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yosoydiego

HPPD is NOT Serotonergic in nature

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I should add the prefix to the subject: "Why I think that", but it would be too long. Consider it added. I'll elaborate some points and quote some sources, but note that many more sources can be found, the conclusion is not based on these sources only.

 

Note that I'll make a conceptual leap: since basically nothing can be said about HPPD due to lack of research and data, I'll treat it as some form of psychosis/schizophrenia, which is widely studied (although not understood anyway), and REMARKABLY similar to HPPD. At the very least, it could be said that HPPD is a mild form of psychosis/schizophrenia, a subset, etc, but it seems very logical to assume that they will share many  characteristics. See second link, about Drug Induced Psychosis

 

 

- The causes of schizophrenia are not understood, and many hypothesis have been proposed, notably: serotonergic causes, dopaminergic causes, and glutamate causes.

While the sertonergic idea is the older, newer studies point in other directions, mainly of stimulatory nature

https://link.springer.com/chapter/10.1007/978-1-4684-8228-7_17

https://www.researchgate.net/publication/314031343_Drug_Abuse_and_Psychosis_New_Insights_into_Drug-induced_Psychosis

 

- Recent studies have indicated the importance of the Dopaminergic system in the effects of LSD, distinguishing between phases of the LSD effects according to the main receptors activated, and proposing as a model for schizophrenia.

https://www.ncbi.nlm.nih.gov/m/pubmed/21352832

https://www.ncbi.nlm.nih.gov/pubmed/15723230

 

- While sertonergic system is mainly associated with mood (depression, anti-depressants), the Glutamate system is more related with the information processing and memory formation.

 

- The relationship between dopamine and glutamate is deep, and many studies are studying their link to each other, and to psychosis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162342/

https://www.ncbi.nlm.nih.gov/pubmed/24524997

https://www.nature.com/articles/s41398-017-0071-9

 

- Going back to David Nichols study about the 2 different phases (sertonergic and dopaminergic) phases of LSD, and comparing that to the description of HPPD, seems clear that HPPD seems more "phase 2". It's usually describe as "the last part of an LSD trip"

 

- For drugs or situations that are well known to trigger or worsen HPPD according to the community, it can be found that they act on the dopamine/glutamate system, but NOT (or barely) on the sertonergic system.
-- coffee

-- stress

-- cocaine

 

- The inverse argument can be seen also: drugs that act directly on the serotonergic system, usually have little effect on HPPD, or make it even worse. Example: anti-depressants (SSRI). Also, the same drugs are not known to cause HPPD.

 

- Of the drugs that have consistently shown usefulness for the HPPD community, 2 of the 4 target the Glutamate system

https://www.reddit.com/r/HPPD/comments/aqzv06/lions_manenaccholinemagnesium/

 

- Some HPPD sufferers are experimenting with Ketamine, with good results. Ketamine's main method of action is through the Glutamate system, not serotonin.

 

- Regarding stress being a trigger for HPPD, the relationship between cortisol and glutamate and PTSD has been already treated, in this example, by no less than David Nutt, one of the most world renowned scientists regarding drugs:

https://www.ncbi.nlm.nih.gov/pubmed/18701640

 

- More about the relationship of psychedelics, anti-psychotics, and 5HT2A and Glutamate receptors can be seen here:

http://blogs.discovermagazine.com/neuroskeptic/2011/12/03/a-psychedelic-tale-of-two-neurotransmitters/#.XaWgWHj5WHs

- More on the relationship of excess glutamate in the PFC and schizophrenia:
 
- Chronic LSD, schizophrenia, glutamate, etc:
 

In sum, for all of the above, I believe it's pretty clear that HPPD has way bigger chances of being glutamate related, than serotonin related.

 

I could also keep going on a bit more about in the hypothesis, but I'll leave that for a follow up text.

 

Looking forward to reading all opinions.

 

Cheers!

