Bit of an idea for possible CURE. Has some weight to it.

[Guest]

Anyone ever thought of starting a Facebook group page to raise awareness and invite research scientists that have actually published data regarding HPPD? Might speed things along.

[Guest]

Maybe make it a closed group by invite only and get these great minds together to solve this problem.

Just a thought.

Maybe get David in on this.

[Guest]

Because as gifted as some of us may be, I don't think anyone here has a a phd nor the connections to apply for grants and do studies. Sourcing the professionals who have already done studies and getting them in their own forum, a think tank if you will, should be the way to go.

[Guest]

I feel like we are no different than a dig chasing its own tail. Wonder if these published HPPD researchers even know about the HPPD grant..

[mgrade]

I've been talking to some doctor friends and they think i have the potential to research with a team for the treatment for HPPD. We just need a trusted PhD or master's/phd student who would be willing to work with us. I think that everybody should participate in the study, one way or another (while i am interested in everybody's story/symptoms/drug reactions). I think the idea is to figure out what the study will be.

We can outline an abstract and so we will have more progress to present for our future dealings. What do you think, hope?

(p.s. don't any phd.s have hppd?)

[mgrade]

There is a new discovery i have made (it has definitely been known but i just learned it recently for myself).

CRH--> ACTH---->Cortisol---->

When cortisol re-enters the brain, there are cortisol-receptors in the hippocampus that when enough of the cortisol has been bound to these receptors, it signals to stop producing CRH. Excess cortisol also causes weakening of the CA3 region of the hippocampus and inhibits the dentate gyrus from growing new brain cells (one of the only places this is done in the brain). There is also something about glucose and glutamate (where they play a definite role). But people with PTSD and anxiety disorders, a lot of them have issues with the hippocampus: whether its dead cells, smaller hippocampus, abnormalities, etc. This i think is the way a lot of these people (us included) have DP and anxiety. I'll see if i can find a treatment. Hold tight.

[mgrade]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/ <--article

Click on image to zoom

[/center]

[mgrade]

^ ^ ^ ^ ^

I think the true way to treat anxiety and DP from HPPD is to treat as if the problem is Cushing's disease (until the hippocampus is less atrophied).

http://www.biologicalpsychiatryjournal.com/article/S0006-3223(99)00203-6/abstract

[zukov]

mgrade: i have something to report about cortisol ... I was sick last week and i consume for several days 4mg of vitamin c (every day). Once cured the cold I kept doing it and notice a big difference, emotionally (less anxiety) and some visual (now I see only one moon!, when i looked before 1 1/2! Sunsets also looks better: D ).

The only explanation (i think) is the large amounts of vitamin C that I take in the morning (along with omega 3 and glutamine) lower down some cortisol levels. Also, my dose of klonopin isnt change and is the only med i take.

By the way, very interesting your last theory

[mgrade]

Sound good...........Vitamin C is very "anti-oxidant". It makes sense. Omega 3 also. Lowering cortisol a bit makes some sense too. I think it has to do with preventing the degradation of the nerve/brain's "insulation", partly. By doing this it reduces stress some.

[Fawkinchit]

Hey guys i'm still here but don't have internet or much time due to work.

Hope - you don't HAVE to have a phd, right there you already failed in curing this, they have a brain, you have a brain, what's the difference? They've spent more time researching.

As for now the problem is somewhere in the CNS, we need to research everything about the CNS

[mgrade]

qaiphyx, you're back. We missd you.

[mgrade]

Lately, I have been interested in the actions of 5HT2b and 5HT3 (also 5HT1a) receptors. But i have been interested in Orexins (hypocretin) and Raphe Serotonin Neurons. I have been looking at drugs like Lisuride, Ramosetron, indazoles, indoles, carbazoles, and even the drug pergoglide <which may totally be bad> but not necessarily these drugs but perhaps drugs that do the exact opposite (orjust for me to understand the connections between 2 different systems). Orexin inhibitors seem interesting. Maybe SK channel blockers or enhancers. I ended back at CRF receptor antagonists. I am also interested in how these drug/potential actions help

RC chemical-induced HPPD (esp. 2cB and DOB). But I need somebody's help to connect the dots; I'm having some trouble.

