The Big & Dandy MDAI Thread

[push]

Having heard many great reports on the combination of MDAI and Methylone this is something I am very much looking to try, especially as it is reported to extend the beautiful methylone high past its 2-3 hour peak and approach something much closer to a MDMA like experience. I have come across the following study concerning mixing MDAI with a cathione and would like to see how the more chemically minded of this forum interpret the report.

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"MDAI in conjunction with dopamine releasing agents such as methylone and butylone causes the death of serotonin neurons via the reuptake of dopamine oxidation products. (ie the mechanism of neuron death with high levels of MDMA)

Serotonin neurotoxicity in rats after combined treatment with a dopaminergic agent followed by a nonneurotoxic 3,4-methylenedioxymethamphetamine (MDMA) analogue.

Johnson MP, Huang XM, Nichols DE.

Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907. There is increasing evidence linking dopamine (DA) to the long-term serotonergic (5-HT) neurotoxic effects of certain substituted amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA). The present study was undertaken to examine the importance of DA metabolism, uptake inhibition and release in the long-term effects of these drugs by combining various dopaminergic agents with an analogue of MDMA that had low neurotoxic liability, namely 5,6-methylenedioxy-2-aminoindan (MDAI). Monoamine and metabolite levels and the number of 5-HT uptake sites (using [3H]paroxetine binding) were determined 3 hours or 1 week after treatments. Combining the monoamine oxidase inhibitors, clorgyline (MAOA selective) or deprenyl (MAOB selective) with MDAI did not result in any long-term reductions of serotonergic markers. Similarly, combining the DA uptake inhibitor GBR-12909 with MDAI did not result in any long-term changes in monoamine levels at 1 week. In contrast, a single pretreatment of posttreatment with the nonvesicular DA releaser S-amphetamine and MDAI resulted in small but significant long-term changes in monoamine levels. More importantly, if a subacute dosing regimen (every 12 hours for 4 days) was utilized, the combination of S-amphetamine with MDAI resulted in a marked long-term decrease in the levels of cortical, hippocampal and striatal 5-HT, 5-HIAA and the number of 5-HT uptake sites. The results are discussed in terms of the significance of DA and especially nonvesicular DA release in the long-term effects of MDMA-like drugs.

If you want to combine MDAI with anything, combine it with dopamine reuptake inhibitors (ie methylphenidate/MDPV) - not dopamine releasers (methylone/butylone/mephedrone/amphetamines/etc)"
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What do others make of this study? In past discussion it was pointed out the risk described here in the combination of MDAI with a substance such as Methylone was comparable to the risk of neuro-toxicity that may be present with MDMA.

 

[atara]

Methylone is neurotoxic on its own, last I checked, so it should be no surprise that it's neurotoxic with MDAI!

The original combo was MDAI and (+)-amphetamine, both of which are relatively nonneurotoxic on their own, but seem to produce neurotoxicity synergistically when used together. By comparison, MDAI and DRIs like MDPV did not produce any neurotoxicity IIRC.

Also I don't think Nichols is advising anyone to take anything.

 

[MagickalKat777]

Methylone wouldn't have its effects if it wasn't neurotoxic... Its impossible to have an MDXX like experience without the neurotoxicity.

 

[DwayneHoover]

Methylone wouldn't have its effects if it wasn't neurotoxic... Its impossible to have an MDXX like experience without the neurotoxicity.

WRONG!!! Please don't help the anti-drug/anti-hedonism LE assholes by spreading such propaganda.

First, the whole thing about MDMA being neurotoxic was garbage science in which they injected monkeys with IMMENSE overdoses of THE WRONG DRUG! (they "accidentally" ised methamphetamine instead of MDMA).

Second, pre-treatment with the human equivalent of 5g of vitamin C TOTALLY PREVENTS oxidative stress (i.e., "neurotoxicity") from MDMA, The neurotoxicity is a side effect of free radicals, NOT an endemic part of the way these drugs work.

