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Finding the cause. To find the cure we need to know the cause.


Fawkinchit
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I wanted to make a reversion of my last thread, a potential cure for hppd, which I feel has gone off track with randomized posts and a strong strife to find a cure than to find the cause. So this thread will have some guidelines and rules.

Guidelines:

We are searching for the cause.

Even if the cause is brain damage we are not hopeless.

When we find the cause we can find the cure.

Make connections.

Rules:

If you post clinical trial information, there must be a brief/simplified description of the information that you have found and how it applies.

Please talk in simplified terms if you can so that everyone can understand. We do have very smart people on this site but not everyone is well versed in biomedical science..

If you guys have any other ideas for the rules or guidelines let me know, or if you guys feel that you would like a rule change let me know as well. I think that so far we have made some really good progress are we are ALL LEARNING ALOT! Which is awesome.

Post #2 will start off a new idea that is a very good lead for the cause.

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A new potential cause that I think is the most logical route to take things is the idea that receptors activate the release of certain chemicals when they are stimulated. Hallucinogens create a very strong agonizing effect on 5ht2a receptors, meaning that, whatever these receptors cause the release of, will be in full effect under the influence of 5ht2a receptors. So there may be a chemical release that has done some damage, or even destroyed, specific localized neurons that are affected by 5ht2a receptors. Under the circumstances of this damage, certain areas of our brains then lack the regulation of neuronal activity, causing high energy flows of things like visual response, anxiety, the inability to balance ones self, etc.

A good example of the effects can sometimes be likened to stroke damage to the cerebellum, where high anxiety, loss of balance, and vertigo are the usual symptoms. It may be the case that there are a large amount of 5ht2a receptors on the cerabellum, and if thats the case it would probably be safe to say that there are probably alot on the visual cortex as well.

The information that I have found that helps this idea is from wikipedia stating what chemicals are effected in release by the activation of 5ht2a receptors.

5-HT2A is expressed widely throughout the central nervous system (CNS). It is expressed near most of the serotoninergic terminal rich areas, including neocortex (mainly prefrontal,parietal, and somatosensory cortex) and the olfactory tubercle. Especially high concentrations of this receptor on the apical dendrites of pyramidal cells in layer V of the cortex may modulate cognitive processes, by enhancing glutamate release followed by a complex range of interactions with the 5-HT1A, GABA, adenosine A1, AMPA,mGluR, mGlu5, and OX2 receptors. In the rat cerebellum, the protein has also been found in the Golgi cells of the granular layer, and in the Purkinje cells.

Excessive levels of glutamate have been shown to cause neuronal apoptosis.

We see 5ht2a activity in the cerebellum of rats

Receptor activity in the neocortex, this will acclimate for a large amount of effects.

Green Areas rich in serotonin receptors

Rcpt_sys_SN2_dist.png

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I highly doubt its brain damage. And there are reports of people who have fully recovered,their numbers would be very very low if it caused brain damage. I am thinking of some kind of change which could be reversed in 5ht2a receptors.

after getting HPPD,my iq scores,reflexes,eye-hand coordination stays the same. if i focus i don't even notice i got HPPD unless i stare at empty surfaces or walls. I still get LSD like visuals if i do it,it feels like i am stuck at the last stage of trip. I am thinking of some sort of chemical change.

I never had DP/DR,maybe it is because i am very introverted and materialistic,but sometimes i can't sleep at nights alone. I still got hope that my brain will fix it on its own,some days it is like 80% gone,on others it is worse. never got as bad as first day though,it's been a month since i got it. I am giving it 2 years max,i will post there if i heal completely.

I am going to take benzos next week or so,probably 4-5 times a week.not that i feel anxiety but i am entering an university exam,any distraction that happens in exam time could possibly ruin my life so i want it under control this year.

http://www.neurosoup.com/john_halpern_interview.htm

http://www.neurosoup.com/henry_abraham_interview.htm

i've found these. seems like some people can't recover from HPPD or it takes longer. Perhaps it has to do with genetics or amount of drugs that has been used?

