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Erowid; 2011 - Neurotoxicity (latest study)

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somedud

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So I stumbled across this on erowid, it was posted on their main page as the newest MDMA study on cognitive performance.

"Abstract
AIMS: In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias.
DESIGN: We compared illicit ecstasy users and non-users while 1 excluding individuals with significant life-time exposure to other illicit drugs or alcohol 2 requiring that all participants be members of the 'rave' subculture and 3 testing all participants with breath, urine and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons.
SETTING: Field study.
PARTICIPANTS:Fifty-two illicit ecstasy users and 59 non-users, aged 18-45 years.
MEASUREMENTS: Battery of 15 neuropsychological tests tapping a range of cognitive functions.
FINDINGS: We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic self-regulation, possibly reflecting increased impulsivity. However, this finding might have reflected a pre-morbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug.
CONCLUSIONS: In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users."

Just thought I'd let you know.
 
Check this, looks pretty legit

"One study of MDMA administered to primates most closely modelled human use and used doses of 2.5mg/kg given every 2 weeks for 4 months (2.5 mg/kg x 8 ) which found no evidence of neurotoxicity[2]. A single- dose study found a decrease in serotonin (5-HT) and it's major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in rhesus monkeys at 5mg/kg but not 2.5mg/kg. Another study gave rhesus monkeys 2.5mg/kg twice daily for four days and found depletions of 5-HT and 5-HIAA, but without any evidence of neurotoxicity from [3H]paroxetine binding to the 5-HT reuptake transporter[3]. The finding that depletions of 5-HIAA could occur in the absense of 5-HT neurotoxicity creates problems in interpreting the results of CSF 5-HIAA reductions in human users, which remains the strongest evidence of putative MDMA neurotoxicity in humans[4]."
 
it's nice to see studies being done in which other substance use/abuse is being considered. i've long wondered about the value of studies on mdma users, when so many other drugs are possible sources of neurotixicity/side effects/short and long term damage.
 
Good contributions, Somedud.

The first study shows that many MDMA users exhibit no detectable cognitive deficits.
Some heavy users will exhibit mild impairment.

The brain region targeted by MDMA is the PFC, which is NOT implicated in IQ.
People with major damage to this region can still pass tests of intelligence, although emotional disturbances are common. Impulsivity is a clue.

MDMA users should not be worried about 'short-term' memory loss or becoming stupid.
Rather, they should be concerned about the depth of their 'visceral' feelings being permanently altered. There is a chance that certain 'gut feelings' are gone forever...

The second study is also interesting. What year is it from?

Testing levels of 5-HT and 5-HIAA in the CSF was determined to be very limited in its relevance many years ago. Spinal taps of MDMA users became much less common once this was understood.
It is a pretty blunt tool, considering the complexity of the network...

Good job.
 
^Its actually in the first post just worded in a different way.

FINDINGS: We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic self-regulation, possibly reflecting increased impulsivity. (gut feeling)

@ First Bad Comedown - Im not sure if this is the study you were talking about (1987?)
 
Bearlove - great observations.
Impulsivity is surely a much greater issue during recovery.
Yes, your second study backs up what I said. I have seen others.
Damage can occur without disruptions to 5-HIAA, although they are often seen concurrently.
It is considered a marker, but not a reliable one. Hell, some people have naturally lower levels without problems!

Splinter-
MDMA is a 'visceral' experience, is it not?

By riding on the intestinal nerves, it evokes a cascade response in the brain that is quite unique and profound. Since MDMA also damages these pathways, it is reasonable to theorize that certain 'visceral' feelings are forever lost, or modified...

This is a personal observation.
It is backed up by the fact that former users of MDMA have a modified endocrine response to MDMA, even after years of abstinence. It appears the 'visceral' experience can be changed, perhaps permanently.

Luckily, the height of that visceral response is hardly necessary for day-to-day life.
This may be why these modifications are difficult to detect in cognitive tests.
I believe that many researchers are asking the wrong questions.
In addition to testing cognitive function, I would focus on the 'visceral' realities of life.
 
Yes.