See the following OUTSTANDING research summary, which was published in 2001, so you really have NO excuse for spreading your lies and propaganda!

Do Antioxidants Protect Against
MDMA Hangover, Tolerance, and Neurotoxicity?
http://www.erowid.org/chemicals/mdma/mdma_article3.shtml

Just a few excerpts from this most excellent and comprehsive article... I strongly encourage everyone to go read the entire page themselves:

"Some very interesting research has been published in the last few years showing that common, over-the-counter antioxidants such as vitamin C, vitamin E, beta carotene, and selenium, can not only substantially reduce or entirely block MDMA neurotoxicity in rats, but can actually reduce tolerance between doses."

"One of the most important recent findings about MDMA neurotoxicity is the fact that damage to the serotonin system appears to be entirely separable from the primary experiential effects"

"But perhaps even more interesting is work done with cheap, well tolerated, and universally available antioxidants such as ascorbic acid (vitamin C) showing similar protection. In the first paper to demonstrate this, G.A. Gudelsky7 found that rats given extreme doses of MDMA (20mg/kg injected under the skin) had lasting damage to their serotonin system, but that rats given this same dose of MDMA with a very high dose of ascorbic acid (250mg/kg injected) showed no sign of serotonin damage."

"Although research has only shown that ascorbic acid, alpha lipoic acid, l-cysteine, and some obscure free radical scavengers are effective at reducing oxidative stress caused by MDMA, there is every reason to believe that other antioxidants would also be effective. Antioxidants appear to work best in combination, interacting to make each other more effective. Vitamin E and C are some of the best studied and most common antioxidants. When the heavier vitamin E (alpha-tocopheryl-acetate) loses its electrons to a free radical, the lighter and water-soluble ascorbic acid can replace the lost electron and then be carried off as an inert waste product"

 

[psood0nym]

Hmm, I'm not sure if the conclusions of that study is still thought to be true. Has it been replicated? Nine years have passed and I think the consensus of people who follow these studies closely is that MDMA is neurotoxic, though the degree of neurotoxicity has certainly been blown out of proportion in the past. You can peruse Advance Drug Discussion to see what I mean.

It's true the anti-drug people have their own agendas, but it's also true that we all would really like to believe we can take some Flinstones vitamins and have carte blanche to pound down the X every weekend and encourage our drug friends to do the same. We naturally seek out information that helps us rationalize pleasurable behavior and dismiss information that contradicts it... The truth is independent of agendas, the anti-drug people's and our own.

 

[Wolfy90]

Does MDAI have a cross tolerance with MDMA I dont want to use MDAI if its going to effect MDMA which I love.

 

[DwayneHoover]

Hmm, I'm not sure if the conclusions of that study is still thought to be true. Has it been replicated? Nine years have passed and I think the consensus of people who follow these studies closely is that MDMA is neurotoxic, though the degree of neurotoxicity has certainly been blown out of proportion in the past. You can peruse Advance Drug Discussion to see what I mean.

It's true the anti-drug people have their own agendas, but it's also true that we all would really like to believe we can take some Flinstones vitamins and have carte blanche to pound down the X every weekend and encourage our drug friends to do the same. We naturally seek out information that helps us rationalize pleasurable behavior and dismiss information that contradicts it... The truth is independent of agendas, the anti-drug people's and our own.

I dont know why you are attempting to belittle the harm-reducing true information I offered, so F.U. "Fintstones" vitamins certainly do not contain anywhere near 5g of C, and none of the specialized antioxidants like alpha-lipoic acid and CO-Q10 that are probably to be recommended. A trip to the specialized vitamin store is where to go, not the grocery. At the amounts to be taken these antioxidants are serious medicine... no one is trying to rationalize mindless over-indulgence, just instruct how to protect yourself if and when you do chose to use such things.

But research has indeed proven that large doses of antioxidants prior to dosing does indeed totally prevent the neuro-damaging effects, which may not even be present at normal dosing, but in case they are, pre-loading with multiple grams of multiple antioxidants most absolutely WILL protect you.

