Questioning the toxicity of Ibotenic acid

[RhythmSpring]

I'm reading the wikipedia article on ibotenic acid (present in Amanita muscaria) (Ibotenic acid - Wikipedia)

and I'm noticing a couple possible holes in the reasoning that ingesting raw amanita muscaria would be toxic because of the ibotenic acid:

1)

Most of ingested ibotenic acid is probably decarboxylated into muscimol so the effects of ingesting ibotenic acid are similar to muscimol's effects.[10]

2)

Because of this, ibotenic acid can be a powerful neurotoxin, and is employed as a "brain-lesioning agent" through cranial injections in scientific research.[2][3]

If we get the idea that ibotenic acid is toxic from a study that involves injecting the isolated chemical directly into the brain, I think we ought to look at whether it will cause brain lesions if ingested normally (orally, in a mushroom). I wouldn't be surprised if the digestive system would take care of (decarboxylate, perhaps) the ibotenic acid before it could cross the blood-brain barrier.

It's kinda like how people started saying that Artemisia absinthium was toxic at high or prolonged doses based on studies involving the isolated constituent artemisinin and anecdotal reports of people getting drunk off their asses with a little of the herb thrown in (absinthe). People take the whole herb daily for years without any adverse effects.

We gotta think level, here. Just because toxicity is being considered doesn't mean we need to stop thinking critically and just err on the side of caution. We can do better.

 

[RoundAbout]

Most of ingested ibotenic acid is probably decarboxylated into muscimol so the effects of ingesting ibotenic acid are similar to muscimol's effects.[10]

Here's Wikipedia's reference:

Ibotenic acid (pantherin, agarin), i.e. a-amino-3-hydroxy-5-isoxazoloacetic acid 1, is colourless (crystals, C5H6N2O4, mol wt 158.11, mp 150–152°C decomposition), readily soluble in cold water. Any attempt of dehydratation leads to decarboxilation yielding quantitatively muscimol, thus suggesting that a meal of the cooked mushrooms, or even after gastric digestion, would only contain the latter substance, and be the agent responsible for the main symptoms. The red skin of the cap and the yellow tissue beneath contain the highest amounts of these substances, so explaining practices in removing it (Catalfomo & Eugster 1970a).

The "a meal of cooked mushrooms... would only contain the latter substance [muscimol]" does not seem correct at all. We could argue about digestion (I doubt it is effective to decarboxylate IA, or consistent), but it is largely irrelevant because the muscimol/ibotenic acid ratio can easily be substantially improved through careful preparation (e.g. boiling in acidic water an appropriate duration). There are publications that establish the procedure. Not using spell check before publishing doesn't inspire confidence either.

There are plenty of references out there indicating that ibotenic acid crosses the blood brain barrier. Orally administering ibotenic acid is effective at causing neurotoxicity in animals (e.g. Behavioural effects in mice orally exposed to domoic acid or ibotenic acid are influenced by developmental stages and sex differences). It is reasonable to believe that taking large, frequent doses of ibotenic acid orally could lead to brain damage from excitotoxicity in people. Maybe there is a safe dose given appropriate preparation.

As far as I have seen, myths like dried mushrooms have no ibotenic acid are still common. Basic harm reduction practices are not even that common. Addressing these are the low hanging fruit IMO.

This is just an anecdote, but I have seen videos of two people who are quite experienced with amanitas acting like they have brain damage (Shaman Hawk and an anthropologist with a PhD who studied traditional use in eastern Russia IIRC). Is that enough to prove anything? No. But it's enough to steer me away.

 

[dithyramb]

This is just an anecdote, but I have seen videos of two people who are quite experienced with amanitas acting like they have brain damage (Shaman Hawk and an anthropologist with a PhD who studied traditional use in eastern Russia IIRC). Is that enough to prove anything? No. But it's enough to steer me away.

Which videos are those?

 

[RhythmSpring]

Most of ingested ibotenic acid is probably decarboxylated into muscimol so the effects of ingesting ibotenic acid are similar to muscimol's effects.[10]

Here's Wikipedia's reference:

Ibotenic acid (pantherin, agarin), i.e. a-amino-3-hydroxy-5-isoxazoloacetic acid 1, is colourless (crystals, C5H6N2O4, mol wt 158.11, mp 150–152°C decomposition), readily soluble in cold water. Any attempt of dehydratation leads to decarboxilation yielding quantitatively muscimol, thus suggesting that a meal of the cooked mushrooms, or even after gastric digestion, would only contain the latter substance, and be the agent responsible for the main symptoms. The red skin of the cap and the yellow tissue beneath contain the highest amounts of these substances, so explaining practices in removing it (Catalfomo & Eugster 1970a).