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I'll be honest, most of that went way over my head. But a few comments based on my own (extremely limited) understanding. The regions of the brain that are apparently overactive in HPPD sufferers are the occipital and temporal lobes. This seems to be similar to tinnitus (something many HPPDers experience) which shows activity in the temporal lobes caused by a loss of inhibition to auditory cortex neurons in which they 'misfire' and cause the person to hear sounds that aren't real. Is a similar misfiring causing HPPD visuals? The latest sound treatment for tinnitus is able ""reset" auditory nerve cells in the brain to stop them misfiring" and "brainwave alterations were also reversed by the therapy." It is believed that GABA drugs, which can increase inhibitory signaling, should be able to have the same effect. So in both cases could it just be the case of finding the right one?

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I highly doubt its brain damage. And there are reports of people who have fully recovered,their numbers would be very very low if it caused brain damage. I am thinking of some kind of change which could be reversed in 5ht2a receptors.

after getting HPPD,my iq scores,reflexes,eye-hand coordination stays the same. if i focus i don't even notice i got HPPD unless i stare at empty surfaces or walls. I still get LSD like visuals if i do it,it feels like i am stuck at the last stage of trip. I am thinking of some sort of chemical change.

I never had DP/DR,maybe it is because i am very introverted and materialistic,but sometimes i can't sleep at nights alone. I still got hope that my brain will fix it on its own,some days it is like 80% gone,on others it is worse. never got as bad as first day though,it's been a month since i got it. I am giving it 2 years max,i will post there if i heal completely.

I am going to take benzos next week or so,probably 4-5 times a week.not that i feel anxiety but i am entering an university exam,any distraction that happens in exam time could possibly ruin my life so i want it under control this year.

http://www.neurosoup...n_interview.htm

http://www.neurosoup...m_interview.htm

i've found these. seems like some people can't recover from HPPD or it takes longer. Perhaps it has to do with genetics or amount of drugs that has been used?

I disagree that most make a full recovery, I feel that most dont, I believe that alot do get better, but so do stroke victims, just their damage is much more extreme and recovery for them is limited. In HPPD it seems very localized to specific sections of the brain dealing with 5ht2a receptors. My DR/DP, and visual snow is gone, I never get it anymore, and my balance has returned, but my anxiety is still there, any contact with to many stimulants makes it pretty bad. So even though yes it is better, its not a full recovery. But I think that most at the point where I am at would say they have recovered.

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I'll be honest, most of that went way over my head. But a few comments based on my own (extremely limited) understanding. The regions of the brain that are apparently overactive in HPPD sufferers are the occipital and temporal lobes. This seems to be similar to tinnitus (something many HPPDers experience) which shows activity in the temporal lobes caused by a loss of inhibition to auditory cortex neurons in which they 'misfire' and cause the person to hear sounds that aren't real. Is a similar misfiring causing HPPD visuals? The latest sound treatment for tinnitus is able ""reset" auditory nerve cells in the brain to stop them misfiring" and "brainwave alterations were also reversed by the therapy." It is believed that GABA drugs, which can increase inhibitory signaling, should be able to have the same effect. So in both cases could it just be the case of finding the right one?

What do those areas of the brain effect/control?

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I disagree that most make a full recovery, I feel that most dont, I believe that alot do get better, but so do stroke victims, just their damage is much more extreme and recovery for them is limited. In HPPD it seems very localized to specific sections of the brain dealing with 5ht2a receptors. My DR/DP, and visual snow is gone, I never get it anymore, and my balance has returned, but my anxiety is still there, any contact with to many stimulants makes it pretty bad. So even though yes it is better, its not a full recovery. But I think that most at the point where I am at would say they have recovered.

do you still have visuals / hallucinations and other stuff? I've always had anxiety(hppd like) after using stimulants(even non stimulants / stim likes like atomoxetine , modafinil)

perhaps your anxiety is something like PTSD,exposure to HPPD for long time is kinda traumatic.

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It's definitely an alteration to the inhibitory interneurons in the visual cortex and probably elsewhere. The 5-ht2a receptors have been altered to the point where they dom't release GABA after the neuron reaches it's max excitatory point to stop the nerve signal so the excitatory currents stick around for much longer than they rightfully should. This is why afterimages linger for so long or why we all have tinnitus or why we see visual snow and etc. etc. etc. It's all evidence that the inhibition that should be occuring to calm the neuronal circuits isn't working like it used to anymore.

My personal opinion is that gene therapy is the only type of medicine that is going to have a sure fire chance at making any REAL permanent improvement to people with the disorder.

