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Hallucinogen Persisting Perception Disorder (HPPD) Support Forum
dasitmane

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

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5-HT2A receptors are found postsynaptically to serotonergic neurons, and are particularly concentrated in the frontal cortex. 5-HT2Areceptors are also found in high density in the claustrum, a region that is connected to the visual cortex, in parts of the limbic system (i.e., amygdala and hippocampus), and in the basal ganglia (Table 15-2). In the cortex, the 5-HT2Areceptor is located on local GABAergic interneurons, as well as on pyramidal projection neurons, which are known to be glutamatergic.

The amygdala is probably the area effected causing severe anxiety.

The claustrum maybe is the area effected causing visual symptoms?

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1 hour ago, dasitmane said:

I can add too that in the case of Risperodone, a 5ht2a inverse agonist, and other anti convulsion medications which are 5ht2a antagonists there is a correlation with palinopsia. Palinopsia being obviously common with HPPD, the most probable reason being, that the 5ht2a specific neurons that underwent glutamate excitotoxic apoptosis, are now gone, and therein laying a lack of 5ht2a input, which would be similar to that of these drugs, being inverse agonists and antagonists. So this gives even more credence that HPPD is caused by 5ht2a induced glutamate excitotoxic apoptosis.

So in that case maybe Chromium GTF can help

 

https://www.ncbi.nlm.nih.gov/m/pubmed/11823896/

“Chromium treatment decreases the sensitivity of 5-HT2A receptors”

Edited by danjoking

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1 hour ago, danjoking said:

So in that case maybe Chromium GTF can help

 

https://www.ncbi.nlm.nih.gov/m/pubmed/11823896/

“Chromium treatment decreases the sensitivity of 5-HT2A receptors”

I could be wrong but I think you would want increased sensitivity. In the case that I make, which could eventually turn out to be wrong but I’m sticking with it from here on out, the Axons simply are just gone, so I honestly don’t see modulating 5ht2a receptors helping very much either way. You could try it but if the axons aren’t there it will do nothing lol. 

Basically you’ll need neurogenesis, and even that may have limitations.

Edited by dasitmane

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9 hours ago, dasitmane said:

I could be wrong but I think you would want increased sensitivity. In the case that I make, which could eventually turn out to be wrong but I’m sticking with it from here on out, the Axons simply are just gone, so I honestly don’t see modulating 5ht2a receptors helping very much either way. You could try it but if the axons aren’t there it will do nothing lol. 

Basically you’ll need neurogenesis, and even that may have limitations.

Ok so i just read a few things about it when you increased sensitivity you should look here.

 

https://area1255.blogspot.co.il/2016/09/herbssupplements-to-increase-5-ht2a.html?m=1

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53 minutes ago, danjoking said:

Ok so i just read a few things about it when you increased sensitivity you should look here.

 

https://area1255.blogspot.co.il/2016/09/herbssupplements-to-increase-5-ht2a.html?m=1

My initial thought, is thats just some guys blog. I'm not saying that we should increase sensitivity, honestly I dont think 5ht2a receptors should be messed with at all. But if you wanted to counter balance serotonin neuronal loss specifically linked to 5ht2a receptors you would want to mildly increase sensitivity to attempt to make up for it, theoretically. I do not however think this would accomplish much.

Although.... Ashwaganda might actually be a good choice for anti anxiety. I have no idea if it would work though.

Also I believe that antipsychotic drugs tend towards antagonist of 5ht2a. But this is different than increasing or decreasing receptors. 

Also I think that Dr. Abraham's thoughts on interneuronal loss(I think he just states they're modified or something though) associated with GABA production is accurate as well. So increasing GABA mildly would be a good idea as well.

Edited by dasitmane

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If I understand this article right, it shows that hallucinogenic effects, are infact, just like I said directly linked to glutamate. Its super hard to understand though.

