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Research that suggest MAOI could attenuate effect of DMT

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Shattered_Symmetry

Shattered_Symmetry

Rising Star
Hi all,

Just finished reading a very interesting article that I thought was worth sharing. It is a summary of research carried out by Jonathan Ott on the effects of MAOI on DMT and LSD.

He discusses that the use of an MAOI is a double edged sword, as while it inhibits Monoamine Oxidase in the intestine preventing the destruction of the DMT it of course causes an increase of serotonin in the brain. His experiments concluded that increased amounts of serotonin reduced the effectiveness of DMT as when a serotonin antagonist such as an antipshychotic were administered before an intramuscular injection of DMT the effects were significantly more pronounced than if an MAOI were taken instead. Thus he says that on balance MAOI does not potentiate the effects of DMT it actually attenuates them. Perhaps if a serotonin antagonist were added to the mixture the SSRI qualities of the Beta Carbolines would be counteracted while succesfully inhibiting the pesky monoamine oxidase, resulting in an insanely powerful long lasting trip?

This may also offer an explanation as to why there is no easy way to dose oral DMT taken with an MAOI. the MAOI may cause some people to release more serotonin than others meaning some people will require a higher dose of DMT and the dose wouldn't be dependent on simple body weight.
 
We've been discussing, elevating serotonin levels to end trips in the 'trip-abortion' thread. Within the nexus there's still a debate going on whether increased levels of serotonin increase or diminish the effects of classic hallucinogens.
I think it will indeed diminish the effects of them.
 
This has been my experience with sublingual harmalas. Too large a dose (over 20mg) requires a larger dose of DMT to get breakthrough effects. A lower dose of 10mg or so slows the experience without noticeably attenuating it (although the slowing itself is no doubt an effect of attenuation).

I once had a visualization of this process during an experience: the harmalas were acting as “gatekeepers” – regulating the rate at which DMT could attach to receptors. The harmalas were in effect controlling the experience.
 
Hmm. This is very interesting. I always assumed that it was better to go with more harmalas. Now it seems there is a sweet spot for both, the harmalas and dmt.

I may have to go back to the drawing board with my pharma experiments.
 
polytrip said:
We've been discussing, elevating serotonin levels to end trips in the 'trip-abortion' thread. Within the nexus there's still a debate going on whether increased levels of serotonin increase or diminish the effects of classic hallucinogens.
I think it will indeed diminish the effects of them.
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It does, because psychedelics compete with serotonin for 5HT binding sites.
I won't elucidate ways to counteract this.
 
This also fits with what I have found with adding extra harmine/harmaline to my changa mixes. I find there is a point at which the changa actually loses spice effects and becomes really quite weak (in fact not even that much, a recent batch with [I think, if my memory serves me right] 5mg harmine & 5mg harmaline per 50mg spice exhibited this effect). I have yet to find the correct amount of extra harmalas to add to changa.
 
This has been my experience with sublingual harmalas. Too large a dose (over 20mg) requires a larger dose of DMT to get breakthrough effects. A lower dose of 10mg or so slows the experience without noticeably attenuating it (although the slowing itself is no doubt an effect of attenuation).
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Thats interesting, when you say it slows the experience do you mean it lasts longer but the effects are as powerful? If that is true then there could be a threshold where it activates the DMT orally without reducing its potency. A threshold Which I imagine would be different for each person.

Maybe the reason that oral DMT is difficult to dose is that the DMT dose should remain constant but the dose of MAOI should be adjusted to find the sweet spot for each person. Once that has been found maybe varying the amount of oral DMT would produce more predictable results in different subjects?

In addition there seems to be some difference of opinion over whether MAO-A or MAO-B destroys DMT. Serotonin is destroyed by MAO-A so perhaps if only MAO-B were inhibited serotonin levels would remain the same but allow for oral activation of the DMT? I have heard that the DMT molecule is similar to serotonin so it might be dealt with by MAO-A also.
 
Melodic Catastrophe said:
Hmm. This is very interesting. I always assumed that it was better to go with more harmalas. Now it seems there is a sweet spot for both, the harmalas and dmt.

