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Trying to "repair" brain after drug use


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#1 awarren

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Posted 02 June 2007 - 06:06 PM


Hi. My name is Anthony. I am 20 years old. From the age of 14 to 15, I used MDMA, though (thankfully) only twice. Scientific consensus seems to be that the long term effects are decreased memory, thinking abilities, and pleasure. I do not think that MDMA has damaged my brain enough for me to say that I feel stupid, more confused, or less happy (in fact, I don't use drugs anymore and life is going pretty well for me), but I am still concerned about my brain health. My girlfriend has taken neuroscience courses and told me that even after one use of MDMA, oxygen uptake is noticably decreased.

It has been 5 years, and I am assuming that some damage has been repaired, but I am looking to nootropics to just be sure. I am currently taking Piracetam for this purpose. It is the Relentless Improvement Brand, and I am taking approximately 800-1600mg 2-3 times a day. I do notice a difference in mental endurance, though I do not know if this is the appropriate drug for repairing damage to the brain after MDMA use. Since many nootropic evidence seems to be anecdotal, I am not convinced that taking these drugs would benefit me.

Can anyone recommend something that would increase oxygen uptake or is known to help "repair" damage? I have heard that Hydergine has been known to help repair the brain if taken for a long period of time, but I do not know if there is any evidence for this claim, not what brand I should take.

I am not considered with price, only quality.

Thank you for reading.

#2 meatwad

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Posted 02 June 2007 - 08:11 PM

Your brain dead, sorry awarren, your brain will NEVER heal. EVER.

Actually, 2 years clean off hard drugs is usually enough to heal almost all damage. don't be stressin - get outside and get some exercise if you want it to heal.
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#3 Mixter

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Posted 02 June 2007 - 08:39 PM

Let's see, repeated, *high* doses of MDMA are neurotoxic in at least two major ways:
1. Downregulate serotonin and damage 5-HT receptors
2. Increase long-term parkinsons risk -> probably damage to substantia nigra

I would probably primarily go for:
1. Serotonin boosters, such as St.Johns wort and Tryptophan, interchangably,
NOT at the same time to avoid dangers serotonine syndrome
2. Structural brain repair: lecithin, fish oil, ginkgo, etc.
3. LOW-Dose Deprenyl to guard against parkinsons risk. But really LOW, e.g.
not more than 1mg per day and 3mg per week. Deprenyl has some great
effects, but can be very irritating on a brain with current problems (esp.
inhibitory<->excitatory neurotransmitter imbalance), in my experience...

Safest way would be to confess this at a neurologist - remember all physicians
are obliged to confidentiality, and ask for a regimen. Especially if symptoms
would get really serious. But personally I suspect what you experience may
just be normal brain aging, anyhow ;-)

Simple references: http://www.dancesafe...show/index.html
and http://www.erowid.or...toxicity1.shtml

#4 doug123

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Posted 02 June 2007 - 10:25 PM

Dear awarren,

First off, please let me state that I am not a doctor and I am by no means qualified to give professional health care advice.

May I please present some preliminary research that suggests that MDMA may be neurotoxic (it seems the evidence strongly suggests MDMA may be neurotoxic in humans but has not been proven to be conclusively as potentially damaging as the case is with METH)?

Three related peer reviews:

Psychopharmacology (Berl). 2007 Jan;189(4):407-24. Epub 2006 Mar 16.

3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings.Baumann MH, Wang X, Rothman RB.

Clinical Psychopharmacology Section, Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. mbaumann@intra.nida.nih.gov

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of ongoing debate.
OBJECTIVE: The present paper reviews four specific issues related to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on monoamine neurons, (2) the use of "interspecies scaling" to adjust MDMA doses across species, (3) the effects of MDMA on established markers of neuronal damage, and (4) functional impairments associated with MDMA-induced 5-HT depletions. RESULTS: MDMA is a substrate for monoamine transporters, and stimulated release of 5-HT, NE, and DA mediates effects of the drug. MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1-2 mg/kg), suggesting that there is no reason to adjust doses between these species. Typical doses of MDMA causing long-term 5-HT depletions in rats (e.g., 10-20 mg/kg) do not reliably increase markers of neurotoxic damage such as cell death, silver staining, or reactive gliosis. MDMA-induced 5-HT depletions are accompanied by a number of functional consequences including reductions in evoked 5-HT release and changes in hormone secretion. Perhaps more importantly, administration of MDMA to rats induces persistent anxiety-like behaviors in the absence of measurable 5-HT deficits. CONCLUSIONS: MDMA-induced 5-HT depletions are not necessarily synonymous with neurotoxic damage. However, doses of MDMA which do not cause long-term 5-HT depletions can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks.

