How does Ayahuasca Work?

[Seraph]

With Ayahuasca the MAOI and DMT are taken together at the same time so how is there enough time for the MAOs in the stomach to be inhibited? Shouldn't the MAOs in the stomach process the DMT and the MAOIs in the stomach together meaning that the DMT is completely processed before the MAOs are inhibited to the point they should be by the MAOIs. How are the MAOs completely inhibited by the MAOIs if the DMT is taken at the same time as the MAOIs? Wouldn't this cause much of the DMT to be processed by the MAOs as the MAOs have not been sufficiently inhibited by the MAOIs at the time the DMT was processed?

 

[The Day Tripper]

I would guess that more harmalas and dmt is used in combined brews. Being that some of the dmt will be metabolized before the mao gets occupied with the harmalas. And more harmalas to speed up the inhibition of mao.

Either that, or something wacky and magical where the harmalas and dmt combine to prevent the breakdown of the molecule. I've also heard anecdotal quotes that the harmalas in the brew buffer the dmt from stomach enzymes. This seems highly unlikely though, due to the fact that the brew/stomach contents will mix as soon as you take the brew. But i think there's more too it than there's more dmt in the brew, and that accounts for some of the dmt getting metabolized.

Possibly some controlled pharma trials could be performed ad hoc by nexus members to compare potency of mixed and seperated brews/liquid pharma, along with differing times in between dosing the harmala/dmt.

 

[MelCat]

If I'm not mistaken, if you go to Amazon and drink a mixed brew with a shaman, it's not uncommon to drink several doses throughout the night.

I would gather that the first dose just sets the pace with the maoi's and then later doses really bring in the light.

 

[Apoc]

Seraph, from my own experience, I don't believe taking the harmalas and dmt together works best. I think you're right, the dmt will work better if the harmalas are previously taken. However, it seems to really work best if harmalas are both previously taken, and also taken with the dmt.

 

[AlbertKLloyd]

With Ayahuasca the MAOI and DMT are taken together at the same time so how is there enough time for the MAOs in the stomach to be inhibited? Shouldn't the MAOs in the stomach process the DMT and the MAOIs in the stomach together meaning that the DMT is completely processed before the MAOs are inhibited to the point they should be by the MAOIs. How are the MAOs completely inhibited by the MAOIs if the DMT is taken at the same time as the MAOIs? Wouldn't this cause much of the DMT to be processed by the MAOs as the MAOs have not been sufficiently inhibited by the MAOIs at the time the DMT was processed?

You are right, not only are they taken together, but effects are reported in under 5 minutes.

The scientific explanation regarding this subject is full of holes, however inhibition of the enzyme can occur at the point of administration.


There is a huge holes in MAOI theory regarding this matter, a lot of MAOI property having molecules fail to activate or potentiate DMT and allies.

While gastric MAO inhibition is an important aspect of aya pharmacology it appears that the effects of the betacarbolines upon glutamate is the primary cause of potentiation. This makes a lot of sense when you review aya additives and discover that their effect upon glutamic acid is a common theme.

Reviewing the data of aya tea composition is worthwhile in looking at this. Then consider that there is a remarkable distinction between the effects on first time users and those who use it regularly. First time users often do not feel it as quickly and can have a block to the effects that require a larger initial dose, for regular users less seems to go further quicker.

 

[Crystalito]

it appears that the effects of the betacarbolines upon glutamate is the primary cause of potentiation. This makes a lot of sense when you review aya additives and discover that their effect upon glutamic acid is a common theme.

Could you please elaborate on this or supply some references that you draw this conclusions from? It sounds a rather interesting area and i think other members would be interested as well.

 

[John Smith]

Also the question lies whenever the harmalas inhibit MAO upon(after) being digested and for a period of time following that, or whenever MAO is inhibited only while harmala's are present in the gut. Personal experience makes latter more plausible, if large dose of dry harmalas are parachuted(with very little liquid) on empty stomach, you get hit with tracers and usual effects pretty fast, but very minor/no effects are felt if main brew is drank 30-40 minutes later. Half a cup of liquid harmala's with admixtures being drank an hour to hour and a half later is usually the way to make oral tryptamines work. From what I've seen though, that doesn't work as well for others.

 

[jamie]

I drank for a long time with brews of caapi and admixture together, and I am am quite certain now after changing to brewing the mimosa seperate and dosing it 15-30 minutes after the caapi that it is much more powerful this way. When I dose the mimosa after the caapi it is like twice as potent in terms of DMT effects than if I dose together.

 

[soulfood]

My strongest experience involved waiting 45 minutes after RIMA administration.

Most of my misfires have been when consumed as one.

Strangley enough though, my longest sessions have been from simultaneous dosing. This leads me to believe it also has a lot to do with the individual's constitution/metabolism at the time.

