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MDMA Folklore

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Oceanking

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Jan 1, 2009
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I'm not sure if this question should be addressed in the basic drug discussion, or here, so please pardon my mistake if it is.

The question is regarding something I've heard about MDMA. A person told me that if it is used more than approximately 3 or 4 times, it has serious potential of "frying" the receptors that it binds with. In such a case, this person said, you run the risk of not being able to experience pleasureful experiences. To me it sounded awful suspicious, so I thought I'd get a more educated opinion.

OK
 
MDMA associated neurotoxicity is definitely real, but assigning a number of experiences is impossible.
 
It depends if you are taking pure MDMA or "ecstasy" pills. The pills can have whatever from DXM to meth and may not even contain any MDMA. Unless you have the pills tested you have no way of knowing what they contain.
 
When I think MDMA I tend to think "molly" powder. Those backalley pressed tablets are just random drugs passed for a street profit. It reminds me of what my mother told me about never to take pills a stranger hands you.

Anyway, doesn't MDMA phosphorylate the dopamine active transporter like methamp? That is pretty much making your receptor "useless" until it internalizes, like killing the usher so dopamine cannot be granted access outside it's area.
 
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Phosphorylation of the dopamine transporter in no way equals neurotoxicity--phosphorylation may certainly induce encytosis of the DAT into recycling endosomes, acutely reducing the number of DATs at the cell surface. But that is not the same thing as neurotoxicity. The greatest neurotoxic property of MDMA is the fact that it is metabolized to a pro-oxidant quinone-like species, causing oxidative stress and insult to mitochondria--and if you piss off those mitochondria enough, they mutiny and induce programmed cell death. Check out the following papers for some great info about the toxic metabolites of MDMA.

Erives, et al. (2008). Accumulation of neurotoxic thioether metabolites of MDMA in rat brain. J Pharmacol Exp Ther. 324: 284-91.

Capela et al. (2007). Neurotoxicity mechanisms of thioether ecstasy metabolites. Neuroscience. 146: 1743-57.

Jones et al. (2005). Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J Pharmacol Exp Ther. 313: 422-31.

And yeah, MDMA has absolutely nothing to do with "Ecstasy." Ecstasy is just a brand name for pressies that could contain absolutely anything (or nothing).
 
Riemann Zeta said:
Phosphorylation of the dopamine transporter in no way equals neurotoxicity--phosphorylation may certainly induce encytosis of the DAT into recycling endosomes, acutely reducing the number of DATs at the cell surface. But that is not the same thing as neurotoxicity. The greatest neurotoxic property of MDMA is the fact that it is metabolized to a pro-oxidant quinone-like species, causing oxidative stress and insult to mitochondria--and if you piss off those mitochondria enough, they mutiny and induce programmed cell death. Check out the following papers for some great info about the toxic metabolites of MDMA.

Erives, et al. (2008). Accumulation of neurotoxic thioether metabolites of MDMA in rat brain. J Pharmacol Exp Ther. 324: 284-91.

Capela et al. (2007). Neurotoxicity mechanisms of thioether ecstasy metabolites. Neuroscience. 146: 1743-57.

Jones et al. (2005). Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J Pharmacol Exp Ther. 313: 422-31.

And yeah, MDMA has absolutely nothing to do with "Ecstasy." Ecstasy is just a brand name for pressies that could contain absolutely anything (or nothing).
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Yeah, this is what I'm talking about, not anything having to do with receptor internalization which is a natural process.
 
Riemann Zeta said:
Erives, et al. (2008). Accumulation of neurotoxic thioether metabolites of MDMA in rat brain. J Pharmacol Exp Ther. 324: 284-91.

Capela et al. (2007). Neurotoxicity mechanisms of thioether ecstasy metabolites. Neuroscience. 146: 1743-57.

Jones et al. (2005). Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J Pharmacol Exp Ther. 313: 422-31.
Click to expand...
Thanks for those. Just what I was looking for.
 
I thought that alpha-methyl dopamine / alpha,N-dimethyl dopamine were the major metabolites, aren't they? I know that conjugates of those two are potent serotonergic neurotoxins.
 
dread said:
It depends if you are taking pure MDMA or "ecstasy" pills. The pills can have whatever from DXM to meth and may not even contain any MDMA. Unless you have the pills tested you have no way of knowing what they contain.
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No it does not depend on that.

Pure MDMA is in and of itself neurotoxic. Anything else added is just to make things worse.
 
Oceanking said:
Is it all relative to how its produced? In other words, some "batches" are worse than others?
Click to expand...

In general: Yes! Can't go into details because this would be readily be a synth-oriented discussion, but with some synthetic methods certain side-products are more likely. These do not cause the described "receptor-frying", but they are certainly not healthy...

- Murphy
 
I thought that alpha-methyl dopamine / alpha,N-dimethyl dopamine were the major metabolites, aren't they? I know that conjugates of those two are potent serotonergic neurotoxins.
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Yep, those are the ones. The ring-hydroxy moieties can be oxidized up to the quinone species and then cysteine or glutathinone can attack at the 5-position, forming the aforementioned toxic "pro-oxidant thioether metabolites."
 
MurphyClox said:
In general: Yes! Can't go into details because this would be readily be a synth-oriented discussion, but with some synthetic methods certain side-products are more likely. These do not cause the described "receptor-frying", but they are certainly not healthy...

- Murphy
Click to expand...

So could it lead to inability to experience pleasure?
 
The problem with pills is the pairing of meth and MDMA often seen in unknown tabs. That's synergetic brain fry in a cute little pill, so stay away from 'em entirely (what I'd do, if I were to ever touch MDMA again), and test if you're gonna eat them.
 
Assuming you had access to pure, unadulterated MDMA hydrochloride, then you would have to take far upwards of 1000 doses at 100mg each to come anywhere close to clinically significant, debilitating neurotoxicity. The world record holder who is now in his late 30's took 40,000 pills over a period of a few years and, although he's seen better days health wise and has clearly created some permanent health problems for himself, he's still alive.

I've taken mdma hundreds and hundreds and hundreds of times at many different dosage levels, some very high, and have experienced zero ill effects. Nada. Zilch. Nothing. The Empty Set. 0
 
Who said that noticable neurotoxic effects develop this fast?! I would think that 10-20 years between MDMA-binges and a nice, shaky Parkinson is still realistic. Apart from this: How much does one example tell us about the general situation? Rhetorical question...

- Murphy
 
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