Edited by yosoydiego

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I think that most probably HPPD has, just as some other psychologic diseases, no exact common etiology. Causes, onset, symptoms, courses, medications that help are so distinct and individual. All etiology studies regarding HPPD are highly speculative and do basically admit that they don't know what they're talking about. For me it seems like the brain is a chaotic system and when it gets the right push at the right time, it somehow develops towards a different attractor.

It's so complex, everything is connected. And our understanding of the brain is so rudimentary. I'm quite sure that there will never be the one solution, the one etiology, the one medication that cures most people. At least not in my lifetime. With cure I don't mean that people somehow find a way to live a good live with reduced symptoms, with cure I mean you feel >= 100% as comfortable as before the HPPD and you have 0% remaining symptoms.

Just take a look at depression. There is so much research about it, but in the end therapies are still very limited. In heavy cases, people still just try one medication after another and if they have luck, they finally find one which helps. In mild cases, people just wait and for most it subsides somehow. Psychotherapy can help, but often isn't a cure. Even if we'd put 100 million dollars to HPPD research, I think that we would surely have a number of small successes, but still wouldn't have anything close to a major breakthrough in the fields of etiology and therapy options.

Edited by AlphaBeta

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22 hours ago, AlphaBeta said:

I'm quite sure that there will never be the one solution, the one etiology, the one medication that cures most people. At least not in my lifetime.

At the rate that technology and medicine advances, I wouldn't say that unless I was 60+ years old....

I don't know how old you are, of course :)

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I agree. If no research is done which is very much the case now then no breakthroughs are to be expected. www.neurogroup.org is going to fix this problem...

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2 minutes ago, hope1 said:

I agree. If no research is done which is very much the case now then no breakthroughs are to be expected. www.neurogroup.org is going to fix this problem...

Research doesn't work that way, is not that straightforward...

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This not schizophrenia or psychosis. It is more akin to a drug induced form of acquired epilepsy due to glutamate overload from psychedelics...

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Name dropping guys like Nichols who gives a damn about us doesn’t score you any points here my friend. Research on this condition is anecdotal. No major attempt at fully elucidating this condition has EVER been performed. Dr. Harry McConnell is going to do what Nutt and Nichols refuse to because they’re all about legalizing psychedelics without any care or consequence should something go wrong as in HPPD!

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In fact, according The the research protocol Dr. McConnell has drafted for HPPD, he believes this condition is reversible! This is not some quack but a distinguished Neuropsychiatrist who is working with PhD that are brilliant and want to help unlike Nutt and Nichols! They’d sooner write us all off instead of helping!

 

Screw them! 

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5 hours ago, yosoydiego said:

At the rate that technology and medicine advances, I wouldn't say that unless I was 60+ years old.... 

I don't know how old you are, of course :)

I didn't say that medicine won't advance, I did say there won't be the one solution. Surely in 40 years HPPD therapy options will be better than today. But I'm very sure that it won't be like "HPPD is an up-regulation of THIS receptor and when you get THAT medicine, it'll cure within 3 months". As I said, just take look at depression. Are the therapy options better than 1980? For sure. Did we have a major breakthrough, a one and only solution what in the brain exactly causes depression and how to fix it? By far, no. So much research was done about it, and we still just can give some relief and help people to cope in most cases, but the cure is mostly still up to mother nature. And I think it'll be similar with HPPD in 40 years.

Yes, medicine did advance. But we're far, far away from an utopy. Damn, we can't even cure a simple cold.

5 hours ago, hope1 said:

I agree. If no research is done which is very much the case now then no breakthroughs are to be expected.

100% true, I didn't say that there should be no research. As I said, I just don't expect big breakthroughs in the fields of etiology and therapy options. Anyhow, I think with relatively few resources some very significant other questions could be answered by research. E.g. questions like: How big is the risk to get HPPD? How long does HPPD usually last? What are consumption patterns that can prevent HPPD with a very high probability? Which medication is helping the best, statistically? Under which conditions does it make sense to start the medical therapy? ...

Edited by AlphaBeta
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29 minutes ago, hope1 said:

All of which are good questions but first an assessment of where the damage to the brain has occurred.  