PMID: 16541247 [PubMed - indexed for MEDLINE]


J Psychopharmacol. 2006 Mar;20(2):194-210.
Ecstasy: are animal data consistent between species and can they translate to humans?Easton N, Marsden CA.
School of Biomedical Science, University of Nottingham, Queen's Medical Centre, UK. neil.easton@nottingham.ac.uk

The number of 3,4-methylenedioxymethamphetamine (ecstasy or MDMA) animal research articles is rapidly increasing and yet studies which place emphasis on the clinical significance are limited due to a lack of reliable human data. MDMA produces an acute, rapid release of brain serotonin and dopamine in experimental animals and in the rat this is associated with increased locomotor activity and the serotonin behavioural syndrome in rats.
MDMA causes dose-dependent hyperthermia, which is potentially fatal, in humans, primates and rodents. Subsequent serotonergic neurotoxicity has been demonstrated by biochemical and histological studies and is reported to last for months in rats and years in non-human primates. Relating human data to findings in animals is complicated by reports that MDMA exposure in mice produces selective long-term dopaminergic impairment with no effect on serotonin. This review compares data obtained from animal and human studies and examines the acute physiological, behavioural and biochemical effects of MDMA as well as the long-term behavioural effects together with serotonergic and dopaminergic impairments. Consideration is also given to the role of neurotoxic metabolites and the influence of age, sex and user groups on the long-term actions of MDMA.

PMID: 16510478 [PubMed - indexed for MEDLINE]


Addiction. 2006 Mar;101(3):348-61.
Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage?Gouzoulis-Mayfrank E, Daumann J.
Department of Psychiatry and Psychotherapy, University of Cologne, Germany. e.gouzoulis@uni-koeln.de

BACKGROUND: The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine: MDMA and some analogues) causes selective and persistent neurotoxic damage of central serotonergic neurones in laboratory animals.
Serotonin plays a role in numerous functional systems in the central nervous system (CNS). Consequently, various abnormalities including psychiatric, vegetative, neuroendocrine and cognitive disorders could be expected in humans following MDMA-induced neurotoxic brain damage. AIMS: In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies with drug users. The aim of this paper was to review this literature and weigh the strength of the evidence for persistent brain damage in ecstasy users. METHODS: We used Medline to view all available publications on 'ecstasy' or 'MDMA'. All available studies dealing with ecstasy users entered this analysis. FINDINGS AND CONCLUSIONS: Despite large methodological problems the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial restitution may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive, particularly memory, impairments with heavy ecstasy use. However, the evidence cannot be considered definite and the issues of possible pre-existing traits or the effects of polydrug use are not resolved. RECOMMENDATIONS: Questions about the neurotoxic effects of ecstasy on the brain remain highly topical in light of its popularity among young people. More longitudinal and prospective studies are clearly needed in order to obtain a better understanding of the possible long-term sequelae of ecstasy use in humans.

PMID: 16499508 [PubMed - indexed for MEDLINE]


I am not sure what pharmacological course of action is best for your particular case, if any, but before taking any supplements or medicines, the safest usual course of action is to have a professional evaluate your case specifics. Why? Well, to start, if you are already taking some particular medicines, supplements, eating a particular diet, or exercising, smoking, drinking, &c. -- or your genetic profile may perhaps indicate that you may have a predisposition to e.g. cancer or heart disease (e.g. your family members were afflicted with such diseases) -- it's probably smartest to disclose all of these factors to your doctor first because there may be particular elements in your diet or lifestyle that perhaps may be more or equally dangerous to compensate for. In addition, there are possible negative interactions and side effects from many drugs and supplements. I'd probably suggest that you start by working with a licensed health care practitioner that specializes in addiction and maybe one that specializes in integrative medicine.

If you are already a heavy drinker of alcoholic beverages, smoke cigarettes, and you do not exercise at all, then it might be equally (or perhaps more) important to quit smoking, drinking so heavily, and perhaps begin exercising appropriately as these elements may be more important to worry about taking this or that pill that has never been proven to induce neurogenesis in humans.

However, that said, there may be some therapies that may have potential to help recovering drug addicts regain "normal" neurological function (if it's true that they may have lost some).

Although most of this evidence may be preliminary (i.e. in rats, mice, small or specialized populations -- i.e. not drug addicts per se), I am reasonably confident that some drugs/supplements/therapies that have shown potential particular neurogenesis effects in rodents and other species -- through the proper clinical trials, of course -- could theoretically be later proven to be effective for the same uses in humans with brain damage inflicted by drug abuse or other types of brain trauma (such as stroke or injury).

If you are a recovering drug addict, you may also find the following topic of interest:

Drug Abuse Strikes 1 in 10 Americans

Take care.

