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MDMA/serotonin inhibit mao enough for DMT?

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yaesutom

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I know i've read MDMA is somewhat of an maoi, I don't know if that means the drug MDMA itself, or being on the drug and the extra serotonin being the thing to inhibit mao-a.

I'm curious (and might try it someday) if you took mdxx, and then sometime later after its kicked in, take some DMT orally, if the mao is tied up enough to let some DMT through? What do you think?

I'd think at SOME dose of DMT you would feel it.

Actually i'm guessing, sober and no other drugs or mao inhibitors, at SOME high dose, DMT would work, because if you ate 20 grams of DMT, the DMT itself would have to tie up the mao enzymes enough..to let some of the DMT get through?
 
All the amphetamines are competetive inhibitors of MAO to some degree, it's just that some are much more potent than others. The measure if inhibition is the Ki value. Harmaline has a Ki of about 10^-6M whereas yohimbine has a Ki of about 10^-4M. This means that to get the same degree of inhibition, you need a concentration of yohimbine that is 100x that of harmaline.

Now plain amphetamine has a Ki of about 10^-1 (if I remember correctly), which means that for the same degree of inhibition, the concentration of amphetamine needs to be 100 000x that of harmaline. I don't know the Ki of MDMA for MAO-A, but unless it's at least of the order of yohimbine, you'll poison yourself before you get anywhere near an effective dose.

Incidentally, that's why AMT isn't particularly dangerous in combination with things like amphetamine etc., because it has a Ki of about 10^-2 (pretty damn weak!)
 
MDMA is in the ~100µM (10^-4) for its IC50... (Slightly higehr for MAO-A than B) you're still never going to get concentrations like that in recreational usage. So MDMA is essentially not a gut MAO inhibitor.

Actually i'm guessing, sober and no other drugs or mao inhibitors, at SOME high dose, DMT would work, because if you ate 20 grams of DMT, the DMT itself would have to tie up the mao enzymes enough..to let some of the DMT get through?
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Yes, at some dose.... MAO would get saturated. What that dose is though, is anyones geuss.
 
Very interesting!

Ok, but what about all the serotonin that is dumped from using MDMA? Does this extra serotonin cause any extra (or enough) mao to get tied up?

.. sorta unrelated but, anyone happen to know how long harmaline/harmala's mao inhibition lasts? half life or anything, I could find info for moclobemide but not harmaline/harmala. My uh, "excessive" DMT usage has shown me, I don't *think* syrian rue extract's maoi effect lasts that long (knowing this from eating multiple redoses of DMT long after taking rue extract) and I did once take MDMA many hours after oral dosing rue extract/DMT not noticing any difference.
 
Ok, but what about all the serotonin that is dumped from using MDMA? Does this extra serotonin cause any extra (or enough) mao to get tied up?
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Yes, I've wondered about that, but I doubt it. For one, I doubt that there is much serotonin released in the liver, and because the density of MAO-A is massive in the liver, I doubt it can saturate it.

I don't know about the second question I'm sorry. Though I find you statement of " I did once take MDMA many hours after oral dosing rue extract/DMT not noticing any difference." Very odd. Perhaps harmaline doesn't make it out of the gut/liver...
 
^ Harmaline has psychoactive effects on its own, so it must make it past the BBB.


And a little errata to contemplate. At similar concentrations, yohimbine would have 1/100th of the inhibiting effect of harmaline, but this doesn't mean that to get the same amount of inhibition you need a soln that is 100x more concentrated, as it's not a linear relationship (I'd thank my wife for pointing that out, but I'll not as she looks so smug at the moment!)
 
Yeah, I suppose so...

But in regards to "At similar concentrations, yohimbine would have 1/100th of the inhibiting effect of harmaline, but this doesn't mean that to get the same amount of inhibition you need a soln that is 100x more concentrated, as it's not a linear relationship " If the Ki is 100x less, and they have the same intrinsic efficacy, then you do need 100x more to get the same effect. (ignoring pharmacokinetic differences).
 
I'd just love some sort of automatic IV injecting machine, you load it up with DMT, and it continuously pumps it into me, with maybe some plus and minus buttons for the level and stuff... yeah.. a DMT addicts dream %)

I've got this recent video, from a miniDV cam, a room full of mostly girls, all DMT newbies, if you put the thing on mute you'd think it was a bunch of crack whores fighting over the homemade pipe once they first toked it. Bwahaha, DMT is great.

Something tells me, if *I* were to do something like take just a teeny weeny bit of harmala extract to activate some DMT after some MDMA, i'd probably be fine. But thats just me and my somewhat fried brain doing calculations tonight. I'd much rather just.. take DMT alone, MDMA sucks argh.

Yeah i was planning on writing a big thing on how DMT is different than other psychedelics, its the neurotransmitter thats been kinda skipped over, it regulates things, .. and stuff, well i'll do that when my brain recovers and i'm not awake too long, and stuff, what was i talking about?
 
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