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Pharmacology How drugs affect the workings of the human body.

 
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  #1  
Old 24-05-2009, 09:27
rocknroll714 rocknroll714 is offline
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On the subject of GABA-A, muscimol, and psychedelia.

I posted this over at Bluelight but I figured I'd give it a run over here too:

So.. muscimol is a selective GABA-A receptor agonist which binds to the same site on the GABA-A receptor complex as GABA itself, unlike allosteric modulators like benzodiazepines, barbiturates, ethanol, neuroactive steroids, and so forth. Interestingly, muscimol is a hallucinogen, with some of the reports I've read indicating that it causes visual distortion identical to 5-HT2A-mediated psychedelics like LSD and magic mushrooms. I'm posting because I'm curious if anyone here knows more about this? There is almost no literature in relation to the GABA-A receptor and its hallucinogenic effects as far as I'm aware. Here's what I've got so far:
  • Gaboxadol, isoguvacine, and imidazoleacetic acid, among others, all bind to the GABA recognition site like muscimol and likely have hallucinogenic effects as well, though I don't think there are any reports on this.
  • I've seen a few reports of the GABA reuptake inhibitor tiagabine causing psychedelic effects in high doses.
  • In relation to the above-mentioned and quite obviously, GABA itself appears to have the potential to cause hallucinogenic effects. Though GABA can't cross the blood-brain-barrier (BBB) when taken orally, picamilon which metabolizes to GABA and niacin can get over the BBB and may have hallucinogenic effects. Can anyone confirm? GABA itself in extremely high doses (~5-10 grams) might work as well, though the peripheral implications of this could be dangerous.
  • Some of the nonbenzodiazepines which bind to the benzodiazepine allosteric site on the GABA-A receptor complex have been known to cause hallucinations like those of muscimol in certain individuals.
  • Many inhalants like nitrous oxide, chloroform, gasoline, and freon are hallucinogenic and are known to bind to and positively modulate GABA-A and antagonize NMDA to varying degrees.
  • Due to their similar psychedelic effects, 5-HT2A, CB1, kappa-Opioid, and GABA-A all are very likely work via a common final pathway (though to varying degrees which explains their differences). The inhibitory mGluR2/3 receptors are also implicated in this pathway as agonists of these receptors block the hallucinogenic effects of 5-HT2A agonists and may block the effects of other psychedelics as well.
Regarding inhalants, I've tried two of them personally, those being nitrous oxide (N2O) and propane. I've also tried dextromethorphan (DXM) on numerous occasions. Propane, DXM, and N2O all gave me the typical dissociative effects, but notably, when I tried N2O, I was shocked to find that I experienced trippiness and mind's eye visuals indistinguishable from those I've experienced on 5-HT2A-mediated psychedelics. Some of my friends who've tried N2O have experienced the same. For a while I just didn't really get it but now I'm starting to wonder if it has something to do with GABA-A activation. I have no idea what site of GABA-A that N2O interacts with though.

Anyway that's all I've really got so far. My main questions:

1) Have any of the other positive allosteric modulators of GABA-A besides the Z drugs and inhalants been reported to cause hallucinogenic/psychedelic effects?
2) Are there any known reports of hallucinogenic effects with L-glutamine (GABA precursor) or GABA supplements, picamilon, GABA-T inhibitors like vigabatrin, or any other GABAergic drugs that I've failed to mention?
3) Which GABA-A receptor subunit is the one most associated with these hallucinogenic effects? α1-containing expressions of GABA-A could be since the Z drugs have preference for it, but that's just a complete guess.
4) Is there any literature in relation to how GABA-A receptor activation causes these hallucinogenic effects downstream? This goes along with what I was talking about above in regards to that final common pathway.
5) How does N2O interact with the GABA-A receptor complex? Which site does it bind to?

That's all for now.

Last edited by Gradient; 03-09-2012 at 05:33. Reason: classy cat
  #2  
Old 24-05-2009, 18:46
imyourlittlebare imyourlittlebare is offline
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Re: On the subject of GABA-A, muscimol, and psychedelia.