I may have to go back to the drawing board with my pharma experiments.
Click to expand...
But harmala's also do other things than elevating serotonin levels. They also boost levels of dopamine and probably do other things, not yet understood. Most harmala's are psychedelic on their own and can make a trip more intense, but just less DMT-like.
I feel that mushrooms become more like LSD when combined with harmala's for instance, gaining the LSD-like stimulation from it's dopaminergic effects.
 
Shattered_Symmetry said:
This has been my experience with sublingual harmalas. Too large a dose (over 20mg) requires a larger dose of DMT to get breakthrough effects. A lower dose of 10mg or so slows the experience without noticeably attenuating it (although the slowing itself is no doubt an effect of attenuation).
Click to expand...

Thats interesting, when you say it slows the experience do you mean it lasts longer but the effects are as powerful? If that is true then there could be a threshold where it activates the DMT orally without reducing its potency. A threshold Which I imagine would be different for each person.
Click to expand...
The peak experience lasts slightly longer. The return to baseline lasts quite a bit longer.

But the main effect is that the experience is literally slowed down: Visuals morph and change at a slower rate. Using an old phonograph analogy, it’s as if the entire experience goes from 78rpm to 33rpm. It makes it much easier to observe what’s going on.
 
Fascinating, swim will have to try that soon, he has not done so yet as was quite comforted by the brevity of smoking freebase alone, as if the trip got too much it was always over soon. Having the events slowed down would be fantastic as they do whiz by very quickly usually making them hard to comprehend.
 
Very interesting thread.

Another variable to throw into the mix is the ROA of the hamalas. Sublingual doses, for instance go to the bloodstream without passing throught the digestive system and, thus, more directly to the brain to inhibit the MAO-A there with greater intensity... but also likely to have more attenuating effects as well. Oral harmala going through the digestive system will use up its MAOI on the MAO in the stomach and digestive tract... thus much less of it making it into the blood and only a tiny fraction getting to the brain.

This would explain SWIM's experience that subligual doses of harmalas are stronger in their harmala effects, but can almost negate the oral DMT. He had assumed this to be simply due to not inhibiting the MAO-A in the digestive system. But considering that MAO-A is not all that prevelent in the brain anyway (and very prevelant in the digestive pathways) sublingual administration overloads the brain with harmalas and they then attenuate any DMT that does make it to the brain.

It seems that for oral DMT admin, taking just over the amount needed to deactivate MAO-A in the stomach and GI tract would be ideal. Maybe with a tiny amount taken sublingually to finish off any MAO-A in the brain...

Any thoughts?
 
That hypothesis sounds feasible to me given the findings documented in the paper. So by administering the harmala sublingually more of it makes it to the brain where it increases serotnin levels leaving less sites for the dmt to bind to, attenuating its effect. Presumably it will be similar for smoked harmalas?

It seems that with MAOI too much is just as bad as too little, does anyone have any thoughts on a way to experimentally determine the correct amount for an individual?
 
Shattered_Symmetry said:
It seems that with MAOI too much is just as bad as too little, does anyone have any thoughts on a way to experimentally determine the correct amount for an individual?
Click to expand...
Of course there are those individuals who seem to be the exception to this rule: Some members here take ayahuasca that’s very heavy on the caapi side yet very light on the DMT side and still they manage to get DMT effects. So it’s not as simple as harmalas totally canceling out DMT effects at a high-enough dose. (Unless these individuals have exceptionally high levels of MAO in the gut?)
 
Years ago, SWIM had a couple vials of what was called 5:1 Harmaline. He figured this stuff was actually 5x Rue extract in alcohol. It certainly wasn't pure Harmaline. It claimed to have 75ml of MAOI alkaloids per dropper, but this was a ridiculous claim as the bottle only contains 30 ml. So, it must have meant 75mg which made more sense to him.

Anyway, due to the dropper, alcohol, easy sublingual admin this product afforded (not holding a ton of foul tasting shyte under the tongue for 20 minutes or whatever) he did a lot of playing with it sublingually and found it to be very potent in every way except oral DMT potentiating. It potentiated shrooms just fine, smoked DMT, an existing Aya experience... what-have-you. Somehow, it never really seemed to work much for oral administered mimosa, hacruna or pharma. After wasting some materials, he did more research and came up with the info about sublingual harmalas not doing diddly to the MAO-A in the stomach. Naturally when swallowed this tincture did work for pharma. He also found out that harmalas can compete with DMT & serotonin for the 5HT receptors once the MAO-A in the brain has been completely deactivated.

