Discusion about neurotoxity of MDMA

[maddee2145]

Is the folowing statement are true or false:

Human brain contain so much neurons as the whole universe contain stars.Miriards. Thats a fact.

If so how something can be toxic for human brain cells? Are mdma metabolits are realy toxic? Or researches doing research in direction that someone leed them to research?
Where is true facts about it?

How many neurons from Miriards should die in brain , to lead for unreturnable changes in it?

I do not believe in it. I think it is somekind of anti-propaganda = bullshit.

 

[Erikmen]

I have no doubts they MDMA are to toxic. It's not BS IMO. People have died taking them, people from a lot of countries. Friends of friends that I know. Not to mention it causes addiction and everyone knows that addiction can be a difficult problem to overcome.

"Especially in high doses it can be toxic to nerve cells that contain serotonin and can cause long-lasting damage to them. Furthermore, MDMA raises body temperature. On rare but largely unpredictable occasions, this has led to severe medical consequences, including death. Also, MDMA causes the release of another neurotransmitter, norepinephrine, which is likely the cause of the increase in heart rate and blood pressure that often accompanies MDMA use."

Although MDMA is known universally among users as ecstasy, researchers have determined that many ecstasy tablets contain not only MDMA but also a number of other drugs or drug combinations that can be harmful as well. Adulterants found in MDMA tablets purchased on the street include methamphetamine, the over-the-counter cough suppressant dextromethorphan, the diet drug ephedrine, and cocaine, Also, as with many other drugs of abuse, MDMA is rarely used alone.

 

[colin681996]

Most drugs ou there are neurotoxic. I think people over hype how toxic MDMA is but is most certainly a neurotoxin as is alcohol, nicotine etc.

 

[Cotcha Yankinov]

When the brain runs low on serotonin, harmful molecules can get sucked into the nerve terminal and can damage not necessarily the cell body but the "branches of the tree", but the trunk is still okay and thus can hopefully sprout more branches.

One thing is for sure, the abstinent MDMA abusers have deficits. The memory deficits are pretty well recorded.

 

[BlueBull]

Interesting reading

 

[Cotcha Yankinov]

Interesting reading

From the studies I've seen comparing MDMA in rats and mice it appears rats are even more susceptible than mice to the negative effects of MDMA. The study makes a good point that needs to be considered - there doesn't have to be "neurotoxicity" for there to be deficits.

But personally I'm much more interested in monkey/human studies.

 

[maddee2145]

But personally I'm much more interested in monkey/human studies.

I am intrested in it too.
Also as far as I know there was long term human studies of MDMA therapy with a great positive result and outcomes. Studies was done according to weekly MDMA uses as a threatment in psychotherapy.

I can agree that MDMA could be toxic in some circumstances as heavy overdosing ,high room temperature,not enough freshair,heavy dehidration,combination with other drugs.

In normal dosage and friedlier for body condition I feel that "toxity" of mdma comes from psyche not body and if you will treat "toxity" right for example fresh air, light physical activity :walking ,camping. More sun light, good food ,fresh air you will not notice any "toxity" at all.

 

[Dracarys]

Incidental use is probably not thát harmfull. When your tolerance is such that you can easily swallow 6 pills a night, you may be fucking up your brain chemistry. But i don't suppose that any wise person would be willing to gamble with his/her own brain like that anyway.

 

[Cotcha Yankinov]

Incidental use is probably not thát harmfull. When your tolerance is such that you can easily swallow 6 pills a night, you may be fucking up your brain chemistry. But i don't suppose that any wise person would be willing to gamble with his/her own brain like that anyway.

I agree, but I think it's important that we don't label MDMA as non-neurotoxic similar to cannabis because some people who binge really have no idea how much damage it can do to them, especially kids. I don't think a lot of us are very wise as kids. The other thing is that by admitting that it can cause harm we can reduce harm with anti-oxidants and other strategies, that otherwise one would have no interest in if they thought MDMA was as safe as cannabis or something.

One more thing to consider is that genetics are playing a role in who is likely to get adverse effects after MDMA, many people can take MDMA conservatively for years but some have long term comedowns after their first couple times.