The "a meal of cooked mushrooms... would only contain the latter substance [muscimol]" does not seem correct at all. We could argue about digestion (I doubt it is effective to decarboxylate IA, or consistent), but it is largely irrelevant because the muscimol/ibotenic acid ratio can easily be substantially improved through careful preparation (e.g. boiling in acidic water an appropriate duration). There are publications that establish the procedure. Not using spell check before publishing doesn't inspire confidence either.

There are plenty of references out there indicating that ibotenic acid crosses the blood brain barrier. Orally administering ibotenic acid is effective at causing neurotoxicity in animals (e.g. Behavioural effects in mice orally exposed to domoic acid or ibotenic acid are influenced by developmental stages and sex differences). It is reasonable to believe that taking large, frequent doses of ibotenic acid orally could lead to brain damage from excitotoxicity in people. Maybe there is a safe dose given appropriate preparation. Maybe the neurotoxicity can be attenuated by supplementation (e.g. taurine maybe, I don't know though).

As far as I have seen, myths like dried mushrooms have no ibotenic acid are still common. Basic harm reduction practices are not even that common. Addressing these are the low hanging fruit IMO.

This is just an anecdote, but I have seen videos of two people who are quite experienced with amanitas acting like they have brain damage (Shaman Hawk and an anthropologist with a PhD who studied traditional use in eastern Russia IIRC). Is that enough to prove anything? No. But it's enough to steer me away.

So, literally none of your arguments qualify as actual arguments for ingesting ibotenic acid being toxic.

First of all, the study you linked shows memory deficits in mice who were administered *domoic acid*, and only *behavioral changes* in mice administered ibotenic acid.

Second of all, your argument about something not "seeming correct" has no actual clout. Furthermore, your "doubt" that "it is effective" (digestion) also comes from… where? And your argument that the above fact is "irrelevant" because there's a preparation available is not true either.

Plenty of references indicating that ibotenic acid cross the BBB? Let's see em. The study you listed doesn't relate to your assertion.

Furthermore, "It is reasonable to believe…" …why??? You're just using persuasive wording without any backup.

And your statement that "myths like dried mushrooms have no ibotenic acid…" is a red herring. So many red herrings, man. Your entire post is a fishnet full of red herrings.

Real arguments, please.

 

[downwardsfromzero]

This is just an anecdote, but I have seen videos of two people who are quite experienced with amanitas acting like they have brain damage (Shaman Hawk and an anthropologist with a PhD who studied traditional use in eastern Russia IIRC). Is that enough to prove anything? No. But it's enough to steer me away.

This in no way informs us of other aspects of their medical history or drug use that may have impacted their on-camera performance. Were they perhaps slightly drunk, or did they have a history of alcohol abuse?

OTOH, there are many tales of people's encounters under the influence of fly agaric where the spirit of the mushroom has demanded - on pain of death or permanent insanity - their reason for its being summoned, so maybe the warnings should be given due consideration. A search through the literature should confirm this anecdote, or group of anecdotes, fairly easily.

 

[Tomtegubbe]

OTOH, there are many tales of people's encounters under the influence of fly agaric where the spirit of the mushroom has demanded - on pain of death or permanent insanity - their reason for its being summoned, so maybe the warnings should be given due consideration. A search through the literature should confirm this anecdote, or group of anecdotes, fairly easily.

I'd be very interested to read some literature on the subject of fly agaric use if you could give some tips. I've always thought them to be way too dangerous even though there has been an ancient culture around them in the regions nearby.

 

[RhythmSpring]

I mean, it sounds like a serious medicine--one that you should only do if you have good reasons to, as with Iboga, or Ayahuasca, or something like that. These are not to be toyed with.

I would also like to see those accounts, but ...

I am starting to get the sense that ibotenic acid by itself is indeed a poison, but the body defuses the bomb, so to speak, by converting it into muscimol, and that process of conversion is part of what colors the trip with such intense stories as that one, where death or insanity (toxicity) is threatened, but then mitigated.

Kambo is also a poison that the body deals with, although I'm not sure that's an adequate comparison.

Another comparison could be made with Iboga--where ibogaine is converted into noribogaine. Not that ibogaine is toxic, but there is a psychoactive substance that the body converts into another psychoactive substance, and the process of converting is part of the "ordeal" of the experience. Just some guesses.

