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There is no mention of normal dose. If someone is caught with 50 grams of extasy is it a lot? How many dose can one make from pure 1 gram of MDMA?--RicHard-59 (talk) 21:45, 27 May 2014 (UTC)[reply]

Channel 4's Drugs Live programme in 2012 used single doses of 83mg in the experiment, which would be almost exactly a twelfth of a gramme, and broadly in line with the average active content in street pills at the time and previously. In the UK someone caught with 50 grammes (i.e. approximately 600 doses, with a street value of at least £2,000) would almost certainly be charged with possession with intent to supply (others), as opposed to simple possession for personal use. Nick Cooper (talk) 12:45, 28 May 2014 (UTC)[reply]

Shulgin's notes [1] suggest a dosage of 80-150mg (his experiments range from 60-200mg). I have frequently heard 100mg, which is in agreement and is also a nice round number: 1 gram = 10 doses. Pills typically have a mass around 100mg, but purity varies widely so it's difficult to equate pills to doses. The legal definition of a dose, if used in a criminal prosecution, might be something else entirely but it should be defined in statute or regulation. Simishag (talk) 19:44, 28 May 2014 (UTC)[reply]

I suspect the 83mg has its origin in it presumably being easier to separate a supposed gramme of powder into twelve "by eye," than it is to divide it into ten. Nick Cooper (talk) 13:06, 29 May 2014 (UTC)[reply]

The source for this statement is a blog post with no references. http://artsbeat.blogs.nytimes.com/2013/09/12/overdoses-of-molly-led-to-electric-zoo-deaths/?_r=0

I personally question the veracity of the statement as well as the appropriateness of using a blog post as the basis of fact in a wikipedia entry. 66.64.59.58 (talk) 16:54, 24 June 2014 (UTC)[reply]

Pretty much every account of dance culture and MDMA use in the UK notes that in Europe it surfaced in Ibiza first (e.g. Saunders, C0llin, and Garratt). Even so, there is a difference between a regular blog, and a New York Times blog. Nick Cooper (talk) 22:27, 24 June 2014 (UTC)[reply]

I agree with User:Nick Cooper on this. Tova Hella (talk) 17:57, 1 November 2014 (UTC)[reply]

The following is meaningless, scientific-sounding gabble, and ought to be removed:

"The positive effects were so large as to achieve statistical significance in spite of the small size of the trials (In one study, the rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. In the other study, a p-score of 1.4% was found for the PDS scale and 1.6% for the CAP scale one year after treatment. A p-score of 5% or less is often considered statistically significant, and the effect found needs to be larger with smaller studies to have statistical significance, ceteris paribus, in order to correct for sample size.) In the second study, positive effect in CAP scale immediately after treatment did not achieve statistical significance (p=6.6%), but may do so with a larger sample size. The patients treated with two or three sessions of MDMA-psychotherapy showed greater improvement than the ones treated by placebo-psychotherapy or placebo-inactive dose of MDMA.[18] This improvement was generally maintained on a follow-up several years later." Dratman (talk) 13:43, 4 August 2014 (UTC)[reply]

Like the title says, I'm going to cut out a lot of the medical content which fails WP:MEDRS and rewrite/resource a few parts. The health effects of MDMA article is redundant with what the article is supposed to include per WP:MEDMOS, so I'm going to merge that article into this one after cutting out its inadequately sourced content. I expect I'll get around to it sometime over the next month or so. Seppi333 (Insert 2¢ | Maintained) 06:22, 22 August 2014 (UTC)[reply]

Others to add:

• ^[1]
• http://dx.doi.org/10.1080/02791072.2014.873690 ^[2]
• http://dx.doi.org/10.1002/hup.2390 ^[3]
• http://dx.doi.org/10.1002/jcph.266 ^[4]
• http://dx.doi.org/10.7748/en2014.02.21.9.32.e1128 ^[5]
• http://dx.doi.org/10.1016/j.lfs.2013.07.014 ^[6]

Adverse + OD

• ^[7]
• ^[8]

PDynamics

• VMAT2^[9]
• TAAR1^[10]

PKinetics+Toxicity

• ^[11]

Seppi333 (Insert 2¢ | Maintained)

Please do me a favor and bring something up on the talkpage - either in this thread or a new one - before reverting a change I make. More than likely I intend to rewrite/resource a section if I completely delete one. Content that I remove is usually indicated for a particular reason in an edit summary.

