Is MDMA neurotoxic and does it cause brain damage?

[bees_knees]

Just wondering what the final word on this is, I read that it's only neurotoxic if you abuse it, others had said it is always neurotoxic. Does it do permanent damage? What sort of research has been done?

 

[JWills20]

Just wondering what the final word on this is, I read that it's only neurotoxic if you abuse it, others had said it is always neurotoxic. Does it do permanent damage? What sort of research has been done?

There is no final word - it's dose dependent. MDMA is obviously neurotoxic in high doses and far less so in lower doses. It's got a steep dose-response curve so that higher doses cause significantly more changes than lower doses. I'm not convinced that MDMA is significantly neurotoxic until you get above 5mg/kg with repeated doses (as with rat studies). Human studies which have administered 1-1.5m/kg found minimal change in relevant biomarkers. Some research has drawn differences in ecstasy vs. non-ecstasy users but this research usually has many methodological flaws which require fixing before we can say the 'final word'. Moreover, some studies have found that while serotonin might not change, long-term ecstasy users are more likely to rate higher on scales for depression than non-ecstasy users. But, why this is the case is not yet known (since clearly serotonin hasn't changed) and this is purely correlational with no actual causation. In order to answer these questions we need to: ensure that all participants are not polydrug users, ensure that they are taking just MDMA (because street ecstasy is notoriously impure), try to create studies which more accurately represent the way in which MDMA is used (not a rat study frying the brain, neither a human study administering small doses in a completely controlled environment, but instead something in between). Body temperature is likely to play a large role in neurotoxicity hence if a study could mimic a rave environment, with confirmed MDMA, at reasonable human doses (let's say 100-300mg as a range) we could compare that to studies just performed in a lab.

Anything caused is unlikely to be permanent, but perhaps withstanding (some studies have found differences well after people have stopped ingesting MDMA). However, none of these changes have actually been causally linked to depression/anxiety. So, even if MDMA does change brain function, it doesn't appear like this causes depression/anxiety. Just because something has changed in the brain doesn't automatically mean something bad has happened. The brain is always changing and this change is influenced by our very own behaviours. For cognitive symptoms to manifest from MDMA it usually requires long-term abuse or, like true psychedelics, trigger an underlying mental disorder.

 

[ScaredFirstTimer]

It's neurotoxic enough to cause statistically significant lower SERT (serotonin transporter) levels in the cortex of current users. Indicating axonal loss aka brain damage.

Cortical Serotonin Transporter Density and Verbal Memory in Individuals Who Stopped Using 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”)

Mean cortical [123I]-CIT-labeled 5-HT transporter density was significantly lower in recent MDMA users than in controls (1.17 vs 1.28 [–9%]) but not in ex MDMA users (1.24 vs 1.28 [−3%]). Recent and ex MDMA users recalled significantly fewer words than did controls on the immediate recall (47.0 and 48.0 vs 60.0, respectively; P=.001) as well as the delayed recall (9.8 and 10.1 vs 13.1, respectively; P=.003). Greater use of MDMA was associated with greater impairment in immediate verbal memory. However, memory performance was not associated with [123I]-CIT binding to cortical 5-HT transporters or duration of abstinence from MDMA.

Since the SERT is located on the presynaptic axons and axon terminals of 5-HT neurons, it is considered to be a reliable marker of 5-HT neurotoxic changes.

Conclusion: The present study suggests that, while the neurotoxic effects of MDMA on 5-HT neurons in the human cortex may be reversible, the effects of MDMA on memory function may be long-lasting.

 

[JWills20]

It's neurotoxic enough to cause statistically significant lower SERT (serotonin transporter) levels in the cortex of current users. Indicating axonal loss aka brain damage.

Cortical Serotonin Transporter Density and Verbal Memory in Individuals Who Stopped Using 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”)

Just saying that there's also some studies which have found no differences in 5-HT nor memory deficits. The debate is still pretty ripe and probably comes down to how well the study has been controlled.

 

[ScaredFirstTimer]

How did they measure 5-HT? Altered levels of 5-HT doesn't necessarily indicate a loss of axons. It definitely depletes after MDMA but that isn't necessarily all that bad. The beauty of the paper I quoted is that they measured SERT levels with a SPECT scan.

 

[JWills20]

How did they measure 5-HT? Altered levels of 5-HT doesn't necessarily indicate a loss of axons. It definitely depletes after MDMA but that isn't necessarily all that bad. The beauty of the paper I quoted is that they measured SERT levels with a SPECT scan.

I can't remember. It's been a while since I read around the MDMA literature. All I know is that usually those sorts of studies look at self-administered, polydrug users so it's always difficult to determine the causal role of just MDMA. The ecstasy group are just people that have consumed what they believe to be MDMA in whatever doses they fancied as much as they wanted. They usually lack the control required basically.

