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psychoactive nature of MAOIs

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S

salviage

Rising Star
Having done a lot of reading and thinking lately, I had the idea that large doses of MAOIs are perhaps not in themselves psychoactive, but they are simply preventing the breakdown of naturally occurring actives in our bodies. This to me would explain why it tends to reach a certain level of activity that does not increase with a larger dose. It's just an idea I wanted to throw out there. Does anyone have any knowledge or thoughts about this?
 
Its rather difficult to say, i think its multifactorial:

First of all which MAO inhibitors are we talking about (i am assuming that you talk more or less about selective MAO A isoform inhibitors)? Beta-carbolines? Moclobemide? Here an experimente can be carried out, someone comparing activity of a beta-carboline vs moclobemide on doses that inhibit MAO A at the same degree. I keep hearing though that moclobemide has a "cleaner" profile, in the sense that you do not feel it much, so beta-carbolines must be doing something extra -and indeed they do,pubmed harmine and harmaline to see they also affect some receptors themselves, i think GABA and also imidazoline receptors.

There is though this trend in many forums that beta-carbolines are "pan-potentiators" , i think many people downplay their role: the most common thing you will keep hearing about them is comments like "Increases the intensity of Y compound X times".
 
Here's an interesting thought - if i understand correctly, MAOI's are things like Xanax, klonapin, etc. Anti-depressants/anti-anxiety meds.
I remember back in the day taking roughly 8-12mg of xanax, and "blacking out" - what if one were to ingest something like 6-10g of mushrooms, and then ingest these MAOI's and "black out" - would the trip then continue? Would you even "black out". I'm interested.
 
SWIM has never gotten to a point where increasing the dosage of harmalas didn't change the effects, both in strength and quality. Where did you get the idea that their individual effects peak at a certain point?
 
RastaNation said:
Here's an interesting thought - if i understand correctly, MAOI's are things like Xanax, klonapin, etc. Anti-depressants/anti-anxiety meds.
I remember back in the day taking roughly 8-12mg of xanax, and "blacking out" - what if one were to ingest something like 6-10g of mushrooms, and then ingest these MAOI's and "black out" - would the trip then continue? Would you even "black out". I'm interested.
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I'm no pharmacist and I may be mistaken, but I believe Xanax and klonapin are benzodiazapiens. They are antianxiety meds not anti depressants. Maybe they have some MAOI effects, I dont know, but they are not classic MAOIs and I wouldnt use them for that.

Now I do know for sure that either one of those drugs are a damn good buzz kill. I have used them before to terminate a high dose mushroom trip that had gone bad and I do know for sure they will terminate a high dose pharma trip pretty good, or LSD for that matter.

It doesnt matter what you are on, If you take enough xanax you will black out.
 
Hmm. I suppose that's good to know for future reference, though it would've also been an interesting trip if you "blacked out" but continued to trip - almost as if dreaming.
Oh well.
 
RastaNation said:
Here's an interesting thought - if i understand correctly, MAOI's are things like Xanax, klonapin, etc. Anti-depressants/anti-anxiety meds.
I remember back in the day taking roughly 8-12mg of xanax, and "blacking out" - what if one were to ingest something like 6-10g of mushrooms, and then ingest these MAOI's and "black out" - would the trip then continue? Would you even "black out". I'm interested.
Click to expand...

Anti-depressants are usually SSRI's. You do not EVER take an SSRI with an MAOI. Harmalas are a common MAOI (caapi, rue). That's bad info mixing that up and could potentially hurt someone.
 
ragabr said:
SWIM has never gotten to a point where increasing the dosage of harmalas didn't change the effects, both in strength and quality. Where did you get the idea that their individual effects peak at a certain point?
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Dealing with Beta-Carboline RIMAs this is most definitely the case, ime. I'd like to second the question of where this "saturation point" idea originated from. Also, as Ice House said, benzo's ≠ MAOI's. Oh yea, and the stuff we get from our plant friends are technically RIMAs (which are really just a special subset of MAOI's, kind of like the relationship between squares and rectangles).
 
I'm sorry, I used the wrong word here. I should not have used psychoactive. What I meant to refer to was the mild psychedelic nature of MAOIs. In my admittedly limited experience with rue extracts and infusions, I have found that perceptive effects, light tracers and slight audio and visual distortions as well as slightly altered headspace don't seem to change much after a point with increasing dosage although they do last longer. I thought that I read something like that elsewhere as well but I could be remembering incorrectly. I apologize for confusing myself.:oops:
 
I can't speak for all MAOIs, but in the case of Caapi (and loads of other MAOIs that are found in food sources naturally) they are **DEFINITELY** psychoactive! It is entirely possible to have a visionary adventure with Ayahuasca alone that is literally every bit as powerful as with a strong dose of DMT. It depends on lots of factors, but it is definitely possible.

Also, in the case of Caapi, there is a threshold for which DMT becomes orally active--but a proper visionary dose is several times what it takes to hit the DMT activity threshold. In my experience, 4-5x what it takes to reach MAO inhibition feels ideal for the Caapi-only visionary quest.

Harmalas rock. If you are curious about DMT, definitely take the time to start reading and researching about Ayahuasca... it's worth every moment. :)

Cheers and welcome. :)
 
The psychedelic effects of many harmala-alkaloids comes from them binding to serotonin (5-HT) receptors just as DMT, psilocin, LSD, bufotenin, etc. do. More accurate the hallucinogenic action is due to binding at 5HT-2A receptors. This action is not something common for all MAOIs or even all harmala-alkaloids. It depends on the molecular structure, as some compounds fit and some not at the receptors in question.

Combined with heightened levels of synaptic serotonin and other monoamines due to inhibited breakdown by MAO, you more or less have the whole answer for the psychoactive effects.
 
but if 5ht2a receptor binding is what explains the psychoactivity, then how do you explain 5ht2a agonists that do not exhibit psychoactive effects? And how does it explain the differences between substances that bind to the same receptors?

pharmacology is very complex, I think receptor binding is just the pathway, but it doesnt talk about the message being sent across, if you know what I mean.
 
Spot on. Even if a compound binds to a specific receptor, it doesn't mean that it activates the receptor to its whole extent. Few do so, but if it would it would be called a full agonist. The substance may activate one or more certain parts of a specific subtype of a specific receptor (as in the example of 5HT-2A, serotonin receptor subtype 2A), while another similar substance may activate other parts. These are called partial agonists.

Many believe psychedelics act by modulating the effects of the receptors rather than just activating them. Such substances are called modulators, but this label is rarely used in psychedelic theory, as we simply have no idea how they modulate or if that is actually what they do. They may be just partial to full agonists, activating certain pathways we rarely or never use in daily-life.

Other substances bind to the receptor without activating or modulating them at all, these are called antagonists. As any other substance is unable to bind to a receptor that has an antagonist bound to it, these substances do show some effect, but rather the opposite of agonists. This is why certain 5HT antagonists may be used to diminsh the effects of 5HT agonists, that is, psychedelics.
 
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