 

[psood0nym]

^Fuck me? This is exactly the kind of unjustifiable anger, defensiveness, and absolute unsubstantiated claims (anti-oxidants totally protect you) expected from people who are having their rationalizations challenged. Hell, I didn't even mention the figure "5 grams of vitamin C," you just totally put words in my mouth to attack a straw man argument. Again, this is totally predictable behavior for someone reacting in a defensive and thoughtless manner.

What about the brain zaps many people get after MDMA use? Zaps are theorized to be isolated seizure activity, and seizures cause brain damage. So there's already some rationale for believing MDMA use causes brain damage independently of free radical formation and I didn't need to cite any of the nine years of evidence accumulated since your unquestioned study that casts doubt on your claims.

And "belittle" harm reduction information? Christ man you're deluded. Ask yourself how questioning doing MDMA whenever anyone feels like it because they use a few oral antioxidants is belittling harm reduction and how championing such behavior is.

Also, you've obviously been willfully ignorant of all the new evidence debunking the free-radical scavenging effectiveness of anti-oxidants in the human brain.

Here's what 5 seconds of self-honest criticality and Google instead of wishful thinking and angry dismissal turned up: New Scientist's The Myth of Antioxidants.

 

[Wolfy90]

Does anyone know the cross tolerance with mdma?

 

[DwayneHoover]

This is exactly the kind of unjustifiable anger, defensiveness, and absolute unsubstantiated claims (anti-oxidants totally protect you) expected from people who are having their rationalizations challenged. Hell, I didn't even mention the figure "5 grams of vitamin C," .

No you did not mention 5 grams of vitamin C. I did. Seems you're reading comprehension is not so good, eh?

Where do you see me promoting an opinion that people ought to just take lots of antioxidants and gobble up massive amounts of MDMA constantly and indiscriminately???

You are the one having delusions of some kind.

If you had bothered to READ the page I linked to, you would see the proof of protection. Obviously you did not. The 5 gram figure is derived from science referenced there.

And this "debunking of antioxidants" is a popular topic among a narrow group of kooks, er, "researchers." There are tens of thousands of published research studies going back decades confirming the usefulness and efficacy of antioxidant supplementation. But that's not what this thread is about. An obvious diversionary tactic. Sorry, not biting today.

Again, I was just stating facts from research. Beyond this, I'm not gonna have an argument with you, who obviously has some axe to grind:

1. FACT: The neuronal damage (and deaths) supposedly caused by MDMA was the result of using methamphetamine (in massive overdose quantities... those poor monkeys, who all died, horribly) in place of MDMA in the classic research (sponsored by anti-drug government agencies)... which has now been retracted by the authors

Ricaurte MDMA Research Controversy - MAPS
http://mail.maps.org/mdma/studyresponse.html

I wont repeat it all here folks... just go read this extensive summary/review page, follow and read some of its many dozens of links, starting with:

"Scientists Retract Story on Ecstasy Brain Damage" - Reuters News Service

I'll also highlight "Deconstructing Ecstasy" by Dr. Charles Grob.
http://www.maps.org/w3pb/new/2000/2000_grob_1139_1.pdf


2. FACT: at least in mice injected with the huge overdoses of MDMA needed to trigger "brain damage", large doses of Vitamin C TOTALLY PREVENTED DAMAGE TO THE NEURONS.

From http://www.erowid.org/chemicals/mdma/mdma_article3.shtml

"Since the damage appears to be caused by oxidative stress, one way to reduce might be to simply increase the amount of antioxidants available to the cells. Some very compelling papers have been published showing that antioxidants alone can prevent neurotoxicity caused by enormous doses of MDMA. In a paper published by Aguierre et al. in 1999, researchers administered 4 high doses of alpha lipoic acid by injection to rats during the 2 days preceding a single neurotoxic dose of MDMA (20 mg / kg, also injected) and found that alpha lipoic acid "completely prevents the loss of 5-HT [serotonin] content and the decrease of ... 5-HT transporters in the frontal cortex, hippocampus and in the striatum and also abolishes the increases in the glial response [another marker of neurotoxicity] observed in the hippocampus 7 days after MDMA."11 Several additional labs have reproduced and confirmed that high-dose, injected antioxidants block MDMA neurotoxicity in rats.1,3,6,7