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do you still have visuals / hallucinations and other stuff? I've always had anxiety(hppd like) after using stimulants(even non stimulants / stim likes like atomoxetine , modafinil)

perhaps your anxiety is something like PTSD,exposure to HPPD for long time is kinda traumatic.

Never really had any other than visual snow and sometimes lighting would seem to get REALLY bright some times.

Anxiety is the biggest issue for me.

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Its a good idea, thats for sure. I will say though that under the circumstances of altered gene expression, how and/or why would there be varying levels of recovery? If a gene is silenced, then it will stay that way, and no changes would occur there after, so why would there be improvements in some people?

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It's definitely an alteration to the inhibitory interneurons in the visual cortex and probably elsewhere. The 5-ht2a receptors have been altered to the point where they dom't release GABA after the neuron reaches it's max excitatory point to stop the nerve signal so the excitatory currents stick around for much longer than they rightfully should. This is why afterimages linger for so long or why we all have tinnitus or why we see visual snow and etc. etc. etc. It's all evidence that the inhibition that should be occuring to calm the neuronal circuits isn't working like it used to anymore.

My personal opinion is that gene therapy is the only type of medicine that is going to have a sure fire chance at making any REAL permanent improvement to people with the disorder.

wanted to correct you on 5ht2a receptors and GABA, they are completely different receptors, they do have interactions but GABA has its own receptor sites. If the problem were a lack of GABA on receptor sites then benzos would be a fix it for HPPD.

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Visual snow now that's what I want to get rid of I think there's a lot of options out there worth trying to help deal with the anxiety side of things I don't get anxiety anymore really only tue visual snow light sensotivty and after images really wanna beat them 3 symptoms

Id take VS over anxiety any day.

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Yeah fair enough point I had one panic attack in my life which was horrible and used to have anxiety before I even had hppd kinda learnt to deal with it and it doesn't bother me now but the visual snow and light sensitivity I really can't seem to deal with it's gets me down more than anything beating them symptoms would be on par with winning the lotto for me lol

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qaiphyx i have had pretty bad anxiety since i was born,i have avoidant personality disorder and many other stuff. i beat it ,i think thats why i don't have hppd anxiety too. you just have to adjust your mindset. if you do that,anxiety fades away. first thing i did was accepting that i create the anxiety not something else. you consciously do it,not subconsciously.

i have full blown hallucinations like LSD when i stare at walls and surfaces like that. dealing with anxiety is almost always the same,be it a personality disorder,post traumatic or hppd. it is hard to not give a crap about something constantly happening but you have to.

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qaiphyx i have had pretty bad anxiety since i was born,i have avoidant personality disorder and many other stuff. i beat it ,i think thats why i don't have hppd anxiety too. you just have to adjust your mindset. if you do that,anxiety fades away. first thing i did was accepting that i create the anxiety not something else. you consciously do it,not subconsciously.

i have full blown hallucinations like LSD when i stare at walls and surfaces like that. dealing with anxiety is almost always the same,be it a personality disorder,post traumatic or hppd. it is hard to not give a crap about something constantly happening but you have to.

This can be easily proven as wrong, maybe you are thinking of social anxiety? This is wrong because shown areas of damage to the cerebellum cause uncontrollable vertigo, stroke victims to this area can NOT consciously or subconsciously control their vertigo, or their anxiety. There are parts of the brain that regulate these things, If they are missing, they cannot function.

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Its a good idea, thats for sure. I will say though that under the circumstances of altered gene expression, how and/or why would there be varying levels of recovery? If a gene is silenced, then it will stay that way, and no changes would occur there after, so why would there be improvements in some people?

gene switches are reverseable. Studies (see the thread i linked to) show that lsd alters gene expression as part of its mechanism of intoxication, but those alterations normally reset themselves. I dont know why they would be less reversable in us than in non-hppders, but then you could ask the same for any postulated mechanism.

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The olfactory tubercle is a multi-sensory processing center due to the number of innervations going to and from other brain regions such as the amygdala, thalamus, hypothalamus, hippocampus, brain stem, auditory and visual sensory fibers, and a number of structures in the reward–arousal system as well as the olfactory cortex. Due to its many innervations from other brain regions, the olfactory tubercle is involved in merging information across the senses, such as olfactory—audition and olfactory—visual integrations, possibly in a behaviorally relevant manner. Thus damage to the olfactory tubercle is likely to affect the functionality of all these area of the brain. Examples of such disruption include changes in normal odor guided behavior, and impairments in modulating state and motivational behavior (Wesson & Wilson 2011) which are common in psychiatric disorders such as schizophrenia (Rupp et al. 2005), dementia (Murphy, Nordin & Jinich 1999) and depression (Negoias et al. 2010).

