Mechanisms of Hallucination. Simpified

[airsh0w]

This is what I have came up with so far. If you have anything to add or correct me on then you're more than welcome to. This is not even close to perfect but nothing anyone could find at this point would be. This is a good starting point for understanding.

NMDA ANTAGONISM [Ketamine, DXM, PCP]

NMDA receptor when blocked can causes sedation and dream-like dissociation when the antagonism is stronger (i.e. greater ligand efficacy). Though I am not quite sure how the NMDA subtypes NR1 and NR2 play into this or if they do.
(non-competitive or uncompetitive antagonist) (PCP works through the DARRP-32 related pathway which might be true for all dream-like dissociatives of this nature)

[Speculation due to olney lesion areas in nonhuman brains]:
The cingulate cortex NMDA antagonism may inhibit emotion, learning, information processing and the NMDA antagonism at the retrosplenial regions responsible episodic memory are inhibited rerouting the neural network of recalling a memory to the imagination to cause dream-like hallucinations]

Some interesting examples of amnesia and hallucinations appearing together.

http://www.mombu.com/medicine/human...c-anxiety-amnesia-hallucinations-2352966.html

http://www.erowid.org/experiences/exp.php?ID=25909

5-HT2A Agonism [LSD, Psilocin, Mescaline]

The 5-Ht2A when activated along with functional selectivity it causes the psychedelia hallucinations. A hypothesis of why is that 5-HT2A agonism mediates higher glutamate levels (perhaps specifically in area IV and V) in the cerebral cortex and activate the DARPP-32 related pathways which are more activated in the brains of schizophrenics which leads to a vulnerability to negative stimuli but potentially beneficial in some aspects of cognition.

GABA A Agonism/Positive Allosteric Modification [Muscimol, Zolpidem]

GABA A agonist/positive allosteric modification can cause deliriant hallucinations depending on functional selectivity by which G-Protein cascades it inhibits and activates.
Ethanol is an GABA A positive allosteric modulator but doesn't due to functional selectivity.

Anticholinergics [Diphenhydramine, Atropine]

Causes realistic delirium but not intense emotionally.


REF: http://www.jbc.org/content/283/16/10470.full.pdf

D2 Agonists [PCP psychotic features, Schizophrenia]

Strong D2 agonism can cause a type of psychotic multi-sensory dysphoric delirium. K-opioid agonism causes an increase in D2 receptors.



REF:

http://www.erowid.org/chemicals/pcp/pcp_effects.shtml (PCP D2 partial agonist mimics schizophrenia)

http://www.ncbi.nlm.nih.gov/pubmed/1706098 (raised Dynorphin levels in schizophrenics)

http://www.ncbi.nlm.nih.gov/pubmed/9236549 (elevated D2 receptors in schizophrenic temporal lobe)

K-Opioid Agonist [Salvia]

This causes a dysphoric dream like dissociative psychosis something like schizophrenia and dissociatives combined but different then them both.

 

[basement_shaman]

Very interesting overview. Have you read the article on how neurons in the visual cortex are stacked, and how these stacks are stacked in superstacks? It explains a lot of math about visual hallucinations, specifically patterns, fractals and form constants. I tried to find the article, but failed. Instead I found this article, which explores a different explanation and is also a very interesting read.

 

[airsh0w]

Very interesting overview. Have you read the article on how neurons in the visual cortex are stacked, and how these stacks are stacked in superstacks? It explains a lot of math about visual hallucinations, specifically patterns, fractals and form constants. I tried to find the article, but failed. Instead I found this article, which explores a different explanation and is also a very interesting read.

I haven't read that but I have heard of the math of visual hallucinations. The article you posted gives me a pretty good idea of the essence of what you are saying. Something like 5-HT2a excites GABAergic and dopaminergic neural pathways in the visual cortex modulating the processing of information.

 

[cannibalsnail]

Is it possible that there other receptor groups which can cause visuals?

