Important questions about muscimol.

[Neuroprotection]

A few years ago I was researching psychedelics, interested in how they worked. As you likely already know, most hallucinogens are either NMDA antagonists, anticholinergics or 5ht2A agonists. however, when I came across muscimol, I was intreeged, since it was a potent gabaA agonist, producing a dreem like state and slowing brain activity after ingestion. There are two main things I want to know about muscimol: 1 Is it addictive, if so how. 2 is the experience generally more pleasant than the state produced by 5ht2A agonists. I realy like the idea of a gabAergic psychedelic. Although I have never tried psychedelics in my life, but I think that muscimol or a shorter acting analog may be a perfect psychedelic for a non experienced user. Hear is my theory please correct me if I am wrong or you disagree: muscimol may produce vivid hallucinations and distortions of perception and reality through wide spread activation of GabaA receptors in the brain. Such hallucinations could possibly cause a bad trip, but through the same mechanism they are induced, the resulting fear is supressed (via gabaA receptors). If I am completely wrong and muscimol often produces bad trips then please say so.

 

[CrypticArc]

From wikipedia:
Ibotenic acid and muscimol are structurally related to each other and to two major neurotransmitters of the central nervous system: glutamic acid and GABA respectively. Ibotenic acid and muscimol act like these neurotransmitters, muscimol being a potent GABAA agonist, while ibotenic acid is an agonist of NMDA glutamate receptors and certain metabotropic glutamate receptors which are involved in the control of neuronal activity. It is these interactions which are thought to cause the psychoactive effects found in intoxication.

I personally would wager that we're missing something, and that muscimol has actvity at the NMDA receptor site. Also I wouldn't be surprised if the Z-drugs (ambien ect) also had some similar activity. Yes, it is addictive, as far as we know in the same way as alcohol and benzos, but theoretically also in the same way as K can be. Also, amanitas contain substances which act on the muscarinic acetylcholine receptors which could potentially cause some form of addiction, by my guess, as they are related to nicotine receptors

A lot of people advise against taking this stuff because of the high risk for a bad experience. I would not recommend this substance for a first time tripper.

 

[Solipsis]

I think the sweating, salivating, loss of motor function / ataxia and possibly vertigo can really derive a person of the relaxation and euphoria that may also be produced.

The hallucinations can also become almost of a delusional nature when you go from a normal waking consciousness to a pseudo-sleepwalking or vivid lucid-or-not dreaming consciousness. This may make a trip on muscimol relatively challenging.

It seems to me these effects make the drug less controllable than psychedelics, and limit the use to only *somewhat* frequently. Although, there might be tolerance but possibly less than with typical psychedelics...
Yes euphoric enjoyable drugs can give it *some* chance of becoming habitual, but the side-effects this kind of drug has may scare a lot of people off from doing it very often. It is probably wise to compare it to a drug like zolpidem, but perhaps with an added anticholinergic. Zolpidem by itself - kinda clean, if potentially superweird - can be interesting for certain types of people to do with some frequency... but mixed with an anticholinergic it is more dirty and fucked up and a little less enjoyable and interesting.

Best to consider this an atypical entheogen which should be done preferably with a sitter and certainly with respect. Not that psychedelics don't deserve a lot of respect, but they range from terribly serious to mild and suitable for lighthearted recreational use.

I once came across gaboxadol, but was then warned by someone that it was likely mislabeled and actually ibotenic acid. I planned to convert that to muscimol but then lost the stuff. Hopefully it surfaces at some point, and even more hopefully it's decarboxylized on its own by then...

Is muscimol available to you as pure compound, cause Amanita Muscaria or - avoid! - Pantherina contain other compounds that may contribute to side-effects... making it incorrect to call the mushroom just 'muscimol'.

 

[Neuroprotection]

I was actually thinking of pure muscimol though I should have made that clearer. I understand that natural sources of muscimol are unfortunately contaminated by what I believe are toxic and norsiating compounds that ruin the experience. Ibotenic acid seems particularly nasty, its used as a excitotoxin to selectively kill brain cells in animal studies of brain damage. However, I have heard that most ibotenic acid is decarboxilated to muscimol before it reaches the brain.

 

[Solipsis]

Yeah it appears to be fine, although I would still want to cure any mushrooms I had picked or to know that my vendor did that properly.. etc.

 

[Neuroprotection]

Interesting. what leads you to believe that muscimol has NMDA activity, is it due to its structural relationship to ibotenic?

 

[CrypticArc]

that and it's visionary properties

 

[Kaleida]

Have there really never been any studies testing the activity of muscimol at NMDA receptors already? That seems absurd given its relationship to ibotenic acid, but honestly I can't recall ever coming across one myself. Time to do some hunting....