 

5-HT2A–mGluR2 Heteroreceptor Complexes

Heteroreceptor complexes between 5-HT2A and mGlu2 receptors were demonstrated in cellular models and implicated in psychosis (Gonzalez-Maeso et al., 2008). mGlu2 receptors were also shown to form heterocomplexes with 5-HT2B but not with 5-HT2C receptors (Delille et al., 2012). Three residues at the intracellular end of transmembrane four (Ala-677(4.40), Ala-681(4.44), and Ala-685(4.48)) were essential for the 5-hydroxytryptamine 2A–metabotropic glutamate 2 (5-HT2A–mGlu2) receptor heteromerization and its psychoactive behavioral function (Moreno et al., 2012). Viral-mediated overexpression in the frontal cortex of wild-type mGlu2 receptor but not of a mutant mGlu2 receptor, which cannot heteromerize with 5-HT2A, rescued the behavioral actions of LSD and other related hallucinogenic drugs in mGlu2 knockout rodents (Moreno et al., 2011, 2012).

An allosteric receptor–receptor interaction exists in this complex since mGlu2 receptor activation produces an increase in the affinity of hallucinogenic 5-HT2A agonists for the 5-HT2A protomer binding site (Gonzalez-Maeso et al., 2008). A bidirectional receptor–receptor interaction is present since 5-HT2A agonistsreduce the affinity of mGlu2 agonists for the mGlu2 protomer binding site. It is of substantial interest that the allosteric receptor–receptor interactions in these heteroreceptor complexes are dysregulated in postmortem brains from schizophrenia subjects (Moreno et al., 2012; Muguruza et al., 2013).

Subsequent work from this group suggests that the 5-HT2A–mGluR2 heteroreceptor complexes make possible a Gq–Gi balance through signaling cross talk, which could be determined by using ion channels in oocytes from Xenopusas markers for Gi/o- and Gq/11-dependent signaling (Fribourg et al., 2011). A drug-induced pattern dominated by high Gi/o signaling predicts antipsychotic potential, while a pattern dominated by high Gq signaling predicts propsychotic potential. In a recent randomized phase II clinical trial (Patil et al., 2007), it was found that an mGlu2/3 agonist prodrug improved negative and positive symptoms of schizophrenia. However, this trial has so far not been confirmed. Selective 5-HT receptor antagonists also produce therapeutic effects, but they are rather weak in contrast to the therapeutic effects of atypical antipsychotic drugs that block 5-HT2A receptors with high potency (Meltzer, 2012, 2013; Meltzer et al., 1989, 2004).

However, the biological relevance of the 5-HT2A–mGluR2 heteroreceptor complexes has been challenged since their formation inter alia does not always lead to effects on second messengers (Delille et al., 2012). Also in view of a limited colocation of 5-HT2A and mGlu2 receptors in the brain, interactions of the two signaling receptor systems through functional brain pathways independent of heteromerization probably play a significant role (Delille et al., 2013). Nevertheless, the molecular integration of the signaling in the 5-HT2A–mGluR2 heteroreceptor complexes via receptor–receptor interactions (Gonzalez-Maeso et al., 2008) remains one relevant mechanism for functional interactions according to the available evidence summarized earlier in the text. Future work will determine which of the two mechanisms operating at the molecular and network level, respectively, plays the leading role in mediating the integration of 5-HT2A and mGlu2 signaling of relevance for psychosis and its treatment.

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5 hours ago, dasitmane said:

My initial thought, is thats just some guys blog. I'm not saying that we should increase sensitivity, honestly I dont think 5ht2a receptors should be messed with at all. But if you wanted to counter balance serotonin neuronal loss specifically linked to 5ht2a receptors you would want to mildly increase sensitivity to attempt to make up for it, theoretically. I do not however think this would accomplish much.

Although.... Ashwaganda might actually be a good choice for anti anxiety. I have no idea if it would work though.

Also I believe that antipsychotic drugs tend towards antagonist of 5ht2a. But this is different than increasing or decreasing receptors. 

Also I think that Dr. Abraham's thoughts on interneuronal loss(I think he just states they're modified or something though) associated with GABA production is accurate as well. So increasing GABA mildly would be a good idea as well.

According to what you say , what can help us by your opinion to gain the best by herbs supplements 

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Every time I have more serotonin in my brain, by taking 5-HTP or MDMA for example, HPPD gets worse.