 

[bees_knees]

Thanks for that!

 

[TheCuriousOne]

Would once-a-month use of 2.5mg/kg MDMA have any noticeable damage after some time?

 

[Black]

It's neurotoxic enough to cause statistically significant lower SERT (serotonin transporter) levels in the cortex of current users. Indicating axonal loss aka brain damage.

cells tend to degrade proteins that are "perceived" to be malfunctioning. like SERT in this case; this doesn't automatically mean destruction of the axon terminal.
rat studies have found a reduction of up to 90% for SERT levels upon repeated SSRI administration. yet nobody calls SSRIs neurotoxic. the conclusion in that study you quote is pretty weak with that kind of reasoning. the fact that the SERT levels can return to their previous level in a matter of just a few weeks also speaks against neurotoxicity.




another interesting point is that mdma itself definitely isn't neurotoxic (in any conceivably normal or even slightly excessive dosage a human might take). what is neurotoxic are the metabolites (i don't know/remember if the toxic metabolite(s) has been identified yet). but what we do know is that humans metabolise mdma in a much less efficient way than how it happens animal models that have shown signs of mdma toxicity, leading to much lower levels of those metabolites.

so with lack of any decent animal models and no conclusive data pointing towards neurotoxicity occurring in humans, my money is on "mdma is not neurotoxic if you don't seriously overdo it".

 

[PJ2]

Of course it's neurotoxic! I've never taken another drug in my life that made me sick for 7 months and counting. Hell, alcohol is neurotoxic depending on your definition. But, I'd have to say through my own experience that MDMA is about as dangerous as it gets.

 

[JWills20]

but what we do know is that humans metabolise mdma in a much less efficient way than how it happens animal models that have shown signs of mdma toxicity, leading to much lower levels of those metabolites.

This is interesting and I've never heard that before. Have you got anything I could read just to confirm?

 

[ScaredFirstTimer]

cells tend to degrade proteins that are "perceived" to be malfunctioning. like SERT in this case; this doesn't automatically mean destruction of the axon terminal.
rat studies have found a reduction of up to 90% for SERT levels upon repeated SSRI administration. yet nobody calls SSRIs neurotoxic. the conclusion in that study you quote is pretty weak with that kind of reasoning. the fact that the SERT levels can return to their previous level in a matter of just a few weeks also speaks against neurotoxicity.

Are you talking about SERT or serotonin here? I didn't know that there was any studies testing SERT levels like you describe here, especially the recovery part. Did you read the study I quoted? They found that SERT levels recovered close to normal after 12 months of abstinence. But despite this recovery the clinical symptoms remained the same.

Please give a reference for the statement about SSRI's and SERT.

 

[Black]

Are you talking about SERT or serotonin here? I didn't know that there was any studies testing SERT levels like you describe here, especially the recovery part. Did you read the study I quoted? They found that SERT levels recovered close to normal after 12 months of abstinence. But despite this recovery the clinical symptoms remained the same.

Please give a reference for the statement about SSRI's and SERT.

i'm talking about sert obviously.
there was a study (i think it was a dutch one. anyway with a prospective design they assessed the effects of a single dose of mdma and found that sert levels return to normal after somethign like 2 weeks to 6 months (with a mean of around 4-6 weeks). iirc we based our recommendations for the spacing out of mdma use around that when the study came out. sadly i cannot fin the original paper right now... ).
yes, i did read it. but there are not really "clinical" symptoms, but rather scores on a test (but that of course depends on the context you use "clinical" in...). by the way, the mdma and ex-mdma users had lower numbers for "years of education" and drastically higher cannabis consumption (which is known to cause memory impairment that takes a while to dissipate) than the control group. so it is not justified to jump to the conclusion that mdma is the cause here.

SSRIs and SERT density.

This is interesting and I've never heard that before. Have you got anything I could read just to confirm?

still looking for the papers. i've posted on this before on bl. damn, i should have bookmarked all those articles

edit: i haven't found the conclusive paper i remember (i think it was by de la torre...?), but i've found some values for hmma (most likely the worst offender here). here and here we see a Cmax (the most important parameter here. for oxidative stress there's always a threshold to cross before it becomes toxic) or around 200-250ng/ml hmma for various doses of mdma in humans. and here we see Cmax values of around 600ng/ml for various dosages in the squirrel monkey.

notice how hmma doesn't increase a lot as the dosage increases (but remember that excessive dosages weren't tested) because mdma inhibits its own metabolism. so it looks like we can never reach plasma levels of hmma in the same range as with squirrel monkeys.

 

[MindOverMatter1]

I'm a living example that MDMA is neurotoxic. I'm dealing with nerve damage symptoms eight months after I ingested MDMA.