This also isn't the first time I've rapidly rewritten a high-traffic article: e.g., methamphetamine (now a GA) and nootropic. Seppi333 (Insert 2¢ | Maintained) 14:16, 16 October 2014 (UTC)[reply]

Thanks for your work on this article (and on previous ones)! DMacks (talk) 14:41, 16 October 2014 (UTC)[reply]

Thanks Seppi333 (Insert 2¢ | Maintained) 20:36, 16 October 2014 (UTC)[reply]

"Butchering" is the right word, especially as regards the "Legal status" section and particularly the "United Kingdom" subsection. I would note that in the process you deleted everything about the ACMD's recommendations on the reclassification of MDMA (discounting them as "court battles and random controversy"), which seems convenient to the agenda you're apparently pushing. Nick Cooper (talk) 09:22, 17 October 2014 (UTC)[reply]

I have virtually no interest in this article topic. If it didn't have abhorrently shitty sources, I wouldn't be editing it. I'm only doing this since I already have a lot of familiarity with MDMA from significantly revising/expanding articles on its pharmacology and on other substituted amphetamines.

A drug legal status section is simply supposed to quickly summarize the global legal status as a controlled substance, with selected countries where editors have supplied supporting citations. It's not a place to cover current perspectives on the legality of drugs. That material would go into a history/society/culture section, and I'm not opposed to covering that material there (without massive blockquotes in the text); that said, I haven't decided whether or not to merge this page's section with history and culture of substituted amphetamines yet though. Seppi333 (Insert 2¢ | Maintained) 10:36, 17 October 2014 (UTC)[reply]

Agree with Seppi that the Legal section was largely a long winded argument that MDMA is over-regulated and was way out of touch with WP:NPOV. The article overall was riddled with advocacy and the use of non-reliable sources (Dancesafe.org???, Ectascydata.org???, theDEA.org??? Seriously?). I think there is room for discussion of specific changes, but the overall need for a cleanup is beyond question.

Seppi has a great track record as an editor of CNS drug related articles and I'm pleased to see him taking this task on. Formerly 98 (talk) 12:39, 17 October 2014 (UTC)[reply]

On what grounds are those sites "non-reliable" in the context that they were originally cited? Or do you take the view that any site that does not take a prohibitionist stance is inherently unreliable? Whether you like it or not, the legal status of MDMA is questioned in a number of countries, not least by the UK government's advisory body. We should refelect such debate, not pander to a line of "Drugs are bad, m'kay?" Nick Cooper (talk) 12:52, 17 October 2014 (UTC)[reply]

WP:MEDRS - the answer to your first two questions - is why it's not ok to cite "Bob's I love ecstasy blog" as a reference for medical information on MDMA. I'm not even remotely interested in its legal status and don't even want to edit content on that - I'm not here to write a DARE pamphlet, just an accurate description of the drug effects and the current evidence of its therapeutic potential. MDMA is neurotoxic, so it borks your brain over the long term; the article will reflect that. MDMA is also a euphoriant, so it makes you feel really good - the article will reflect that too. Seppi333 (Insert 2¢ | Maintained) 13:41, 17 October 2014 (UTC)[reply]

Take a look at WP:MEDRS. Secondary sources published in peer reviewed medical journals or medical textbooks are required for health related content. And advocacy sites and blogs fail even the lower standard of WP:RS Formerly 98 (talk) 13:32, 17 October 2014 (UTC)[reply]

I'd also suggest taking a look at WP:NPOV and WP:UNDUE. The central concept is that Wikipedia describes controversies, it does not take sides in them. The POVs of each side are given space in proportion to their predominance among experts. Selectively hunting down and quoting documents suggesting that MDMA is over-regulated violates both of these. And no, its not "Mmm, drugs are bad, ok?' I would be equally opposed to an overdrawn discussion endlessly restating the risks of these drugs and selectively quoting those who feel that greater enforcement activity is warranted. We're not here to write editorials. M'kay? 2605:E000:1C0C:80F7:1DD5:6CD2:EB00:6646 (talk) 14:01, 17 October 2014 (UTC)apologies, forgot to login Formerly 98 (talk) 14:49, 17 October 2014 (UTC)[reply]

