amphetamine/mdma neurotoxicity

[syraq]

Is there something like an ok time window between the use of amphs and mdma to avoid the neurotoxicity of this combo ?
I'm guessing a bit of amph in the morning to get home after a party with mdma dropped at like 1 am is too soon.

 

[myr]

All people saying is that it's potentially more neurotoxic than MDMA alone which all we know about is that scientist gave stupid amounts (10-20mg/body kg instead of usual recreational doses of 1,5-2,0mg/kg in humans) of substances every 3-4(!) hours to gene manipulated rodents for days and they were able to show signs of reversible neurotoxicity.
That's like someone taking a gram of MDMA several times a day.
If anyone able to provide a reputable source of information saying otherwise, I'm open for that.

I went through 6-7 studies in google's library and I found two things stated by two separate scientists: hyperthermia is necessary for dopaminergic neurotoxicity and 5mg/kg is called a "sub-toxic" dose of MDMA. No proof of any damage so IMHO you can take the amph whenever you want.
Do not let your body overheat and give a chance to neurotoxicity, stay hidrated, wear light clothes, use common doses of every substance. That's it.

 

[BlueBull]

It will make the crash and subsequent hangover worse. It could also lead to a bit of over-stimulation with assorted physical symptoms (muscle spasms, restless legs, bruxism,...) more so than MDMA on its own. You will likely feel very cracked out on the tail end and afterwards

However I think it's very unlikely to lead to neurotoxicity. Best thing to do HR-wise is to not take them so close together as there will be consequences. That being said I think you'll be fine should you decide to dose a bit of amp. Watch your fluid intake a bit more closely than you normally would and make sure you have eaten more than enough nutritious food in the days leading up to your roll, you will likely not have an appetite for a while longer than you normally would on MDMA alone so make sure you have some reserves

 

[St3ve]

All people saying is that it's potentially more neurotoxic than MDMA alone which all we know about is that scientist gave stupid amounts (10-20mg/body kg instead of usual recreational doses of 1,5-2,0mg/kg in humans) of substances every 3-4(!) hours to gene manipulated rodents for days and they were able to show signs of reversible neurotoxicity.
That's like someone taking a gram of MDMA several times a day.
If anyone able to provide a reputable source of information saying otherwise, I'm open for that.

I went through 6-7 studies in google's library and I found two things stated by two separate scientists: hyperthermia is necessary for dopaminergic neurotoxicity and 5mg/kg is called a "sub-toxic" dose of MDMA. No proof of any damage so IMHO you can take the amph whenever you want.
Do not let your body overheat and give a chance to neurotoxicity, stay hidrated, wear light clothes, use common doses of every substance. That's it.

Converting animal doses to human doses purely based on mg/kg is flawed thinking... There's a lot of factors that come into play including different physiological factors such as metabolism and drug absorption, transportation to the brain, etc. But also body size and surface area. According to this paper (http://www.fasebj.org/content/22/3/659.long) you need to apply conversion factors when comparing rat/mice data to obtain a human equivalent dose. Following their formula for a 20mg/kg dose of MDMA in mice you'd first multiply by 3 and then divide by 37 to get the human dose. This would be equal to about 1.6mg/kg dose, which for a 70kg person would be 113mg of MDMA (standard medium dose). Of course these are only guidelines and not universal rules for all drugs, as each substance is different and interspecies differences also come into play.

 

[Black]

Converting animal doses to human doses purely based on mg/kg is flawed thinking... There's a lot of factors that come into play including different physiological factors such as metabolism and drug absorption, transportation to the brain, etc. But also body size and surface area. According to this paper (http://www.fasebj.org/content/22/3/659.long) you need to apply conversion factors when comparing rat/mice data to obtain a human equivalent dose. Following their formula for a 20mg/kg dose of MDMA in mice you'd first multiply by 3 and then divide by 37 to get the human dose. This would be equal to about 1.6mg/kg dose, which for a 70kg person would be 113mg of MDMA (standard medium dose). Of course these are only guidelines and not universal rules for all drugs, as each substance is different and interspecies differences also come into play.

the usual conversion cannot be applied for mdma. what's neurotoxic are the metabolites and smaller animals usually have a faster, more efficient metabolism (which is also why they usually get larger doses), so with "equivalent" scaled doses you'll get disproportionately more of the toxic metabolites. rats also show comparable behavioural responses at the same mg/kg doses as humans.
the thing that really is important is that the concentrations of the active substances in the bloodstream should be equal.

