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MDMA brain damage

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stormyweathers

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Jan 3, 2010
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I remember reading a while back that the brain damage caused by MDMA was not intrinsic to the serotonin release, but a side effect of a toxic metabolite

that if MDMA was injected (into the brain?) the damage to serotonin neurons would not happen

does anybody know which metabolites cause this?

basically it boils down to:
MDA has the same problem as well, no?

what about MMDA?
MMDMA?
M1?
 
MMDA is a selective serotonin releaser. I believe it is nonneurotoxic. Same logically follows for MMDMA, which may in fact have a selectivity for release over reuptake inhibition that is closer to MDMA than does MDAI. This paper, which I can't get, apparently indicates this:

http://linkinghub.elsevier.com/retrieve/pii/0091-3057(91)90005-M

Methylone is almost certainly similar to MDMA wrt serotonin axon degeneration. All members of the class of SNDRAs have some neurotoxicity, even the unrelated-to-MDMA compounds 4-fluoroamphetamine and 5-iodoaminoindane.
 
mdma releases so much serotonin that afterwards serotonin has less effect on receptors.

thats what it feels like anyway
 
i feel like i have brain damage from MDMA. how would one know this? brain scans?

anyway, if anything i'd say the MDA after it's metabolized screws you up. it makes you hallucinate, visuals and audio hallucinations, up to a week after even. serotonin depletion in general causes what mimics that of brain damage anyway because serotonin controls nearly every aspect of enjoyment in your mind. it creates anxiety, insomnia, depersonalization, depression.
 
Some have suggested that alpha-methyldopamine (MDA with the methylene group removed) as the toxic metabolite. It is a neurotoxin, it does have a fairly long half life and is a known a metabolite of both MDMA and MDA, possibly more is produced after ingestion of MDA but I'm just guessing.
 
molly897 said:
i feel like i have brain damage from MDMA. how would one know this? brain scans?
Click to expand...

Assuming you have brain damage without solid evidence that you do, in fact, have brain damage, is a really good way to screw up your life. I get mad sometimes at people who run around yelling about neurotoxicity because convincing someone that their brain is permanently damaged always does more harm than good.

Even if you do something monumentally fucking retarded, a typical MRI will show no abnormality.
 
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so the analogues methoxy ring substitution are likely to metabolize into something other than aMD

Turing, do you have a source for that info about aMD?
 
stormyweathers said:
I remember reading a while back that the brain damage caused by MDMA was not intrinsic to the serotonin release, but a side effect of a toxic metabolite

...

does anybody know which metabolites cause this?[1]

...

basically it boils down to:
MDA has the same problem as well, no? [2]
Click to expand...

[1] The MD-bridge gets metabolized to the 3,4-dihydroxy-derivative, which is a redox-active ortho-quinone. This one can react e.g. with any thiol-sidechain nearby, thus deactivating any protein it meets.
Edit: I just saw that Turing Machine already named it.

[2] Yes, same problem for MDA as with MDMA, at least in theory.

Please note that the metabolites on their own are not solely responsible, but hyperthermia plays a significant role, too, as does dehydration and lack of antioxidant (read: vitamins 'n stuff).


Peace! - Murphy
 
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^what about methoxy ring-substituted ananlogues?
do you agree with atara that MMDA and MMDMA would be non-neurotoxic?
 
MMDA and MMDMA can both form again an ortho-positioned aromatic diol (=ortho-quinone) by cleavage of the MD-bridge. If this gets taken up into dopaminergic neurons (or serotonergic ones, dunno), they would still be neurotoxic. IF they actually are transported I can't say with certainty. The additional steric bulk of one methoxy-group is not really spectacular (...suggests that they are transported; but as said before, I'm not sure here).

I'm convinced somebody else can chime in here; we discussed this before...


- Murphy
 
Free radical oxidized versions of dopamine and serotonin will form regardless of whether or not the MDMA ring is o-demethylated I'm pretty sure. So, there's no way around it. It's already been shown that alpha-ethyl tryptamine is also a serotonergic neurotoxic, along with a number of other structurally unrelated tryptamines.

The problem is:
1. 5HT release
2. DA/NE release (oxidation occurs of this molecule because of peroxide produced from mitochondria when broken down by MAO-B)
3. 5HT2A/C agonism (elevated temperatures spur on the above)

The reason Naphthylisopropylamine is not neurotoxic is probably something to do with its lack of affinity for 5HT2A and just poor ability to release monoamines, coupled with long duration.
 
^So would this mean psychedelics + MDMA would be more neurotoxic because of the added 5-ht2A/C activation?
 
so theres no way around the neurotoxicity eh?
well thats annoying haha

I guess it really is only safe once every couple months
 
^antioxidants are a potential way around it. Several have been shown to prevent up to 100% neurotoxicity in rats at least.
 
chaos_destroy said:
^antioxidants are a potential way around it. Several have been shown to prevent up to 100% neurotoxicity in rats at least.
Click to expand...
And until now, in rats only! That antioxidants reduce the oxidative stress caused by these drugs in humans is - unfortunately - only speculative. It won't cause harm to take some supplements with your next trip, but I wouldn't count too much on it.

And capsaicin reduces hyperthermia? Sounds interesting. Any reference available?


- Murphy
 
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^true although the same could be said about neurotoxicity in humans too right? Is there evidance that mdma causes neurotoxicity in humans not rats or monkeys at recreational doses?
 
MurphyClox said:
And capsaicin reduces hyperthermia? Sounds interesting. Any reference available?


- Murphy
Click to expand...

The question isn't as resolved as I'd thought. Capsaicin receptor (TRPV1) antagonists cause hyperthermia, and capsaicin agonism at TRPV1 causes hypothermia, yet it does not have reported antipyretic effects.

Apparently, it causes both heat loss and heat production by separate mechanisms:

http://www.ncbi.nlm.nih.gov/pubmed/10992721

I should have said "capsaicin agonists" (which includes paracetamol, and is in fact the mechanism by which it controls hyperthermia) but apparently not capsaicin itself!

On a side note, shouldn't an AM404 preparation have been made available already? It should be more potent and thereby less toxic than paracetamol.
 
chaos_destroy said:
^true although the same could be said about neurotoxicity in humans too right? Is there evidance that mdma causes neurotoxicity in humans not rats or monkeys at recreational doses?
Click to expand...

For single, recreational doses (read: no binges, no repeated use within short time!) neurotoxicity could not be confirmed for MDMA to my best knowledge.

Heavy use is harmful beyond any doubt!

- Murphy
 
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