 

[airsh0w]

Is it possible that there other receptor groups which can cause visuals?

Yes through paradoxical reactions or undocumented types. This is just the best that I could come up with any degree of certainty. We know some of them more than others. We know for a fact that 5-HT2A partial agonists of a certain functional selectivity cause hallucinations but it is hard to say with 100% certainty which muscarinc receptor needs to be blocked [and to what functional selectivity if any] to cause hallucinations due to poor selectivity of muscarinc antagonists. But it seems likely that it is M1.

 

[Captain.Heroin]

You're missing anticholinergic deliriants, although I'm so stoned I may just not see it up there.

 

[airsh0w]

You're missing anticholinergic deliriants, although I'm so stoned I may just not see it up there.

No it's up there. M1 = Muscarinic. I'm fairly convinced it is M1 from what I have read.

 

[MagickalKat777]

Probably a stupid question but if it is as simple as 5HT2A agonism then why is it that different psychedelics produce different visual stimulus? I would expect that would be due to other serotonin subtypes being affected. LSD has the widest range of site activity as far as I know and the visuals from LSD are nowhere near comparable from what one would get with, say, mescaline, which is rather benign in the visual sense?

 

[airsh0w]

It's actually a good question that hasn't been fully explored yet.

Fairly certain that if you bock the 5-HT2A receptor site then you will not see any visuals. The different visual stimulus is perhaps mediated by what is called functional selectivity. Different G-protein mediated cascades happen from different agonists/partial agonists.

Other receptors may play indirect roles in the subjective interpretation of the experience and physiological differences which may cause a slightly different type of hallucinations but there is a limit when 5-HT2A is the root of it.

Functional selectivity is when different processes are mediating within a cell leading to a different result of the agonist.

 

[MagickalKat777]

I was curious about this as my friend had her first trip yesterday (mescaline) - we took it together - and she takes two atypicals (Zyprexa and one I had never heard of before called Invega) which should have completely blocked the hallucinogenic effects of mescaline but she was flying high just like I was. I had even warned her ahead of time that because of her meds she probably wouldn't feel much but she wanted to try it. We ended up on a very intense trip together, the two of us sharing the experience... So I'm curious if 5-HT2A is responsible for what we know as hallucinations how her mescaline usage resulted in a full-blown psychedelic trip which she loved thoroughly and plans to take again since both olanzapine and paliperidone have 5-HT2A blockade...

 

[Captain.Heroin]

No it's up there. M1 = Muscarinic. I'm fairly convinced it is M1 from what I have read.

You can have it from other acetylcholine receptors as well but we can leave it as it is for now. Some ADD folk can be more nit-picky than I am they may be able to tell if I'm actually right or not. I'm not going to do lots of in-depth reading on anticholinergics right now, still getting over a cold, etc.

It's actually a good question that hasn't been fully explored yet.

Unique drug molecule stimulates a total number of these listed receptors, and more, in depth.

You have to realize, what we know about drugs, drug receptors now, is still not set in stone. There are still things we build upon our current knowledge of as time goes along, there may be one day where we have to edit / change a great deal of once-thougth-to-be-widely -accepted-truth about drug receptors/etc as a result of assumptions we have to make while making drug discoveries, like, there is some correlation between drug structure and drug effect. We find this to be true. To what degree, it's almost like it'd take a large volume of words to get to explaining.

Anyways, we don't have all the answers, some people would philosophize we know nothing, but we know a lot more than we all once did.

 

[airsh0w]

I was curious about this as my friend had her first trip yesterday (mescaline) - we took it together - and she takes two atypicals (Zyprexa and one I had never heard of before called Invega) which should have completely blocked the hallucinogenic effects of mescaline but she was flying high just like I was. I had even warned her ahead of time that because of her meds she probably wouldn't feel much but she wanted to try it. We ended up on a very intense trip together, the two of us sharing the experience... So I'm curious if 5-HT2A is responsible for what we know as hallucinations how her mescaline usage resulted in a full-blown psychedelic trip which she loved thoroughly and plans to take again since both olanzapine and paliperidone have 5-HT2A blockade...