So you're making a value judgement that other editors have been "Selectively hunting down and quoting documents suggesting that MDMA is over-regulated"? Like the ACMD report, you mean? Nick Cooper (talk) 15:20, 17 October 2014 (UTC)[reply]

So which sites are your characterising as "Bob's I love ecstasy blog" and why? You claim that you are "not even remotely interested in its legal status and don't even want to edit content on that" when that's precisely what you have done. The scope of this page has long been far wider than, "an accurate description of the drug effects and the current evidence of its therapeutic potential," but you've arbitrary decided to narrow the focus. Nick Cooper (talk) 15:20, 17 October 2014 (UTC)[reply]

For all intents and purposes, I'm characterizing all of the above, and anything which is not recently published by a governmental drug agency/entity, a credible professional medical entity, or an academic authority in pharmacology, as "Bob's I love ecstasy blog." Why? Because all those things (i.e., the vast majority of possible things you could cite) fail WP:MEDRS, which is an extremely strict standard. Edit: you misunderstand my meaning; my only objective in this article is to bring that part of this article (drug effects and therapeutic potential) up-to-date. I'm not going to work on the rest other than to fix grammar/flow issues, make appearance tweaks, and possibly add citations to the non-medical sections. Seppi333 (Insert 2¢ | Maintained) 15:37, 17 October 2014 (UTC)[reply]

...forgot to add: and delete massive blockquotes. Seppi333 (Insert 2¢ | Maintained) 15:58, 17 October 2014 (UTC)[reply]

Sounds to me that both you and Formerly 98 have got a load of ready made excuses for deleting whatever you don't like, and are doing it in a manner that makes it virtually impossible for any other editor to proper scrutinise your edits.

You're still ignoring the question as to why you eviscerated the "Legal status" section while claiming to be "not even remotely interested in its legal status and don't even want to edit content on that." Nick Cooper (talk) 08:40, 18 October 2014 (UTC)[reply]

Read the highlighted text.

If you feel we're overzealously enforcing WP:MEDRS by removing sources in the article, you can seek a second opinion from other medical project editors if you like. There's currently a section on this article on the project talkpage if you want to reply under it: WT:MED#3,4-Methylenedioxymethamphetamine merge. Seppi333 (Insert 2¢ | Maintained) 12:47, 18 October 2014 (UTC)[reply]

By the time I'm done sourcing and copyediting the article, it won't look much different than its current revision. I don't intend to change the layout or delete content from any additional sections, except in pharmacokinetics, at the moment; pharmacokinetics contains some trivial material - also needs medical sources. Seppi333 (Insert 2¢ | Maintained) 16:22, 18 October 2014 (UTC)[reply]

It may have escaped your notice, but this page is within the scope of a number projects, and one doesn't get to dictate that the page can only conform to its own rules. Nick Cooper (talk) 08:40, 19 October 2014 (UTC)[reply]

MEDRS is not just a policy of the Medicine Project, but of Wikipedia overall. Take a look at WP:RS Formerly 98 (talk) 11:50, 19 October 2014 (UTC)[reply]

What happened to the MDMA page??? I agree with Nick Cooper, it is unacceptable to delete large sections of an article without discussion. Seppi333 deleted large sections of the history of regulation and harm assessment of MDMA, including quotes from official reports and respected NGOs. For instance, all mention has been deleted of the 1985/86 DEA court hearing which concluded that MDMA did not fit the criteria for Schedule I. You can't just delete history. Please, Nick, could you revert these changes? Tova Hella (talk) 17:35, 1 November 2014 (UTC)[reply]

I'm going to immediately delete any blockquote that I see on this page. If you want to re-add content on a blockquote that I deleted or moved inside a ref's quote parameter, summarize it and cite the source; otherwise, you can expect my impending revert.
As I've already stated, I had/have no issue with anything else related to that blockquote content - the citation and material covered in the blockquoted text were fine for inclusion on this page, but the coverage of that material using a massive blockquote is not fine. That said, placing blockquoted text in a citation's quote parameter is both an acceptable and useful way of quoting a large amount of text; I did that with nearly every reference I added to this page. Seppi333 (Insert 2¢ | Maintained) 18:20, 1 November 2014 (UTC)[reply]

