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MAO-A inhibitors with phenetylamines

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Ginkgo

Ginkgo

Rising Star
MAO-A generally breaks down tryptamines, while MAO-B generally breaks down phenetylamines. Mescaline is a phenetylamine, so is the 2C-family. Harmala-alkaloids are selective MAO-A inhibitors. Then why does harmala-alkaloids seem to have a MAOI effect with phenetylamines? What am I missing here?
 
It seems that Mescaline is not broken down by MAOs at all, but rather by SSAOs (Semicarbazide-sensitive amine oxidase). Then why the potentiating of effects? Is it because the harmala-alkaloids are psychoactive in their own, so we got a synergistic effect here?
 
That's an excellent question.

I think it's because the harmala alkaloids are themselves psychoactive. I believe it's similar to how micro-doses of hyoscyamine potentiate mescaline, there's no MAOI activity involved there at all, its just their combined pharmacological effects that amplify each other.

When harmine is taken with mescaline, you get a more speedy trip generally, also the trip is about 2 times as strong. The same is true for harmaline, pretty much. But when you combine mescaline with THH (about 200 mg), the mescaline is made about 2 times as strong but the speedy effect is decreased, so it doesn’t really sound like MAOI potentiation to me.

Also, there’s an MAOI present in San Pedro (and Achuma I believe), and quite a lot of it. It’s able to greatly potentiate the effects of LSA, but does very little for mescaline.

SWIM has taken mescaline with Kava, and noticed no potentiation at all. Kava contains an MAOI-B inhibitor. The combination is quite nice, but not any stronger.

SWIM found the best boosters of mescaline to be a standard dose of caffeine and a micro dose of hyoscyamine, especially when taken together. The two potentiate the effects of mescaline in a very positive way.
 
Thank you ron, a lot of great information there! Then it does indeed seem that the stronger effects come from synergy. The SSAO enzymes are totally new to me, is it possible to inhibit them? Or would that be potentially dangerous? I guess I should read up on SSAO's role in our bodies.
 
After a short visit to Wikipedia:
SSAO's role is to catalyze the oxidation of amines to aldehydes, whereas MAO's role is to catalyze the oxidation of monoamines. Just as we have to be careful with what monoamines we consume while under (and before) the influence of MAOIs, we probably need to be careful with what amines we consume if we should inhibit SSAO. What amines generally available through food or drinks could be toxic if the metabolism is inhibited?

It does exist inhibitors for SSAO, such as semicarbazide, other hydrazines, hydroxylamine (toxic) and propargylamine. Better inhibitors are in development, see here and here.

Now, if we were to inhibit SSAOs, we need reversible inhibitors, not irreversible as some pharmaceutical MAOIs are. We also have to keep in mind, as already said, what amines we consume. I do not think anyone should try to inhibit SSAO at this point, that is not my intention! I am merely looking into a new territory for me, and likely a new territory for others. We should research this properly before any future experimentation.
 
I would NEVER mix an MAOI or any other type of drug with Trichocereus or Lophophora cacti.

I think there could be possibly negative interactions (no matter how slight).
 
[quote='Coatl]I would NEVER mix an MAOI or any other type of drug with Trichocereus or Lophophora cacti.

I think there could be possibly negative interactions (no matter how slight).
[/quote]
Why would you think so? What kind of negative interactions? With what substances? And why? Your thoughts is always welcome, but it would be great if you can state the reasoning behind them.

I have had beautiful experiences with Peruvian Torch combined with a small amount of Syrian Rue.
 
I also think its overall a bad idea. One can always find the perfect doses to potentiate cacti or mescaline because the doses for mescaline and cacti are rather high. This can be done safely but that doesn't mean its always safe.

Cacti contain many other alkaloids and tyramine. I would not recommend combining research phenylethylamines with MAOI's either thats very risky. Especially the more amphetamine like ones. Could lead to dangerous situations.

The good thing is that harmine and harmaline are reversable MAOI-A inhibitors. So things like tyramine are not really a problem when one eats foods containing it etc. But potentiating alkaloids that may not be safe (unlike mescaline) is very risky. Strong irreversable MAO inhibitors could be VERY dangerous even deadly.
 