Quote:
Originally Posted by rocknroll714 View Post
I posted this over at Bluelight but I figured I'd give it a run over here too:

So.. muscimol is a selective GABA-A receptor agonist which binds to the same site on the GABA-A receptor complex as GABA itself, unlike allosteric modulators like benzodiazepines, barbiturates, ethanol, neuroactive steroids, and so forth. Interestingly, muscimol is a hallucinogen, with some of the reports I've read indicating that it causes visual distortion identical to 5-HT2A-mediated psychedelics like LSD and magic mushrooms. I'm posting because I'm curious if anyone here knows more about this? There is almost no literature in relation to the GABA-A receptor and its hallucinogenic effects as far as I'm aware. Here's what I've got so far:
  • Gaboxadol, isoguvacine, and imidazoleacetic acid, among others, all bind to the GABA recognition site like muscimol and likely have hallucinogenic effects as well, though I don't think there are any reports on this.
  • I've seen a few reports of the GABA reuptake inhibitor tiagabine causing psychedelic effects in high doses.
  • In relation to the above-mentioned and quite obviously, GABA itself appears to have the potential to cause hallucinogenic effects. Though GABA can't cross the blood-brain-barrier (BBB) when taken orally, picamilon which metabolizes to GABA and niacin can get over the BBB and may have hallucinogenic effects. Can anyone confirm? GABA itself in extremely high doses (~5-10 grams) might work as well, though the peripheral implications of this could be dangerous.
  • Some of the nonbenzodiazepines which bind to the benzodiazepine allosteric site on the GABA-A receptor complex have been known to cause hallucinations like those of muscimol in certain individuals.
  • Many inhalants like nitrous oxide, chloroform, gasoline, and freon are hallucinogenic and are known to bind to and positively modulate GABA-A and antagonize NMDA to varying degrees.
  • Due to their similar psychedelic effects, 5-HT2A, CB1, kappa-Opioid, and GABA-A all are very likely work via a common final pathway (though to varying degrees which explains their differences). The inhibitory mGluR2/3 receptors are also implicated in this pathway as agonists of these receptors block the hallucinogenic effects of 5-HT2A agonists and may block the effects of other psychedelics as well.
Regarding inhalants, I've tried two of them personally, those being nitrous oxide (N2O) and propane. I've also tried dextromethorphan (DXM) on numerous occasions. Propane, DXM, and N2O all gave me the typical dissociative effects, but notably, when I tried N2O, I was shocked to find that I experienced trippiness and mind's eye visuals indistinguishable from those I've experienced on 5-HT2A-mediated psychedelics. Some of my friends who've tried N2O have experienced the same. For a while I just didn't really get it but now I'm starting to wonder if it has something to do with GABA-A activation. I have no idea what site of GABA-A that N2O interacts with though.

Anyway that's all I've really got so far. My main questions:

1) Have any of the other positive allosteric modulators of GABA-A besides the Z drugs and inhalants been reported to cause hallucinogenic/psychedelic effects?
2) Are there any known reports of hallucinogenic effects with L-glutamine (GABA precursor) or GABA supplements, picamilon, GABA-T inhibitors like vigabatrin, or any other GABAergic drugs that I've failed to mention?
3) Which GABA-A receptor subunit is the one most associated with these hallucinogenic effects? α1-containing expressions of GABA-A could be since the Z drugs have preference for it, but that's just a complete guess.
4) Is there any literature in relation to how GABA-A receptor activation causes these hallucinogenic effects downstream? This goes along with what I was talking about above in regards to that final common pathway.
5) How does N2O interact with the GABA-A receptor complex? Which site does it bind to?

That's all for now.
Youve asked alot of questions. I think your confused about muscimol. While youre correct with its GABA-A activity, it has effects on muscarinic receptors which are related to nicotinic receptors and have a variety of effects on bodily functions and possibly perception. Its affected by acetycholine, which alot of drugs affecting the cholinergic pathway can have hallucinatory effects. In fact, they are the only drugs causing true hallucinations.