 

[John Smith]

I think that still implies that MAO is inhibited only while harmalas are present in the gut, since it takes a while to digest a sizeable b.caapi brew. Anybody try dry harmalas via parachuting(or from a spoon) on empty stomach followed by a main brew half an hour to an hour later ? With high enough dose to get to get definite harmala intoxication(tracers, etc) PRIOR to drinking the main brew ?

 

[obliguhl]

However, it seems to really work best if harmalas are both previously taken, and also taken with the dmt.

This matches my experience. Everytime i take it at the same time, it fails me. I normaly drink the tea, wait 30-45 minutes until i feel it. Then, i might drink the DMT with some tea leftovers (the sediments).

 

[Enoon]

if I take the harmalas before the dmt I purge before the dmt is absorbed... if I take them together often I get no effect. If I fast and then take together and with some juice or something to kick start my metabolism then it usually works... will test further. I think I remember at one of the conferences I visited having heard that harmalas start working really fast, like within minutes. I don't remember who it was though that presented that information.

 

[AlbertKLloyd]

it appears that the effects of the betacarbolines upon glutamate is the primary cause of potentiation. This makes a lot of sense when you review aya additives and discover that their effect upon glutamic acid is a common theme.

Could you please elaborate on this or supply some references that you draw this conclusions from? It sounds a rather interesting area and i think other members would be interested as well.

This post here has some information about it.

http://www.shaman-australis.com/forum/index.php?showtopic=27628

I've been looking into the action of a lot of alkaloids, including caffeine, various PEAs and Tryptamines and other medicinal and psychoactive agents
something that I am learning for the first time is the significance of GABA, glutamate, NMDA receptors, and seratonin.

I recently read an article stating that blocking glutamate receptor activity attenuated the effects of LSD, I also read that Ibogaine was a NMDA antagonist, interestingly enough so is caffeine.

We next tested its efficacy in both wild type animals and in an ALS animal model of disease and demonstrated that harmine effectively increased GLT-1 protein and glutamate transporter activity in vivo.

Harmine, a natural beta-carboline alkaloid, upregulates astroglial glutamate transporter expression.
Li Y, Sattler R, Yang EJ, Nunes A, Ayukawa Y, Akhtar S, Ji G, Zhang PW, Rothstein JD.
Source

Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.

there has been a lot of speculation about MAOI effects being involved in the pharmacology of various traditional ethnobotanicals, however there has been very little if any evidence to support this notion, however there is a very strong indication that the effects involved involve NMDA and glutamate and it is interesting to learn that very recently harmine was shown to affect this.

looking at the list of NMDA antagonists (from wiki) a pattern begins to emerge:
ketamine (K),
dextromethorphan (DXM),
phencyclidine (PCP),
nitrous oxide (N2O)

when you consider that NMDA is a glutamate receptor, and that harmine affects this, the pharmacological action of harmine in traditional ethnobotanical applications becomes explainable in terms of the effects it has upon the glutamate receptor pathway, as opposed to MAOI activity


scanning through the NMDA antagonist list we find Rhynchophylline, this interesting alkaloid is found in some Uncariaspecies, which are known additives to ayahuasca!

it is interesting that caffeine is known to stimulate glutamate release and is also found in plants added to ayahuasca, such as Ilex guayusa

then you can look at nicotiana species and see that not only do they play a major role in traditional use of things like ayahuasca, nicotine also stimulates glutamate release!

I find it interesting to note that nicotine containing species are also used in a traditional setting in conjunction with both peyote and san pedro cacti.

note that known potentiators of psychedelics are NMDA antagonists, and so are numerous additives to ayahuasca, and so is harmine itself

then there are many cases of MAO inhibiting drugs that do not potentiate psychedelics or orally activate DMT,

please note also that Neuropharmacology. 2011 Jun;60(7-8):1168-75. Epub 2010 Oct 27. is the publication data for the harmine paper above, it is rather recent and not something that has had much time for people to become aware of

so while the RIMA effect does seem responsible for the oral activation of dmt by betacarbolines, it does not seem to be responsible for some of the effects of harmine, for example low doses of harmaline were said by Ott to potentiate tryptamines, that ref is here:

Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine.

there is more data to this, but i am lazy and don't want to write a big post about it right now

ok i edited this to add this:
Identification of a Novel Serotonin/Glutamate Receptor Complex Implicated in Psychosis
this is the paper that discusses the finding of the hallucinogenic effects of LSD and other similar agents to be related to the serotonin/glutamate receptor interaction, hitting only the serotonin receptor does not result in activity, likewise removing the NMDA (glutamate) receptor from the picture abolished the psychedelic activity, in this sense also it makes sense that stimulating the NMDA receptor and also affecting glutamic acid can increase subjective effects, combine this with the harmine data showing how it affects glutamate and this offers a probable explanation of potentiation of psychedelic effects via the effects of harmine upon glutamate.