I think every time I have ever ingested cactus I have always predosed with wither Rue or caapi, the theory being to reduce the need to ingest more cactus...many times as well...and I never ever had a problem. Lophora might be more risky maybe, with all those extra alks. That's just me though...
 
Beta carbolines - Several people reported to me that they had potentiated mescaline with Harmala compounds such as Syrian rue (Peganum harmala). The average amount ingested was around 3-5 grams of powdered or extracted seeds. Powdered seeds can be put into gel-caps to hide the intense bitterness. It is said that this method can increase the intensity of the trip 3 fold, and up to double the duration. It is said that frequent use of this combination will bring about a marked tolerance. Exercise caution as harmala compounds are MAOI's. The preferred method of ingesting Syrian rue is the water extraction technique.
Click to expand...

Erowid Cacti Vaults : Visionary Cactus Guide - Combining Mescaline and Other Substances

The San Pedro Fanatic - Visionary Cactus Guide
www.erowid.org

I dunno , why should this increase tolerance buildup ?
 
Cacti contain many other alkaloids and tyramine. I would not recommend combining research phenylethylamines with MAOI's either thats very risky. Especially the more amphetamine like ones. Could lead to dangerous situations.
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Exactly.

Perhaps you get some rare strain of Trichocereus or Lophophora that contains some trace compound that doesn't interact well with the MAOI. I just think it's taking unneeded risks and I don't think it makes the mescaline trip any better.
 
Caapi and peyote are an excellent combination, although i didn't take a full ayahuasca dose of caapi when i tried it. It makes the mescalin experience extremely euphoric.

Maybe the synergy is caused by the strenghtening effect harmalines have on synaptic connections of the serotonergic system. That could strengthen the 5-ht-2 receptor activity of mescalin maybe.

Another thing is that maybe an increased level of serotonin itself, amplifies and alters the effects of mescalin. MDMA and related susbstances elevate serotonin levels, so mescaline might become more of an euphoriant because of this effect. I personally find that when taken with caapi, peyote becomes more XTC-like indeed.
The combination beats XTC in every way.
 
Should one be cautious about mescaline and mao b inhibitors ?
Selective MAO-B inhibitors

* Catechin (found in cat's claw)
* Desmethoxyyangonin (found in kava kava)
* Epicatechin (also found in cat's claw)
* Fo-Ti (active constituent unknown)
* Hydroxytyrosol (found in olive oil)
* Lazabemide
* Pargyline (Eutonyl)
* Piperine (found in pepper)
* Rasagiline (Azilect)
* Selegiline (Deprenyl, Emsam)
 
Should one be cautious about mescaline and mao b inhibitors ?
Selective MAO-B inhibitors
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Yes. One should always be cautious when combining substances like these. Seriously.

Really the only ones that are safe are things as week as harmaline and harmine and thats only because they wear off rather quickly. Most of the irreversable MAO inhibitors A or B are way to strong to be taking and could cause a seretonin syndrome or hypertensive crisis.

Weak MAOI's also is probably not a problem.
 
Yes, it is a really bad idea to use strong irreversible MAO inhibitors. However, the main part of Observant's list is weak reversible MAOIs. None of these are dangerous to use in combination with mescaline! Secondly, a selective MAO-B inhibitor will not have the possibility to induce Serotonin syndrome, as serotonin is metabolized by MAO-A. Third, there are no use in trying to potentate mescaline (or any other entheogen for that matter) with MAO-B, as they are metabolized by MAO-A (and in mescaline's case, SSAO).

I am wondering if there is some reversible SSAO inhibitors available in plants... I guess it is too early to tell, as the role of SSAO has not been explored much. It does, however, seem fairly safe to inhibit SSAO, as SSAO inhibitors have been developed to use as anti-inflammatory agents.
 
