The Big & Dandy MDAI Thread

[hugo24]

The magic of racemic MDMA seems in some way related to having a DA:NE release ratio somewhere near/less than 0.66 or so. This norepinephrine release seems to be important, since S-MDMA (the more potent enantiomer) has about an even DA:NE release while R-MDMA is much more divided with a ratio of about 0.15. S-MDMA is more potent of releaser of monoamines, however.

The stereochemistry for agonism of the 5HT2A and 5HT2C receptors is inverted, with R-MDMA and the active metabolite R-MDA having the much greater affinity and assumably acting as the agonist.

Interesting point nuke,doesen't that ring bells in mathematicians about The Golden Cut and Fibonaccis #'s !??

 

[nuke]

I suppose so, it's been peculiar in that it's awfully had to duplicate. If you flip it to NA:DA, it's almost the golden ratio of 1.62 (values from studies range from 1.5 to 2.0 or so).

 

[Coolio]

The magic of racemic MDMA seems in some way related to having a DA:NE release ratio somewhere near/less than 0.66 or so. This norepinephrine release seems to be important, since S-MDMA (the more potent enantiomer) has about an even DA:NE release while R-MDMA is much more divided with a ratio of about 0.15. S-MDMA is more potent of releaser of monoamines, however.

The stereochemistry for agonism of the 5HT2A and 5HT2C receptors is inverted, with R-MDMA and the active metabolite R-MDA having the much greater affinity and assumably acting as the agonist.

S-MDMA is the magic part of the racemic, in my experience.

 

[LunarSylph]

Shouldn't MDAI + L-Deprenyl (MAO-B inhibitor) = MDMA-like damage to 5-HT receptors?

Question:

Shouldn't MDAI + L-Deprenyl (MAO-B inhibitor) = MDMA-like damage to 5-HT receptors?

There is conflicting data on this point that I would like help in parsing, if any one here has the time/inclination/knowledge.

Earlier in this thread someone mentioned the white paper:
http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=691

I'll quote the relevant bits to establish some premise:

Pretreatment with either clorgyline or deprenyl before MDAI resulted in a dopaminergic profile similar to that seen after MDMA. More specifically, the combination produced increases in DA and decreases in DA metabolites, as contrasted with the increases in both DA and its metabolites seen with MDAI alone. [...] The monoamine profile after deprenyl plus MDAI gave the closest similarity to that seen after MDMA alone.

However, neither the clorgyline nor the deprenyl pretreatments before MDAI resulted in any significant decrease in the levels of 5-HT at 1 week after dosing.

[...]

The DOPAC/DA ratio can be altered by a number of agents, including: MAO inhibitors [such as L-Deprenyl], DA uptake inhibitors, and nonvesicular DA releasers. [...] ...if this DOPAC/DA ratio was a key indicator of the neurotoxic effects of MDMA, treatment with agents that decrease this ratio in combination with a non-neurotoxic MDMA analogue such as MDAI, should result in a short-term mono-amine profile similar to that seen with MDMA. [therefore this combination might result in MDMA-like neurotoxicity]

From what I understand, MDAI is not toxic because it has no affinity for dopaminergic synapses. This paper seems to believe the DOPAC/DA ratio is the key to why MDAI (when taken alone) is a non-neurotoxic releasing agent. It theorizes that MDAI + [Increased Dopamine Activity] should cause neurotoxicity similar to MDMA.

Yet this same paper also relates that MDAI + L-Deprenyl as a combination, which should feel subjectively very similar to taking MDMA, appears to have zero long-term serotonin receptor damage. MDAI + amphetamine, on the other hand, does cause MDMA-like neurotoxicity. L-Deprenyl seems inexplicably exempt from the rule.

It is already documented that L-Deprenyl, a dopamine-increasing substance (among other MAO-B effects), counter-intuitively works to help reduce the amount of MDMA serotonin receptor damage.

A Google search on L-Deprenyl's effects on the DOPAC/DA ratio yields talk of neuroprotective effects that are supposed to help maintain this ratio while under attack by neurotoxic releasing agents, such as PMA/MDMA/etc.