When I say true hallucinations, PCP and the acetylcholine drugs I mentioned are related to hallucinations. However, if you give acid to a schizophrenic in remission, his symptoms do not come back and he is able to tell the difference between the various hallucinations of that drug and schizophrenia. Also, alot of anti-psychotics decrease glutamate, acetylcholine, dopamine and histamine receptor activity. There is a link between these NT systems but not in the way your thinking. Its more like..... using a true strong acid. You put it on the right surface it will burn the hell out of it. However, the right conditions such as putting it in an aqueous solution with a base will have a different effect. The brain is a big puzzle. NTs play a role, but its neuronal circuits were interested in.

GABA cannot cross the blood brain barrier. Its made from glutamate basically and amino acids build up chemicals that can be manufactured into these chemicals. Increasing levels of an NT wont get you anywhere unless its at the right place. For example, increased dopamine in certain areas yields rewards, other places it effects movement. Its inhibitory. Mainly in sleep. There are so many NTs, receptors, combinations of activity, its practically impossible to answer alot of your questions. Some of your answers may not be linked to GABA receptor activity at all, but what its inhibiting.

Ive never heard of tiagabine causing these effects. Also, GABA is an amino acid that you can take. It wont have an effect, you will poop it out.

The medications involving GABA that you mentioned is most likely due to its effect on sleep. So, perhaps, they are not paralyzed and experiencing what narcoleptics experience with sleep problems and hallucinations. Or they have a predisposition to psychotic problems anyway such as depression that could lead to psychosis.

This was quick response. Ill respond more, my GF needs me to do yard work and I got work work to do.

Its a very complicated matter. After I finish my dissertation in 4 years Ill get back to you and see if theres an answer lol ;P
  #3  
Old 25-05-2009, 02:55
rocknroll714 rocknroll714 is offline
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Man tell me something I don't know. None of that was useful or even really applied to the main subject. I mean I don't mean to sound offensive and I'm sorry for saying this, but your post was just.. a ramble about basic and random bits of pharmacology. The way you talk makes it sound like you know everything and nobody else knows anything. Thanks for the clarification about GABA being an amino acid for example. C'mon, seriously. I asked you over here in the thought that you might know a thing or two about this whole muscimol/GABA/psychedelia subject, but all you really did was say you thought I was confused and filled my head with random off-topic facts. If you're not really familiar with the subject then just don't say anything, don't go off on a random lecture.

Anyway.. muscimol's effects are clealy psychedelic, not deliriant/anticholinergic. We're talking strong CEVs, walls morphing, tripping balls, meeting god, etc. This is well-established. Indeed, muscimol as an analogue of muscarine may have antimuscarinic effects and personally I wouldn't be surprised one bit if it did (I've even heard people experiencing anticholinergic visual quirks in the corners of their eyes while on it), but the hallucinogenic effects I'm talking about here are not mediated by that property. They're mediated by GABA-A and this is further supported by the fact that the Z drugs and tiagabine, which don't any anticholinergic activity whatsoever (that I'm aware of at least), still retain the capability of causing psychedelic effects.

If you're unfamiliar with muscimol's psychedelic effects, I'd recommend you see here to get an idea of them:

http://www.erowid.org/experiences/su...Amanitas.shtml

Also here's a single report on tiagabine causing psychedelic effects:



(source: http://www.erowid.org/experiences/exp.php?ID=29090)

I'm sure there are more laying around but I'm too lazy to dig them up.

As for GABA not crossing the BBB, it's not completely incapable of crossing, it's just very weak at doing so. Just about anything can get across in sufficient doses to my knowledge. It may very well have typical GABAergic effects (as well as perhaps psychedelic effects) at some point (i.e., 10 grams ingested orally), but a number of people have suggested that this could be very dangerous. Notably I think I read someone tried 3 grams orally and experienced trouble breathing. Supposedly there are peripheral GABA receptors which regulate very important processes and if disrupted, could potentially be fatal (such as respiration perhaps). Whether respiration modulated by GABA is controlled peripherally or centrally I don't know, but I sure as hell wouldn't want to risk it.

Also something interesting I found:

http://designer-drugs.com/pte/12.162...iomuscimol.txt

Last edited by Gradient; 03-09-2012 at 06:19.
  #4  
Old 25-05-2009, 03:54
imyourlittlebare imyourlittlebare is offline
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Re: On the subject of GABA-A, muscimol, and psychedelia.