"But perhaps even more interesting is work done with cheap, well tolerated, and universally available antioxidants such as ascorbic acid (vitamin C) showing similar protection. In the first paper to demonstrate this, G.A. Gudelsky7 found that rats given extreme doses of MDMA (20mg/kg injected under the skin) had lasting damage to their serotonin system, but that rats given this same dose of MDMA with a very high dose of ascorbic acid (250mg/kg injected) showed no sign of serotonin damage."

The original research is referenced there. The page goes on to attempt to extrapolate to humans, which results in an oral dose of 4-11grams, an amount commonly consumed by people.

I would recommend the Ester-C products, which are retained in blood and cells for much longer than traditional ascorbic acid, are non-acidic, and can be found with additional and beneficial bioflavonoids. I would also add other antioxidants as outlined by the general "phenethlamine protection" regimen discussed in

Phenethylamines, Free Radicals, and Antioxidants
Brian Leibovitz, Ph.D.
http://www.maps.org/news-letters/v04n1/04134pea.html

"This information is for those who experiment with phenethylamines as well as those with patients who use these compounds.... "

Undoubtedly the posting of this helpful, science-oriented summary of research will also piss off psood0nym. Oh well.

It's all there folks, just go read the linked pages, which have extensive references to published scientific research.

IF YOU ARE GOING TO TAKE MDMA OR OTHER PHENETHYLAMINES OR STIMULANTS, START TAKING ANTIOXDANTS TO PROTECT YOUR BRAIN. TAKE A LARGE EXTRA AMOUNT PRIOR TO DOSING. (THIS IS NOT AN ENDORSEMENT OF ANY DRUG USE. BUT IF YOU DO CHOOSE TO DO SO, USE THEM INFREQUENTLY. AND FOLLOW THE ABOVE PRECAUTIONS.)

 

[Matsuo Munefusa.]

are you talking 5g of ascorbic acid or 5g of the vitamin C complex? Ascorbic acid is merely one component of vitamin C complex.

 

[psood0nym]

No you did not mention 5 grams of vitamin C. I did. Seems you're reading comprehension is not so good, eh?

Where do you see me promoting an opinion that people ought to just take lots of antioxidants and gobble up massive amounts of MDMA constantly and indiscriminately???

You are the one having delusions of some kind.

If you had bothered to READ the page I linked to, you would see the proof of protection. Obviously you did not. The 5 gram figure is derived from science referenced there.

And this "debunking of antioxidants" is a popular topic among a narrow group of kooks, er, "researchers." There are tens of thousands of published research studies going back decades confirming the usefulness and efficacy of antioxidant supplementation. But that's not what this thread is about. An obvious diversionary tactic. Sorry, not biting today.

Again, I was just stating facts from research. Beyond this, I'm not gonna have an argument with you, who obviously has some axe to grind:

1. FACT: The neuronal damage (and deaths) supposedly caused by MDMA was the result of using methamphetamine (in massive overdose quantities... those poor monkeys, who all died, horribly) in place of MDMA in the classic research (sponsored by anti-drug government agencies)... which has now been retracted by the authors

Ricaurte MDMA Research Controversy - MAPS
http://mail.maps.org/mdma/studyresponse.html

I wont repeat it all here folks... just go read this extensive summary/review page, follow and read some of its many dozens of links, starting with:

"Scientists Retract Story on Ecstasy Brain Damage" - Reuters News Service

I'll also highlight "Deconstructing Ecstasy" by Dr. Charles Grob.
http://www.maps.org/w3pb/new/2000/2000_grob_1139_1.pdf


2. FACT: at least in mice injected with the huge overdoses of MDMA needed to trigger "brain damage", large doses of Vitamin C TOTALLY PREVENTED DAMAGE TO THE NEURONS.