[mgrade]

Here is evidence: I feel i am getting closer to a treatment for something, if not HPPD.

http://www.jneurosci...17/14/5591.full

http://jn.physiology.../85/5/2224.full

http://www.jneurosci...20/20/7728.full

http://www.jneurosci...22/20/8850.full

http://www.ncbi.nlm....les/PMC1279673/

http://ebm.rsmjourna.../226/5/468.full

http://www.mendeley....rgic-neurons-1/

http://www.cnsspectr...?articleid=1581

http://en.wikipedia...._adipose_tissue

http://en.wikipedia.org/wiki/5-HT3_receptor

http://en.wikipedia.org/wiki/5-HT2B_receptor

[morbide]

If i wouldn't work 12 hour shifts then i would have the energy to understand what you are saying, I barely get anything but i love you guys for doing so well! I feel like an annoying mosquito not being able to help...

[mgrade]

You don't have to force yourself to try to understand everything, but look at the last 2 links and scroll down a bit and see how these receptors can effect different parts of the body, different systems in the body. A lot of cures/treatments have been found by accident or when treating for other diseases.

***Also take note: In most cases, aside from "classic" examples, papers and/or studies that have been published in the field of neurochemistry 5 or more years ago are usually outdated or a dead-end.

[mgrade]

1. I have been looking into Imitrex and Zantac together with NSAIDs as a treatment. [deceptively simple].

2. Also as much as i don't want to say it, Seroquel.

It's used for sleep; it's an antihistimine. It's taken at night when it has antagonist works across the board.

But in the morning, it has basically metabolized into a NRI.

[homeopathic dose].

[Gmo]

I'm no scientist or anything but I have a question regarding all these theories you guys have. If HPPD/DP/DR are a result of some sort of chemical imbalance, structural change to the brain, down regulation of some particular receptor or any of the other theories that were mentioned......then how is it that people often find themselves getting hit with symptoms weeks or months or in some instances years after ingesting hallucinogens???? I'm not trying to be negative or say you guys are wrong or anything, I'm just genuinely curious. If these issues really were a result of some sort of physical brain issue then wouldn't the symptoms manifest at least within a few days, if not instantly???? I just know for me personally I had very very minor visual disturbances initially that gradually worsened even though I quit all my psychedelic usage, with the exception of one ecstasy experience, so it's hard for me to understand why it would take so long for the symptoms to really hit if they're a result of physical brain abnormalities due to drug use whenever, at that point, I had stopped my drug use. DP was the same way, I didn't get hit with it till like 6 months down the road.

[mgrade]

I had a revelation when i was stricken with intense persistant hallucinations, dp, and anxiety/panic. Even if there is an issue that seems purely psychological, environmental, or caused by intangible external stimuli: essentially the result influences the brain and body on a physical level.

For instance, stress can cause physical symptoms, genetic changes, illness, shorter life; even if the stress is primarily mental or psychological.

Another thing that i realized is that there maybe a lag period from doing the drug and the onset of the disorder. This is similar to the theory that "for every day you miss, it will take 2 days of practice to get back to the level you were at". It's also the "tough guy" syndrome------like if you take a hard fall in public----and you think you are ok----you say i'm fine, it's nothing, i;m no wuss,it's ok, i'll walk it off. Then you realize wow--my ankle kind of hurts. And i kind of hit my head pretty hard. The next day you feel like you feel bad but you think you will be fine. A few days later you say man i think i broke a little bone in my foot. And I think i was concussed; but i should get better soon. Then two weeks later you say you think you got some brain damage from the fall. Then a month later you might find it a little hard to concentrate. The farther you get away from the high cognitive functioning, the more your "compromised self" becomes a reality. And the "measuring standard" begins to drop lower and lower. ....And at some point you realize that you have lost a function or a skill or part of your senses or a feeling of wellbeing, this brings about shock, fear, panic and regret, and a feedback loop for anxiety, dp, and depression. By 3 months, it is revealed that you may be damaged permanently.

--Plus a lot of these drugs such as Ecstasy, PCP, 2cx, Nitrous, etc., the effects may INCLUDE anxiety and dissociation/DP.

............Another way of looking at things would be to say that this disorder is a pure phenomenon. .....