Quote:
Originally Posted by rocknroll714 View Post
Man tell me something I don't know. None of that was useful or even really applied to the main subject. I mean I don't mean to sound offensive and I'm sorry for saying this, but your post was just.. a ramble about basic and random bits of pharmacology. The way you talk makes it sound like you know everything and nobody else knows anything. Thanks for the clarification about GABA being an amino acid for example. C'mon, seriously. I asked you over here in the thought that you might know a thing or two about this whole muscimol/GABA/psychedelia subject, but all you really did was say you thought I was confused and filled my head with random off-topic facts. If you're not really familiar with the subject then just don't say anything, don't go off on a random lecture.

Anyway.. muscimol's effects are clealy psychedelic, not deliriant/anticholinergic. We're talking strong CEVs, walls morphing, tripping balls, meeting god, etc. This is well-established. Indeed, muscimol as an analogue of muscarine may have antimuscarinic effects and personally I wouldn't be surprised one bit if it did (I've even heard people experiencing anticholinergic visual quirks in the corners of their eyes while on it), but the hallucinogenic effects I'm talking about here are not mediated by that property. They're mediated by GABA-A and this is further supported by the fact that the Z drugs and tiagabine, which don't any anticholinergic activity whatsoever (that I'm aware of at least), still retain the capability of causing psychedelic effects.

If you're unfamiliar with muscimol's psychedelic effects, I'd recommend you see here to get an idea of them:

http://www.erowid.org/experiences/su...Amanitas.shtml

Also here's a single report on tiagabine causing psychedelic effects:



(source: http://www.erowid.org/experiences/exp.php?ID=29090)

I'm sure there are more laying around but I'm too lazy to dig them up.

As for GABA not crossing the BBB, it's not completely incapable of crossing, it's just very weak at doing so. Just about anything can get across in sufficient doses to my knowledge. It may very well have typical GABAergic effects (as well as perhaps psychedelic effects) at some point (i.e., 10 grams ingested orally), but a number of people have suggested that this could be very dangerous. Notably I think I read someone tried 3 grams orally and experienced trouble breathing. Supposedly there are peripheral GABA receptors which regulate very important processes and if disrupted, could potentially be fatal (such as respiration perhaps). Whether respiration modulated by GABA is controlled peripherally or centrally I don't know, but I sure as hell wouldn't want to risk it.

Also something interesting I found:

http://designer-drugs.com/pte/12.162...iomuscimol.txt
I wasnt going for an "im greater" attitude, its just the same as barbs vs benzos. They use muscimol to gauge binding to the GABA-A site, however, through work experience I know that there is no cross tolerance btwn muscimol and barbituates esp when it comes to anesthetic or lethal dosages. So alot of it has to do with specificity. Take Z drugs, very precise. Expected number of people to experience any types of effects your speaking of are less than 1%. Were talking pathways and way different, general GABA-A binding. Heres a good article that might help you on your quest. But your looking the wrong way. The muscarinic activity, along with GABA-A inhibition that may lead to a certain specific set of neuronal changes that induce hallucinations in 5 ht 2a receptors or increased activity in certain cortical areas triggering I guess the vague term is "memories" that would be a mixure of experiences combined with current perception which may or may not be related to acetylcholine effects. heres the article. And again, knowing how to post articles. If you could hook it up id totally appreciate it.

Acetylcholine and Hallucinations - Disease-Related Compared to Drug-Induced Alterations in Human Consciousness






References and further reading may be available for this article. To view references and further reading you must purchase this article.


Perry E. K. and Perry R. H.

Newcastle Gen Hosp, Mrc, Neurochem Pathol Unit, Westgate Rd, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England and Newcastle Gen Hosp, Dept Neuropathol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England



Available online 24 April 2002.