@gibran2 I don't think that oral harmala will generally make it to the brain in any large amounts. Even if it disables the gut MAO-A completely and enters the blood, there is a lot of MAO in the tissues it will encounter along the way to the brain. I would think that less than 10% of the excess harmala would ever get there. This attenuation effect is more an issue for smoked or sublingual admin IMO.

Anyone here know the exact amounts of the various beta-carbolines needed to deactivate MAO in the digestive path off hand? With this information, it should be easy enough to only take a bit more than needed and thus hit the sweet spot.
 
Depends on personal metabolism, there is no standard amount of MAOs that is present in every single person around the world. The amount that after years of experimentation people have found was that around 100mg harmaline or 200mg harmine is a good oral dose, but this depends a lot. People who eat a lot of tyramine containing food might naturally have more MAOs and might need more, others might need less. Ive tried using less than 200mg harmine and the oral dmt experience was always way too short.. I can take up to 250mg harmine or 150mg harmaline, but more than that and there's too many side effects and I dont feel it improves the experience (Im not sure if I notice the DMT effects diminishing but its possible)
 
Hyperspace Fool said:
@gibran2 I don't think that oral harmala will generally make it to the brain in any large amounts. Even if it disables the gut MAO-A completely and enters the blood, there is a lot of MAO in the tissues it will encounter along the way to the brain. I would think that less than 10% of the excess harmala would ever get there. This attenuation effect is more an issue for smoked or sublingual admin IMO.
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This doesn't make sense to me, as oral harmalas in what I consider proper dosages are extremely visionary on their own.
 
ragabr said:
Hyperspace Fool said:
@gibran2 I don't think that oral harmala will generally make it to the brain in any large amounts. Even if it disables the gut MAO-A completely and enters the blood, there is a lot of MAO in the tissues it will encounter along the way to the brain. I would think that less than 10% of the excess harmala would ever get there. This attenuation effect is more an issue for smoked or sublingual admin IMO.
Click to expand...
This doesn't make sense to me, as oral harmalas in what I consider proper dosages are extremely visionary on their own.
Click to expand...

This depends a great deal on what you consider proper dosage. Heheheh.

My comment was made in the context of the amounts used to potentiate DMT... as per the thrust of the thread. Obviously, you can take a large abount of beta-carbolines and have them be visionary on their own. This would be after they have disabled the MAO in the gut and entered the bloodstream in sufficient amount to make it to the brain, disable the MAO there, and then begin binding en masse to the 5HT receptors there.

SWIM has had this effect and enjoys it, but is curious at the moment about the attenuation vs. potentiation of DMT.
 
Just to complicate things a bit further, this source on erowid shows this table:

Code: 
 Table II-C--Reported Analyses of Ayahuasca Potions

Source                     # Samples Beta-Carbolines  DMT

Der Marderosian et al 1970   1        20 mg           30 mg 
Rivier & Lindgren 1972       9        40 mg           25 mg
McKenna et al 1984           5       401 mg           36 mg
Liwszyc et al 1992           1       144 mg           26 mg
                            ===      ==========      =========
Overall Average             16       158 mg           29 mg

Are those values in line with anyone’s experience? If you throw out the outlying samples reported by McKenna, the averages are 48mg harmalas and 26mg DMT!!
 
I dont agree with alot of Ott's conclusions on harmalas to be honest..he also thought they were just sort of sedatives-which we all know is not true..harmalas have psychedelic effects on they're own..and quite powerful ones at the proper doses..

Yes I find harmalas can mediate the effects of the DMT somewhat..and the DMT comes on slower when smoked after ingesting harmalas..but often times I will smoked my regular dose after ingesting like 50g of caapi and it is ALOT stronger..I would never ever say that the experience is weakened or dampened by the presence of harmalas..even if the DMT is modulated the harmalas synergise with it..and if you take a proper ayahuasca style of harmala dose, you will be having an experience from the harmalas alone already, so the DMt only adds to the base of the trip-the harmalas..

This has been one that I dont really find Ott's explaination adequate at all..and maybe he just never had much experience with full doses of harmalas.
 
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