In the event it's not obvious, there's a WP:POV issue with expanding sections excessively by adding blockquoted text like this - it adds excessive coverage to subtopics that should not have that much WP:weight placed upon them. So, I actually can delete large amounts of text that give undue weight to a topic like that. Seppi333 (Insert 2¢ | Maintained) 18:20, 1 November 2014 (UTC)[reply]

Tova Hella It will be much more helpful if you describe specific changes that you object to rather than WP:JDL. And BTW he did describe exactly what he planned to do almost 2 months before he did it and no one voiced any objection or responded to his notice in any way during those 2 months, making the complaint about "massively editing the article without prior discussion" a little incomprehensible. The article was a nightmare of statements supported solely by sources that do not meet Wikipedia's quality standards for medical content (please see WP:MEDRS) prior to Seppi's cleanup, and I fully support what he has done. Formerly 98 (talk) 06:20, 2 November 2014 (UTC)[reply]

--83.80.250.145 (talk) 19:30, 22 August 2014 (UTC) Hallo,[reply]

What I miss in most drug-related texts is the "set". By this I mean to say that it is very important who is taking the drug and under which circumstances. In some cases the effect of the drug can be detrimental and long-lasting. It is like the Jellinek Clinic in Holland in former website articles said: You are your own laboratory rabbit!

Sincerely,

J.P. Clifford

At the beginning of the section MDMA#Long-term effects on serotonin and dopamine, there is a red link that goes to serotonin reuptake transporter. Corresponding articles already exist at serotonin and reuptake transporter (which redirects to monoamine transporter), and it could be fixed. 50.32.195.213 (talk) 23:49, 26 August 2014 (UTC)[reply]

Done AlanS (talk) 03:00, 27 August 2014 (UTC)[reply]

119.93.155.200 (talk) 01:59, 3 September 2014 (UTC)[reply]

You have not specified an edit and I have therefore closed the request. - Camyoung54 ^talk 02:56, 3 September 2014 (UTC)[reply]

First paragraph, second and third lines need to be changed...they confuse ecstasy, pure MDMA, and Molly

MDMA is a chemical.

Molly is **PURE** MDMA that is made to be used as a recreational drug.

Ecstasy is **adulterated** MDMA, usually "cut" with methamphetimines, cocaine, acid, or cheap heroin

MDMA = chemical

Molly = pure MDMA as a recreational drug

Ecstasy = adulterated MDMA — Preceding unsigned comment added by 71.222.52.34 (talk) 19:03, 5 September 2014 (UTC)[reply]

I guess I'm aging myself here, but as I knew things 15 years ago in Los Angeles, "Molly" meant MDMA powder (presumably relatively pure) and "Ecstasy" (or "E" or "X" or "XTC" or whatever) meant pressed MDMA pills (again, presumably relatively pure). Today, "Ecstasy" (et al) means just about anything, and "Molly"... well, I'm not really sure what that means. "MDMA" and/or "3,4-methylenedioxymethampehtamine" is a very distinct and clear representation. Anything else is just an uncited street name, whose meaning can vary widely by location. Still, "Ecstasy" has pretty much always implied "MDMA". Sources for/against would be welcome. Simishag (talk) 18:58, 17 October 2014 (UTC)[reply]

2.197.50.141 (talk) 20:05, 28 October 2014 (UTC)[reply]

The "research"-paragraph is biased to the point of being blatantly wrong. The research on MDMA - and especially MDMA as an adjunct in psychotherapy - is divided into proponents and repudiators, with not much common sense in the middle ground. At the moment the paragraph pretty much relies on the papers of one scientist (A.C. Parrott) who is known as a radical prohibitionist and alarmist when it comes to psychoactive substances (while actually being clueless about psychotherapy). He has devoted much of his academic career to literally "fight ecstasy". That is not to say that his position is invalid but simply that his position is unbalanced - he simply has the position of a researcher on the adverse effects of "Ecstasy"-abuse.

