Can MDMA cause Neurotoxicity? Serious Question.

[Kratom777]

I have taken MDMA a few times and it really helped me. I would like to take it 3 times a year tops but am rethinking it as I have read more reports on it inducing neurotoxcity. I know there are people on here who know a lot more than the average person when it comes to MDMA and can shed some light on this issue.

My question: Is it possible that MDMA is a neuro-toxic chemical? Can it lead/cause or make one more prone to developing degenerative diseases like Parkinsins, ALS or Alzheimer disease? I know there isn't much information on MDMA but there has to be some. Thinking of this causes me great anxiety. Again, I want to use MDMA in the future as it helped me greatly with dealing with past fears, having a mild form of PTSD.

 

[Cotcha Yankinov]

If you keep the following rules in high esteem

1. Thoroughly test the product and confirm it is indeed MDMA

2. Keep dosage reasonable (60-120mg depending on body weight, but kept as low as possible)

3. Dosages are spaced out over long intervals such as months

4. The rolls themselves are kept under control (no overheating/dehydration, no mixing with alcohol, take it earlier in the day so you can get some sleep et cetera)

5. Antioxidants are used (there are probably many threads on this)

- then the risk of neurotoxicity is pretty darn nil, if it works for PTSD then that is definitely worth it even in terms of neurodegenerative disease because PTSD is no good for the brain either, so it's the lesser of two evils in that sense.

Concerns of neurotoxicity arise when we're talking about hundreds of lifetime uses with many pills binges on with every use, especially with overheating and polydrug use.

But responsible use a few times a year, I definitely wouldn't lose any sleep over it. People tend to have a lot of anxiety about neurotoxicity with various substances they've used though even if they didn't actually have symptoms within weeks of the use, and ironically this seems to cause them the most distress (anxiety is a monster I suppose)

As a caveat, adverse effects of drugs don't have to be due to neurotoxicity

 

[Swim15]

^thats a solid answer OP. To be *optimally* safe, those are the standards I would follow

 

[JWills20]

Hi there

I have read more reports on it inducing neurotoxcity

You can't read 'reports' on neurotoxicity unless you're talking about proper science reports. People on a forum claiming neurotoxicity 'because they feel bad/fucked up' is null evidence to proving neurotoxicity itself. Remember that neurotoxicity is typically the degeneration/death of neurons resulting from toxicity. You can't claim this subjectively just because you're feeling bad. Comedowns are not evidence of neurotoxicity and can be a result of may more plausible explanations such as: serotonin depletion, exhaustion/fatigue, lack of nutrition/hydration, mixing drugs. The latter often occur after raves.

Is it possible that MDMA is a neuro-toxic chemical?

It's definitely possible and perhaps even likely at high enough doses (as rat studies suggest). But this is at very high doses, usually much higher than most recreational users. Studies typically administering 2.5mg/kg repetitively injecting directly into rat brain. So like the equivalent of a gram of MDMA in humans. At human doses ranging between the standard 100-300mg it's probably pretty unlikely for any actual neurotoxicity to be occurring.

Can it lead/cause or make one more prone to developing degenerative diseases like Parkinsins, ALS or Alzheimer disease?

Highly unlikely. The whole parkinsons thing was media slur.

 

[Swim15]

Not sure what you read literature wise but there are definitely reports showing neurotoxicity in humans even at standard doses OP

 

[BlueBull]

Not sure what you read literature wise but there are definitely reports showing neurotoxicity in humans even at standard doses OP

Please provide a source for this claim. As far as I know, no human studies have been done (yet) but if I'm mistaken I'd love to read up on that

*edit*
I should have said reliable human studies. The control measures in place in most studies on humans are in my opinion usually insufficient (poly-drug users, small sample group, no double blind,...)

 

[Swim15]

I've found this to be a fairly good compilation of information in terms of literature that's out there

http://jamanetwork.com/journals/jamapsychiatry/fullarticle/211305#qundefined

 

[BlueBull]

I've found this to be a fairly good compilation of information in terms of literature that's out there

http://jamanetwork.com/journals/jamapsychiatry/fullarticle/211305#qundefined

From that study

Histologic studies22 in animals have shown that large doses of MDMA are associated with neurodegeneration particularly affecting the terminal portions of axons; fibers and raphe cell bodies are spared. However, there is no firm evidence of MDMA-induced neurodegeneration in humans.

Furthermore the study talks about SERT binding being affected. A quote from this study or rather summary of past research

With regard to MDMA-induced neurotoxicity, it seems that 5-HT deficits are not always synonymous with axonal death because doses of MDMA which cause marked depletions of brain tissue 5-HT in rats (e.g., 10–20 mg/kg) are not associated with silver-positive staining, reactive gliosis, or loss of SERT protein.