[VisualDude]

I was thinking that maybe these very potent agonist of the 5ht2a receptors cause such an extreme push that things become out of balance

"extreme push" is the problem. Drugs (or whatever) pushed things so they operate different now. Many, many interactions, feedback loops, feedforward loops, changed synapsis, and in some cases ‘burnt’ circuits.

So the solution is complex. Largely it relies on the body healing itself and us doing what we can to help the process.

Ok so has anyone tried to take dopamine aaand seratonin at the same time. Would there be a way to get seratonin binding again

Yes. For me they both weaken each other … which isn’t so bad

That could also mean because most hppdrrs have past anxiety or depression issies ( ie naturally low seratonin ) the seratonin receptors could be turned off totally

Anxiety and/or depression issues make one move vulnerable for brain disorders. However depression isn’t simply low serotonin. In my case doctors say I’ve had plenty serotonin my whole life … it is low dopamine that is the problem.

wait, did our serotonin receptors get permanently worse or better? My guess would be that they got permanently worse, in which case the 5-ht2a antagonist would help. i always got the impression that more serotonin = worse HPPD (ie: ssris making hppd worse)

The whole system is out of balance … not just one type or subtype. Dr A’s study showed a class of individuals who clearly have dopamine problems causing symptoms. Yet a large number (50% ?) had no response to increasing dopamine.

Some meds such as MAOI increase many neurotransmitter. Tricyclic antidepressants are called ‘dirty’ because they affect so many things. Again, cocaine and LSD affect several types.

Have any of u guys, visual in particular thought about applying for the grant? I would fully support that movement

Sorry, what is this grant? [ Note: I heard the ‘Joker’ in Colorado had a grant ]

So it could have overexcited the neurons and for some reason they are stuck in this state, or something may have been damaged from the overexcitation

"Disinhibition" is the word used … on a system-wide basis the brain is overactive. In some cases, reduced/corrupt info from the retina will cause the brain to overwork and cause some of our symptoms.

… Synaptic overstimulation can be as detrimental as understimulation. Cocaine, for example, interferes with the synaptic reuptake of the neurotransmitters dopamine, norepinephrine and serotonin, leading to an excessive amount of dopamine in the synaptic cleft …

Ironically, some receptors are inverse, thus the over-abundance caused by cocaine actually reduces activity down some paths. For example, D2, D3, D4 are inverse (reduce activity such as typically seen in GABA connections).

Wheres visual at when u need him

after the forum dies a few weeks, I got busy elsewhere … mini vacation. Just found this thread today.

Looks like lots of excitement – which is good.

You said you are going to reduce cheese. Any affect?

We CAN fix this if we all work together and pitch in with ideas and stay focused …

Yes, much can be done. And we don’t have to put all our hopes in ‘big business’. But time, effort, trials, and life style changes are likely.

　

This thread is massive. With 120 posts so far, I’m worn out trying to read it ( overactive brain ? )

A lot has been discussed on the neurotransmitter level. But it also is good to remember that huge systems are involved. We need to look at systems as much as molecules.

Will have to leave it there at the moment…

[mgrade]

What are your symptoms to make you believe your problem is reduced concentration of dopamine?

Do you feel you are coming down with a little of the ADD ?

*I don't believe in the "push/pull" model of transmission (except if you are talking about resistance in term of ohms, or conductance)

K (more resistance) ------Ca (less resistance)

One observance is: It seems though that Ca seems to bring about more K

[mgrade]

Today: I am looking into ion channels, electrophysiological resistance/conductivity,

cellular and synaptic pH, and drugs often used in ER and/or hospitals.

Drugs like atropine, quinidine, valium IV, epinephrine, etc. .............quinidine is a K+ blocker

........hold on I gotta eat........i'll be back in a little bit

[VisualDude]

What are your symptoms to make you believe your problem is reduced concentration of dopamine?

Do you feel you are coming down with a little of the ADD ?

It grabbed my attention when reading the cognitive problems on advanced parkinson's. Then looking at 43 other neurological diseases (including MS), only PD had relevance. Of course the clincher has been the response to dopamine increasing meds. For example, contrast adjustment is done in the retina via dopaminergic neurons. Contrast problems were among the first symptoms. Some (in not all) negative afterimaging is due to 'recharge' time of photoreceptors coupled with the dopaminergic neurons 'deciding' how much of the signal is relevant.