 

[Cotcha Yankinov]

I am intrested in it too.
Also as far as I know there was long term human studies of MDMA therapy with a great positive result and outcomes. Studies was done according to weekly MDMA uses as a threatment in psychotherapy.

I can agree that MDMA could be toxic in some circumstances as heavy overdosing ,high room temperature,not enough freshair,heavy dehidration,combination with other drugs.

In normal dosage and friedlier for body condition I feel that "toxity" of mdma comes from psyche not body and if you will treat "toxity" right for example fresh air, light physical activity :walking ,camping. More sun light, good food ,fresh air you will not notice any "toxity" at all.

I agree I think MDMA should be utilized by psychiatrists, but even if there was some neurotoxicity in that therapeutic setting it wouldn't matter much because medicine is about benefit vs. risk, but recreational use on the other hand I think I personally would really try to avoid anything that might harm the brain.To each their own, I mean some people are super hedonistic and don't have any problem trading brain cells for euphoria, I just think people need to be aware of the risks and educated so they can make a decision for themselves.

 

[Dracarys]

Yeah you're right. What i actually meant to say was that there is so much evidence to indicate that there ÍS some neurotoxicity there, that it's just wise to just assume that it is neurotoxic. In my opinion, MDMA is more fun when it's done very incidentally anyway, instead of weekly.

 

[terarc]

MDMA therapy involves 3 doses of MDMA (typically low, 75mg usually, 120mg tops), spaced around 5 weeks apart. MDMA is not given to the patient again afterwards.I think the number of people presenting with problems seemingly related to MDMA use is pretty strong evidence that it can cause some issues... it's just that we don't really know specifically what it is doing and how. Like the study BlueBull linked; MDMA induced persistent anxiety-like behaviours in the rats which seemed unconnected to their observations on the serotonin system itself.Remember however that most people do not present with problems from MDMA use. I think if you do your best to determine that your MDMA is indeed MDMA and of high quality, and proceed to use sensible (1-2mg/kg) doses and avoid re-dosing (at least not more than once), avoid mixing with other drugs or alcohol, and use it as sparingly as you possibly can (once every three months max.)... you should not run into any of these issues. There is definitely some preliminary evidence to suggest supplement regimens such as those described at rollsafe.org could aid in shielding the brain from the impact of MDMA and its metabolites; it can't hurt to try this out too if neurotoxicity is a concern for you.

 

[JWills20]

My general understanding of it is:

Very high, repeated doses of MDMA = dangerously significant neurotoxicity. We're talking 5-10mg/kg taken multiple times successively. High one-off doses = moderate neurotoxicity. Say a one-off dose of 5-10mg/kg. Particularly towards the end of this dosage range. You could probably get away with doing one-off doses of 5-6mg/kg with adverse effects being reversable. Average-low doses = no strong evidence of any neurotoxicity. I don't honestly believe that doses between 80-300mg throughout a night-out would cause any kind of significant cell death.

Honestly, the main thing that makes neurotoxicity an issue to any 'normal' recreational user of MDMA is taking it in very high doses, re-dosing or taking it successive days. That's not to say that MDMA won't cause you problems if you are just taking normal-high doses occasionally and not re-dosing frequently, it's just that any negative effects are unlikely to be a result of actual cell death (I.E. neurotoxicity) and likely to be because of something else occurring. Serotonin depletion is more likely for example.

 

[terarc]

I don't know if it is purely a dose issue...at least not for everyone. I used MDMA approximately 12 times in two years. Never above 200mg in a night and most of them were one ~130mg dose and that was it. I started to experience problems (which I initially didn't think was the MDMA) after too many month-after-month successive uses; and in two cases a month where I used two weeks in a row. Cessation from MDMA for around 8 months removes all symptoms completely (anxiety, brain fog, minor HPPD, mood issues, feeling 'fried', etc). Taking it again brings them all back, like night and day. I have to stick to around once per year or less now to avoid these problems.

 

[BlueBull]

I don't know if it is purely a dose issue...at least not for everyone. I used MDMA approximately 12 times in two years. Never above 200mg in a night and most of them were one ~130mg dose and that was it. I started to experience problems (which I initially didn't think was the MDMA) after too many month-after-month successive uses; and in two cases a month where I used two weeks in a row. Cessation from MDMA for around 8 months removes all symptoms completely (anxiety, brain fog, minor HPPD, mood issues, feeling 'fried', etc). Taking it again brings them all back, like night and day. I have to stick to around once per year or less now to avoid these problems.

