Methyl chavicol is forming n,n-dimethyl-4-methoxy-phenethylamine

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69ron

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#21 [url]

May 13 08 4:37 AM

Hendrix, I think I just verified your theory. But without the proper equipment to probe into my body, I can’t be 100% sure, but I’m 99% positive you are right.

I did a test today with methyl chavicol taken 20 minutes after taking 100 mg of German chamomile oil, 100 mg of cinnamon bark oil, and 250 mg of quercetin.

The trip experienced was VERY DIFFERENT. Quercetin inhibits CYP2D6, as well as a lot of other enzymes. Quercetin weakens and prolongs the effects of codeine as well as elemicin because it inhibits CYP2D6. These both seem to require CYP2D6 enzymes in order to elicit their proper effects. But the opposite happens with methyl chavicol.

My test with methyl chavicol answers the question posed above. Unlike elemicin, a CYP2D6 inhibitor does NOT prolong the effects of methyl chavicol, nor does it shorten the effects. But rather it makes the effects far less stimulating and more visually psychedelic.

This means methyl chavicol is being converted into hordenine (or something very similar) by CYP2D6 and producing stimulant effects. With CYP2D6 inhibited it no longer produces stimulant effects, but is almost entirely psychedelic and seems to lower blood pressure a little bit. At least that’s my impression of it. This means something like n,n-dimethyl-4-methoxy-phenethylamine is actually the active metabolite here.

I think this helps shed some light on elemicin’s active metabolite. Rather than the active being O-demethylated at the middle, the active metabolite is probably O-demethylated on the 1st or 3rd methlyl group on the benzene ring, so that the active is something like n,n-dimethyl-3,4-dimethoxy-phenethylamine or n,n-dimethyl-4,5-dimethoxy-phenethylamine and not n,n-dimethyl-3,5-dimethoxy-phenethylamine as I previously speculated.

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toastus

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#22 [url]

May 13 08 4:12 PM

So the only thing for which CYP2D6 is required is Elemicin? Do we still need clove oil for elemicin?

So this should be the appropriate inhibitor setup:
Apiole: German Chamomile oil, 250 mg Quercetin
Elemicin:
German Chamomile oil, Cinnamon Bark oil, Clove Leaf oil
Estragole:
German chamomile oil, Cinnamon bark oil, 250 mg Quercetin.
Methyl Eugenol: ???
Myristicin:
German Chamomile oil, 250 mg Quercetin
Safrole: German Chamomile oil, Cinnamon Bark oil, 250 mg Quercetin

Also, I'm wondering whether Methyl Chavicol is converted into N,N-Dimethyl-Chavibetol to be active, now that we know it isn't converted into hordenine. Elemicin might follow a similar route. This also leads to some possible activity for Eugenol!






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69ron

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May 13 08 10:39 PM

So the only thing for which CYP2D6 is required is Elemicin? Do we still need clove oil for elemicin?

-toastus

That seems to be correct. The 3 methoxy groups on elemicin’s benzene ring seem to prevent psychedelic action. Safrole, myristicin, and methyl chavicol don’t have that issue. For elemicin, at least one of the methoxy groups needs to be converted to a hydroxyl group by CYP2D6 before psychedelic action is possible. It’s probably either position 3 or 5, but not position 4 that must be hacked away by CYP2D6.

I think if position 4 gets demethylated it’s no longer psychedelic, but one or both of the other methoxy groups should be demethlylated. I base this hypothesis off of the fact that CYP2D6 inhibition makes methyl chavicol more psychedelic by preventing the 4 position’s methoxy group from converting to a hydroxyl group. With methyl chavicol CYP2D6 makes it have stimulant effects like hordenine. So the 4 position probably needs to be a methoxy group.

I think one reason the effects of elemicin are more iffy than the others is that sometimes CYP2D6 demethylates the wrong methoxy group leading to inferior effects. Sometimes it’s a mix, and sometimes only the right one is demethylated producing effects that rival those of mescaline. It’s been my experience that the effects are different each time I use elemicin (with CYP1A2, CYP2A6, and CYP2E1 inhibited). Sometimes it’s more like a phenethylamine, sometimes it’s more like a tryptamine, sometimes it’s not so interesting.

