twitching is interesting.

Sorry guys, I can't be of much help for a while. Last couple of months of uni, got to put my research on hold. Am starting a Biomedical course later this year though so will be able to get fully on the research  . Wishing you well, in case you don't hear from me much for a while (I'll still check the boards everyday though)

I was thinking about mentioning this as a general point in recovery.. really important to make sure your airways are clear... especially when you sleep. If you are sleeping with a blocked nose, you are not giving your brain a chance to recover properly. I sleep with an inhaler by my bed and blow my nose before I sleep. Might seem really trivial, but over long periods of time, things like this could make a huge difference.

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

'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.