Also (from the wiki):

Antioxidants such as ascorbic acid and MAO-B inhibitors like selegiline [i.e. L-Deprenyl], [...] are neuroprotective, and can fully block the damage induced by neurotoxic releasing agents.

Here, L-Deprenyl is specifically mentioned as being a general neuroprotective tool against neurotoxic releasing agents.

_________________________________________________

My one personal experience taking [100mg MDAI as a base] while on 5mg of L-Deprenyl is that it feels too good to believe doses once every 12 hours over 4 days (as was done in the white paper's study) could not be neurotoxic...

Yet that's what this data would appear to suggest

Perhaps I just read something wrong somewhere along the way? If not, I would call this possibly one of the greatest nontoxic, long-term anti-depressant combinations discovered by human kind...

The fact that it dilates your pupils for up to 6 or 7 hours is another indicator to me that long-term use should cause problems. But again, the data appears to conflict on this point.

Yet you do indeed remain clear-headed while on it, and there is no hint of hangover or physical or mental strain during or after the experience... Heart-rate doesn't seem to change either. So I'm really at a loss how to interpret the dangers of MDAI + L-Deprenyl.

 

[Sturnam]

LunarSylph: The short version to your question about why deprenyl doesn't cause damage - look up the combination of MDAI + DARI (dopamine reuptake inhibitor). There's actually a few posts in this thread about it, and there might be a link to the article by Nichols somwhere. The mechanism by which deprenyl increase dopamine concentrations is different than DARI's or dopamine releasing agents, but I'm guessing the effect on deprenyl on dopamine concentration is more similar to a DARI (i.e. a smaller increase of dopamine compared to dopamine releasing agents.)

MDAI + DARI is also non-neurotoxic, probably because it doesn't increase dopamine concentrations as much as dopamine releasing agents, and doesn't cross the threshold needed for neurotoxicity. The MDAI + DARI is also said to mimic MDMA very well without neurotoxicity. I hope to try the combination when I am no longer taking an SSRI.

The fact that it dilates your pupils for up to 6 or 7 hours is another indicator to me that long-term use should cause problems. But again, the data appears to conflict on this point.

Not at all. Simply means that there's a physiological response (dilated pupils) to a drug. Just because opioids cause miosis (tiny pupils) doesn't mean that they will do long term damage (physically, at least).

 

[LunarSylph]

Thank you for confirming things.

I'll drop a little more info here for the sake of the curious and uninitiated.

-

MDAI + L-Deprenyl (MAO-B inhibitor)

Some notable effects:

1. As someone mentioned earlier, it gives you cold palms/extremities when it first hits. i.e. you definitely feel it when it comes on.
2. Initial euphoria followed by relaxed cozy feeling that sustains for quite some time.
3. Unusually, my heart rate never once changed at any point during the experiment, though I wasn't measuring blood pressure.
4. I also experienced brightened colors. More so than you get with DMT or LSD, but of course without any other entheogenic visual properties.
5. Clear-headedness maintained throughout experiment, in spite of this being a pupil-dilating, obviously powerful substance.

As someone with no previous MDMA exposure (i.e. no MDMA-desiring expectations, but years of entheogenic "research") I can say the combination of L-Dep and MDAI is a significantly potent one. Especially when it first strikes (even more so if you previously read about MDAI, heard that it was a weak substance, and wasn't expecting it!).

Hearing about people taking upwards of 300mg to feel the effects does not compute with me. But it could be that the MDAI is at least partly metabolized by MAO-B enzymes, and therefore it is understandable that 100mg of MDAI while on 5mg of L-Deprenyl will come on as strongly as it does. I would not think of dosing beyond the 100mg point, and will try lower numbers until I find a more reasonable threshold.

Something of a sudden explosion when it hits (within 30 minutes) that very gradually tapers off into a comfortably relaxed state. This is more of a "sit down" experience, IMO.