So this should be the appropriate inhibitor setup:
Apiole: German Chamomile oil, 250 mg Quercetin
Elemicin: German Chamomile oil, Cinnamon Bark oil, Clove Leaf oil
Estragole: German chamomile oil, Cinnamon bark oil, 250 mg Quercetin.
Methyl Eugenol: ???
Myristicin: German Chamomile oil, 250 mg Quercetin
Safrole: German Chamomile oil, Cinnamon Bark oil, 250 mg Quercetin

-toastus

That’s about right.

For elemicin, keep the clove oil very low. It takes away from the euphoria if too much is added.

I think in most cases cinnamon bark oil is beneficial. Although, quercetin might make up for what cinnamon does enzymatically. It inhibits a heck of a lot of P450 enzymes. It’s weak for inhibiting CYP1A2 though, and that one kills a lot of these oils, so German chamomile is a must for all of these oils. CYP2A6 also kills a lot of these oils. If quercetin’s effects on CYP2A6 are good enough, cinnamon can probably be removed from most of these mixes. However, cinnamon’s effects are pleasant and as long as the dose is small, it seems to go well with the effects of these oils.

The bonus of using quercetin is that it also inhibits MAO-B, which should help the transamination process complete without being cut short quickly thereafter.

If you mix myristicin, safrole, and elemicin together, CYP2D6 seems to prefer to attack elemicin. The same seems to be true when you mix methyl chavicol with elemicin. I think CYP2D6 has a higher affinity towards elemicin than these others. Because of this, elemicin effectively acts like a competitive CYP2D6 inhibitor for these other oils. That’s why they are more potent when mixed with elemicin, I believe.

So if you want a more visual experience from these other oils, predose with Gerrman chamomile and cinnamon bark oil, and use elemicin as a competitive CYP2D6 inhibitor. If you want a less visual experience, use quercetin instead of elemicin.

Also, I'm wondering whether Methyl Chavicol is converted into N,N-Dimethyl-Chavibetol to be active, now that we know it isn't converted into hordenine. Elemicin might follow a similar route. This also leads to some possible activity for Eugenol!

-toastus

N,N-Dimethyl-Chavibetol? That has an extra hydroxyl group added to it on the 5 position. What’s your reasoning for thinking a hydroxyl group would be added to it at the 5 position for activity?

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toastus

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May 14 08 2:59 AM

It's based on an incomplete understanding of the actions of the enzymes. It assumes that some of the enzymes are capable of hydroxylating (which some are, look at hydroxysafrole). You've also speculated about its metabolism before, along with the metabolism of methyl eugenol, saying that methyl eugenol might be converted into chavibetol to become active. However, if it's possible that methyl eugenol becomes a compound similar to dopamine instead of chavibetol, then it's possible that Estragole is converted to Chavibetol, considering their similar structures.

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toastus

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May 21 08 1:43 AM

Hey, if Elemicin and estragole need the central methoxy group to be active, and elemicin is activated by removal of one or more of its peripheral methyl groups, then that helps explain Eugenol , Methyl Eugenol, and Chavibetol!

Eugenol doesn't have the central methoxy group, only a hydroxy. I'm thinking that the altered central group (which is needed for visionary activity) produces the drunken/ toxic effects by abnormally interacting with the same systems that elemicin and estragole interact with. This fits seamlessly with the explanation of elemicin and estragole metabolism.

Methyl Eugenol starts out with the central methoxy group, so it can turn into the opposite of eugenol: Chavibetol. The methoxy and hydroxy groups are switched between Eugenol and Chavibetol, so theoretically chavibetol should be an active visionary compound.

However, methyl eugenol also has the capability of being active on its own. It doesn't need demethyl-metabolism to be active, as far as I know, because Estragole doesn't have methyl groups and yet is active without de-methylation.

Unless a hydroxy group is necessary for visionary activity? It would have to be situated around a central methoxy group (which is opposite the allyl tail). Elemicin could have it on either side. Estragole could have it on a single side, turning it into Chavibetol. Methyl Eugenol could turn into elemicin! looool (unless, of course, elemicin actually adds another hydroxy group on the 2 or 5 positions...)