So my theory would be : less serotonin = less glutamate = less HPPD. 

Am I missing something ?

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On 4/13/2018 at 7:45 PM, dasitmane said:

I like how you apologize for you behavior, but then continue to berate me, you just cant help it can you? lmao

beats-me.gif

I was apologizing for getting sucked into a flame war with you and overreacting when I should have just ignored you. I wasn't apologizing to you.

Moving on...I'm creating a thread with my mRI results from February 2016 in the interests of science or whatever.

@David S. Kozin add it to your research if you like.

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18 minutes ago, dayum_son said:

You haven't moved on :lol:, it's been a month ago and you're still talking about it.

I felt it necessary to respond because mane was curious about my mRI. If he needs it for further research, he can use it in whatever way he likes, as can Kozin. I haven't been on the forum in a month and I'm responding to what he said. 

But thanks for butting in with your opinion which is of no consequence whatsoever.

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On 5/15/2018 at 10:58 PM, dayum_son said:

You haven't moved on :lol:, it's been a month ago and you're still talking about it.

200.gif

 

On 5/15/2018 at 9:47 PM, TheMythos said:

I was apologizing for getting sucked into a flame war with you and overreacting when I should have just ignored you. I wasn't apologizing to you.

Moving on...I'm creating a thread with my mRI results from February 2016 in the interests of science or whatever.

@David S. Kozin add it to your research if you like.

“Danjoking, you're right. I apologize for my behavior” - TheMythos

Jennifer-Lawrence-ok-thumbs-up.gif?ssl=1

Yah post it if you want, it’s beneficial to compile all information we can. To be honest though I think everything is pretty much summed up and come to an end as far as the cause of HPPD. If you haven’t read the last couple pages, it’s gone over pretty thoroughly. Not that you’ll agree.

Also please do not be rude to productive members like dayum_son. 

Edited by dasitmane
  • Upvote 1

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On 5/12/2018 at 1:59 PM, danjoking said:

According to what you say , what can help us by your opinion to gain the best by herbs supplements 

For now sedatives work just fine. Anything thats relaxing to the nervous system. GABA agonists of course, like benzos, or natural ones if you can find any. Lemon balm always helped my anxiety and I pretty much carry it with me everywhere I go. I've noticed that cowslip, which is good for sleeping, if I drink it at night the next day my anxiety is not so bad, but cowslip is hard to find so its not the best choice really. 

As for visuals I cant really comment because mine eventually went away and so did the DR/DP. Unless I drink A LOT of coffee then the DR/DP comes back slightly.

I'm working on some other things but nothing that I will post on here as of yet. If I think of anything else I'll let you know.

Edited by dasitmane

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Curious if anybody's heard some of Michael Pollan's interviews for his new book on psychedelics, and if so what your opinion is. Here's a good interview he did for Fresh Air: https://www.npr.org/programs/fresh-air/2018/05/15/611301978/fresh-air-for-may-15-2018-michael-pollan-on-the-new-science-of-psychedelics?showDate=2018-05-15

I've long subscribed to the glutamate toxicity theory as has been mentioned above, however I've always remained open to other ideas if they made sense. The only thing I feel pretty comfortable saying is that HPPD is the result of axon damage or death to some degree across multiple areas of the brain, likely in the limbic system and likely in connection with the parasympathetic or sympathetic nervous system. I think which nervous system is damaged depends on how the damage occurred, however. For example, excitotoxicity would likely affect the sympathetic given fight or flight is stimulatory while a stroke of some kind would be parasympathetic. 

One thing I find interesting in listening to Pollan's interviews is his repeated mentioning of the Default Mode Network (DMN) and how during psychedelic trips it basically goes offline. Depersonalization symptoms are essentially the result of a malfunctioning or nonexistant DMN and given the connection between DP and HPPD it's not too far of a jump to suggest HPPD is the result of a damaged DMN or simply one that never reboots due to lost connections or damaged axons. Many parts of the brain are connected through lengthy axons and I'm wondering if during the downregulation of the DMN when bloodflow decreases some of these axons are damaged via stroke of some kind. 