About 4-6 hours all said and done, though pupils appeared dilated for some time after I believed the substance's effects had completed. And the day after is hangover-free with a warm afterglow similar to post-DMT but less stimulated.

This is without a doubt more of a relaxing substance than a stimulant. Even the unexpected shock at how effective the substance was when it hit didn't produce a rise in heart rate or anxiety.

With the inclusion of MAO-B inhibition, MDAI does not feel (subjectively) like one is experiencing something that is likely to be damaging to the mind or body. I still hesitate to consider taking it more than maybe twice a week though...

 

[Black]

Something of a sudden explosion when it hits

this is quite normal for first times with entactogens. happened to everyone i know the first time(s) with mdma. i suppose it will become less and less sudden the more often you take such substances.


but thanks for all that information. have you also tried mdai without deprenyl?

a more general question: isn't deprenyl partially metabolised to (meth)amphetamine? (thus contributing to the dopamine side of things...)

 

[hamhurricane]

^^^
yes but its l-MA & l-AMP (unless your using racemic selegiline) which i believe are not psychoactive but ill have to double check. also i have never been clear where those metabolites form,, is it in the liver or the brain?

 

[Persoon]

Does anyone here have subuxone medication, and have tried MDAI. Im not myself at the medication, but would be grateful if someone could tell how it worked with the subuxone medication. So i would know if i can give it to her.

 

[idle cicle]

The first few times that I tried this substance, I loved the experience, but felt that it lacked any type of physical energy. I usually don't like stimulants, but they are nice for music events with dancing. Last night I went to a concert at a small venue, and decided to drink 2 cups of coffee before ingesting the MDAI. While this would not increase any euphoria (like adding a DARI most likely would), it did give me the energy to dance around. The previous time that I took it at a concert, I had a great time, but half way through the show I could barely bob my head to the beat of the music, let alone dance, because I was getting physically tired. I also find this compound to be much more useful mixed with cannabis. It makes up for the lack of euphoria with it alone. After this trial, I am very interested in an MDAI, MDPV combo. But having never tried MDPV alone, and suspect there may be added neurotoxicity with this combo, I am a bit apprehensive

 

[bkny]

I've had heartburn the first time I took Methylone and needed a antacid, for some reason it rushed me with energy and magnified the euphoria.

I tried MDAI again and took an antacid on the comeup - what a difference it made, it must breakdown something in my gut to help in release dopamine some how (I'm sure this is my bodies chemistry) I've read reports here of some finding it somehow makes the roll of both MDMA and Methylone stronger, while some report no effect.

 

[MeDieViL]

Does tolerance build fast to this compound?

 

[Delsyd]

I've had heartburn the first time I took Methylone and needed a antacid, for some reason it rushed me with energy and magnified the euphoria.

I tried MDAI again and took an antacid on the comeup - what a difference it made, it must breakdown something in my gut to help in release dopamine some how (I'm sure this is my bodies chemistry) I've read reports here of some finding it somehow makes the roll of both MDMA and Methylone stronger, while some report no effect.

ive heard of antacids making rolls stronger.
never tried it myself though to see if it were true.

Do you take one of those instant ones like tums or something like prevacid which is a pill.

Also this compound has become alot more interesting now that we have reports of it combined with a DARI (if only i knew what a DARI was)

 

[Solipsis]

Antacids potentiate this type of substance (many entactogenic phenethylamines) because the absorption in your stomache is supposed to be better in alkaline (basic) environments. Sort of the same - but opposite - of what happens to psilocybin in an acidic environment.

 

[Jamshyd]

I've been pretty interested in this substance for a while.

So far, all MDx compounds I have taken (MDMA, MDA, Methylone, and MDPV), all leave me with a terrifying comedowns where I feel incapacitated and suicidally-depressed for AT LEAST 1 week (3 weeks in one case which I believe was MDA + Meth). It seems I am far more sensitive to comedowns than most people.

So I am wondering how MDAI compares to these compounds w.r.t. the comedown, if any?

I'd appreciate any input from those who have tried it on its own.

Btw, with that said, I find it shocking how many people here are mixing it with mephedrone/methylone on their first tries.