ARGH, I just opened a can of worms, lol...

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hendrix

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May 24 08 7:15 AM

Yea it looks like the middle methoxy group on the exact opposite side from the tail is important for visual effects. Methyl chavicol has that, and taking it with a CYP2D6 inhibitor that prevents it from becoming a hydroxyl group makes it more visual like Ron said (I tried methyl chavicol with 2 cups of white grapefruit juice and confirmed it myself). Eugenol has a hydroxyl group there instead of a methoxy group and so it’s not visual. Elemicin has it there, plus two on either side, and it is visual, but it needs CYP2D6 to chop off one of the side methoxy groups. Taking elemicin with a CYP2D6 inhibitor fucks it up, so we can’t have a methoxy group on each side of the center one, but probably 1 on one side is fine. CYP2D6 probably doesn’t always chop off the same methoxy groups ones on every elemicin molecule, and that would explain why each trip is a little different.


Myristicin is basically elemicin, but with two of the methoxy groups tied together making a methylenedioxy group. Myristicin has a lot more mental psychedelic effects because of this change. A high dose of myristicin is mind blowing. Elemicin is mostly just a visual beast. Myristicin is more like acid.


Safrole is myristicin with the untied methoxy missing. I don’t know much about this one’s effects.

 

Methyl eugenol is probably active if taken with the right inhibitors. It’s basically safrole without the methoxy groups tied together. The methoxy groups of methyl eugenol are in the same position as safrole’s and myristicin’s methylenedioxy groups and these are active, at least I know myristicin is for sure, I’m not 100% sure about safrole, so methyl eugenol is probably active.


I bet methyl eugenol is active with a strong CYP2D6 inhibitor and a strong CYP1A2 inhibitor. I bet the same is true for chavibetol. I never tried these. I would like to. My idea is to try them with 2 cups white grapefruit juice for CYP2D6 inhibition, and 4 drops of German chamomile oil for CYP1A2 inhibition. I would like to see what the difference is between these two beasts.

Between the eyes and ears there lie The sounds of colour and the light of a sigh

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toastus

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#27 [url]

May 24 08 1:35 PM


Eugenol has a hydroxyl group there instead of a methoxy group and so it’s not visual.


-hendrix

I wasn't stating that it's not visual because of the missing methyl group, I was stating that the missing methyl group makes it toxic and depressive to the nerves like it is. It's ok in small doses, but I'm saying that's probably why it's toxic. Unless Eugenol doesn't interact with 5-HT2 at all... lol
But then again, it might still work, because we don't know exactly where any of these essential oils once converted bind at all. They might bind to more than just the 5-HT2 receptor.


CYP2D6 probably doesn’t always chop off the same methoxy groups ones on every elemicin molecule, and that would explain why each trip is a little different.



-hendrix

But it wouldn't matter if it chopped off the left or right one, because this molecule isn't stereoscopic. The molecule would be exactly the same whether the left or right methoxy groups were severed, because the allyl tail would reorient itself to fit the new molecular shape. So really the trips would be different from whether CYP2D6 severs either one or both of the methoxy groups.

Myristicin is basically elemicin, but with two of the methoxy groups tied together making a methylenedioxy group. Myristicin has a lot more mental psychedelic effects because of this change. A high dose of myristicin is mind blowing. Elemicin is mostly just a visual beast. Myristicin is more like acid.


-hendrix


Interesting. I can't wait to try it, I've just got to get away from life for 2 days... lol


Safrole is myristicin with the untied methoxy missing. I don’t know much about this one’s effects.


-hendrix


Definitely a worthwhile entactogenic experience.
 

Methyl eugenol is probably active if taken with the right inhibitors. It’s basically safrole without the methoxy groups tied together. The methoxy groups of methyl eugenol are in the same position as safrole’s and myristicin’s methylenedioxy groups and these are active, at least I know myristicin is for sure, I’m not 100% sure about safrole, so methyl eugenol is probably active.