 

[SilentRoller]

I feel there is a fair bit of scaremongering on this thread...

From personal experience, I have used MDMA in doses ranging from 200 - 500mg, and whilst the latter dosage left me feeling pretty shit for a week of two afterwards (brain zaps etc...not to be repeated), I made a full recovery a short while after. My message is this - just fucking enjoy yourself. Don't sit there wigging out about how MDMA may or may not be neurotoxic, just enjoy it and don't take liberties. I would say that MDMA is one of the safest drugs you can do, and I have never once felt in danger or permanently brain damaged on any dose. People complaining of "nerve damage" and "8 month long comedowns" are either giving themselves psychosomatic symptoms caused by an anxiety loop, or didn't get MDMA to begin with...(more likely the former).

The amount of scaremongering in ED is sometimes absurd

 

[protectorofdarealm]

I feel there is a fair bit of scaremongering on this thread...

From personal experience, I have used MDMA in doses ranging from 200 - 500mg, and whilst the latter dosage left me feeling pretty shit for a week of two afterwards (brain zaps etc...not to be repeated), I made a full recovery a short while after. My message is this - just fucking enjoy yourself. Don't sit there wigging out about how MDMA may or may not be neurotoxic, just enjoy it and don't take liberties. I would say that MDMA is one of the safest drugs you can do, and I have never once felt in danger or permanently brain damaged on any dose. People complaining of "nerve damage" and "8 month long comedowns" are either giving themselves psychosomatic symptoms caused by an anxiety loop, or didn't get MDMA to begin with...(more likely the former).

The amount of scaremongering in ED is sometimes absurd

Always good to be safe though, I have only ever done mdma over 2 days once and that was the first ever time I tried it. Left me feeling bad for 2 weeks but I didnt eat well back then. Anyways, I've been rolling a while now since and last time was about 5 weeks ago. Im goin to a festival next week and contemplating rolling twice again once friday then once on sunday? Wanna know what people think, i've felt like mdma has affected me in the past but since adopting healthy life style changes the side effects have completely disappeared. Just worried about getting them again haha.

 

[protectorofdarealm]

Last year at the festival i got some peru coke and saved my pills till the last night of the festival. Debating whether to even bother with coke cause I had a shitty ass roll and blame the coke. Although i hadnt rolled that day id been on the coke 2 days prior, had little sleep and had the shittest md experience which was intended to be the highlight of my weekend. So its either risk coke ruining my rolls or rolling twice haha.

 

[Nambo]

Yes it is neurotoxic. I have brain damage as a result and life is virtually unbearable.

 

[Black]

I feel there is a fair bit of scaremongering on this thread...

From personal experience, I have used MDMA in doses ranging from 200 - 500mg, and whilst the latter dosage left me feeling pretty shit for a week of two afterwards (brain zaps etc...not to be repeated), I made a full recovery a short while after. My message is this - just fucking enjoy yourself. Don't sit there wigging out about how MDMA may or may not be neurotoxic, just enjoy it and don't take liberties. I would say that MDMA is one of the safest drugs you can do, and I have never once felt in danger or permanently brain damaged on any dose. People complaining of "nerve damage" and "8 month long comedowns" are either giving themselves psychosomatic symptoms caused by an anxiety loop, or didn't get MDMA to begin with...(more likely the former).

The amount of scaremongering in ED is sometimes absurd

this.

it's also worth mentioning that the threads about "nerve damage", "long term comedowns" and the like have increased tenfold or something since RCs exploded on the streets and people are snorting insane quantities of unknown purity "molly" instead of dropping a set amount of pills.

but of course mdma does facilitate getting stuck in an anxiety loop, but so do cannabis and psychedelics in general.


besides: amphetamine, methamphetamine, alcohol, ghb, some benzos (and i'm sure i probably forgot a few others now) are known to be neurotoxic. dissociatives very likely fall into the same category (i don't know if it has definitively been proven by now). if you take any of these drugs in a sensible manner (which is probably a bit harder with meth), you can lead a normal life and not experience any problems, but you'll definitely run into problems if you abuse them.

 

[ScaredFirstTimer]

I feel there is a fair bit of scaremongering on this thread...

Please point to the fear mongering. If the definition of fear mongering is to be found in this thread, then the discourse of MDMA toxicity on this forum is really getting ridiculous. If people can't add their subjective experiences of complications arising from MDMA or point to observations in research you are creating some circular rationalization where whoever tries to point to the neurotoxic potential of MDMA is seen as a fear mongerer.

Edit:

increased tenfold or something since RCs exploded on the streets and people are snorting insane quantities of unknown purity "molly" instead of dropping a set amount of pills.

I wish the MDMA I did was for instance methylone or mephedrone, as MDMA is far more neurotoxic(in animal models) than any of them. Unfortunately my product was pure.