I wouldn't count out GABAergic mechanisms as a cause of hallucinations though.... Surely something as complex as the primary inhibition drive of the brain could cause some severe alterations in consciousness when messed with the right way, no? Anyway, all I can say is that my experiences with Amanitas and zolpidem didn't really resemble my dissociative trips at all, not more than like psychedelics or something do anyway.

As for whether they're addictive, I think the process of digesting the mushrooms is a little unpleasant for that, but I bet pure muscimol could be somewhat abusable, because I've heard of it being used at a successful trip dose with a complete lack of nausea before. And muscarias give me sweats and stuff, but when I take the pantherinas which supposedly lack muscarine the nausea at the beginning is the only side effect for me, and then I feel great. I don't think it's too likely though, and it would have to be at lower doses.... It definitely does feel emotionally easier for me than other equally powerful psychedelics, there is a genuine anti-anxiety effect to it, but with that said the trip is still very deep and potentially quite delirious.... It's a powerful trip, not something I would recommend to a first timer if I wanted to show them a fully hallucinogenic dose of something. But I do think it could be a helpful ally to beginners who are familiar with other psychedelics in lower doses.... Being able to appreciate the state more will definitely bring out the more pleasurable effects better.

Just my two cents.

 

[Kaleida]

Well, not that exactly, but here's something interesting that just came up.

Excitation of nigral dopamine neurons by the GABAA receptor agonist muscimol is mediated via release of glutamate

Previous electrophysiological studies have shown that the GABAA-receptor agonist muscimol is able to markedly increase the firing rate of rat nigral dopamine (DA) neurons. This action of the drug is paradoxical since local microiontophoretic application of the drug is associated with a clearcut inhibition of this neurons. In the present electrophysiological study, an attempt was made to analyze the mechanism of this action of the drug. Administration of muscimol (0.25–4.0 mg/kg, i.v.) was associated with a dose-dependent increase in firing rate as well as an increased bursting activity of the nigral DA neurons. Both these effects of muscimol were clearly antagonised by intravenous administration of the NMDA receptor antagonist MK 801(1 mg/kg) or by intracerebroventricular administration of the broadspectrum excitatory amino acid receptor antagonist kynurenic acid. Furthermore, pretreatment with PNU 156561A (40 mg/kg, i.v., 5–8h), a compound that raised endogenous kynurenic acid levels about 9 times, also clearly antagonised the actions of muscimol. Indeed, this treatment reversed the excitatory action of muscimol into an inhibitory effect on the nigral DA neurons. Here, we report that the excitatory action of muscimol is mediated indirectly by release of glutamate.

This is a good example I think of how activity at a site for the inhibitory system could have paradoxically excitatory effects of the kind that could theoretically lead to altered states of consciousness, and notably it's inhibited by a NMDA antagonist.

 

[Fresnel]

2 is the experience generally more pleasant than the state produced by 5ht2A agonists.

I have had muscimol in the form of dried amanita muscara. The effects were mild and floaty, slightly dissociative, slightly euphoric. Not at all tryptamine or phen like. Didn't have any of the reported negative effects, though I'm assuming my dose was low.

 

[burn out]

I have taken a lot of amanita muscaria and you are correct that it relieves anxiety. the trip is much slower paced compared to seterogenic psychedics. its still very possible to have a bad trip, usually from taking too much. the wonderful thing about this mushroom it is very effective in very low doses. great for meditation, healing introspection and virtually zero chance of a bad trip, in small doses.

now, the way to dose it is you take a little bit at a time. you nibble on one of the big caps. If things are going well, you eat a little more and let the high build up. if things are going poorly, you just dont eat anymore that day. its the most divine, wonderful substance. a gift from heaven.

Its definitely possible to have a bad trip, usually from taking too much or having the wrong intention. every time ive taken a lot all at once ive had bad/poor experience. every time ive taken it a lot or little but dosing a little at a time, wonderful experience.

I was actually thinking of pure muscimol though I should have made that clearer. I understand that natural sources of muscimol are unfortunately contaminated by what I believe are toxic and norsiating compounds that ruin the experience. Ibotenic acid seems particularly nasty, its used as a excitotoxin to selectively kill brain cells in animal studies of brain damage. However, I have heard that most ibotenic acid is decarboxilated to muscimol before it reaches the brain.

its not unfortunately contaminated. the mushroom is perfect as it is and actually causes very few unpleasant effects when you know what youre doing.

 

[Neuroprotection]

I am interested to hear that you find muscimol containing mushrooms emotionally easier for you. I think a big part of that is the gabaA activation, by which the trip is produced. Is it possible to extract pure muscimol using a mixture of solvents e.g. water, alcohol or napther/other non poler hydrocarbons

 

[Solipsis]

Don't extract with a mixture like that, added napthta would turn it into an acid/base extraction which is liquid-liquid extraction. Which is possible but best thought of as the second step for purification after initially getting the product out.
For just plain extraction from the mushroom would you may use methanol, this dissolves the muscimol fairly and IMO it is best to avoid water (more messy) but yes you can do that. Methanol also extracts ibotenic acid, but with heating you can convert it to muscimol. Do not heat methanol solutions with an open flame! But do evaporate the methanol as completely as possible as it is toxic (though acceptable in trace amounts).