Granted, but you have no way of knowing it is in fact caused by actual neurotoxicity. There are a million other things that can cause problems. Neurotoxicity also does not heal, in most cases it is permanent so the symptoms wouldn't go away, you would just learn to cope with it a bit. I agree with JWills on this, research seems to indicate the same though it is far from proven

 

[Cotcha Yankinov]

Genetics are definitely playing a role in adverse MDMA reactions, so I think it's important not to make generalizations. I personally have a lot of issues from years past MDMA/ecstasy abuse, and it turns out I have the serotonin transporter gene that is associated with increased negative effects after MDMA and tryptophan depletion (and MDMA neurotoxicity really occurs during the period when there is serotonin depletion). There could be several other mechanisms by which genetics contribute to an adverse response to MDMA or contribute to HPPD susceptibility, and unfortunately for our ability to observe these effects even anecdotally, they overlap with mental illness.

Neurotoxicity also does not heal, in most cases it is permanent so the symptoms wouldn't go away, you would just learn to cope with it a bit. I agree with JWills on this, research seems to indicate the same though it is far from proven

Squirrel monkey studies show there is some degree of recovery after MDMA binge administration, although some areas recover better than others and some areas don't recover very well at all. Some areas close to the center of the brain actually hyper-reinnervate. Who knows how this translates to humans, but there is a possibility that you can recover (albeit abnormally) from genuine serotonergic injury.

Now that being said, a serotonin deficit is not necessary to explain MDMA users issues (though it has been observed and correlated to the degree of functional deficits), there are other mechanisms by which MDMA could cause permanent symptoms without damaging cells, and many mechanisms by which it can cause effects that persist a year or so. Time will tell what mechanism is causing what problems in MDMA users.

 

[Jabberwocky]

My general understanding of it is:

Very high, repeated doses of MDMA = dangerously significant neurotoxicity. We're talking 5-10mg/kg taken multiple times successively. High one-off doses = moderate neurotoxicity. Say a one-off dose of 5-10mg/kg. Particularly towards the end of this dosage range. You could probably get away with doing one-off doses of 5-6mg/kg with adverse effects being reversable. Average-low doses = no strong evidence of any neurotoxicity. I don't honestly believe that doses between 80-300mg throughout a night-out would cause any kind of significant cell death.

Honestly, the main thing that makes neurotoxicity an issue to any 'normal' recreational user of MDMA is taking it in very high doses, re-dosing or taking it successive days. That's not to say that MDMA won't cause you problems if you are just taking normal-high doses occasionally and not re-dosing frequently, it's just that any negative effects are unlikely to be a result of actual cell death (I.E. neurotoxicity) and likely to be because of something else occurring. Serotonin depletion is more likely for example.

Serotonin depletion is a myth --

In PIHKAL Shulgin describes an MDMA tolerance study where subjects were given 120mg -160 mg MDMA daily at 9 am for 6 days -- resultin in complete tolerance on day 6 (not even dilated pupils) on day 7 MDA was administered -- resulting in the completely expected effects of MDA intoxication -- proving no cross tolerance between MDA and MDMA.

If serotonin depletion actually happened as a result of MDMA use, no serotonergic effects would have been observed when MDA was administered.

The same hold true for psychedelics.

 

[Jabberwocky]

Genetics are definitely playing a role in adverse MDMA reactions, so I think it's important not to make generalizations. I personally have a lot of issues from years past MDMA/ecstasy abuse, and it turns out I have the serotonin transporter gene that is associated with increased negative effects after MDMA and tryptophan depletion (and MDMA neurotoxicity really occurs during the period when there is serotonin depletion). There could be several other mechanisms by which genetics contribute to an adverse response to MDMA or contribute to HPPD susceptibility, and unfortunately for our ability to observe these effects even anecdotally, they overlap with mental illness.



Squirrel monkey studies show there is some degree of recovery after MDMA binge administration, although some areas recover better than others and some areas don't recover very well at all. Some areas close to the center of the brain actually hyper-reinnervate. Who knows how this translates to humans, but there is a possibility that you can recover (albeit abnormally) from genuine serotonergic injury.