From http://www.erowid.org/chemicals/mdma/mdma_article3.shtml

"Since the damage appears to be caused by oxidative stress, one way to reduce might be to simply increase the amount of antioxidants available to the cells. Some very compelling papers have been published showing that antioxidants alone can prevent neurotoxicity caused by enormous doses of MDMA. In a paper published by Aguierre et al. in 1999, researchers administered 4 high doses of alpha lipoic acid by injection to rats during the 2 days preceding a single neurotoxic dose of MDMA (20 mg / kg, also injected) and found that alpha lipoic acid "completely prevents the loss of 5-HT [serotonin] content and the decrease of ... 5-HT transporters in the frontal cortex, hippocampus and in the striatum and also abolishes the increases in the glial response [another marker of neurotoxicity] observed in the hippocampus 7 days after MDMA."11 Several additional labs have reproduced and confirmed that high-dose, injected antioxidants block MDMA neurotoxicity in rats.1,3,6,7

"But perhaps even more interesting is work done with cheap, well tolerated, and universally available antioxidants such as ascorbic acid (vitamin C) showing similar protection. In the first paper to demonstrate this, G.A. Gudelsky7 found that rats given extreme doses of MDMA (20mg/kg injected under the skin) had lasting damage to their serotonin system, but that rats given this same dose of MDMA with a very high dose of ascorbic acid (250mg/kg injected) showed no sign of serotonin damage."

The original research is referenced there. The page goes on to attempt to extrapolate to humans, which results in an oral dose of 4-11grams, an amount commonly consumed by people.

I would recommend the Ester-C products, which are retained in blood and cells for much longer than traditional ascorbic acid, are non-acidic, and can be found with additional and beneficial bioflavonoids. I would also add other antioxidants as outlined by the general "phenethlamine protection" regimen discussed in

Phenethylamines, Free Radicals, and Antioxidants
Brian Leibovitz, Ph.D.
http://www.maps.org/news-letters/v04n1/04134pea.html

"This information is for those who experiment with phenethylamines as well as those with patients who use these compounds.... "

Undoubtedly the posting of this helpful, science-oriented summary of research will also piss off psood0nym. Oh well.

It's all there folks, just go read the linked pages, which have extensive references to published scientific research.

IF YOU ARE GOING TO TAKE MDMA OR OTHER PHENETHYLAMINES OR STIMULANTS, START TAKING ANTIOXDANTS TO PROTECT YOUR BRAIN. TAKE A LARGE EXTRA AMOUNT PRIOR TO DOSING. (THIS IS NOT AN ENDORSEMENT OF ANY DRUG USE. BUT IF YOU DO CHOOSE TO DO SO, USE THEM INFREQUENTLY. AND FOLLOW THE ABOVE PRECAUTIONS.)

So your response to my asking you to post newer replications of these findings is to link to studies from the 1990s and early 2000s and to give a blanket dismissal of research critical of the effectiveness of antioxidants as th work of "kooks"?

Yes I am angry. You began your last post with "Fuck you," and you've ignored my attempts to reason with you. Where is your response to the brain zaps argument (which also applies to MDAI)? What about the fact that MDMA elevates body temperature, which itself causes brain damage, especially when people dance on MDMA? Even if you don't accept newer double blind placebo controlled studies that are critical of the claims of the many early antioxidant marketer supported studies there are other routes to brain damage than free radical production.

Sorry, MDMA may be the love drug but it's got serious issues. I like it, too, but I accept that I'm doing some damage to my brain and body when I take it, and so use it in moderation (around 4 times per year). Telling people that they can totally protect themselves by using antioxidants and then saying that you're not advocating over indulgence is silly. What part of "total protection from damage" supplies a reason for not indulging in a drug that makes people feel great and empathetic? "Feel awesome with no substantial health consequences! But don't do it a lot!"