You would also do well to realize that while this GABAergic action for a trip would make it act more on memory and fantasy related brain circuits. If there is not serotonergic action for the psychedelia, then it is hard to compare it since the full range of thoughts and feeling are not really the basis for your trip. So I'd expect that the therapeutic or self-developmental potential is more limited and instead going through the trip itself may change you or reveal something to you as dreams can also do.

So while muscimol containing mushrooms might have their merits, for sure it can be interesting, but stand entirely on their own in what they do (well with the few other GABAa agonist hallucinogens), don't think it is a great idea to consider them a substitute for serotonergic psychedelics.

Seems wise to weigh the potential negatives with the positives. I tried amanita's once but they did not work. Actually I find psilocybe mushrooms to be cryptic enough in their visionary potential, and much prefer the more lucid phenethylamines or the nicely balanced 4-HO tryptamines like 4-HO-MET.

 

[burn out]

Don't extract with a mixture like that, added napthta would turn it into an acid/base extraction which is liquid-liquid extraction. Which is possible but best thought of as the second step for purification after initially getting the product out.
For just plain extraction from the mushroom would you may use methanol, this dissolves the muscimol fairly and IMO it is best to avoid water (more messy) but yes you can do that. Methanol also extracts ibotenic acid, but with heating you can convert it to muscimol. Do not heat methanol solutions with an open flame! But do evaporate the methanol as completely as possible as it is toxic (though acceptable in trace amounts).

You would also do well to realize that while this GABAergic action for a trip would make it act more on memory and fantasy related brain circuits. If there is not serotonergic action for the psychedelia, then it is hard to compare it since the full range of thoughts and feeling are not really the basis for your trip. So I'd expect that the therapeutic or self-developmental potential is more limited and instead going through the trip itself may change you or reveal something to you as dreams can also do.

So while muscimol containing mushrooms might have their merits, for sure it can be interesting, but stand entirely on their own in what they do (well with the few other GABAa agonist hallucinogens), don't think it is a great idea to consider them a substitute for serotonergic psychedelics.

Seems wise to weigh the potential negatives with the positives. I tried amanita's once but they did not work. Actually I find psilocybe mushrooms to be cryptic enough in their visionary potential, and much prefer the more lucid phenethylamines or the nicely balanced 4-HO tryptamines like 4-HO-MET.

Wow, I am impressed with your knowledge. You are correct that it acts more on fantasy than other drugs. When I eat enough amanita, I feel like I am a kid in a magical fairy tale kingdom and I love to listen to fantasy/fairy music.

. So I'd expect that the therapeutic or self-developmental potential is more limited and instead going through the trip itself may change you or reveal something to you as dreams can also do.

This is an interesting comment as well. First of all, I wouldn't say the self-development potential is more limited, it's just different. The great developmental advantage is that amanita works at a slow pace, so you can really meditate and explore yourself without your consciousness flickering off into some other area like constantly happens with psilocybin. Your level of awareness, is much more closer to how you are sober vs being vastly accerlated like on psilocybib. The advantage of this is that it makes it easier to bring the insights back. It also helps slow down your mind and bring you into an awareness of presence. Psilocybin on the other hand, accelerates thinking to such a degree that you are actually further from having a still mind. A still mind is a great spiritual advantage.

The real value of amanita is the vibration it transmits. It has the highest vibration of any known entheogen and accoding to the soma shamans (google them) they say the red and brown amanitas are even more powerful, even higher in vibration than your standard red ones.

Amanita is not really a substitute for other psychedelics, the effects are quite different. But if I had to choose one, I would choose amanita over all else.

Biblically speaking, the manna the israelites at in the dessert was psilocybin and the Eucharist or bread of life was amanita muscaria. JD arther did alecture on this which i believe can be found on youtube.

using both amanita and psilocybin, one can transform their entire being in a very Christian sense. I am undergoing that process now. I call it "the mushroom treatment".

One question I have is does anyone use them both at the same time? I generally use them separately because I am scared of what might happen were I to take both at the same time.

 

[burn out]

I am interested to hear that you find muscimol containing mushrooms emotionally easier for you. I think a big part of that is the gabaA activation, by which the trip is produced. Is it possible to extract pure muscimol using a mixture of solvents e.g. water, alcohol or napther/other non poler hydrocarbons

why do you wanna do an extraction if you havent tried the mushrooms themselves first? They are fine, you dont need to do extractions. If you are scared of nausea you can smoke them. Ive never experience any stomach discomfort from smoking them and the effects dont last as long so its a great introduction.

You can also drink your urine after consuming them, which is like an extraction method in itself. Good luck.