 

[bkny]

Jamshyd I've seen your posts in other forums here - mainly seeing you try MDxx's and the horrible comedowns and depression which have followed, MDAI is a non-neurotoxic serotonin releaser which I'm sure you've read about - it's does not affinity for the dopamine system hence no speedy euphoric high.

From what I've seen you complain about it seems your depression is due to serotonin loss and serious downregulation of its' system. Have you tried pretreatment and post-treatment with 5-htp along with vitamins rich in B complex as a replacement for serotonin loss? If so then your problems is the downregulation and if you feel suicidally depressed stay away from these drugs man.

 

[bkny]

Delsyd:

the antacid I used was tums

 

[bkny]

A lot has been mentioned here about experience with MDAI plus a DARI. Ratios of DA to NE are thrown around, and Nichols 1991 paper (http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=691) has been haphazardly explained.

LunarSylph is correct that the MAO-B inhibitor L-Deprenyl is qualitatively the closest to MDMA, as Nichols states in the paper - it's DOPAC/DA ratio is nearly the same as well as maintaining the 5-ht numbers that MDMA (and MDAi) exhibit alone yet is not neurotoxic even a week after the mice were tested.

However it should be noted, the reason for this study by Nichols was done not to have us raging lunatics enjoy a MDMA like high without the neurotoxicity that MDMA produces, it was done to replicate the neurotoxicity that MDMA produces using MDAI coupled with a pretreatment of 4 drugs:

1. Clorgiline
2. L-Deprenyl
3. Vanoxerine (GBR-12909) a piperazine derivative which is a potent and selective DRI (this is very different than Raitlin, ie Methylphenidate (MPH) which is a derived from amphetamine.)
4. S-amphetamine

The only neurotoxic regimen was the S-amph.

LunarSylph states that with the L-Deprenyl vita-veta-regimen he had a sudden explosion which very gradually tapered off into a comfortably relaxed state. most reports of L-Deprenyl here state that it produced a huge pluse rate increase and a general overheating and sweating response, needless to say I'm not interesting in finding out if my bodies reacts to L-Deprenyl the way in which LunarSylph states or to the majority.

Hamhurricane has also sighted the same paper and states that he believes that a DARI like Raitlin would replicate Nichols findings, since he used a DARI in the study - problem is that Raitlin is a amph derivative where as the DRI which Nichols used was a piperazine derivative.

I think that any DARI may not be the key to giving MDAI the nonneurotoxic equivalent of MDMA.

 

[Jamshyd]

Jamshyd I've seen your posts in other forums here - mainly seeing you try MDxx's and the horrible comedowns and depression which have followed, MDAI is a non-neurotoxic serotonin releaser which I'm sure you've read about - it's does not affinity for the dopamine system hence no speedy euphoric high.

From what I've seen you complain about it seems your depression is due to serotonin loss and serious downregulation of its' system. Have you tried pretreatment and post-treatment with 5-htp along with vitamins rich in B complex as a replacement for serotonin loss? If so then your problems is the downregulation and if you feel suicidally depressed stay away from these drugs man.

I appreciate your advice but I honestly don't think I can pin down my depression to any one transmitter, especially that it is cured by drugs that are neither serotonergic nor dopaminergic directly. These drugs include Gabapentin and Ketamine.

So no, I don't think my depression has much to do with serotonin (or DA, or NE) downregulation specifically. Btw, I crash just as hard from Cocaine and Amphetamines, it just doesn't last as long. Also remember that MDPV, which to my knowledge has almost no affinity for SERT, is actually one of the worst offenders.

For the record, I tried all sorts of supplements - 5-htp, L-PA, SAMe, SSRIs, a galaxy of vitamins and minerals and antioxidents. All garbage.

One thing worth mentioning: There are two drugs of this class/family I tried that never gave me any real comedown: 2-Aminoindane (the closest thing to MDAI), and 4-FA.

 

[bkny]

Jamshyd

did you enjoy being on 2-Aminoindane? can you describe the experience?