Edited by adam_kamil, 02 June 2007 - 11:36 PM.


#5 woly

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Posted 03 June 2007 - 01:57 AM

Im with mixer. if you are really worried about damage then speak to a neurologist. MDMA neurotoxicity is a controversial topic and while there is a large amount of supporting evidence to suggest that it does cause some sort of damage, 2 doses of MDMA taken a few years ago is IMO nothing to worry about. however a good nooptropic stack couldnt hurt. I read somewhere that Ashwagandha helped regrow brain cells in rats so that might be something to look into.

#6 luv2increase

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Posted 03 June 2007 - 02:42 AM

I did ecstacy about 40 times or so when I was 17 and once when I was 19. I'm 24 now, and I am fine. My memory and mood is top notch, even before nootropics. I'd say that you have nothing to worry about. It is good though that you are concerned. Just don't do it ever again along with any 'hard' drugs for that matter, and you should be fine.

Time heals especially with proper nutrition, exercise, and rest.

#7 shamus

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Posted 03 June 2007 - 09:32 AM

Posted Image




Anthony?? Dude? Chill...

2 pills 5 years ago will not affect you* in the slightest (see: noticeably). The bump on your head last week will affect you more 'today' than those couple of pills. In fact, your mental predictions (this has a technical term) about your reduced capacity will be lessening your potential, so stop it! :)

Of course I'm assuming they were fairly standard peaks, and you didn't starve yourself for the next week. That said, I've absolutely trashed my brain on hundreds of peaks, with countless pills, and seem able to function better than any of the degenerates I work with at uni.

I'd love to see your 'long-term oxygen' source though?


For the record, whenever I peak nowadays, I supplement with lotsa piracetam, vitamin E, C, ala, selenium and other things to reduce my scatness...





* I might be concerned though of how jaded you've become? luv2increase for example... :p

#8 luv2increase

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Posted 03 June 2007 - 10:29 PM

* I might be concerned though of how jaded you've become? luv2increase for example... :)


I'm guessing that you may be British or Australian because you refer to college as a 'uni'. I am not up to date on the slang of your culture. What is the meaning of your statement. Thanks.


If it has something to do about me not recommending MDMA use, then you have to realize that this is a 'brain enhancement' forum. MDMA use is anything but brain enhancement; therefore, I will not recommend it. Also, once or twice here and there isn't going, IMO, to do any serious harm, but why take the 'potential' risk? When you can be just as happy with life living a healthy, productive lifestyle; drugs are not needed. Finds friends and a gf/bf that isn't in to anything that is going to affect you negatively, and you will be happier than ever.

#9 shifter

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Posted 03 June 2007 - 11:06 PM

eat some blueberries every day :) Great brain food

#10 khanzas

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Posted 04 June 2007 - 10:30 AM

2 doses of MDMA taken a few years ago is IMO nothing to worry about


Exactly.

edit:

I am not up to date on the slang of your culture


I am. I didn't quite get it either, so I don't think that lack of slang is the problem.

#11 medievil

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Posted 04 June 2007 - 12:02 PM

dude are you serious? i take MDMA twice weekly, once up to 15 pill's and i'm not even as worried as you
a SSRI could work for MDMA damage but i'm not sure, i saw it mentioned before without any refs

again you where smart enough not to touch meth, if you did that one be very worried
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#12 luv2increase

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Posted 04 June 2007 - 02:59 PM

dude are you serious? i take MDMA twice weekly, once up to 15 pill's and i'm not even as worried as you
a SSRI could work for MDMA damage but i'm not sure, i saw it mentioned before without any refs

again you where smart enough not to touch meth, if you did that one be very worried


Dude are you serious, seriously? :)

#13 luv2increase

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Posted 05 June 2007 - 03:59 AM

Are you not aware, medieval, that a lot of ecstacy is laced with meth? "Once up to 15 pills", not smart. You must of had some 'bunk' X. I've never heard of anyone needed that much before, ever.

#14 meatwad

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Posted 05 June 2007 - 04:55 AM

he must of have some bunk X?

I know your aware of how tolerance works...what is so unbelievable about 15 pills?