I bet methyl eugenol is active with a strong CYP2D6 inhibitor and a strong CYP1A2 inhibitor. I bet the same is true for chavibetol. I never tried these. I would like to. My idea is to try them with 2 cups white grapefruit juice for CYP2D6 inhibition, and 4 drops of German chamomile oil for CYP1A2 inhibition. I would like to see what the difference is between these two beasts.


-hendrix


Niceeeeee
I want to try them too but I don't know where to get them.

Also some cool things to think about are Apiole and Allyl-tetra-methoxy-benzene. They all have 4 groups on them instead of elemicin and myristicin's three groups. Apiole has an extra methoxy group compared to myristicin, and Tetra-MeO-Allylbenzene (there are many ways to orient it's name; I like this one, but I think the official name is the first one: Allyl-tetra-methoxy-benzene) has an extra methoxy compared to Elemicin. I do know that Penta-MeO-Phenethylamine is supposed to be just like mescaline (Tri-MeO-PEA) except 100 times more potent, so maybe Tetra-MeO-PEA is formed out of Allyl-tetra-methoxy-benzene and it's better than elemicin.

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69ron

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#28 [url]

May 25 08 12:19 AM

Well for methyl eugenol you can use Mexican allspice. It would better to use the oil, but the powder is not that bad tasting when mixed with milk and some sweetener.

I've tried Mexican allspice before at 5 grams along with 6 drops cinnamon oil, 5 grams German chamomile flowers, 10 drops methyl chavicol, and I got lot lasting effects from it (about 24 hours). I could not feel the methyl chavicol at all. It felt like it was on the verge of being psychedelic, but never became psychedelic despite having an active dose of methyl chavicol added to it. It had a strong “tryptamine” feel to it. I felt a little cut-off from reality, slightly sedated, similar to the “melatonin” effect I get from elemicin sometimes if I don’t use enough inhibitors with it. As it was, it was very different from the other oils I’ve tried and nothing like eugenol, so my Mexican allspice is probably very low in eugenol. The fact that the methyl chavicol added to the mix could not be felt at all sort of suggests that the effects of methyl eugenol might anti-psychedelic at this dose.

One thing missing from the test however was a good CYP2D6 inhibitor.

With the knowledge that methyl chavicol is more psychedelic if CYP2D6 is inhibited as well as CYP1A2 and CYP2A6, the next time I try this I’ll use it with quercetin and cinnamon bark oil.

Quercetin is known as a potent inhibitor of CYP1A2, CYP2C8, CYP2C9, and CYP3A4, with some effects on CYP2A6 and CYP2D6. It seems in me that at 250 mg quercetin is a potent CYP2D6 inhibitor. For me, 250 mg are able to delay the onset of the psychedelic effects of elemicin by about 6 hours. That means it inhibits CYP2D6. That dose also greatly improves the effects of methyl chavicol for me, making it far more psychedelic, again showing that it inhibits CYP2D6 greatly in my body.

So my next test with methyl eugenol will utilize the same 5 gram dose of Mexican allspice powder along with 250 mg of quercetin and 6 drops of cinnamon bark oil. It’s possible quercetin will inhibit CYP2A6 enough that the cinnamon bark oil is not needed, but I’ll add it just in case.

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69ron

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#29 [url]

May 25 08 12:27 AM

Interesting. I can't wait to try it, I've just got to get away from life for 2 days... lol

-toastus



I’ve used the high boiling fraction of nutmeg oil which contains only myristicin, elemicin, and safrole, and the effects are very nice. It lasted a total of about 10 hours not 2 days.


If you use pure myristicin you don’t need 2 days for it. Pure myristicin doesn’t last that long. The reason it lasts that long when you use nutmeg is that nutmeg contains compounds in it that greatly extend the effects of myristicin.


I do know that Penta-MeO-Phenethylamine is supposed to be just like mescaline (Tri-MeO-PEA) except 100 times more potent, so maybe Tetra-MeO-PEA is formed out of Allyl-tetra-methoxy-benzene and it's better than elemicin.

-toastus



Penta-MeO-phenethylamine is like mescaline but 100 times more potent? I’m having a hard time finding information on this molecule. What’s the CAS number of this molecule? Is it in PiHKAL?