It depends on her dosage, its bio availability, whether they are competitive antagonists but even so if those drugs were in her system at any substantial dosage so she should of had a a very watered down trip if anything. It could also do with her interpretation of the experience since it was her first trip. Did she hallucinate and describe her hallucinations?

I couldn't find one report of this combination anywhere. It could of been many things but a new mechanism for hallucination? Unlikely.



REF:

http://www.ncbi.nlm.nih.gov/pubmed/18666267

http://www.erowid.org/experiences/exp.php?ID=58833 (5-HTA antagonist ending Shroom trip)

http://www.erowid.org/experiences/exp.php?ID=71071 (5-HTA antagonist ending LSD trip)
http://www.erowid.org/experiences/exp.php?ID=29950 ---------------------------------------

 

[airsh0w]

You can have it from other acetylcholine receptors as well but we can leave it as it is for now. Some ADD folk can be more nit-picky than I am they may be able to tell if I'm actually right or not. I'm not going to do lots of in-depth reading on anticholinergics right now, still getting over a cold, etc.



Unique drug molecule stimulates a total number of these listed receptors, and more, in depth.

You have to realize, what we know about drugs, drug receptors now, is still not set in stone. There are still things we build upon our current knowledge of as time goes along, there may be one day where we have to edit / change a great deal of once-thougth-to-be-widely -accepted-truth about drug receptors/etc as a result of assumptions we have to make while making drug discoveries, like, there is some correlation between drug structure and drug effect. We find this to be true. To what degree, it's almost like it'd take a large volume of words to get to explaining.

Anyways, we don't have all the answers, some people would philosophize we know nothing, but we know a lot more than we all once did.

I have to realize? The first thing I said was to correct me if you knew I was wrong. I present this to show and simplify what is currently theory. I would be surprised if that was all of them and I was spot on but we've got to build out knowledge on some base and this is a pretty good base. I did much research to come to M1 for sure but they are so unselective that their could in-fact be more but its difficult to prove. I would love to be proved wrong and that is partially why I posted this. I changed it to accommodate the uncertainty.

 

[MagickalKat777]

It depends on her dosage, its bio availability, whether they are competitive antagonists but even so if those drugs were in her system at any substantial dosage so she should of had a a very watered down trip if anything. It could also do with her interpretation of the experience since it was her first trip. Did she hallucinate and describe her hallucinations?

I know your automatic response is to say that she had a rare reaction or that it was all placebo but if you read enough about (or have experienced) mescaline - it tends to lend itself well to having a synchronous trip - basically everything I saw, she saw, and vice-versa. I would estimate her dose to be at 300mg and mine at 500mg and it was HCl... I can not explain what she experienced in words. It really shocked the hell out of me that she was tripping WITH me not BESIDE me... it was like she was experiencing what I was at the exact same time... looking at Ki for H-HT2A - she should not have seen a single hallucination based on your model.

The only other model that half-way works is the "spiritual" model but being an atheist I highly doubt that was the case. Maybe 5-HT2a doesn't have the significance that we think it does??

 

[airsh0w]

I know your automatic response is to say that she had a rare reaction or that it was all placebo but if you read enough about (or have experienced) mescaline - it tends to lend itself well to having a synchronous trip - basically everything I saw, she saw, and vice-versa. I would estimate her dose to be at 300mg and mine at 500mg and it was HCl... I can not explain what she experienced in words. It really shocked the hell out of me that she was tripping WITH me not BESIDE me... it was like she was experiencing what I was at the exact same time... looking at Ki for H-HT2A - she should not have seen a single hallucination based on your model.

The only other model that half-way works is the "spiritual" model but being an atheist I highly doubt that was the case. Maybe 5-HT2a doesn't have the significance that we think it does??