And to hippies such as yourself (kidding!) you guys know too much is never enough. You could probably smoke 1/1000th of the amount you smoke now and be pretty addled, but you still smoke like a chimney regardless...
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#15 medievil

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Posted 05 June 2007 - 02:26 PM

Are you not aware, medieval, that a lot of ecstacy is laced with meth?  "Once up to 15 pills", not smart.  You must of had some 'bunk' X.  I've never heard of anyone needed that much before, ever.

i could take 3 pills and have a good time, but with a lot of pills you are floored

about the meth thing, this shitty drug is not in my country, there isnt anyone here that knows what it is, you cant find it either, we dont have a lot of shitty pills here either, when you buy pills here it are good ones (we got pills with amphetamines but they are the "apples" no matter what color if its an apple its amphetamine
i dont know why meth is so popular in the us, is it cool there to be addicted? if you tell someone here you used a very addictive drug like heroine or something you arent making yourself popular, and ppl would actually ignore you a bit
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#16 woly

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Posted 05 June 2007 - 03:19 PM

1. How do you know you dont have meth in your pills?
2. where do you live?
3. the colour and logo of a pill do not always indicate the content. being a black market, content varies due to different producers and batches.
4. being addicted is teh coolizt

now back on topic
i read a study that showed that rats who took large amounts of ALA before and after MDMA had no signs of neurotoxicity.

#17 medievil

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Posted 05 June 2007 - 03:56 PM

ALA does indeed work againt neurotoxicity as does a high dose of vitamine C or deprenyl
i beleive the negative effects of certain drugs can be fully prevented with certain nootropics

1. its not availible in my country
2 belguim
3 not here, when you buy a certain batch thats known to be good it IS good, i never heared of any bad versions of a batch, its might happen but its very very rare
4 but is it? i read alot about peer pressure in america, i dont know whats the situation there

Edited by medievil, 05 June 2007 - 05:11 PM.

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#18 synaesthetic

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Posted 05 June 2007 - 05:25 PM

awarren I had similar concerns, but you don't need to worry about doing just two, the brain can heal.

I recommend gingko, blueberries, gotu kola and ashwaganda.


Neurogenesis Thread

#19 awarren

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Posted 05 June 2007 - 06:26 PM

Thank you for your suggestions.

#20 pSimonKey

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Posted 05 June 2007 - 10:27 PM

selegiline
ginkgo
vincamine
hydergine
idebenone
ALA
fish oils
lecithin
B-vits
good diet
excercise

I lived in Amsterdam for 3 years, 7 years ago and was v.very involved in the MDMA scene.
Don't sweat it awarren you'll be fine, just work yourself towards a better way, one step at a time, day by day. It's good to hear that you are already heading in the right direction. Shine on.

#21 doug123

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Posted 05 June 2007 - 11:31 PM

Dear awarren,

First off, please let me state that I am not a doctor and I am by no means qualified to give professional health care advice. 

May I please present some preliminary research that suggests that MDMA may be neurotoxic (it seems the evidence strongly suggests MDMA may be neurotoxic in humans but has not been proven to be conclusively as potentially damaging as the case is with METH)?

Three related peer reviews:

Psychopharmacology (Berl). 2007 Jan;189(4):407-24. Epub 2006 Mar 16.

3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings.Baumann MH, Wang X, Rothman RB.

Clinical Psychopharmacology Section, Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. mbaumann@intra.nida.nih.gov

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of ongoing debate.
OBJECTIVE: The present paper reviews four specific issues related to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on monoamine neurons, (2) the use of "interspecies scaling" to adjust MDMA doses across species, (3) the effects of MDMA on established markers of neuronal damage, and (4) functional impairments associated with MDMA-induced 5-HT depletions. RESULTS: MDMA is a substrate for monoamine transporters, and stimulated release of 5-HT, NE, and DA mediates effects of the drug. MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1-2 mg/kg), suggesting that there is no reason to adjust doses between these species. Typical doses of MDMA causing long-term 5-HT depletions in rats (e.g., 10-20 mg/kg) do not reliably increase markers of neurotoxic damage such as cell death, silver staining, or reactive gliosis. MDMA-induced 5-HT depletions are accompanied by a number of functional consequences including reductions in evoked 5-HT release and changes in hormone secretion. Perhaps more importantly, administration of MDMA to rats induces persistent anxiety-like behaviors in the absence of measurable 5-HT deficits. CONCLUSIONS: MDMA-induced 5-HT depletions are not necessarily synonymous with neurotoxic damage. However, doses of MDMA which do not cause long-term 5-HT depletions can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks.

PMID: 16541247 [PubMed - indexed for MEDLINE]


J Psychopharmacol. 2006 Mar;20(2):194-210.
Ecstasy: are animal data consistent between species and can they translate to humans?Easton N, Marsden CA.
School of Biomedical Science, University of Nottingham, Queen's Medical Centre, UK. neil.easton@nottingham.ac.uk

The number of 3,4-methylenedioxymethamphetamine (ecstasy or MDMA) animal research articles is rapidly increasing and yet studies which place emphasis on the clinical significance are limited due to a lack of reliable human data. MDMA produces an acute, rapid release of brain serotonin and dopamine in experimental animals and in the rat this is associated with increased locomotor activity and the serotonin behavioural syndrome in rats.
MDMA causes dose-dependent hyperthermia, which is potentially fatal, in humans, primates and rodents. Subsequent serotonergic neurotoxicity has been demonstrated by biochemical and histological studies and is reported to last for months in rats and years in non-human primates. Relating human data to findings in animals is complicated by reports that MDMA exposure in mice produces selective long-term dopaminergic impairment with no effect on serotonin. This review compares data obtained from animal and human studies and examines the acute physiological, behavioural and biochemical effects of MDMA as well as the long-term behavioural effects together with serotonergic and dopaminergic impairments. Consideration is also given to the role of neurotoxic metabolites and the influence of age, sex and user groups on the long-term actions of MDMA.