Also, where can allyl-tetra-methoxy-benzene be found? I would like to test this.

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toastus

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May 25 08 6:34 PM


I’ve used the high boiling fraction of nutmeg oil which contains only myristicin, elemicin, and safrole, and the effects are very nice. It lasted a total of about 10 hours not 2 days.

If you use pure myristicin you don’t need 2 days for it. Pure myristicin doesn’t last that long. The reason it lasts that long when you use nutmeg is that nutmeg contains compounds in it that greatly extend the effects of myristicin.

-69ron

This is great news. What about the effects from Parsley oil high in myristicin and low in apiole? The parsley oil is near 50% myristicin. How long would that last?
Also I've noticed that quercetin inhibits CYP1A2, so shouldn't that allow us to omit the Chamomile and only use Quercetin and Cinnamon oil?


Penta-MeO-phenethylamine is like mescaline but 100 times more potent? I’m having a hard time finding information on this molecule. What’s the CAS number of this molecule? Is it in PiHKAL?

Also, where can allyl-tetra-methoxy-benzene be found? I would like to test this.

-69ron


Oops, never mind, it's 8 times more potent than mescaline: http://bitnest.sslpowered.com/external.php?id=%257DbxUgXXC%2540EGjxy%2504%2505QSQ%2505WJ

Check out these sources:
http://books.google.com/books?id=2AEtSKfB2nUC&pg=PA66&lpg=PA66&dq=allyltetramethoxybenzene&source=bl&ots=VxAl5k3JYP&sig=cI0TJNHVnQ_yN5yFHLt7i21of9k&hl=en&ei=GvehTYKXOJO2tgfq2eGNAw&sa=X&oi=book_result&ct=result&resnum=8&ved=0CDoQ6AEwBw#v=onepage&q=allyltetramethoxybenzene&f=false

http://www.springerlink.com/content/t450361g3v831967/

They say that Allyltetramethoxybenzene can be found in Leaf Parsley seeds up to 12.8%!

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69ron

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May 25 08 7:44 PM

This is great news. What about the effects from Parsley oil high in myristicin and low in apiole? The parsley oil is near 50% myristicin. How long would that last?

-toastus

I’ve tried it a few times. With parsley seed oil high in myristicin you feel the effects of the myristicin for about 48 hours. I’m not sure what’s in parsley seed which causes this. I’ve read that parsley seed oil contains MAO inhibitors.

Parsley has a speedier effect than the high boiling fraction of nutmeg has. You definitely feel a slight amphetamine-like effect from it. Perhaps that’s the small amount of apiol causing that effect?

Each time I tried parsley seed oil I used it as is without any inhibitors. It seems to contain its own inhibitors, and works in me as is. But that might not be the case for everyone.

Also I've noticed that quercetin inhibits CYP1A2, so shouldn't that allow us to omit the Chamomile and only use Quercetin and Cinnamon oil?

-toastus

Yes quercetin potently inhibits CYP1A2 and it can be used stand along with methyl chavicol, and probably also myristicin and a few others except elemicin; quercetin ruins the effects of elemicin because it inhibits CYP2D6. If using quercetin, there’s no need for cinnamon oil with methyl chavicol. I’ve confirmed that in my own tests where I took 250 mg of methyl chavicol 20 minutes after taking 250 mg of quercetin and nothing else. The methyl chavicol was very effective that way. If using quercetin, I’ve found that German chamomile and cinnamon bark are completely unnecessary.

Whenever quercetin can be used in place of German chamomile oil and cinnamon oil, I think it’s a good idea to use it instead because it lowers the amounts of essential oils your body needs to process.

Also taking trimethylglycine (betaine anhydrous) with these oils is a good idea health-wise. TMG helps the body remove oils from the liver by means of methylation. It’s this liver “detoxifying” mechanism where the liver methylates essential oils which I believe is a necessary step for transamination of allybenzenes to occur. Some people are deficient in this ability, and supplementation with TMG normally fixes that issue. I think I’m not deficient in this ability, so it’s hard for me to say if its really working for me or not. At any rate, I’ve found that taking TMG doesn’t hurt, and since I’ve been using it, my allybenzene experiences seem to be working more completely.