Not really convinced. On the contrary I think this is more an indication that bonafide neurotoxicity is very unlikely at recreational doses.

 

[Cotcha Yankinov]

I've found this to be a fairly good compilation of information in terms of literature that's out there

http://jamanetwork.com/journals/jamapsychiatry/fullarticle/211305#qundefined

The problem is making the jump from decreased serotonin transporter labeling/increased 5-HT2A labeling to the conclusion of serotonin neurotoxicity. Transporters can be downregulated as a homeostatic compensation, so decreased serotonin transporter expression can't be outright concluded to be due to neurotoxicity. There is a similar debate in regards to amphetamine users and some observed dopamine transporter downregulation

Another type of imaging used to detect neuronal loss and dysfunction (magnetic resonance spectroscopy imaging of N-acetylaspartate) has suggested that there isn't any actual neuronal loss in MDMA abusers in one study, although there is a conflicting study using the same imaging technique


"there are definitely reports showing neurotoxicity in humans even at standard doses"

Neuroimaging studies in MDMA users can find some abnormalities (once again, not explicitly neurotoxicity) in the heavy abusers but the heavy abusers category is far from standard usage, we're talking about hundreds of lifetime uses in exacerbating environments, very likely many pills with every use

So I don't necessarily know what you're defining as a standard dose, but we're definitely not talking about 120mg a few times a year when we look at these neuroimaging studies. I'm unaware of neuroimaging abnormalities found in light users.

To me, neurotoxicity is all about dosage and susceptibility. I'm sure there are dosages that will produce some amount of neurotoxicity, especially in susceptible people, but lets not fear monger about responsible low-dose usage

 

[Cotcha Yankinov]

Furthermore the study talks about SERT binding being affected. A quote from this study or rather summary of past research

5-HT deficits are not always synonymous with axonal death because doses of MDMA which cause marked depletions of brain tissue 5-HT in rats (e.g., 10–20 mg/kg) are not associated with silver-positive staining

Just to clarify a bit, one issue is that the evidence of synapse/terminal degeneration (as opposed to axon/fiber degeneration) is only around for a very short period of time and can be hard to detect because the terminals are so small.

Silver staining must be done with 24 hours or so to detect terminal degeneration but many studies wait for longer to try and map axon degeneration (which can take longer to occur)

 

[Clocktower]

The science isn't perfect, but the best available answer is: Probably yes if you use too much or too often, probably no if you practice good HR and use in moderation. Same as alcohol.

 

[Kratom777]

The whole thing about neurotoxicity causing degenerative diseases makes me nervous as hell. Not trying to be a b1tch but it does. I heard you are supposed to pre-load with anti-oxidants before rolling. Supplements like Vitamin C, E, N-A-C, ALA are all good. Do any of you pre-load before taking MDMA???

Thank you for all your help.

 

[Swim15]

I usually take vitamin c, e, magnesium, R-ALA and metformin 1-2 hours prior to dropping and then again about an hour and a half into the roll and it definitely helps the comedowns.

I also wouldn't put myself in the category of your typical drug user though. That said, you have to go ahead and accept some amount of risk using these drugs and be okay with it. Just mitigate it as best you can

 

[Cotcha Yankinov]

I certainly wouldn't worry about increasing the risk of neurodegenerative disease from using responsibly a few times a year.

The disease people treat with meds (be it PTSD, depression or anxiety) are going to have a lot bigger impact on the likelihood to develop neurodegenerative disease, and neurodegenerative disease tends to be uncommon anyways (in the sense that its not like you have a 50/50 chance of getting Alzheimer's by the time you're 85, if any of us are lucky enough to make it to 85 anyways)

 

[56nights]

I certainly wouldn't worry about increasing the risk of neurodegenerative disease from using responsibly a few times a year.

The disease people treat with meds (be it PTSD, depression or anxiety) are going to have a lot bigger impact on the likelihood to develop neurodegenerative disease, and neurodegenerative disease tends to be uncommon anyways (in the sense that its not like you have a 50/50 chance of getting Alzheimer's by the time you're 85, if any of us are lucky enough to make it to 85 anyways)

Lucky enough to make it to 85 shit i think ill have enough of this shitty ass place by 50

 

[Inds]

The body converts 10-15% of MDMA to MDA which is known to be neurotoxic. So the answer is yes.

 

[rrandy]

oral doses of 4-5mg/kg are definitely neurotoxic in squirrel monkeys and there is no reason to believe that humans are less susceptible. Even the organization MAPS, which is trying to make MDMA legal for therapy estimates the neurotoxic threshold to be very close to 2,5mg/kg in humans.