Now that being said, a serotonin deficit is not necessary to explain MDMA users issues (though it has been observed and correlated to the degree of functional deficits), there are other mechanisms by which MDMA could cause permanent symptoms without damaging cells, and many mechanisms by which it can cause effects that persist a year or so. Time will tell what mechanism is causing what problems in MDMA users.

There is no such thing as serotonin depletion. Please stop spreading that myth. Unless a person is fasting or on a tryptophan deficient diet -- serotonin depletion does not happen.

If serotonin depletion occurred, LSD, 2-CB, etc would not work after a few days of MDMA use.

In PIHKAL Shulgin describes an MDMA tolerance study where subjects were given 120mg -160 mg MDMA daily at 9 am for 6 days -- resultin in complete tolerance on day 6 (not even dilated pupils) on day 7 MDA was administered -- resulting in the completely expected effects of MDA intoxication -- proving no cross tolerance between MDA and MDMA.

If serotonin depletion actually happened as a result of MDMA use, no serotonergic effects would have been observed when MDA was administered.

serotonin synthesis is constantly occurring in the body and brain

 

[Cotcha Yankinov]

There is no such thing as serotonin depletion. Please stop spreading that myth. Unless a person is fasting or on a tryptophan deficient diet -- serotonin depletion does not happen.

If serotonin depletion occurred, LSD, 2-CB, etc would not work after a few days of MDMA use.

In PIHKAL Shulgin describes an MDMA tolerance study where subjects were given 120mg -160 mg MDMA daily at 9 am for 6 days -- resultin in complete tolerance on day 6 (not even dilated pupils) on day 7 MDA was administered -- resulting in the completely expected effects of MDA intoxication -- proving no cross tolerance between MDA and MDMA.

If serotonin depletion actually happened as a result of MDMA use, no serotonergic effects would have been observed when MDA was administered.

serotonin synthesis is constantly occurring in the body and brain

We may still talk about whether or not serotonin depletion is occurring chronically (I would say it more certainly is occurring acutely, between the VMAT inhibition and inhibition of tryptophan hydroxylase) but we should not make too many judgments concerning the vesicular pool of serotonin based on how agonists are binding to serotonin receptors. MDA is an agonist and it's agonist action is independent of the quantity of serotonin, because it mimics serotonin and binds to 5HT2A regardless of the level of stored serotonin, where as MDMA etc. work more primarily by reversing the serotonin transporters and dumping serotonin out into the synapse. A caveat, we shouldn't even assume immediately that MDMA tolerance means that the vesicular pools are being depleted, because it could have something more to do with reduction of serotonin transporters and thus reduction of SERTs available to be reversed (A radioligand serotonin transporter study could attempt to sort that out, to see if reductions in SERT or receptors are large enough to account for the reduced effects of MDMA or if we might assume it is more to do with stores of serotonin).

Although when I said "A serotonin deficit has been observed" I wasn't necessarily talking about vesicular pools, but rather markers that may be related to serotonin function, and not the stored pool of serotonin.

 

[Jabberwocky]

Although when I said "A serotonin deficit has been observed" I wasn't necessarily talking about vesicular pools, but rather markers that may be related to serotonin function, and not the stored pool of serotonin.

A deficit on the function of the serotonergic system -- i will agree to that. Whether that = bad for everyone is what is at issue. For instance ASD (autism spectrum disorder) is characterized by high blood serotonin and low brain serotonin -- due to an over functioning of the SERT. This is due to an identified mutation in genes that encode SERT in ASD persons. The mutated SERT pulls the serotonin out of the cleft too quickly -- leaving the receptors in a constant deficit. This results in hypersensitivity of the receptors as well as issues during development that rsult in the sensory and social issues of ASD. Long term down-regulation of SERT, and the downregulation of serotonin receptor binding seems to be an effective treatment for such persons.

Because their SERT is always synthesized by the mutated gene over function will always be present as new sert is made.

Inhibition of tryp hydrox was only 50 % at 10mg/kg dose -- and some literature indicates anti-oxidants eliminate such inhibition -- normal human dosage would lead to 10-20% inhibition --not much really.