DESIGN: We compared illicit ecstasy users and non-users while 1 excluding individuals with significant life-time exposure to other illicit drugs or alcohol 2 requiring that all participants be members of the 'rave' subculture and 3 testing all participants with breath, urine and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons.
Click to expand...
 
Unfortuneately the visceral "experiences" are valued much more than your intelligence in the run of life.

What's the point in being smart if you can't enjoy yourself, or experience the magical feelings splurged through our amazing, natural wiring.

FBC, I have a question.

Does this destruction interfere with emotional intelligence, and social bonding? Or once you overcome whatever depression it causes you, does this re establish itself?

Also, for some reason I feel as if the brain gut connection, can be much more easily "rewired" around the gut than the brain, but that's just a thought.
 
I mean this just proves what I've known for years. If MDMA made people any more "stupid" then I wouldn't be in college right now receiving great grades. I also wouldn't have scored my best grades in a grading period in high school in the middle of a 2 months MDMA binge haha.

Seriously though, this doesn't prove anything as far as neurotoxicity goes, which makes it kind of weird that that is the title of the thread. Just because it doesn't set your IQ back 6 months (in the words of MasterSplinter ha), doesn't mean it isn't harmful to other areas of your life. It is obviously harmful to social aspects of life, as well as emotional... we know this.

It is good to have this information out there so there aren't people out there convincing themselves they have "rolled themselves stupid".... I hate when people say they've rolled too much and can't do well in school, etc... dumb as hell IMO. Just try for once.
 
Keep in mind folks, that downregulation can still cause major problems, even for years after abuse.

Scientists don't count it as neurotoxicity because well, it is reversible...it can just take a long ass time.
 
^ I already mentioned that the names probably not the best considering what I posted, read up a few posts.

As for the school thing, it does seem to affect my learning ability, but in a sense it's more due to peoples depression and sleeping problems that effect their schooling ability.
 
Somedud -

The answer to your question is YES.

Some visceral feelings are powerful and more pronounced, such as sex, eating, and basking in the sunlight.

Others are more subtle and intricate, such as hearing your favorite song, feeling delight upon seeing a baby, or interacting in a social setting. Bonding is also on this list.

It seems like these 'subtle' parts of our visceral reality are more greatly affected by the destruction of the 'brain-gut' circuitry.
I would argue that these higher emotional functions and complex feelings require function of the PFC, which is obviously compromised by MDMA.

It is also the area of the brain responsible for the most euphoric and meaningful effects of MDMA. Aren't these subtle and complex feelings turned way UP when rolling, especially after the peak?

I don't think the intestines are re-wiring themselves - I believe they have a firm connection into the spinal cord and brainstem. But the brain itself, is quite malleable. This is why I think you will eventually find emotional bonding and social interaction improves.

Take from the people who REALLY know.
Some sufferers of long-term effects of SSRIs have described feeling 'un-human, flat, emotionless'. They also describe complete lack of libido, regardless of porn or stimulation. If they can manage to get it up anyways, they often describe complete lack of all sensation, even with orgasm! Women describe contractions that should indicate orgasm, but feel like nothing. I read one that claimed to have completely painless child-birth!

Another told me that 'I would kill myself, but I lack the strong feelings to do it'!

They also describe themselves as machines that cannot perceive the emotions of other people. Forget about higher functions like empathy, they feel nothing.
Scary shit.

And this has gone on for YEARS in some people.
Talk about destruction of PFC function!

But the point is this: I see a trend of recovery in this group, as well!
There are quite a few examples of people that describe emerging from this hell after 1-2 years. There are others that take 3-4, but amazingly, they still emerge!

Yes, there are horror stories that don't 'recover' even after 7-10-20 years. But there seems to be a trend towards the other categories, even among a group of very long-term and sensitive SSRI users!

And I have seen contributions from the 'permanent' group that do indicate some limited recovery of life, and even sexual function with injections...

Even for the most severe cases of PFC destruction, there is a trend of at least partial recovery. The real trend is towards substantial recovery. :)

MDMA and SSRI sufferers have much to learn from each other.
Ironically, I have come across a few SSRI users that developed complete sexual anhedonia from 2 doses! These often belong to the long-term group.
Some people are just more sensitive...
Considering the amount you took, you are not likely in the sensitive group.