 

[Cotcha Yankinov]

oral doses of 4-5mg/kg are definitely neurotoxic in squirrel monkeys and there is no reason to believe that humans are less susceptible.

There are fair differences in species however, I certainly wouldn't equate squirrel monkeys and humans. The other thing to consider is that hyperthermia is typically a requisite that is employed in the labs to help induce neurotoxicity, so we may not want to think about dosage in isolation from the elevated temperatures that the studies use to help them study the neurotoxicity

Another thing to consider is that typically it takes multiple doses (dosing over a period of time) to produce neurotoxicity because of the specific mechanisms involved - as an example, meth can certainly be a neurotoxin but it probably takes several days of use before the antioxidant defenses of our brain cells start to wear out. Only then does terminal loss start to occur, and plenty of people use meth and are seemingly normal (no "LTC")

 

[rrandy]

There are fair differences in species however, I certainly wouldn't equate squirrel monkeys and humans. The other thing to consider is that hyperthermia is typically a requisite that is employed in the labs to help induce neurotoxicity, so we may not want to think about dosage in isolation from the elevated temperatures that the studies use to help them study the neurotoxicity

Another thing to consider is that typically it takes multiple doses (dosing over a period of time) to produce neurotoxicity because of the specific mechanisms involved - as an example, meth can certainly be a neurotoxin but it probably takes several days of use before the antioxidant defenses of our brain cells start to wear out. Only then does terminal loss start to occur, and plenty of people use meth and are seemingly normal (no "LTC")

1. I mention squirrel monkeys because they are among the most comparable to humans. People often cite the rat studies on bluelight and believe you need 10mg/kg injections into your brain for neurotoxicity to occur.
I think oral doses to primates are the best measure we have for this.
Do you really think humans are less susceptible than smaller primates?

2. It takes only a single 5mg/kg dose for neurotoxicity to occur in these species though.

3. Are they raising the temperature actively in the labs?

 

[Cotcha Yankinov]

1. I mention squirrel monkeys because they are among the most comparable to humans.

I'm not sure if they are used because they are the most comparable in terms of neurology/metabolism but rather they may be the easiest in terms of acquisition/housing/ethics, compared to say, an orangutan. There certainly differences between smaller primates, great apes and humans. There are also certainly differences between mice and rats in terms of MDMA neurotoxicity, even though we would knee-jerk reaction assume they are similar

People often cite the rat studies on bluelight and believe you need 10mg/kg injections into your brain for neurotoxicity to occur. Do you really think humans are less susceptible than smaller primates?

Just to clarify, direct injection into the brain itself actually doesn't do that great of a job of producing neurotoxicity (a recent study actually examined why and basically found it was due to poor perfusion though)

But anyways regarding interspecies scaling, to some degree the higher doses used in rats are justified because rats have stronger defenses against the oxidative stress

In some sense, a larger brain would be a better model to study the serotonin degeneration. There are observed differences between species with different brain volumes - as example von economo neurons aka spindle neurons are a feature rather selectively of larger brains (they may have evolved to transfer information quickly back and forth between larger brains) - these are specific to great apes and other very large mammals like whales.

There is also the issue of body temperature and the degree to which various species are prone to MDMA induced hyperthermia. Rats can show a marked increase in hyperthermia at 7.5mg/kg i.p. doses while 1.5mg/kg i.p. does not produce hyperthermia in said rats.

Doses many times higher can however produce both hyperthermia and long term serotonin depletions, but I'll take care here to differentiate between 5-HT depletions and 5-HT neurotoxicity as many studies don't specifically looked for markers of neurodegeneration, they've just measured 5-HT content and assumed neurotoxicity

Part of the reason for MDMA's neurotoxic effect on 5-HT neurons is due to hepatic metabolites which different species may also produce/clear at different rates (smaller species generally have higher metabolisms).

What some research has shown is that MDMA can be very behaviorally active in rats at doses which do not produce any neurotoxicity or long term serotonin depletions. The behaviorally active doses in animals can be scaled to behaviorally active doses in humans and it appears that 120mg genre (1-3mg/kg) doses aren't of much concern, its really more about binging on many pills with exacerbating factors.

2. It takes only a single 5mg/kg dose for neurotoxicity to occur in these species though.

Can you post that specific study? Typically 5mg/kg injected is starting to get to the point of neurotoxic concern but a neurotoxic regimen can often look something like 5mg/kg MDMA injected twice per day for 4 days.

3. Are they raising the temperature actively in the labs?

Scientists do sometimes raise ambient temperature to study the neurotoxicity, but amphetamines raise body temperature by themselves at high doses