In summary, the present results reveal a number of new and important findings with regard to MDMA pharmacokinetics in rats. First, when rats receive 2 mg/kg MDMA by the intraperitoneal or subcutaneous route, MDMA and HMMA Cmax are comparable to those in humans given recreational doses of the drug. Our Cmax data may explain why rats and humans discriminate the same dose of MDMA and argue against the arbitrary use of interspecies scaling to adjust MDMA doses across species (de la Torre and Farré, 2004; Baumann et al., 2007).

additionally in ricaurte's experiments with monkeys, some monkeys die as a result of what according to him is equivalent to a normal recreational dose for humans. come on, if that's a reliable model for mdma toxicity then dropping stones on ants is a reliable model for what happens when humans are exposed to falling snowflakes.
___

@myr
they're not genetically modified rats. just regular lab strains

 

[myr]

According to this paper (http://www.fasebj.org/content/22/3/659.long) you need to apply conversion factors when comparing rat/mice data to obtain a human equivalent dose.

I found this:
http://link.springer.com/article/10.1007/s00213-006-0322-6
"MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1–2 mg/kg), suggesting that there is no reason to adjust doses between these species."

MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1–2 mg/kg), suggesting that there is no reason to adjust doses between these species.

@Black: I have definitely seen mentioned that they use knockout rats whose ability to produce necessary enzymes to metabolize phenetylamine-based subatances is turned off.
Same thing confirmed by the vice president of MAPS Hungary.

Ok I found it.

http://www.sciencedirect.com/science/article/pii/S0091305799001161

Dark Agouti Inbred rats (provided by Harlan Labs) which are the in vivo models of MDMA's serotonergic neurotoxicity experiments have a deficiency of the enzyme CYP2D1 thus serving as a model of poor human metabolism.

I guess this answers why there's no need for scaling too.

 

[Black]

@Black: I have definitely seen mentioned that they use knockout rats whose ability to produce necessary enzymes to metabolize phenetylamine-based subatances is turned off.
Same thing confirmed by the vice president of MAPS Hungary.

Ok I found it.

http://www.sciencedirect.com/science/article/pii/S0091305799001161

Dark Agouti Inbred rats (provided by Harlan Labs) which are the in vivo models of MDMA's serotonergic neurotoxicity experiments have a deficiency of the enzyme CYP2D1 thus serving as a model of poor human metabolism.

I guess this answers why there's no need for scaling too.

of course they're an inbred strain, but they aren't knockout mice. they're deficient in cyp2d1 because of the inbreeding.
they're just as much genetically modified as a siamese cat or a great dane .

checking how humans deficient in cyp2d6 react and trying to establish a rat model wasn't entirely pointless either, but presenting the result as "this is what mdma does to anyone who takes mdma" certainly is. besides, it now looks rather as if the rat homologue of cyp2d6 is cyp2d2 rather than cyp2d1...
actually, with what we know now, i don't even think it makes a huge difference. once you go over something like 100mg, we're all poor metabolisers due to mdma inhibiting cyp2d6.

 

[myr]

of course they're an inbred strain, but they aren't knockout mice. they're deficient in cyp2d1 because of the inbreeding.
they're just as much genetically modified as a siamese cat or a great dane

Well, in a sense they are :D But thanks for clarifying that

 

[mew4]

im very interested in this as well cuz ive had this combo be problematic for me in the past.

 

[myr]

What problems did you have and how much did you use? Was it TESTED?
Street speed is notoriously cut and mdma is usually not mdma.

Almost forgot. To the OP:
You can drop an SSRi (like prozac) AFTER the roll and BEFORE the speed to protect your serotonin releasers from incidental damage caused by dopamine. If you take it with mdma, you won't roll. This has been proven, i'm lazy to look for the study.