The Olfactory tubercle is directly effected by 5ht2a receptors, more proof that there may be some form of brain damage.

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This is Qaiphyx's Topic. Since this is his topic, the goal is to cure visual snow, photosensitivity and anxiety related to past drug use. This is the main center of interest for his topic: 5HT2A Receptors. Secondary points of interest are: Glutamate & GABA.


The Nature of Receptor regulation

Cells can increase (upregulate) or decrease (downregulate) the number of receptors to a given hormone or neurotransmitter to alter its sensitivity to this molecule. This is a locally acting feedback mechanism.


Receptor Creation and Recycling

After the receptor and ligand unite, they enter the cell packaged in a container called a vesicle, which delivers them to an even larger container inside the cell called an endosome. From the endosome, receptors can take one of three routes: they can travel to the lysosome and be degraded; travel to the Golgi apparatus and be processed; or the receptor can separate from its ligand and recycle back to the cell membrane via a finger-like offshoot called a tubule.
Some receptors, like nutrient receptors, are recycled back to the cell membrane very quickly through a continuous and unregulated process called bulk recycling. In the case of signaling receptors, researchers noticed that they seemed to recycle at a slower rate and in a more regulated manner. The signaling receptors took minutes to return to the cell surface, indicating that they might not be following the same bulk pathway as other classes of receptors. [http://www.scienceda...1222112110.htm]

Edit:  please allow this as fair use:  http://www.sciencedaily.com/releases/2010/12/101222112110.htm

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Long-Term 5HT2A Receptor Dys-regulation and Paradoxical Feedback

A striking observation that has arisen through studies on 5-HT2A receptor levels is that chronic application of agonists like DOI, 5-HT and LSD, as well as antagonists like mianserin, ketanserin, and pipamperone, cause down-regulation of the receptor. The biochemical mechanisms behind this “paradoxical regulation” of the 5-HT2A receptor are unknown. Agonist-induced long-term regulation has been examined in numerous studies. In vitro studies report variable results depending on the cell type used with up-regulation shown in MDCK cells, no difference observed in NIH 3T3 cells, and down-regulation in AtT-20 cells [125]. In vivo studies, on the other hand, have consistently reported receptor down-regulation on chronic agonist application [116,126,127].
With the exception of SR 46349B, all currently available 5-HT2A antagonists cause down-regulation of the receptor. It is postulated that antagonist-mediated 5-HT2A receptor down-regulation is brought about by receptor internalization followed by lysosomal degradation of internalized receptors. It has also been suggested that this down-regulation may be the way that antipsychotics wield their therapeutic effect [60,80].
["]http://www.ncbi.nlm....books/NBK1853/]     [For educational purposes we ask for the ability to fair use of information TY:    http://books.google.com/books?id=8c2AFRTQZUwC&pg=PA124&lpg=PA124&dq=%22postulated+that+antagonist-mediated+5-HT2A+receptor+down-regulation+is+brought+about+by+receptor+internalization+followed+by+lysosomal+degradation+of+internalized%22&source=bl&ots=Dhmxa-grP8&sig=P2K9LcwBW5MI56z8fvMqny-p--Q&hl=en&sa=X&ei=XN7rU_GBOYO_sQSIyIGIBQ&ved=0CB0Q6AEwAA#v=onepage&q=%22postulated%20that%20antagonist-mediated%205-HT2A%20receptor%20down-regulation%20is%20brought%20about%20by%20receptor%20internalization%20followed%20by%20lysosomal%20degradation%20of%20internalized%22&f=false

GABA Synthesis

GABA does not penetrate the blood–brain barrier; it is synthesized in the brain. It is synthesized from glutamate using the enzyme L-glutamic acid decarboxylase and pyridoxal phosphate (which is the active form of vitamin B6) as a cofactor via a metabolic pathway called the GABA shunt. This process converts glutamate, the principal excitatory neurotransmitter, into the principal inhibitory neurotransmitter (GABA).[33][34] [http://en.wikipedia.org/wiki/Gamma-Aminobutyric_acid]

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