 

[jamie]

I eat fresh amanita every time I pick. I have never felt poisoned. I have only eaten small doses fresh..a few mouthfulls maybe. The effects felt consistent with amanita muscaria. Perhaps it only becomes unpleasant if ingested in large doses?...or perhaps it's part myth. I will continue eating fresh amanita in the field as it feels healthy.

I am very familiar with it's effects when dry. I pick around a kilo dry every year and I ingest it as a tea multiple times a week to deal with intense muscle cramping, joint pain and anxiety due to ankylosing spondylitis. I took benzos for a minute and started taking muscimol instead. Benzos are just bad news all around. If anyone reading this is addicted to them look into muscimol.

I do not have anything else to add, other than when dry I do enjoy higher visionary doses.

 

[Tomtegubbe]

I eat fresh amanita every time I pick. I have never felt poisoned. I have only eaten small doses fresh..a few mouthfulls maybe. The effects felt consistent with amanita muscaria. Perhaps it only becomes unpleasant if ingested in large doses?...or perhaps it's part myth. I will continue eating fresh amanita in the field as it feels healthy.

I am very familiar with it's effects when dry. I pick around a kilo dry every year and I ingest it as a tea multiple times a week to deal with intense muscle cramping, joint pain and anxiety due to ankylosing spondylitis. I took benzos for a minute and started taking muscimol instead. Benzos are just bad news all around. If anyone reading this is addicted to them look into muscimol.

I do not have anything else to add, other than when dry I do enjoy higher visionary doses.

What do you consider a safe dosage?

Is there any truth to the claim that amanitas act like deliriants so that you have hard time distinguishing what is happening in the shared layer of reality (true world) from your subjective reality (drug-induced fantasies)?

 

[Exitwound]

From my experience with Amanitas (I will be talking about muscaria unless mentioned otherwise) - you shouldn't really trip on them. Like, just don't take trip doses.

They are also tricky because potency varies greatly by: location, time of the year, form (Dried or fresh), preparation. Each batch has to be bioassayed carfully before working with them.
In my case threshold trip dose was around 5-6g dried.
Below trip dose - it is a wonderful synergetic substance, it pairs well with oral cannabis for example. It is also used often for microdosing, giving you energy boost and clarity and ability to focus and do things.
On trip doses it's a powerful dissociative and you literally don't control what your body does while your consciousness is away, you leave your "ape" meatsuit here and what it will decide to do meanwhile? Nobody knows in advance.
There are many many many instances (just read trip reports yourself) of people stepping out of the window, or cutting part of their bodies, or thrashing their house.

I advise against working with trip doses of amanitas, however on low-mid doses it's a wonderful substance. Many people dive into amanitas and trip on them, because it is legal even in countries where psychedelics are illegal. Typically it is just considered "poisonous".

Regarding ibotenic acid, I can't for the life of me find the link rn, but there is a research paper around the internet, about optimal circumstances for conversion of ibo->musci.
Basically there is this russian youtuber "баба Маша" who knows a lot about amanitas, so she was our source for the most of information about them. The tek to be safe with ibo is to first dry them slowly over 30-40 days, then simmer dried and powdered caps with lemon juice on a low heat for 2-2.5hours.
I can say from my own experience and from experience of couple of my friends who also took the same mushroom batch, that boiling them slowly with lemon potentiates it substantially. For comparison, from the same batch just raw 6g dried consumed were equal to 3-4g slowly simmered with lemon.

Also if you decide to work with amanitas anyways, just like with any substance, listen to the mushroom, it will tell you if it is a good idea to consume them on a given day or not. They also sometimes come on slowly, so have a mechanism to prevent compulsive or unsober decisions about redosing, it can fuck up your life.

P.s. Be very very careful with pantherinas, they are MUCH more powerful than muscarias. I personally avoid them. Watch Phil Stamets' trip report video about his experience with pantherina if you want a good example of what it is like to have a dissociative trip on amanitas.

 

[jamie]

I eat fresh amanita every time I pick. I have never felt poisoned. I have only eaten small doses fresh..a few mouthfulls maybe. The effects felt consistent with amanita muscaria. Perhaps it only becomes unpleasant if ingested in large doses?...or perhaps it's part myth. I will continue eating fresh amanita in the field as it feels healthy.

I am very familiar with it's effects when dry. I pick around a kilo dry every year and I ingest it as a tea multiple times a week to deal with intense muscle cramping, joint pain and anxiety due to ankylosing spondylitis. I took benzos for a minute and started taking muscimol instead. Benzos are just bad news all around. If anyone reading this is addicted to them look into muscimol.