PMID: 16510478 [PubMed - indexed for MEDLINE]


Addiction. 2006 Mar;101(3):348-61.
Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage?Gouzoulis-Mayfrank E, Daumann J.
Department of Psychiatry and Psychotherapy, University of Cologne, Germany. e.gouzoulis@uni-koeln.de

BACKGROUND: The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine: MDMA and some analogues) causes selective and persistent neurotoxic damage of central serotonergic neurones in laboratory animals.
Serotonin plays a role in numerous functional systems in the central nervous system (CNS). Consequently, various abnormalities including psychiatric, vegetative, neuroendocrine and cognitive disorders could be expected in humans following MDMA-induced neurotoxic brain damage. AIMS: In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies with drug users. The aim of this paper was to review this literature and weigh the strength of the evidence for persistent brain damage in ecstasy users. METHODS: We used Medline to view all available publications on 'ecstasy' or 'MDMA'. All available studies dealing with ecstasy users entered this analysis. FINDINGS AND CONCLUSIONS: Despite large methodological problems the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial restitution may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive, particularly memory, impairments with heavy ecstasy use. However, the evidence cannot be considered definite and the issues of possible pre-existing traits or the effects of polydrug use are not resolved. RECOMMENDATIONS: Questions about the neurotoxic effects of ecstasy on the brain remain highly topical in light of its popularity among young people. More longitudinal and prospective studies are clearly needed in order to obtain a better understanding of the possible long-term sequelae of ecstasy use in humans.

PMID: 16499508 [PubMed - indexed for MEDLINE]


I am not sure what pharmacological course of action is best for your particular case, if any, but before taking any supplements or medicines, the safest usual course of action is to have a professional evaluate your case specifics. Why? Well, to start, if you are already taking some particular medicines, supplements, eating a particular diet, or exercising, smoking, drinking, &c. -- or your genetic profile may perhaps indicate that you may have a predisposition to e.g. cancer or heart disease (e.g. your family members were afflicted with such diseases) -- it's probably smartest to disclose all of these factors to your doctor first because there may be particular elements in your diet or lifestyle that perhaps may be more or equally dangerous to compensate for. In addition, there are possible negative interactions and side effects from many drugs and supplements. I'd probably suggest that you start by working with a licensed health care practitioner that specializes in addiction and maybe one that specializes in integrative medicine.

If you are already a heavy drinker of alcoholic beverages, smoke cigarettes, and you do not exercise at all, then it might be equally (or perhaps more) important to quit smoking, drinking so heavily, and perhaps begin exercising appropriately as these elements may be more important to worry about taking this or that pill that has never been proven to induce neurogenesis in humans.

However, that said, there may be some therapies that may have potential to help recovering drug addicts regain "normal" neurological function (if it's true that they may have lost some).

Although most of this evidence may be preliminary (i.e. in rats, mice, small or specialized populations -- i.e. not drug addicts per se), I am reasonably confident that some drugs/supplements/therapies that have shown potential particular neurogenesis effects in rodents and other species -- through the proper clinical trials, of course -- could theoretically be later proven to be effective for the same uses in humans with brain damage inflicted by drug abuse or other types of brain trauma (such as stroke or injury).

If you are a recovering drug addict, you may also find the following topic of interest:

Drug Abuse Strikes 1 in 10 Americans

Take care.


Here's a quick update on the potential neurotoxicity potential of MDMA. I am quoting myself because it seems I made a statement above that suggests that MDMA might not be neurotoxic; this new evidence published in the today in the media and in AJP a bit earlier might suggest otherwise.

MedPage Today: News Source

Posted Image

Low-Dose Ecstasy Use Linked to Decline in Verbal Memory
 
By Judith Groch, Senior Writer, MedPage Today

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

June 04, 2007
   
MedPage Today Action Points

o Explain to patients who ask that even a low cumulative dose of Ecstasy (over six to seven weeks, for example) can cause a decline in verbal memory in new users.
 
