How does psilohuasca work?

[maranello551]

Why does inhibiting MAO before ingesting mushrooms change the nature of the trip? Are there different dmt analogs besides psilocybin and psilocin that are broken down by MAO normally?

 

[jamie]

harmine is a visionary compound on its own. it does not just inhibit MAO.

 

[maranello551]

Right but when one takes mushrooms with harmine the effects are far greater and different than the sum of the two.

 

[Ryusaki]

Thats because the Psilocybin is reinforced by the harmine/harmala alkaloids and vice versa, the psychoactive effects of harmine is reinforced by the psilocybin/psilocyn.

Seretonin and Dopamine are metabolized by both MAO-A and B, but by inhibiting A you still increase the amount of their availability.

The amount of serotonin upregulation is higher with harmala alkaloids in the mix.
Also with this combi i feel more euphoria than without.

 

[ShamanicYogi]

The use of Peganum harmala, Syrian rue tends to potentate the use of tryptamines. I am not sure about it potentating the use of phenethylamines.

 

[Auxin]

The ß-carbolines are not magic-bullet MAO-A inhibitors.
In addition to inhibition of MAO-A at ordinary dosing and MAO-B at high dosing, ordinary doses modulate the activity of the CYP metabolic enzymes.
Harm(al)ine induces CYP1A2, 2C19, and 3A4 activity and inhibits CYP2B6, 2D6 and 2E1 activity.
I forget if its harmine/harmaline or the other P. harmala alks that inhibits CYP1A1 (a pro-carcinogen activating CYP).

This is relevant because after alkaloids get into the blood they are primarily metabolized by the CYP system, so it should be expected that they will effect phenethylamines, tryptamines, acetaminophen, other stuff, etc.
To muddy the waters, some drugs are really pro-drugs. Mescaline seems to be in this class. If I remember right, mescaline can be metabolized primarily by 3A4 or 2D6. Many anecdotal reports relate a potentiation of mescaline with harm(al)ine, those reports seem more consistent than potentiation-by-grapefruit reports. Perhaps CYP3A4 is the pro-drug activating metabolic pathway and 2D6 is the pro-drug destroying pathway, for instance.

Anyway, point is ß-carbolines have nuanced pharmacological 'personalities', to think of them only as RIMAs is overly simplistic.

 

[nexalizer]

The ß-carbolines are not magic-bullet MAO-A inhibitors.
In addition to inhibition of MAO-A at ordinary dosing and MAO-B at high dosing, ordinary doses modulate the activity of the CYP metabolic enzymes.
Harm(al)ine induces CYP1A2, 2C19, and 3A4 activity and inhibits CYP2B6, 2D6 and 2E1 activity.
I forget if its harmine/harmaline or the other P. harmala alks that inhibits CYP1A1 (a pro-carcinogen activating CYP).

This is relevant because after alkaloids get into the blood they are primarily metabolized by the CYP system, so it should be expected that they will effect phenethylamines, tryptamines, acetaminophen, other stuff, etc.
To muddy the waters, some drugs are really pro-drugs. Mescaline seems to be in this class. If I remember right, mescaline can be metabolized primarily by 3A4 or 2D6. Many anecdotal reports relate a potentiation of mescaline with harm(al)ine, those reports seem more consistent than potentiation-by-grapefruit reports. Perhaps CYP3A4 is the pro-drug activating metabolic pathway and 2D6 is the pro-drug destroying pathway, for instance.

Anyway, point is ß-carbolines have nuanced pharmacological 'personalities', to think of them only as RIMAs is overly simplistic.

Would you know if Warfarin metabolism would be affected by harmalas?

 

[Aeternus]

Welcome Home! - Psilohuasca.com

High dosed Psilocybin & 5MeO DMT 1:1 / 1:2 sessions with experienced caretaker & spiritual coach Oliver Martin to achieve Non Duality / Enlightenment.

www.psilohuasca.com

What would be the dosage?
I would like to obtain equivalent of 5 grams pure mushrooms.

 

[Auxin]

Would you know if Warfarin metabolism would be affected by harmalas?

Of the six known metabolic routes for warfarin, harmalas would be expected to speed up three of them.
So yes, it would effect metabolism to some degree. Most likely producing an accelerated clearance of warfarin from the blood. How big of an effect it would have can really only be guessed at. The strength of the effect would vary from person to person, particularly within groups of white people (because of CYP2C9 polymorphisms).

Keep in mind I am not a pharmacologist, or your doctor
Be safe

 

[maranello551]

Welcome Home! - Psilohuasca.com

High dosed Psilocybin & 5MeO DMT 1:1 / 1:2 sessions with experienced caretaker & spiritual coach Oliver Martin to achieve Non Duality / Enlightenment.

www.psilohuasca.com

What would be the dosage?
I would like to obtain equivalent of 5 grams pure mushrooms.

For swim, on an empty stomach, it would be around (3.5g) with MAOI for a 5g alone level of intensity. Swim is still trying to figure out how different amounts of MAOI affect the same dose of psilocybin (aka 4g+mush 2g rue vs 4g mush+4g rue).

 

[pitubo]

Would you know if Warfarin metabolism would be affected by harmalas?

Of the six known metabolic routes for warfarin, harmalas would be expected to speed up three of them.
So yes, it would effect metabolism to some degree. Most likely producing an accelerated clearance of warfarin from the blood. How big of an effect it would have can really only be guessed at. The strength of the effect would vary from person to person, particularly within groups of white people (because of CYP2C9 polymorphisms).

I am curious how this works. When I read the question, I thought "well warfarin is not a monoamine, so it has no interaction with harmalas". But you say it does in some way and now I wonder what other metabolic effects harmalas have in this case (and others). Could you be so kind to point me to where I can read a little more about this?

Thanks in advance!

 

[Auxin]

The relevant data is kind of scattered around the scientific literature.
[1] and [2], for instance, establish Peganum harmala as altering the effects of various phase 1 metabolic enzymes. These are the critters that metabolize most drugs (including non-amines) and metabolize/biosynthesize various things your body makes on its own, like steroids and other hormones.

The CYP metabolic system should be taken seriously, its why combining grapefruit juice with ecstasy can be deadly.