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


Fawkinchit

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A good question to ask there is what are the effects of down/up regulations of 5ht2a receptors?

Mainly is what this is showing is that receptor sites will minimize to counter the use of hallucinogens, however after a short time period the synapses will replace the receptors after agonist usage is discontinued.

Everything seems to be pointing to specific localized 5ht2a rich neuronal apoptosis.

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I do not believe that necessarily. I think there are less post-synaptic 5ht2A receptors in HPPD.

[for longer than average terms]

[Note: There may be:

"more Glutamate receptors/less GABA receptors." also]

Do some research on ssris and 5ht receptor down regulation, its very common and always reverts back to the norm after ssri use discontinued.

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SSRIs work mainly with inhibiting the reuptake duct

[hence the name Selective Serotonin Reuptake Inhibitor].

The actual SSRI chemicals do not bind to 5HT2a receptors.

"Paradoxical Regulation" of 5HT2a is relegated to agonists, antagonists, inverse agonists, etc.

SSRIs [in general] do not agonize, antagonize, etc. 5HT2a receptors.

Show me the evidence for your claims.

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SSRIs work mainly with inhibiting the reuptake duct

[hence the name Selective Serotonin Reuptake Inhibitor].

The actual SSRI chemicals do not bind to 5HT2a receptors.

"Paradoxical Regulation" of 5HT2a is relegated to agonists, antagonists, inverse agonists, etc.

SSRIs [in general] do not agonize, antagonize, etc. 5HT2a receptors.

Show me the evidence for your claims.

Regardless of their action, they still down regulate 5ht receptors, all receptors in regards to down/up regulating act in the same manner.

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This is why i think anti-psychotics work half-assed for the serotonin system. If you antagonize the 5HT receptors, there is still down-regulation of 5HT receptors & "down-regulation" of 5HT (serotonin levels).

Then you have to start piling on more drugs to get a balance; so you must tread lightly with overlapping actions of different drugs.

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Mr. Qaiphyx:

I would like to get people like Visual and David Kozin to affirm my statement: to see if what i am saying is valid.

The truth of the matter is: I do not know for sure. Our main focus, here, is the 5ht2a receptor.

I will make an effort to not make any tangential leaps, and concentrate my posts to these focuses.

-mg

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Mr. Qaiphyx:

I would like to get people like Visual and David Kozin to affirm my statement: to see if what i am saying is valid.

The truth of the matter is: I do not know for sure. Our main focus, here, is the 5ht2a receptor.

I will make an effort to not make any tangential leaps, and concentrate my posts to these focuses.

-mg

I agree, thats what this is about, making connections, and our first connection is the 5ht2a receptor.

I dont think that will we be able to definitely prove a solid diagnosis for this but I believe that we can deduce to the most reasonable and probable cause. Something should make the most sense. So we need to just get ideas and make deductions based on those ideas, ideas made through connections.

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D1s [D1 + D5], D2s [such as D4, D3, D2], and 5HT1a, 2c, 2b. Circadian Rhythm problems, dehydration, regular illnesses, Antibiotics [such as Cipro], sleep apnea, prescription drugs [such a Halcion] can all cause hallucinations. I'm not sure you have the information to validate the causes for those actions.

While 5HT2a may be the focus, then why are selective 5HT2a drugs generally less effective than non-selective counterparts?

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Glutamate Receptors

Depressed NMDA receptor function is associated with an array of negative symptoms. For example, NMDA receptor hypofunction that occurs as the brain ages may be partially responsible for memory deficits associated with aging.[5] Schizophrenia may also have to do with irregular NMDA receptor function (the glutamate hypothesis of schizophrenia).[6]Increased levels of another NMDA antagonist, kynurenic acid, may aggravate the symptoms of schizophrenia, according to the "kynurenic hypothesis".[7]NMDA receptor antagonists can mimic these problems; they sometimes induce "psychotomimetic" side effects, symptoms resembling psychosis.[8]Such side effects caused by NMDA receptor inhibitors include hallucinations,paranoid delusions, confusion, difficulty concentrating, agitation, alterations in mood, nightmares,[9] catatonia,[10] ataxia,[11] anaesthesia,[12] andlearning and memory deficits.[13]

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  • 3 weeks later...
  • 3 weeks later...

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.

The 5ht2a sites on the inhibitory interneurons should trigger an inhibitory response down"stream" from them. This is part of Dr. Abrahams hypothesis. The 5ht2a receptors on inhibitory interneurons in probably the V1 circuit have been downregulated or altered so they no longer respond and the resulting inhibitory response ceases to exist thus resulting in altered perception like similar visual disturbances seen on hallucinogenic drugs.

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A whole bunch of parts of the brain are interconnected; so it is not just one part that works, to provide us with consciousness.

My guess is that the cortex, frontal/prefrontal cortexes, sensory cortexes, etc plays a direct part. Maybe even raphe neurons.

It seems like the same things are at play here: serotonin, dopamine, and glutamate.

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Binding Affinities for LSD

LSDaffinities.GIF

Summary

VERY IMPORTANT TO NOTE WHEN VIEWING THIS GRAPH: Ki Values are reported in such a way that the lower the number is, the higher affinity the structure has for the receptor. This means that the LOW values on the graph are the relevant information NOT the taller bars.

I created this file from public source data (http://pdsp.cwru.edu/pdsp.php). The black horizontal line represents the plasma level of LSD in humans during recreational use (Aghajanian & Bing, (1964) Clin. Pharmacol. Ther. 5, 611-614) and hence receptors which LSD has an affinity for above the line are unlikely to be affected by recreational LSD doses.

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Ok, interesting. Also, LSD is an agonist right??? So, wouldn't all these issues we experience possibly be a result of either down regulation or prolonged excitation of these particular receptors?? And I know I'm really over simplifying all of this, but I'm just trying to get a basic understanding of what might be going on.

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The psychedelic effects of LSD are attributed to its strongpartial agonist effects at 5-HT2A receptors as specific 5-HT2Aagonists are psychedelics and largely 5-HT2A specific antagonistsblock the psychedelic activity of LSD.[79] Exactly how this produces the drug's effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex and therefore excitation in this area, specifically in layers IV and V.

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I'd like to point out that it's very unlikely that a complex system such as the brain vision can be described by it's underlying structure alone (neurons and neurotransmissors). That is like trying to understand how Photoshop works by learning the iteration of transistors. It's a separate layer of abstraction. Learning about the vision mechanics itself is much more important, and I believe there is some good literature on that.

Have you guys ever heard of those machines used to

? While very primitive, the technology works. Maybe we could research about that tech, in order to find how it was implemented and what kind of studies it is based on. Whatever they are, they certainly do contain very useful information.

Not sure the community will agree with that, but, if anyone does, please do that for us. Anyone can do this. I could do it myself, but I'm too busy with work ATM.

tl;dr forget about neurotransmissors for a moment and lets find papers about the mechanics of the vision instead!

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Why I find this important: suppose, for example, that we find some research about the 'afterimages' phenomena, which describe why/how it happens, with very specific information on it's mechanics. We could, then, find out which neurons/transmissors are involved on it in order to develop specialized remedies that will selectively inhibit them, healing the problem. (This is just to illustrate the idea, not trying to be technically correct.)

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