Review

AMSTERDAM, The Netherlands, June 4 -- New users who took the street drug Ecstasy for a mean 1.6 months at low cumulative doses showed a decline in verbal recall and recognition.

There is growing evidence that Ecstasy, the street name for ±-3,4-methylenedioxy-methamphetamine (MDMA), is potentially neurotoxic in human beings, wrote Thelma Schildt, M.Sc., of the University of Amsterdam, and colleagues in the June issue of the Archives of General Psychiatry.


However, they said, most studies have been done on frequent Ecstasy users and there have been no human data regarding the sustained neurocognitive effects of a single or low dosage use of the drug among novice users.

To examine that question, the researchers conducted a prospective cohort study, part of the Netherlands XTC Toxicity study. The original sample consisted of 188 healthy, Ecstasy-naive volunteers (mean age, 22) who said they had considered starting to use Ecstasy in the near future.

The initial enrollment took place from April 10, 2002 to April 28, 2004, with a follow-up within three years.

Of the original 188 subjects, 58 started using Ecstasy (mean cumulative dose, 3.2 tablets; median cumulative dose 1.5 tablets in a mean period of 1.6 months). The average follow-up was over 11.1 months.

They were compared with 60 subjects who had never used Ecstasy and were matched for age, sex, intelligence, and use of substances other than Ecstasy.

Subjects were paid for their participation, depending on the number of assessment sessions. Differences in cognition between Ecstasy users and non-users were adjusted for differences in use of cannabis and other recreational drugs.

At the initial examination, the two groups showed no statistically significant differences in any of the neuropsychological test scores, the researchers said.

At follow-up, however, scores for change on immediate and delayed verbal recall and verbal recognition were significantly lower in those who'd taken Ecstasy compared with the non-users. The changes, the researchers noted, were still within the normal range.

For example, on the Rey Auditory Verbal Learning Test (RAVLT), which tests the immediate recognition of words, the change score for the Ecstasy users was 0.86, compared with 3.90 for the nonusers.

The mean recognition of words score at the initial examination for the Ecstasy users was 29.95 (SD 0.2) and 29.66 at follow-up, with 22.4% of subjects showing a decline.

The initial score for the non-users was 29.88 and at follow-up 29.93, with 6.7% of subjects showing a decline (P=0.02).

There were no significant differences on other test scores, the researchers reported. At follow-up, the Ecstasy users reported to have used a mean of 3.2 tablets (range 0.5-50 tablets; median 1.5 tablets) in a mean period of 1.6 months during the average follow-up of 11.1 months. Mean follow-up for the non-users was 19.1 months.

The assessment took place on average 11.8 weeks after the last Ecstasy use, unlike the much shorter durations in other studies, the researcher noted.

At follow-up, the Ecstasy users also reported having used more cannabis and cocaine in the previous year than the non-Ecstasy users. The non-users also drank less alcohol at follow-up, the researchers reported.

The current findings are consistent with numerous previous studies that reported a specific negative effect of Ecstasy use on verbal memory, the researchers said.

In this study, they noted, the association between Ecstasy dose and verbal memory performance was rather weak. This was not surprising, they said, given the relatively low doses that were used and the short duration of Ecstasy use.

No differences between the two groups were observed on other neurocognitive tests, nor was sex a factor, the researchers said. Some explanations include a possible combined effect with cannabis, a possibility that cannot be excluded.

Another possible confounding effect might have been depression, leading to higher levels of sensation-seeking. Yet, this would not explain why only verbal memory test scores were affected, whereas scores on other highly demanding tests were not affected, the investigators wrote.

It can be hypothesized, they said, that the medial temporal lobes, particularly the hippocampal area, are specifically vulnerable to Ecstasy. It is possible, they said, that the main underlying factor is depletion of serotonin, involved in several cognitive functions, but possibly especially relevant to learning and memory, while attention remains unaffected.

The researchers acknowledged several limitations of the study, including the prospective design, which limited evidence of causality. There was also a potential confounding of lifestyle differences, the pattern of drug use and its environment, and the lack of control of the purity of the amount of MDMA in the tablets.

Moreover, they said, the sample was not representative of the general population of young adults, which might limit the generalizability of the results.

A final limitation, the researchers said, is that the study did not answer the question of whether the observed short-term effects will remain after quitting the drug. Monitoring this cohort would be worthwhile, they said.

Although the performance of the group of Ecstasy users was still within the normal range and the immediate clinical relevance of the observed deficits is limited, the researchers concluded, the long-term consequences cannot be excluded.

This study was supported by a grant from the Netherlands Organization for Health Research and Development as part of their Addiction Program. No financial disclosures were reported.