I do not have anything else to add, other than when dry I do enjoy higher visionary doses.

What do you consider a safe dosage?

Is there any truth to the claim that amanitas act like deliriants so that you have hard time distinguishing what is happening in the shared layer of reality (true world) from your subjective reality (drug-induced fantasies)?

Like was said above, I tend to stick to 5 grams and under. At 5g brewed into a tea with lemon I begin to experience some minor dissociation(sort of like ketamine sort of like gaba?) as well as soneirogenic effects. It can be relaxing and euphoric...mildly analgesic...insightful.

Beyond that it seems to be a serious dissociative. I have not taken super high doses, and stick to under 10 grams or so. I went a bit higher a few times. I have never experienced a deliriant effect, only strong sedation followed by dissociation and oneirogenic visions.

 

[dragonrider]

Do you get withdrawals if you don't take it? I'm asking because i believe it is supposed to be a GABA-ergic.

 

[RhythmSpring]

There's probably a fine line between "withdrawals" and "recurrence of symptoms."

 

[Tomtegubbe]

From my experience with Amanitas (I will be talking about muscaria unless mentioned otherwise) - you shouldn't really trip on them. Like, just don't take trip doses.

They are also tricky because potency varies greatly by: location, time of the year, form (Dried or fresh), preparation. Each batch has to be bioassayed carfully before working with them.

Thank you for your detailed response. I'd like to ask about this one: how do you bioassay the batch? Are there other ways of testing it besides taking a very careful dose before doing more?

 

[Exitwound]

@Tomtegubbe

I don't know of any other than eating them I just take 2-3gr freshly dried and see how strong is effect. You should feel "something is different" from this amount.



@dragonrider

I never felt any withdrawals like symptoms and never heard about peole having them. Trust me it's not a substance that will let you abuse it.

I'd say quite the opposite. Get acquainted, be respectful like with any entheogen, listen to your inner feelings and mushroom will "tell" you when it's okay to take it. I still have remainders of the batch I used to microdose. Some days it felt like it was a good idea to eat them and some days I just didnt feel like it.

 

[RoundAbout]

First of all, the study you linked shows memory deficits in mice who were administered *domoic acid*, and only *behavioral changes* in mice administered ibotenic acid.

These are quotes from the paper I linked (IA is ibotenic acid if that wasn't clear):

In the FZ test, the rate of freezing during conditioning tended to decrease in males in both DA- and IA-treated groups. The male IA-10w group particularly revealed a significant decrease. Thus, cued learning was impaired and less likely to make short-term memories in the male DA- and IA-treated groups.

Therefore, the male and female DA-10w groups and the male and female IA-treated groups had impaired spatial memories. In the cued fear test, we observed no significant difference in the freezing rate (following the cued tone). However, it tended to decrease in the male DA-10w and IA-10w groups, compared to the vehicle groups. Thus, cued memory retrieval was impaired in the above-mentioned groups.

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Second of all, your argument about something not "seeming correct" has no actual clout. Furthermore, your "doubt" that "it is effective" (digestion) also comes from… where? And your argument that the above fact is "irrelevant" because there's a preparation available is not true either.

Boiling is an example of cooking: Change in Ibotenic Acid and Muscimol Contents in Amanita muscaria during Drying, Storing or Cooking* shows ibotenic acid is still present in significant quantities... drying can also preserve much of the ibotenic acid (both contrary to the review referenced by Wikipedia). Method for producing muscimol and/or reducing ibotenic acid from amanita tissue is also related (for those looking for references on converting ibotenic acid to muscimol by boiling in acidic water).

When I said it was irrelevant, I meant that spending a short time preparing the caps prevents the need to argue about whether digestion is effective. There are simple, inexpensive, consistent, clearly established ways of converting most of the ibotenic acid to muscimol (improving the ratio to be more precise). Anyways, I would guess it is insufficient assuming decarboxylation is much slower at body temperature than 100°C, considering it still takes a while at 100°C. Yeah, maybe it is relatively effective for people with low gastric pH and emptying rate assuming they chew thoroughly. Those variables still wouldn't really apply to drinking tea from dried mushrooms though, which isn't too uncommon either.

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Plenty of references indicating that ibotenic acid cross the BBB? Let's see em. The study you listed doesn't relate to your assertion.