 

[Black]

Almost forgot. To the OP:
You can drop an SSRi (like prozac) AFTER the roll and BEFORE the speed to protect your serotonin releasers from incidental damage caused by dopamine. If you take it with mdma, you won't roll. This has been proven, i'm lazy to look for the study.

ssris are powerful medicines with lots of possible side effects. i really wouldn't recommend them to anyone who doesn't absolutely need them. i personally know two people who had bad reactions that required hospitalisation from a single dose.
yes, they protect from mdma neurotoxicity (which - i think we agree - isn't likely at all from recreational doses). but the "dopamine gets taken up into serotonergic neurons" hypothesis has been disproven for some time (i cannot find paper with the conclusive evidence right now but this one gives a short overview concerning dopamine's role in neurotoxicity). right now the candidates which are by far the most likely to cause the toxicity are HMMA and HMA and of course hyperthermia (which is also where amphetamine with its potential for raising body temperature further comes in). so instead of taking an ssri, the better course of action imho would be to make sure you're not overheating.

 

[JWills20]

Neurotoxicity from MDMA doesn't occur until high doses. If you're keeping doses of both MDMA and amp low then the neurotoxicity is unlikely to be significant. That's not to say you won't get a shittier comedown consisting of higher exhaustion, muscle spasms, face chewing etc. Combining stimulants causes far more side effects than either alone usually. I'd keep the MDMA within the 100-200mg range and the amp dose at a purely therapeutic dosage to minimize side-effects.

 

[myr]

ssris are powerful medicines with lots of possible side effects. i really wouldn't recommend them to anyone who doesn't absolutely need them. i personally know two people who had bad reactions that required hospitalisation from a single dose.
yes, they protect from mdma neurotoxicity (which - i think we agree - isn't likely at all from recreational doses). but the "dopamine gets taken up into serotonergic neurons" hypothesis has been disproven for some time (i cannot find paper with the conclusive evidence right now but this one gives a short overview concerning dopamine's role in neurotoxicity). right now the candidates which are by far the most likely to cause the toxicity are HMMA and HMA and of course hyperthermia (which is also where amphetamine with its potential for raising body temperature further comes in). so instead of taking an ssri, the better course of action imho would be to make sure you're not overheating.

That's quiet a read, the part about toxicity is beyond my knowledge of neurochemistry to be honest.

It's interesting that you personally know people who had adverse reactions to SSRIs that required hospitalisation on a single dose, since I wasn't able to find any data about it online (I'm not saying my methods of research are flawless ).
There's a chance of adverse reactions no doubt (like with any painkiller too). Still, psychiatrist prescribe it to millions of people every day. They only asked me about my allergies when I've been treated with depression, no check ups or anything.

OP:
I also say what Black said and virtually all the studies reflect that hyperthermia is the biggest threat when it comes to serotonergic toxicity.
Using recreational doses of MDMA and amphetamine, also looking after your body temp (breaks from physical activity, regular water intake) should be sufficient to protect yourself from irreversible effects.

 

[Black]

It's interesting that you personally know people who had adverse reactions to SSRIs that required hospitalisation on a single dose, since I wasn't able to find any data about it online (I'm not saying my methods of research are flawless ).
There's a chance of adverse reactions no doubt (like with any painkiller too). Still, psychiatrist prescribe it to millions of people every day. They only asked me about my allergies when I've been treated with depression, no check ups or anything.

i certainly haven't seen a representative example here and i don't think it happens that often (in the one case where i was actually present at the hospital, the doctors didn't really know what to make of it. they suspected either an allergic reaction, serotonin syndrome or a panic attack and proceeded with treatment for all three...).
yeah, there isn't really anything doctors can check for when they prescribe ssris (except other medication). another thing is that if you're one of those people who get major unpleasant (not necessarily dangerous) side effects from, you'd (as far as i have seen/heard) get them right at the beginning of therapy and develop a tolerance to some of them in the coming weeks until the therapeutic effects set in (for those people that profit from ssris). so the dosage for therpeutic use is normally increased slowly. but for a single dose (i don't know what the effective dose for cutting off mdma's effects would be) that is obviously not an option and you'd likely feel the full force of the side effects.

 

[myr]

Well, it seems it doesn't worth the risk.