You are making giant leaps based on this experience. You couldn't possibly know if she still had those antipsychotics flowing through her brain at the point of taking mescaline. Not everything is how it appears. This is a study that blocked the effects of mescaline with a 5-HT2A antagonist.

http://lib.bioinfo.pl/pmid:2138338

I have never tripped with somebody who I was close with and not had the "same" trip. Who knows? Try writing down what you see and then comparing and see if its not just you guys talking about what you are seeing then your minds creating it or something. I'm not trying to say don't be curious and wonder but be-careful to draw your definite conclusions.

 

[MagickalKat777]

We are gonna write a trip report... She still remembers it... I am absolutely amazed about the fact that she quit antipsychotics like 2 weeks before... Those ones in particular have a very strong bind to 5-HT2A from what I read and she really shouldn't have tripped that hard.... Especially since the dose was a "starter" dose of about 300mg... In most drug terms she should have been flying but in mescaline terms? Isn't that like threshold.......

 

[airsh0w]

We are gonna write a trip report... She still remembers it... I am absolutely amazed about the fact that she quit antipsychotics like 2 weeks before... Those ones in particular have a very strong bind to 5-HT2A from what I read and she really shouldn't have tripped that hard.... Especially since the dose was a "starter" dose of about 300mg... In most drug terms she should have been flying but in mescaline terms? Isn't that like threshold.......

No threshold is 100mg

http://www.erowid.org/chemicals/mescaline/mescaline_dose.shtml

You both have already shared so much information by talking that confounding variables would make it impossible to tell.

If she quit 2 weeks ago then there wasn't any in her system.

 

[strat54]

It's actually a good question that hasn't been fully explored yet.

Fairly certain that if you bock the 5-HT2A receptor site then you will not see any visuals. The different visual stimulus is perhaps mediated by what is called functional selectivity. Different G-protein mediated cascades happen from different agonists/partial agonists.

Other receptors may play indirect roles in the subjective interpretation of the experience and physiological differences which may cause a slightly different type of hallucinations but there is a limit when 5-HT2A is the root of it.

Functional selectivity is when different processes are mediating within a cell leading to a different result of the agonist.

the same receptor can activate different pathways depending on the status of the cell. if different hallucinogens are transported to different parts of the brain then they could have different effects. just my guess

 

[MagickalKat777]

No threshold is 100mg

http://www.erowid.org/chemicals/mescaline/mescaline_dose.shtml

You both have already shared so much information by talking that confounding variables would make it impossible to tell.

If she quit 2 weeks ago then there wasn't any in her system.

Well she's been on various ones for like 17 years... Anyway, we took 2C-T-7 yesterday and she did a lot more than I did and I was falling in and out of consciousness (like I do when I'm peaking on MDMA) and tripping balls, she didn't have much of a trip at all.

There is some weird variable going on here because she should have been a lot more messed up than I was from the 2C-T-7 (although that drug has a habit of one dose sending someone flying to the heavens and the same dose barely doing anything at all to another so there is that variable too).

I just found it curious that after all those years of antipsychotics she was able to trip so hard on mescaline. She kept seeing asians everywhere LOL!

 

[airsh0w]

Well she's been on various ones for like 17 years... Anyway, we took 2C-T-7 yesterday and she did a lot more than I did and I was falling in and out of consciousness (like I do when I'm peaking on MDMA) and tripping balls, she didn't have much of a trip at all.

There is some weird variable going on here because she should have been a lot more messed up than I was from the 2C-T-7 (although that drug has a habit of one dose sending someone flying to the heavens and the same dose barely doing anything at all to another so there is that variable too).

I just found it curious that after all those years of antipsychotics she was able to trip so hard on mescaline. She kept seeing asians everywhere LOL!

What else is she on? SRI? The antipsychotic doesn't accumulate in your brain otherwise she wouldn't be alive. I'd have to know all the facts to speculate on what is going on.