I think that study may relate, but OK. In general, the difference between the psychoactive effects of muscimol and ibotenic acid suggest it crosses the blood brain barrier. A couple examples:

Intraperitonal injection in rats increases noradrenaline, unlike muscimol: Monoamines in the brain under the influence of muscimol and ibotenic acid, two psychoactive principles of Amanita muscaria . Glutamine injection/NMDA receptor activation in general can mediate noradrenaline release it seems (I did not look into this in particular, just browsing abstracts in a subject I am quite ignorant about). I mean intracerebral injection of glutamine or in vitro, glutamine clearly does not cross the blood brain barrier.

Here's a report of oral self-experimentation in humans found here, 237 is the primary reference:

Ibotenic acid, 20mg: Face flushing (paresthesias), no changes in blood pressure and heart rate. Migraine attack the next day postingestion; headache (occipitally localized) for the next 2 weeks.

There aren't too many studies on ibotenic acid administration in humans (perhaps unsurprisingly). Animal models are better than nothing.

In general, the assumption that ibotenic acid crosses the blood brain barrier is implicit in a lot of studies. Muscimol and ibotenic acid do have fairly similar structures.

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And your statement that "myths like dried mushrooms have no ibotenic acid…" is a red herring. So many red herrings, man. Your entire post is a fishnet full of red herrings.

I would call it harm reduction in this case. Some people do not even distinguish between sun dried vs. air dried vs. oven dried caps. Some people just assume vendors prepare them properly, and that if they arrive dried they should be ready for consumption.

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Real arguments, please.

I feel like a little bit more of the burden of evidence should be on the person asking the question. This thread was inspired by reading the Wikipedia entry, and now we're talking about feelings and our bodies defusing bombs. I'm also not sure if you read the paper you're saying is completely irrelevant (it may not be particularly relevant, but...). Making a response like this takes a long time, and it is still sloppy.

I shouldn't have mentioned any anecdotes. I'd remove them if it didn't create a gap in the discussion.

 

[jamie]

There's probably a fine line between "withdrawals" and "recurrence of symptoms."

Well yeah this^ , to some extent. I only dose it maybe 3x a week and have never noticed the type of anxiety rebound that I experience after taking valium or gabapentin for even a week. I could not take either beyond about 10 days because I can feel myself becomming physically dependent on these types of gaba agonists.

While it is true that muscimol is a gaba agonist, it's mode of action differs from other gaba agonists like ethanol or diazapam. It acts as a GABAA agonist, and afaik is more of a true GABA analogue?...working directly at the receptor site. It does not feel physically addictive, the way caffeine or benzos do...and neither do GABA supplements, which I do seem to respond to in higher doses.

It's a good question to ask when any gabaergic drugs are involved I think. Certainly among my friends/family I have seen benzos do damage and felt the pull of the spiral for a moment myself. Be careful.

 

[RhythmSpring]

For RoundAbout:

Cued learning was "impaired." Maybe the mice didn't give a crap because they were tripping. Or maybe they were impaired, but was this impairment long-lasting? And does this necessarily translate to being administered whole mushroom (where muscimol is also present)? No, it does not. There are still way too many assumptions you would have to make in order to say that that study points to eating raw Amanita muscaria being toxic.

"the assumption that isotonic acid crosses the blood brain barrier is implicit in a lot of studies." With scientific studies, you can't be implicit about things--you've got to be explicit. And I don't see any explicit proof yet that ibotenic acid from the amanita muscaria crosses the BBB.

Still, all of your arguments are weak. There may be many of them, lol, but they're still weak.

"I feel like a little bit more of the burden of evidence should be on the person asking the question." …what? I've been perusing studies just like you have, and have found no actual evidence to what I am questioning. I stand by my question.

This thread was not inspired by the Wikipedia entry, although I did use it for reference.

Mush love.

 

[RoundAbout]

Cued learning was "impaired." Maybe the mice didn't give a crap because they were tripping. Or maybe they were impaired, but was this impairment long-lasting?

This is weeks later... behavioral analysis at 12 - 13 weeks. Administered at 2 or 10 weeks... you still haven't even read it (which is your choice, but don't make baseless criticisms without reading it). I'm not even saying it's a good study. ??? Feel like I'm derailing at this point.

I've been perusing studies just like you have, and have found no actual evidence to what I am questioning. I stand by my question.

Sure.

The reason I have already formed an opinion is because I wondered the same thing in the past. My questioning was probably inspired by Wikipedia . I have used amanitas.

Best regards,

 

[RhythmSpring]

I don't have access to the full study from my computer. It's not my choice…
Could you copy and paste the section that says that the mice who were given only ibotenic acid orally remained *impaired* after 12 weeks?