Suicide has happened quite suddenly in some susceptible SSRI users.
Did you know that the kids that shot up Columbine HS were on SSRIs?
And they aren't the only ones...
http://www.archive.org/details/TheRoleOfSsriAnti-depressantsInTheColumbineShooting
http://www.drugawareness.org/recent...pressant-2008-finnish-school-shooting-10-dead
http://www.the3report.com/index.php/blog/revealing_the_link_ssris_and_school_shootings1/

It seems that serotonin loss in the PFC really does destroy what makes us human.
Sadly the capacity for suffering seems to be enhanced...

Moving on...

The innervation seen in the PFC are axonal extensions from the cell body of distant serotonin nerves. These fiber-like endings have a lot more distance to travel to reach their target during recovery. That is why many axons never make it.

But some will.
I have no doubt about that.
Even the Riccaurte study shows this!
Years later, some significant re-innervation CAN be found.

I suspect that there is a period of loss, before gains can begin.
Remember, this is a 're-organization' of an 'ascending structure'.
That means the re-wiring starts way back on the cell body, first.

As new axons pop up, they may be altering the flow of serotonin down the network, resulting in a further loss of function in other PFC receptors!
Perhaps the pruning process continues...

Only after a great period of suffering and patience, can these extensions once again touch-down upon the distant shores of your most complex emotional pathways.

However, I also consider it possible that the abnormal re-innervation patterns seen in the PFC represent altered function, or even loss of function.
Remember - serotonin has an inhibitory effect upon cellular function.
It drags blood vessels through this tissue!

I would suspect that the way the PFC functions in general, is modified during this process.

So there are two separate reasons that this takes so damn long.
Not only does the 're-organization' suggest something more complicated than simple 're-innervation', but the abnormal PFC structure that remains must be adapted to as well.

Chitown -

You are absolutely right. Even at the height of my suffering, I was still capable of learning and reciting information. I even tested myself with vocabulary lists, and I remained as capable as I ever was. This was during the 'worst' of the recovery.
However, it did require forcing myself to TRY.

Those that push themselves may be surprised of their intact mental capabilities.
Who knows, some may even read enough research to feel qualified to preach on BL like a fucking neurologist! :D

I would classify those in recovery from MDMA or SSRIs to be a new species.
This species has the intelligence and mental capacity for suffering that a human does...
But with the emotional depth and presence of an Ape!

We remain smart enough to know what we have lost, and we suffer immensely because of this awareness. The loss of 'visceral joy' causes a unique and insidious suffering, that has been described as the 'utter destruction of my soul'. :(

Perhaps this is the brain's way of restoring our humanity.

Which it does, mostly.
Perhaps the final result is not such a 'new species' after all.
Perhaps it more closely resembles some of our distant human ancestors in emotional capacity...

These have been Thoughts, with First Bad Comedown...
 
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somedud, you rock!

Mega-thanks for your post! I did neuropsych. testing for years and reading this surprises me not in the least. It's funny being on both sides. So happy you shared the data.
 
Not a problem :)

Glad I could help. Btw thanks again FBC, some people knock your posts, but you clearly aren't making this stuff up.

I feel as though it's not entirely as serious as it sounds, as we never completely destroyed our 5HT network. That would result in crippling anxiety, depression to the point where you couldn't move, and social capabilities of a rock, along with no desire for food or ability to sleep.

I'd say with exercise supplements diet and time, we could eventually get back that visceral feeling, along with emotional capabilities, atleast I hope.

Because of course, even though if got some bad symptoms from my use, I only rolled 10 times in 16 weeks, never back to back nights, never more than 1 maybe two pills, and never redosed, besides my last usuage 9 months ago, which is the one that set me off.

And the pills I got were cheap, so presumably had around 70 my MDMA, if that per press.

It's strange how the last usuage can cause so much damage huh?
 
But I must say, what really boggles me is that I got chronic insomnia after my last roll which I never had before, in still dealing with it 9 months later.. And it wasn't even a large dose.. 2 pills in 2 hours.
 
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