Primary source: Archives of General Psychiatry

Source reference:
Schilt T, et al "Cognition in Novice Ecstasy Users With Minimal Exposure to Other Drugs: A Prospective Cohort Study" Arch Gen Psychiatry 2007; 64: 728-736.

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News Source: Archives of General Psychiatry

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Cognition in Novice Ecstasy Users With Minimal Exposure to Other Drugs
A Prospective Cohort Study

Thelma Schilt, MSc; Maartje M. L. de Win, MD, PhD; Maarten Koeter, PhD; Gerry Jager, PhD; Dirk J. Korf, PhD; Wim van den Brink, MD, PhD; Ben Schmand, PhD

Arch Gen Psychiatry. 2007;64:728-736.

Context  Ecstasy (street name for [±]-3,4-methylenedioxymethamphetamine [MDMA]) use has been associated with cognitive deficits, especially in verbal memory. However, owing to the cross-sectional and retrospective nature of currently available studies, questions remain regarding the causal direction and clinical relevance of these findings.

Objective  To examine the relationship between Ecstasy use and subsequent cognitive performance.

Design  A prospective cohort study in Ecstasy-naive subjects with a high risk for future first Ecstasy use, as part of the Netherlands XTC Toxicity study. The initial examination took place between April 10, 2002, and April 28, 2004; follow-up was within 3 years after the initial examination.

Setting and Participants  One hundred eighty-eight healthy Ecstasy-naive volunteers (mean age, 22 years) were recruited. Of these, 58 subjects started using Ecstasy (mean cumulative dose, 3.2 tablets; median cumulative dose, 1.5 tablets). They were compared with 60 persistent Ecstasy-naive subjects matched on age, sex, intelligence, and use of substances other than Ecstasy. Differences in cognition between Ecstasy users and Ecstasy-naive subjects were adjusted for differences in cannabis and other recreational drug use.

Main Outcome Measures  Change scores between the initial examination and follow-up on neurocognitive tests measuring attention, working memory, verbal and visual memory, and visuospatial ability.

Results  At the initial examination, there were no statistically significant differences in any of the neuropsychological test scores between persistent Ecstasy-naive subjects and future Ecstasy users. However, at follow-up, change scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-naive subjects. There were no significant differences on other test scores.

Conclusions  Our findings suggest that even a first low cumulative dose of Ecstasy is associated with decline in verbal memory. Although the performance of the group of incident Ecstasy users is still within the normal range and the immediate clinical relevance of the observed deficits is limited, long-term negative consequences cannot be excluded.

Author Affiliations: Amsterdam Institute for Addiction Research (Ms Schilt and Drs Koeter and van den Brink), Amsterdam, the Netherlands; Departments of Psychiatry (Ms Schilt and Drs Koeter and van den Brink), Radiology (Dr de Win), and Neurology (Dr Schmand), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre, Utrecht, the Netherlands (Dr Jager); and Bonger Institute of Criminology (Dr Korf) and Department of Psychology (Dr Schmand), University of Amsterdam, Amsterdam, the Netherlands.


It seems to probably not be a good idea to take this drug if you care about your brain.

There may be, however -- future treatments to help recovering MDMA addicts restore brain function, if it's true they may have lost some. I imagine high resolution MRIs might be required to determine the degree of damage inflicted and also to determine if any damaged regions may be restored to normal. However, future potential therapies for recovering drugs addicts are not -- at least at this time -- indicated for and therefore it may require alterations to DSM so doctors may prescribe such drugs without fear of malpractice suits.

It would likely take a lot of work to get these changes implemented; however, with the current size of the METH epidemic and the rate that it seems to be growing, the future demand for therapies to restore cognitive function should make the effort profitable for the pharmaceutical companies involved in such work.

Take care.

#22 Jack of all trades

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Posted 27 February 2014 - 05:31 AM

Hi Anthony

I've been a relatively frequent user of MDMA for several years and I can confidently say that it has had a noticeable affect on my brain.

In your case I don't feel you have anything to worry about. (Then again I also believe that it affects each individual differently so you never know...)

I'm no expert and I sure don't know what the actual effects of long term damage are especially an unspecified dosage but I can safely say that after cutting it out of my life, exercising regularly, eating well and getting lots of fresh air that I have seen significant changes in my mental health.

I don't believe that 5 years after such a small dose will have a significant affect on your brain to warrant a need to look to prescription drugs.

Glad to hear your off it now!
Living a healthy life is the best high. In my opinion!
#Don't do drugs kids
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#23 Nobility

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Posted 27 February 2014 - 01:21 PM

Fish Oils, SLEEP, Exercise , Diet.