Abstract

Newly proposed criteria for Lewy body dementia include alterations in consciousness. Lewy body dementia is also associated with a disturbance in cholinergic transmission; neocortical cholinergic deficits in this disorder are more extensive than in Alzheimers disease and are correlated with symptoms commonly associated with delirium, such as visual hallucinations. The traditional view that derangements of the basal forebrain cholinergic system in Alzheimers disease relate specifically to memory impairment is assessed in terms of a more general role for cortical acetylcholine in consciousness. This extends the concept that cortical acetylcholine enhances neuronal signal to noise ratio. It is suggested that muscarinic receptor activation in the cortex is involved in confining the contents of the discrete self-reported conscious ′stream." In the absence of cortical acetylcholine, currently irrelevant intrinsic and sensory information, which is constantly processed in parallel at the subconscious level, enters conscious awareness. This is consistent with the ability of anti-muscarinic drugs administered medically, recreationally, or ritualistically to induce visual hallucinations and other perceptual disturbances. The hypothesis is explored through comparisons between muscarinic and nicotinic receptor psychopharmacology and between the pathology of the basal forebrain as opposed to pedunculopontine cholinergic systems in different diseases of the human brain affecting consciousness and cognition. The paradoxical effects of muscarinic receptor blockade to induce hallucinations and of REM sleep-associated cholinergic activation of the thalamus to induce dreaming may be related to the differential distribution and activity of muscarinic receptor subtypes or to the differing responses of intrinsic GABA neurons in cortex and thalamus.

imyourlittlebare added 3 Minutes and 2 Seconds later...

and I dont trust case studies. And the way the drug works.... I dont know it works through probably inhibiting alot of stuff. Like take for instance the insular cortex. Only reason I can think of why a drug with no nicotinic or stimulant activity decreases nicotine craving but not heroin. I dunno. Epilepsy drugs in normal people are hard to gauge. Who know what the guy took the other day or anything about him. I like contolled stuff. No offense. I like erowid but its not my cup of tea. No offense though. Your a cool dude. and like i said. Before the GF had me runnin, now she is back. So ill catch ya later dude.

Last edited by imyourlittlebare; 25-05-2009 at 03:54. Reason: Automerged Doublepost
  #5  
Old 25-05-2009, 05:17
rocknroll714 rocknroll714 is offline
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Quote:
Originally Posted by imyourlittlebare View Post
I wasnt going for an "im greater" attitude, its just the same as barbs vs benzos. They use muscimol to gauge binding to the GABA-A site, however, through work experience I know that there is no cross tolerance btwn muscimol and barbituates esp when it comes to anesthetic or lethal dosages. So alot of it has to do with specificity. Take Z drugs, very precise. Expected number of people to experience any types of effects your speaking of are less than 1%. Were talking pathways and way different, general GABA-A binding. Heres a good article that might help you on your quest. But your looking the wrong way. The muscarinic activity, along with GABA-A inhibition that may lead to a certain specific set of neuronal changes that induce hallucinations in 5 ht 2a receptors or increased activity in certain cortical areas triggering I guess the vague term is "memories" that would be a mixure of experiences combined with current perception which may or may not be related to acetylcholine effects. heres the article. And again, knowing how to post articles. If you could hook it up id totally appreciate it.

Acetylcholine and Hallucinations - Disease-Related Compared to Drug-Induced Alterations in Human Consciousness






References and further reading may be available for this article. To view references and further reading you must purchase this article.


Perry E. K. and Perry R. H.

Newcastle Gen Hosp, Mrc, Neurochem Pathol Unit, Westgate Rd, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England and Newcastle Gen Hosp, Dept Neuropathol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England



Available online 24 April 2002.

Abstract

Newly proposed criteria for Lewy body dementia include alterations in consciousness. Lewy body dementia is also associated with a disturbance in cholinergic transmission; neocortical cholinergic deficits in this disorder are more extensive than in Alzheimers disease and are correlated with symptoms commonly associated with delirium, such as visual hallucinations. The traditional view that derangements of the basal forebrain cholinergic system in Alzheimers disease relate specifically to memory impairment is assessed in terms of a more general role for cortical acetylcholine in consciousness. This extends the concept that cortical acetylcholine enhances neuronal signal to noise ratio. It is suggested that muscarinic receptor activation in the cortex is involved in confining the contents of the discrete self-reported conscious ′stream." In the absence of cortical acetylcholine, currently irrelevant intrinsic and sensory information, which is constantly processed in parallel at the subconscious level, enters conscious awareness. This is consistent with the ability of anti-muscarinic drugs administered medically, recreationally, or ritualistically to induce visual hallucinations and other perceptual disturbances. The hypothesis is explored through comparisons between muscarinic and nicotinic receptor psychopharmacology and between the pathology of the basal forebrain as opposed to pedunculopontine cholinergic systems in different diseases of the human brain affecting consciousness and cognition. The paradoxical effects of muscarinic receptor blockade to induce hallucinations and of REM sleep-associated cholinergic activation of the thalamus to induce dreaming may be related to the differential distribution and activity of muscarinic receptor subtypes or to the differing responses of intrinsic GABA neurons in cortex and thalamus.