My "axe to grind" is with your potentially dangerous intellectual shortsightedness and dismissal of counter evidence. It's hardly the personal grudge you seem to want to believe it is.

 

[atara]

I really hope MDAI doesn't disappear from the RC market. It wasn't terribly popular, but it was unique, and while not totally safe, it seemed to be the sort of thing you could get away with doing every weekend.

Methylone wouldn't have its effects if it wasn't neurotoxic... Its impossible to have an MDXX like experience without the neurotoxicity.

There's no reason to believe that, really.

What about the brain zaps many people get after MDMA use? Zaps are theorized to be isolated seizure activity, and seizures cause brain damage.

This sounds pretty made-up to me. Are there any actual researchers postulating this, or is this some kid's theory after he took a bunch of MDMA and read a Wikipedia article?

First, the whole thing about MDMA being neurotoxic was garbage science in which they injected monkeys with IMMENSE overdoses of THE WRONG DRUG! (they "accidentally" ised methamphetamine instead of MDMA).

No, MDMA's neurotoxicity has been accurately demonstrated in rats for a long time. The relevance of its long-term effects on the brain to actual behavioral and psychological changes is rather slim.

New Scientist's The Myth of Antioxidants.

While I personally believe that anyone who takes Vitamin C in the hope of preventing brain damage might not have much left to lose, it's a bit sad to see you taking New Scientist as though it were a scholarly publication.

So your response to my asking you to post newer replications of these findings is to link to studies from the 1990s and early 2000s

That's the most errant red herring I've seen in a while. A study published in a peer-reviewed journal twenty years ago, and not debunked, is probably as valid today as it was then. The methodology may be questionable, of course; there's plenty of peer-reviewed crap.

IF YOU ARE GOING TO TAKE MDMA OR OTHER PHENETHYLAMINES OR STIMULANTS, START TAKING ANTIOXDANTS TO PROTECT YOUR BRAIN.

Someone probably works for the vitamin industry. Really, there's not a whole lot of knowledge on what prevents damage from MDMA and other stimulants. I've heard pretty convincing stuff about MAO-B inhibitors (deprenyl, kava), cannabis, alcohol (yes really), and aspirin. There's also not a whole lot of data about what degree the changes in brain structure caused by MDMA are clinically relevant.

...there is, however, a good bit of data on amphetamine psychosis. That, alone, is an important reason to use your drugs responsibly.

Does anyone know the cross tolerance with mdma?

Just a guess: MDAI will cause serotonin depletion after use, during which time MDMA will not take effect as strongly as normal. However, it will not provide a significant metabolic cross-tolerance; a person taking a reasonable dose of MDAI may be able to feel full effects from MDMA in as little as four days to a week.

 

[windows78]

Loving the MDAI at the moment!! Real good at 50mg+ but proper burns your nose.....I like it after a while tho ;-) Re dose all night tho but that's all good imo!!

Good to have a proper RC back again as I think vendors have been selling some pretty crap mdai for a while now!!

 

[MagickalKat777]

I highly doubt that MDAI is anything special... did you ever try methylone?

 

[Brian.Badonde]

yeah MDAI feels like pure heaven to me. i get it from a reliable vendor too

 

[Morpheus19]

Took the white MDAI, felt exactly how it should like at 150mg oral. Nothing special, but worth it's price.

 

[plomari]

friend has a blood test (to find the cause of her heart sometimes spontaniously deciding to go to 115 bpm) upcoming. she took mdai on last thursday(at least I think so, was a pretty wild party :D ), will it show up?

 

[kingme]

mdai most probably will not show up in blood tests (especially after almost a week). even less since they will not be looking for that compound. i wouldnt worry about it.
however, if she does have a heart condition then she really shouldnt be taking anything until she figures out what the cause is, as heart arrytmias can be serious health problems.

 

[plomari]

yeah, I have been telling her to get it looked at. she also has a heart rate at rest of 80-90... well, it was the 3rd time it happened, I'm happy that she finally went to a doctor.