Careful on the vitamins. The vitamins I was taking were making me very dizzy (and they are only a b complex)

#24 Jeoshua

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Posted 27 February 2014 - 05:43 PM

5-HTP Preloading with a few grams spread out over a day or two, followed by a normal dosing of MDMA, then 500mg 5-HTP afterwards, will eliminate all mood abberations and seriously potentiate the effects of the drug. I don't recommend using MDMA, but if you do, be kind to your neurotransmitter levels.
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#25 Epigenesis

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Posted 28 February 2014 - 03:09 AM

From the study posted above:
"At 180 days almost all functional changes in sleep were normalized together with 5-HTT mRNA expression in the examined raphe nuclei and the recovery of 5-HTT-IR fibre density in most brain areas."
So, after 5 years, I think your brain has healed itself.

It's a shame that MDMA has negative effects, as it can be a wonderful experience while it last. However, as are most hard drugs, those hours of unparalleled bliss come with a hefty price on health. I dabbled with it in the past with no plans to continue, fortunately only a handful of times.

And to the guy who said he took 15 pills: you could have easily died. MDMA has a very low overdose threshold in comparison to effective dosage. Besides that, most pills have a cocktail of ingredients, you never how much MDMA is in each one, far less than 15 could result in an OD. Lastly, there are a verity of research chemicals and analogues sold as MDMA, it is rampant, taking 15 pills is really like playing russian roulette, but perhaps with worse odds.

#26 Jeoshua

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Posted 28 February 2014 - 03:49 AM

Very true, Epigenesis. All that had to happen with those 15 pills is for one of them to be a "bunk" pill filled with DXM and *boom* Serotonin Crisis.

Let's face it, party pills are not exactly from a pharmacy. You're playing with your life when you take them.

But the OP's worry that it had fried his brain permanently after 2 pills, 5 years ago? Extremely doubtful, and even moderately healthy living since then would have smoothed over any old scars that might have formed.

#27 SmarterNootropics

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Posted 28 February 2014 - 04:50 PM

5-HTP Preloading with a few grams spread out over a day or two, followed by a normal dosing of MDMA, then 500mg 5-HTP afterwards, will eliminate all mood abberations and seriously potentiate the effects of the drug. I don't recommend using MDMA, but if you do, be kind to your neurotransmitter levels.


From what I understand, 5-HTP is converted to serotonin in a non-regulatory fashion, much the same as L-dopa is to dopamine.

I can't imagine 500mg 5-HTP + MDMA is going to do anything other than supercharge all aspects of serotonin release and trash the brain even further.

Would it not be wiser to take the 5-HTP AFTER the MDMA to replenish serotonin stores?

#28 Jeoshua

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Posted 28 February 2014 - 05:23 PM

The negative effects of MDMA while it's in the body are not directly related to the amount of Serotonin in your body, but it's subjective entactogenic and hallucinogenic effects are, so the reason for pre-loading would be to overcome any Serotonin defficiencies and get a good experience out of it. 5-HTP is going to be much less dangerous than ever escallating amounts of MDMA pills of questionable sourcing, so it's a safety measure designed to make 1 pill potentially just like that "first time MDMA experience" every time, instead of giving in to tolerance and taking more and more and then seriously hurt yourself. And I am speaking from experience when I say it works.

I did say to take 5-HTP afterwards, as well. The depression often reported post-ecstasy is due to low Serotonin levels, and you do NOT want your brain readjusting to that level.

1 pill + Preloading had much more of an effect than several friends' 3-5 pills, and taking one pill afterwards to reestablish my Serotonin levels left me feeling absolutely fine the next day, no hangover, no depression.

And I don't understand why that post keeps getting downvoted. Come out of the woodwork and explain yourselves, guys. What do you hate so much about harm reduction?

Edited by Jeoshua, 28 February 2014 - 05:27 PM.


#29 SmarterNootropics

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Posted 28 February 2014 - 08:00 PM

Thanks for the clarification, I think that makes a lot of sense especially comparing preloading vs taking multiple doses. I have absolutely nothing against harm reduction and my capitalization of AFTER may have come across the wrong way. However I do think it's important to be careful how much 5HTP is taken due to the non-regulatory conversion so as to avoid too much, but should reduce harm compared to multiple doses of MDMA.

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#30 Michael Rian

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Posted 09 May 2014 - 11:31 PM

I did say to take 5-HTP afterwards, as well. The depression often reported post-ecstasy is due to low Serotonin levels, and you do NOT want your brain readjusting to that level.

 

 

Hello, I hope you dont mind me asking for your advice.  I was wondering what would be the protocol for someone whose brain may have adjusted to low Serotonin levels?  Would Serotonin receptor up-regulation via St.Johns Wort or SSRI be an idea?  I apologize if I sound like an idiot, I am just learning now about neurotransmitters and how they work.  Thank you to anyone who can shed some light for me.
 






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