imyourlittlebare added 3 Minutes and 2 Seconds later...

and I dont trust case studies. And the way the drug works.... I dont know it works through probably inhibiting alot of stuff. Like take for instance the insular cortex. Only reason I can think of why a drug with no nicotinic or stimulant activity decreases nicotine craving but not heroin. I dunno. Epilepsy drugs in normal people are hard to gauge. Who know what the guy took the other day or anything about him. I like contolled stuff. No offense. I like erowid but its not my cup of tea. No offense though. Your a cool dude. and like i said. Before the GF had me runnin, now she is back. So ill catch ya later dude.
Some of the things you say are really hard to follow you know that? Like with your first paragraph I was just like, "What does muscimol/barbiturate cross-tolerance have to do with anything?" in my head. Please try to be more clear when you talk and notably it'd be nice if you could just include like a sentence or something as to why you mention certain things (like the above-mentioned example for instance). That would help a lot.

Anyway, yes of course, selectivity is a major factor in this whole thing. For the others here, I'll go into a little detail because it's important to clarify why some GABAergics can cause hallucinogenic effects while others can't as some of you might be wondering..

There are a number of different sites on the GABA-A receptor complex. There is the main GABA binding site which muscimol and GABA bind to and activate, and there are a variety of different allosteric sites for other drugs, including respective sites for the benzodiazepines, barbiturates, neuroactive steroids, inhalants, and alcohol, among others. The main site directly opens the chloride ion channel pore (i.e., activates the receptor), whereas the allosteric sites simply act by controlling the ability of the main site to cause this to happen. Though direct activation and allosteric modulation can exert similar effects, unlike the main site which is located on every single GABA-A receptor protein, the allosteric sites are expressed varyingly in different areas, with some GABA-A receptors not even having certain allosteric sites at all. As a result, direct receptor activation can be considered complete, whereas allosteric activation may in many cases only exert partial effects. Depending on the allosteric sites, those partial effects may even be more or less complete. The barbiturate allosteric binding site is expressed more prominently than the benzodiazepine site for example, and as a result, the barbiturates are much stronger than the benzodiazepines in many ways. The variations in allosteric binding sites explains in part many of the substantial differences in the different kinds of drugs that work on the GABA-A receptor.

In relation to psychedelia, it appears that many of the allosteric modulators of GABA-A like the benzos and barbs nearly completely miss the GABA-A receptors necessary for inducing hallucinogenic effects. I say nearly completely because some, such as some of the Z drugs, still have a weak capability for doing so. Other allosteric sites, such as nitrous oxide's, according to my own speculation, may be strongly expressed on the GABA-A receptors necessary for causing these effects. Also it's important to note that as GABA fully activates all of the GABA-A receptors, anything that indirectly increases GABA activity by elevating GABA concentrations such as tiagabine or vigabatrin, should in concept be capable of inducing these kinds of effects, as tiagabine has apparently demonstrated already.

I've personally got a theory.. I believe that GABA-A receptors may be co-located with 5-HT2A receptors in certain parts of the brain, and that their activation facilitates 5-HT2A-mediated neurotransmission to cause the psychedelic effects seen with muscimol. Though GABA-A receptors are inhibitory, they may inhibit another inhibitory intermediate which would normally act to lower 5-HT2A activity, ultimately causing an excitatory effect. The reason I think 5-HT2A receptors are directly involved here is because of how incredibly similar muscimol is to 5-HT2A-mediated psychedelics like LSD and shrooms. The psychedelic effects seem to match very closely and muscimol even causes visual field morphing and dilated pupils, just like the 5-HT2A psychedelics. The other psychedelics like CB1 and kappa-Opioid agonists don't cause the latter two effects to my knowledge, so I think their involvment in the psychedelic pathway comes into play more downstream. Though muscimol has been said to be more "dreamy" than 5-HT2A psychedelics, this could simply be because of the other effects of GABA-A receptor activation such as sedation and amnesia, as well as perhaps muscarinic acetylcholine receptor antagonism which could also contribute.