Also, with regards to glutamate, one of the biggest triggers for excess glutamate inside the brain is inflammation. If you eat a diet high in bread (wheat being the most inflammatory food known to man), oils and other inflammatory foods (essentially the standard American and Westernized diets) then your chances of having some sort of autoimmunity sky rocket. I also don't think we should entirely rule out the hypothesis that HPPD could be the result of our brains attacking our own brains after the ingestion of drugs which could very well mimic invaders our brains are already used to attacking. 

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What happens is that LSD and other hallucinogens diminish the flow of blood going to certain parts of the brain (hippocampus or hippothalamus ? Or both ? Don't remember), that's why the DNM is not working properly or completely turned off (in the case of an ego-death for example).

I always thought this to be the most logical theory to DP/DR since it's basically the same thing : feeling of detachment of one's self from it's own brain, and the outside world.

For example for me, I never had ego death during acid trips, and never had DP/DR. Looks like some people are more sensitive to this than others.

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2 hours ago, dasitmane said:

For now sedatives work just fine. Anything thats relaxing to the nervous system. GABA agonists of course, like benzos, or natural ones if you can find any. Lemon balm always helped my anxiety and I pretty much carry it with me everywhere I go. I've noticed that cowslip, which is good for sleeping, if I drink it at night the next day my anxiety is not so bad, but cowslip is hard to find so its not the best choice really. 

As for visuals I cant really comment because mine eventually went away and so did the DR/DP. Unless I drink A LOT of coffee then the DR/DP comes back slightly.

I'm working on some other things but nothing that I will post on here as of yet. If I think of anything else I'll let you know.

Everybody machine works different, mine the most disturbing thing is the visual, and emotion numbness felling(i cant feel like normal person) i have not anxiety, like the old times , I miss this shit it feel me more alive , nowadays it’s semms my visual at night getting worst overtime(trailing motion only works with led , lights especially cars ), and i only had used weed and alcohol, thats a shit story for me , eventually I’m still in process im on my 4 month cleaner, i hope i will have successfully recovery both visual and emotion , like the old me . 

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4 minutes ago, dayum_son said:

Damn, that's a long time :/

Yes i know , and its not getting better the visuals, the parnoia i had in the beginning went away , i did mri 3 weeks ago I’m still waiting for my answer, maybe it wil help to see if something happened there

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3 minutes ago, dayum_son said:

Have you tried any of the usual meds ? Lamictal, Keppra etc ?

I thought about them but its substance and i read about the side effects so , i can mange with my correct condition , anyway only at night it worse

Edited by danjoking

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Vasodilators ? Anyone tried that ? 

If we follow the Default Mode Network theory, hallucinogens act as vasoconstrictors on certain parts of the brain, lowering blood flow, thus inducing ego death.

Now, if we say DP/DR is like a mini-ego death, could we reverse the process, at least temporarily, using a vasodilator ?

I wouldn't recommend Viagra however. It can mess up with visual processing. Not the best for us.

Just my 0.02.

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15 hours ago, dasitmane said:

200.gif

 

“Danjoking, you're right. I apologize for my behavior” - TheMythos

Jennifer-Lawrence-ok-thumbs-up.gif?ssl=1

Yah post it if you want, it’s beneficial to compile all information we can. To be honest though I think everything is pretty much summed up and come to an end as far as the cause of HPPD. If you haven’t read the last couple pages, it’s gone over pretty thoroughly. Not that you’ll agree.

Also please do not be rude to productive members like dayum_son. 

I won't agree because you aren't a neuroscientist and I don't think you know what you're talking about. I read the entire thread. I play devils advocate and remain skeptical in the name of science and finding answers. For that I'm attacked as somehow denying reality because it's my way of dealing with brain damage...or something.

The most plausible theory we have of how psychedelics work in the brain is that they desynchronize certain brain regions, altering the brain waves and magnetic field around the brain. Why couldn't that be off or altered in some way? Why does it have to be cell death caused by glutamate excitotoxicity?

You don't get to determine who's a productive member of this forum and who isn't. You've already been banned once for insulting people, so I don't really think you have any leg to stand on like you're this paragon of civility and tolerance on this forum.

 

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