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69ron

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May 25 08 7:52 PM

They say that Allyltetramethoxybenzene can be found in Leaf Parsley seeds up to 12.8%!

-toastus

That's impressive. But what is "leaf parsley seeds"? How is that different from normal parsley seeds? Is this something we can purchase somewhere?

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toastus

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May 25 08 8:30 PM


That's impressive. But what is "leaf parsley seeds"? How is that different from normal parsley seeds? Is this something we can purchase somewhere?

-69ron

1.) Leaf parsley, I'm assuming, is parsley bred for leaf production, while Root Parsley is bred for root production.

2.) So parsley seed oil lasts for 48 hours, but pure myristicin lasts only 10 hours?
What about combining parsley seed oil with Quercetin?

3.) Also, do you think its a good idea to use Soy Lecithin granules to help your body absorb these oils, or does that have no effect?

4.) So it's possible to not need any essential oil inhibitors for everything (except for elemicin)? So we can use quercetin as the universal inhibitor (minus elemicin)?

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69ron

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May 25 08 9:53 PM

So is the typical Parsley seed oil of the curly leaf variety which is high in myristicin also the "leaf parsley" variety or is it the “root parsley” variety?

The curly leaf variety is pretty much the only kind of parsley seed oil you can buy. I have never seen the flat leaf variety available for sale. The flat leaf variety, also known as Italian parsley, is high in apiol, and because of that the oil is almost solid. Its very difficult to use it for aromatherapy because the oil is almost solid, and tends to form crystals on the shelf, so stores don’t stock it. That’s why you can’t find it for sale at aromatherapy shops.

I’m guessing the typical Parsley seed oil from Hungary, which is the curly leaf variety high in myristicin, is also the “leaf parsley”. I don’t see the curly leaf variety ever called “root parsley”. Does anyone know for sure if that’s correct?


Using quercetin with parsley seed oil is questionable because it inhibits CYP2D6 in addition to CYP1A2, CYP2A6, and the others. If it contains allyltetramethoxybenzene, then CYP2D6 is probably essential to getting decent effects from that oil.

Perhaps the allyltetramethoxybenzene content of parsley seed oil is why the oil is super potent? It seems more potent that it should be.


I’ve not noticed much difference in using soy lecithin. I do usually add a little vegetable oil, and eat something with fats and oils (like peanut butter or whole milk) after taking these oils because that helps you digest them. Soy lecithin is supposed to help you digest oils though. It’s also supposed to help protect the liver. I can’t see a reason not to use it.  But I haven’t noticed a real benefit from it.


It seems like quercetin can be used as a near universal inhibitor for allylbenzenes, except in cases where CYP2D6 cannot be inhibited. So that means it can’t be used with elemicin (I verified this myself), and very likely something like allyltetramethoxybenzene.

If we knew exactly which metabolite of elemicin via CYP2D6 is the active metabolite, that would be very helpful. There are likely 4 metabolites of elemicin created by CYP2D6: one with either side converted to a hydroxyl, one with the center converted, one with a side and center converted, and one with all converted. Which ever is the main active metabolite, I’m sure there exists such a metabolite already found in nature. The active allylbenzene is likely one with one or two sides converted, but not the center. Such an allylbenzene would need to be taken with a CYP2D6 inhibitor in order to be active. This would be perfect. Having to rely on CYP2D6 to hack away the molecule to get an active metabolite is not good. This is the main reason why elemicin is so unpredictable in a lot of people. CYP2D6 levels vary on a daily bases, vary be genetics, etc. Some people totally lack CYP2D6 and cannot trip from elemicin at all. But if the proper CYP2D6 metabolite was identified, then people who can’t trip from elemicin should be able to trip from such a metabolite by taking it with a CYP2D6 inhibitor.

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toastus

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#35 [url]

May 26 08 3:25 AM

Using quercetin with parsley seed oil is questionable because it inhibits CYP2D6 in addition to CYP1A2, CYP2A6, and the others. If it contains allyltetramethoxybenzene, then CYP2D6 is probably essential to getting decent effects from that oil.
Perhaps the allyltetramethoxybenzene content of parsley seed oil is why the oil is super potent? It seems more potent that it should be.