To imyourlittlebare, I really don't think the muscarinic acetylcholine receptors have anything to do with muscimol's psychedelic effects whatsoever. I think they may contribute to the overall hallucinogenic effects slightly with mild to moderate deliriant effects, but as mentioned above, the psychedelic effects are quite distinct from these and I'd even go as far as considering the deliriant effects as nothing more than "side effects". As for uploading articles.. I don't know sorry.

Last edited by Gradient; 03-09-2012 at 06:18.
  #6  
Old 25-05-2009, 18:19
imyourlittlebare imyourlittlebare is offline
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Re: On the subject of GABA-A, muscimol, and psychedelia.

Ok now I have time so ill go over your theory, cite a few articles, and talk about your theory and what I meant in what I was saying. First off, the hallucinogenic effects of the Amanita muscaria mushroom and muscimol is its activity on the acetylcholine receptor dubbed the muscarinic receptor (Rossum, J.M. van. Atropine-like actions of muscarine isomers.) The reason muscimol is used in laboratories such as the one I work in is to determine a drugs ability to bind to the GABA-A receptor at certain sites so that was what I was talking about on top of the fact that the hallucinogenic effect is similar to other deleriants.

Another thing I wanted to mention is that glutamate turns into GABA. and the glutamanergic system is involved along with the GABA-A system with nitrious oxide. Answering all your questions is hard. We need to take this one step at a time and try to figure out a way to ask a question and see if I know or the literature I have access to does. Bc I can tell you that the hallucinations of muscimol are caused by muscarinic activity. Along with you mentioning hallucinations with the use of GABA-A drugs, that can happen with anti-histamines. Histamine receptors also play a role. So does AGE. young children and old adults should not use benzos because it can be excitatory and have paradoxal effects such as excitation, aggitation, hallucinations etc. When your a baby, GABA is excitatory. CB-1 is not hallucinatory. It has a psychotropic effect, but not hallucination wise. Kappa opiod receptors too. Tiabagine has been shown to cause confusion, sedation so it could be confusing a dream for a hallucination.

Now as for your theory, yes. There is a huge amount of GABA receptor distribution with many different receptors not to mention GABA-B1a and 1b which decreases activity of the GABA-A receptor so that also could be modulating or affecting the inhibition of inhibition of activity at hallucinogenic sites. They are all over the brain and have so many effects involving whether or not you get a taste aversion, gustatory effects, different types of memory, perception. I dont know its all over. So its very likely your right, that GABA can inhibit activity that would eventually lead to hallucinogenic activity seen with schizophrenics, LSD use, deleriants, and other hallucinogenic drugs in the raphe nuclei or other areas or with huge amounts of dopamine, NMDA antagonism and such. However, the body adapts quickly and can compensate even with the use of drugs to decrease effects your proposing with GABA.

Like I dunno, sometimes weird stuff happens. Z drugs can wake comatose patients. Decreasing the reuptake of norepinephrine doesnt lead to increased mania in bipolar people, people getting off opiates (very very rarely) see hallucinations. It also depends on what types of hallucinations were talking about. There are other inhibitory receptors like glycine receptors and such that can have an effect on these areas as well as GABA-B, all the various types of calcium channels and individual biology. Lets take it one thing at a time if this hasnt helped. Ill tell you if I can help you answer it or if its not answerable. Hows that? Best if we meet with you at a library unless you have access to literature or new psychpharm books.

imyourlittlebare added 0 Minutes and 43 Seconds later...

and sorry, I really really need to finish my manuscript on kava and test-anxiety. Ill have to chat later. Cya man

Last edited by imyourlittlebare; 25-05-2009 at 18:19. Reason: Automerged Doublepost

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gaba, gaba receptor subtypes, gaba receptors, muscimol, neuroscience, pharmacology, psychedelics

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