As for ADD, always had problems multitasking but was able to bury self with extreme focus on the topic/job at hand. Now am vulnerable to the slightest distraction as well as vulnerable to complete exhaustion.

I don't believe in the "push/pull" model of transmission

Please explain. As the opening of this thread began, "Everything in our universe is quite simple, Push/pull concept, up down black white red blue north pole south pole day night sun black hole etc etc etc... "

ALL neuronal communication is pulses of electricity (due to the accumulation of ions through synapses). A neuron is just an integrator (add/subtract machine) that fires when the sum reaches a certain level (action potential) of about -55 millivolts.

There are two main types of neuronal communication responses. Klonic (continuous firing) which exists in a push/pull balance in larger circuits. And Phasic (one shot) that fires due to change of stimulus.

Brain wave are simply the rhythmic patterns of feedback systems (push-pull). In electronics you may be familiar with "phase-lock loops" ... same kind of thing.

Dopaminergic systems are often described as controlling "signal-to-noise ratio". This controls the relevance of information passing through. D1 family receptors activate [push] (like glutamate and often on glutamate neurons). D2 family receptors deactivate [pull] passing signals (like GABA). So, in short, dopaminergic neurons filter and decide what to pay attention too. So you can see how this affects movement and perceptions. Decisions are affected too but more the ability to make them rather than how conclusions are derived.

These systems are 'little programs' that form and operate at the unconscious decision level - such as how to grab a glass of water and drink it. And much is learned over time - watch an infant learn to grab and control fingers ... or a musician learn to play a piece. Much fine tuned coordination is through the Cerebellum which is not dopamine dominant but has some http://www.ncbi.nlm....pubmed/16035192

ADD/ADHD is often blamed on norephinephrine as well as dopamine. Norepinephrine is mainly used in the locus coeruleus (90%). These two blue dots are big switching centers for what parts of the brain are dominant. The 3 main modes are: sleep, vigilance and concentration. However the locus coeruleus is controlled by the front part of the brain thus more of a relay station. But again this system is measured by pulse rates and patterns - push/pull.

So unlike dopaminergic circuits which are at lower level functions, this center controls what parts of your thinking is dominant ... huge systems. When you think about it, vigilance is a type of attention ... not concentration but hyperawareness (is there a tiger behind those trees? ...)

The development and use of SNRIs is largely experimental ... "Let's see what happens when we change these chemical concentrations ..." And of course it does change the balance of certain systems.

At any rate, you can see how anything that affects dopamine and/or norepinephrine could have profound effects. While HPPD is largely described as cerebral disinhibition (and thus GABA/benzo help to quiet it), dopamine may also quiet overactivity by fueling the system to regain control of itself -- if low fuel is a factor. Or to filter out noise that the brain is trying to make sense out of.

[mgrade]

The pigmented nuclei are the locus coeruleus, substantia nigra etc. While a lot of norepinephrine is created in the locus c., it can also be created by dopamine that is being recycled.

The locus c. takes signals from the emotional centers and turns them into noradrenaline.

You can refer to things as "push/pull", but i believe for most of us that conjures up the image of a tug-o'-war battle. A lot of what you are talking about is polarization, depolarization, and repolarization, and small changes in the conductance of synapses derived from the regulation of the ion channels.

The brain and/or body system is more like constantly moving mechanics: clockwork and cascading events. Of course, there are drawbridges and doors and couriers and guards (to add to the tug-o'-war Nottingham imagery).

But there are so many receptors of all different kinds (some more viable in certain localized areas in the brain), it is hard to offer a practical model considering for physical symptoms and selective neuroreceptor actions.

While things can be binary (1s and 0s, Yes and No, etc.), there are grey areas and states of equilibrium in which they are not being held together by 2 opposite forces, like a tightrope walker.

It's like trying to explain the complexity and phenomenology of biology or life in terms of the Hubble Ultra Deep Space models. And it takes your own phenomenological existence to perceive these concepts.

[mgrade]

How do you explain GABA action which mediates in the synapse?

And how does that related to the tug-o'-war model aside from the result of an event being a plus (+) and 1 of possibly many different results being a minus (-) ?