Believe me, that's not the right approach. You won't find the one damage. As I said, depression research has (and will always have) so much more resources and they didn't find "the damage". Or take a look at epilepsy. Much research about it, they didn't find "the damage". All explanations are very rudimentary and do not play a significant role during treatment. Our understanding of the brain and human consciousness is too basic, it's too early. It's like you're trying to build an airplane though you didn't even invent a hammer yet.

HPPD research is resource-limited. It should focus on the easy questions instead of wasting resources with the hard ones that we can only really answer with a toolset that we don't have yet.

 

 

Edited by AlphaBeta
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You don’t know that I’m fact unless you have a PhD attached to your name you don’t know anything. The dysregulation between excitory and inhibitory Interneurons is found in epilepsy as well as other neurotypical diseases like autism.  It is theorized that the glutamate overload in psychedelics affects the neurocoherence of the brain in a similar manner. That’s the beauty of neurological disease; they each have their own flavor. Again, none of this matters without research being conducted. You are telling us to give up without even trying. Another pro psychedelic pawn trying to sweep as under the rug to make way for a for profit renaissance without any regard or plan to address anyone harmed by psychedelics. I’d kick your ass if ever we met you life life piece of shit.

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11 hours ago, hope1 said:

You are telling us to give up without even trying.

No. I'm just telling that etiology research won't bring fast results and the ratio between costs and output / relevance for clinical practice is bad. When you put the money on more easy questions that are also not even answered yet, you'll have more results in less time and also have more improvement for HPPD patients and hallucinogen drug consumers. Also, the more information you have in general about the disease, the easier etiology research gets. That's why I say, it's too early to search for the cause, because we e.g. don't even know the prevalence and miss some general data like maybe some pre-existing conditions which encourage HPPD or effectiveness of currently used medications. As soon as we have all the basic data, sure we can also put focus on etiology research.

As I said, when you're trying to build an airplane without even having a hammer yet, you'll fail. That's why you should focus to get the hammer now instead of getting stuck with dreaming of an airplane. Otherwise your dream will never come true.

Edited by AlphaBeta
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There been research on this condition since the 1960’s. Dr. Henry Abraham spent four decades researching this disorder. Your suggestions are basically bullshit. Get out of the way, stop discouraging us while we take things to the next level. If Dr. McConnell didn’t think his research protocol wouldn’t reveal something, it wouldn’t be done.

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10 hours ago, hope1 said:

Dr. Henry Abraham spent four decades researching this disorder.

And still, we have just highly speculative numbers of prevalence and not much more than a bunch of case reports. This doesn't mean Abraham's work did not matter. In fact it's really important and a big part of what we currently know. But still, there are many basic question which are not answered with the necessary confidence yet.

10 hours ago, hope1 said:

Get out of the way, stop discouraging us while we take things to the next level. If Dr. McConnell didn’t think his research protocol wouldn’t reveal something, it wouldn’t be done. 

I don't want to discourage anyone. In the end we want the same thing. Being hopeful and positive is always good. I'm just a realistic and skeptical guy. Also, I'm an engineer. I always concentrate on problems that can be solved in the near future.

Edited by AlphaBeta
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Haven't read the post just figure I blurt an answer. Glutamate function is suggested I figure glumate because it sounds like the brains main voltage system if that makes sense.

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Has anyone thought about trying to get an FMRI? I asked a doctor to help get me one but he said good luck finding an insurance company that will pay for it. I've also tried to get neuropsychological evaluation. I think you can get a whole bunch of tests that gauge your working memory, attention. verbal fluency, all sorts of stuff to assess your overall cognitive capacity. I was told that's only give to people if they have severe enough brain trauma by the same doctor.

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Nobody gives a shit because HPPD is not part of any social or scientific dialogue especially coming from researchers like Nutt and Nichols who are actively engaged in psychedelic drug research. They won’t lift a fucking finger to do an FMRI much less ANYTHING else to help us!

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