Bumping this old thread to ask the question: what would be the problem using harmalas with extracted mescaline? I understand people liken mescaline to MDMA which is also a phenethylamine, but MDMA releases serotonin and correct me if I'm wrong but mescaline does not ? So what would all the fuss be about not taking mescaline with MAOIs ?

Add to this the dozens of people who have taken mescaline (including that which hasn't been extracted on it's own) and reported the combination caused no side effects.

Mesc + MAOI= BAD... A myth ?
 
^ I am pretty sure that the positive reports do not imply safety. That is, I suspect that a bunch of people have used MDMA with mild doses of harmala without having any adverse effects.

Having said that, the main reason behind the caution is that both MDMA and Mescaline trigger a release of serotonin, which will be increased by the use of MAO-A inhibitors. The relative rate this increase is taking place is totally unknown, which means that while some may get away with the combination, there is a very real danger of causing a serotonin syndrome (too much serotonin - leading to seizures) and/or hypertensive crisis (too much serotonin, leading to major increases in blood pressure and heart rate - leading to seizures).

Again, the reason for the caution is that we simply do not know the threshold that a wonderful experience may end up a life-threatening nightmare.
 
There have been reported death cases published in literature of people using reversible MAOIs (moclobemide) and MDMA.

Neural, do you have any source for the `mescaline releasing serotonin'? I know it is a serotonin 5-HT2 agonist but that is not the same thing...

I do not know the safety of consuming mescaline and MAOIs, but I know several people were consuming it (House would call caapi and san pedro as San Paapi and did extensive experimentation with it). As Neural said, that isn`t necessarily a proof it is safe, since it would be important to look into doses involved, possible personal sensitivities and metabolism. Of course everything is a poison at some dose but maybe it is nowhere near what people will usually consume (or maybe it is excessively close to the normal doses). Combinations of substances and using enzyme inhibitors make the whole thing much more complex of course.

We should take a look at mescaline metabolism and post information here, what enzymes are involved, what are the metabolites, etc, so we can have a better idea. Or maybe someone else who has already done that research can save us work and post the findings.

I remember one user posted a thread recently about DMPEA (a natural phenetylamine present in many cactus) and MAOI bioassay. Also it seems mimosa itself has trace amounts of phenetylamines (n methyl PEA being one of them), and people consume it regularly with MAOIs. It would be interesting to look at the pharmacology of individual phenetylamines since it isn`t possible to generalize safety issues for all phenetylamines or tryptamines at all doses.
 
The Neural said:
^ I am pretty sure that the positive reports do not imply safety. That is, I suspect that a bunch of people have used MDMA with mild doses of harmala without having any adverse effects.

Having said that, the main reason behind the caution is that both MDMA and Mescaline trigger a release of serotonin, which will be increased by the use of MAO-A inhibitors. The relative rate this increase is taking place is totally unknown, which means that while some may get away with the combination, there is a very real danger of causing a serotonin syndrome (too much serotonin - leading to seizures) and/or hypertensive crisis (too much serotonin, leading to major increases in blood pressure and heart rate - leading to seizures).

Again, the reason for the caution is that we simply do not know the threshold that a wonderful experience may end up a life-threatening nightmare.
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I wouldn't go as far as to put out that it's assuredly safe just yet. But it seems so far like there is no immediate cause for alarm, despite popular reaction. As I said, so far as I have looked into it there does not seem to be a case for mescaline being a serotonin releaser in the first place. This is what I meant by people lumping it with MDMA, when in reality the two work quite differently.

Endlessness, great suggestions as always, but why stop there ? What about psilocin and LSD ? Would the risk not be an equal unknown with these and MAOI ?
 
Orion said:
I understand people liken mescaline to MDMA which is also a phenethylamine, but MDMA releases serotonin and correct me if I'm wrong but mescaline does not ?
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My bad, I got influenced by the phrasing! No it is not known if mescaline binding triggers any release of serotonin, at least different from the established rate.

However, I see Ginkgo's input on the second post, mentioning that mescaline is not being metabolised by MAO "at all". Study on dogs says it does. Anyone has any study that shows no relation between mescaline and MAO activity?
 
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