-69ron

We should probably test this out. I still need to test the parsley oil by itself, but its effects with oil inhibitors should be tested with that of quercetin as an inhibitor. Compare how it feels with oils and with quercetin. I'm not sure if that report about Tetra-MeO-Allylbenzene is accurate for all essential oils of parsley, so it may not be in your essential oil sample. But it might, so we should test it.


If we knew exactly which metabolite of elemicin via CYP2D6 is the active metabolite, that would be very helpful. There are likely 4 metabolites of elemicin created by CYP2D6: one with either side converted to a hydroxyl, one with the center converted, one with a side and center converted, and one with all converted. Which ever is the main active metabolite, I’m sure there exists such a metabolite already found in nature. The active allylbenzene is likely one with one or two sides converted, but not the center. Such an allylbenzene would need to be taken with a CYP2D6 inhibitor in order to be active. This would be perfect. Having to rely on CYP2D6 to hack away the molecule to get an active metabolite is not good. This is the main reason why elemicin is so unpredictable in a lot of people. CYP2D6 levels vary on a daily bases, vary be genetics, etc. Some people totally lack CYP2D6 and cannot trip from elemicin at all. But if the proper CYP2D6 metabolite was identified, then people who can’t trip from elemicin should be able to trip from such a metabolite by taking it with a CYP2D6 inhibitor.

-69ron

Is it possible to find out where this metabolite exists naturally? Could we do chemical modifications of elemicin/mescaline and test it out (remove one or both methyl groups)?

Also, what if Methyl Eugenol was converted to the active metabolite of elemicin? It might not be de-methylated, but it might gain a hydroxy group. :O

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69ron

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May 26 08 10:41 AM

The fact that the body can add hydroxyl groups to the benzene ring makes this somewhat difficult to plot out. I’m trying to avoid thinking about that for now, it really complicates things. I hope it’s not essential, but it might be.


I have still not tried methyl eugenol with a CYP2D6 inhibitor. CYP2D6 causes methyl eugenol to form chavibetol and eugenol, this is a known fact. I don’t think this is desirable at all. My guess is that it will be psychedelic with a CYP2D6 inhibitor (as long as CYP1A2, CYP2C9 and CYP2E1 are also inhibited, as these are the main 1-hydroxylation enzymes for methyl eugenol).


Quercetin strongly inhibits CYP1A2, CYP2C8, CYP2C9, and CYP3A4, with some effects on CYP2A6, CYP2D6, and CYP2E1 (I’ve just learned). At 250 mg quercetin for me CYP2D6 seems to be completely inhibited. With methyl eugenol you also need CYP1A2, CYP2C9 and CYP2E1 inhibited or 1-hydroxylation occurs, which is bad news. So quercetin might not be good enough stand alone with methyl eugenol unless the CYP2E1 inhibiting action of quercetin is strong enough at 250 mg. If not, cinnamon bark oil might also need to be used.


I think I’ll try it with just quercetin as a first test. According to one study quercetin’s CYP2E1 inhibition actions are as potent as it’s CYP2D6 inhibition actions, and since at 250 mg it’s CYP2D6 inhibition seems complete in me, it’s CYP2E1 inhibition action should be good enough at that dose.

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toastus

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Posts: 1,663

#37 [url]

May 26 08 3:14 PM

The methyl eugenol test would be a good break from PEA.

So this could theoretically mean that Methyl Eugenol becomes the same thing as elemicin and mescaline, with one hydroxyl group and two methoxyl groups. Test out Methyl Eugenol, and if it's active like elemicin with Quercetin then we will have found out exactly how all three compounds are metabolized. If you get no effects, then up the dosage. Haha

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hendrix

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#38 [url]

May 27 08 7:57 AM

Guys the TMG supplementation is a very good idea. It helps clean up these oils from the liver.

I think though it's not the "missing piece" to all of this. I think it is a vital piece of the transamination process. But there is something else that is missing from this.

If you take TMG with methyl chavicol and use grapefruit juice and German chamomile as I've done, it doesn't increase the visuals or do anything noticeable UNTIL YOU EXERCISE! Then WHAM! SUPER VISUALS! The missing piece has something to do with exercise and TMG. Without the TMG the exercise does boost the effects a little, but with the TMG it boosts the visuals like crazy. I'm not talking about simple exercise like walking. It needs to be vigorous enough to make you sweat.

We know that exercise increases methylation. TMG helps fuel methylation but it doesn't cause methylation. Exercise causes methylation to occur.

So I think the missing piece is a methylation booster. What stimulates methylation? Taking a TMG supplement ensures that you have the building blocks for the methylation, but doesn't cause it to happen. I think that's the missing piece.

The free sample elemicin "activator" tablets I got once which caused super amazing visuals with elemicin gave me a feeling similar what I get if I do vigorous exercise while on one of the oils. It was like a mild adrenalin boost. I think the actives in those "activator" tablets were something high in TMG, some inhibitors (chamomile, cinnamon, etc.), and something that caused a tiny adrenalin boost. Maybe cayenne pepper? I didn't write down the ingredients. I think it did have cayenne pepper extract in it. But I'm not too sure about it.

I think these are all the pieces we need:

1 - P450 enzyme inhibitors (chamomile, cinnamon, etc.)
2 - TMG to fuel the methylation process that turns these oils into dimethylphenethylamines.
3 - Adrenalin (or something like it) to jump start the methylation process.

I think we have 1 and 2 nailed down. That part is solid. Piece 3 is missing. We could always just run a marathon while using elemicin, TMG, and the inhibitors. It works really well. Without the TMG it doesn't work so well. TMG is the fuel, but doesn't provide the jump start to get the methylation going. Something about exercise jump starts the methylation process. Exercise increase methylation and this is a proven fact and I can give references to it if you like.

I propose that we search for an herb extract that does piece 3 without physical exercise. I'm thinking a high dose of cayenne pepper might work. I will try it myself. Cayenne has the same problem cinnamon has though, they mess with your stomach and can cause heart burn. That ain't cool. I've had heart burn from both of them a few times.

You can't have piece 3 without piece 2. They go hand in hand. You can't drive to work in a car without gas, and you can't drive to work on a bucket of gas. You need to put the gas in your car, and then you can drive to work. Piece 2 and 3 are like that. TMG provides the fuel, but only exercise starts the process going.

So what herb extracts can trigger methylation just like exercise does?

Between the eyes and ears there lie The sounds of colour and the light of a sigh

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#39 [url]

May 27 08 9:29 AM

For your general entertainment I'm telling  how I purchased Betaine.
In my south-european country, at least in my area, at first I was not able to find TMG: the doctor refused the prescription stating  he does not know what it is, the pharmacist refused to purchase without a doctor recipe, natural food-herbs or integrator shops never heard of Betaine before.
I developed an increasing determination to get this stuff because i realized it is very useful to improve my compromised liver condition.
Finally I found it, 100 % pure... at an online fishing shop located not far from my province: it appears Betaine is a wonderful ingredient for baits.  It costed me € 10 per 100 grams, home forwarding included.
I learned also that TMG is recommended as supplement for horses health.
I was little disappointed when i felt the smell of this stuff, which is a sperm\fishy odor, but incapsulated it becomes manageable.
--------
The exercise factor is not new, the "elders" here should know : it emerged in analog discussion on another board the last year ( but i came across it only recently) and it seemed overcome by the cytochrome issues. Instead thank to you Hendrix, this factor  re-establishes its importance.
Very good! 


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#40 [url]

May 27 08 12:15 PM

my pizza-baker, who is also a skilled latin dancer, told me recently that when he goes to the ballroom he is normally sweating just before the end of the first 3 mins song.

Or do you you prefer Shaking Meditation? Maybe running in the wild ? It's fantastic !
I think it's a fine opportunity to have the exercise as component of the trip: it subtracts power from the drug returning it to the living system. Or are you too lazy for a 5 mins dancing ?
This aspect of movement raise a big interest on the role of ritual dancing in many ecstatic cultures.

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