The state of the research on MDMA in psychotherapy is not so dubious as the paragraph implies. This also includes the dangers associated with clinical application of MDMA. There is sufficient published high quality info on those topics to give a more balanced view on those issues. Unfortunately I have no time for working on this... :( — Preceding unsigned comment added by 2.197.50.112 (talk) 10:59, 28 October 2014 (UTC)[reply]

There's two reviews in the article that cover the therapeutic use of MDMA. The second one - PMID 24648791 - is slightly older and authored by a different individual, but takes essentially the same position. It's not cited in that section though. Seppi333 (Insert 2¢ | Maintained) 12:57, 28 October 2014 (UTC)[reply]

2.197.50.141 (talk) 20:05, 28 October 2014 (UTC) You write: "takes essentially the same position". And there's the problem ;). There are fundamental differences between abuse oriented/forensic/pathogenetic - that is: naturalistic - investigations on Ecstasy and experimental (sic!) clinical trials with MDMA (iirc H. Sumnall has written on this issue). These problems have nothing to do with ideology but control over variables and quality of data. Unfortunately a few researchers do not seem to recognize these problems. And then there is also a "pathology in -> pathology out" principle. F. Vollenweider et al. as well as D. Nutt and R. Carhart-Harris (all of them quite renowned researchers in their fields) have conducted extremely well controlled clinical studies and have not found evidence for neuronal damage - let alone functional deficits. The same goes for the few but also well controlled therapeutical studies with MDMA. Btw: The studies conducted [NOT by MAPS-staff but sponsored] by MAPS were designed and conducted as RCTs, however it is obviously not possible to 100% successfully double blind trials with strong psychoactive substances - I won't bother looking it up but the blinding-rate was still not as bad as one might think (they were definitely not "unblinded"). In the Oehen-study (the one that "failed to demonstrate a statistically significant effect" - the inclined reader may have a look at the number of subjects and effect sizes!..) an active placebo has been used to tackle that issue - a strategy that carries its own problems. Ad effect sizes: Did the author of this paragraph actually read and understand the Mithoefer studies?![reply]

Don't get me wrong: There is no doubt that there is pre-clinical and (some) naturalistic evidence that chronical and/or high dose MDMA-abuse is detrimental to mental health and functioning. However there is also evidence that controlled application of 2-3 known doses of pure MDMA does not cause detrimental effects - not even a significant "hangover" btw [and besides healthy subjects we are also talking about extremely vulnerable treatment resistant PTSD-patients here]. (Research on) abuse of Ecstasy and clinical application of MDMA has to be treated differently for methodological reasons.

You see: I tend a little bit to the proponents-side of the spectrum... ;) Hey I could rewrite the paragraph in the same style it is written now but with unlike signs and it would sound like MDMA could be the second coming materialized in a substance... ;) -> As it is now it is just not scientific. It is actually misleading and simply wrong in some points (I refrain to say: "lies"). Summarizing the literature I could also say that it actually reflects a position that is increasingly on the fringe.

Unfortunately research in this field almost always comes with a "spin". There is always ideology involved. Maybe describing both sides would be helpful. 2.197.50.141 (talk) 20:05, 28 October 2014 (UTC)[reply]

I'm not sure what your issue with the language in that section is given your argument. Parrott argues that MDMA does have efficacy based upon the Mithoefer study; the section reflects this by stating it has limited efficacy. That study didn't examine the presence of neurotoxicity or functional impairments in memory in the study participants. In any case, this article can't make medical statements without a medical review supporting a particular claim. Seppi333 (Insert 2¢ | Maintained) 15:03, 30 October 2014 (UTC)[reply]

5.168.234.124 (talk) 19:13, 30 October 2014 (UTC)[reply]

OK; /my/ issue is, that it reflects an academic position, which I oppose. Actually it reflects the position of an author I actually refuse to cite in my own work as he, in my opinion, has a few times too often crossed the line of scientific depiction towards "moral" founded fear mongering, using the means of exaggeration and misrepresentation. (Despite doing valuable work in some cases.)

However it's not just me to make up this academic controversy, it's been going on for I think over 20 years - and much of it is published (caveat emptor this, caveat emptor that, response to this, response to that). This controversy should be reflected in the article.

/My/ second issue is that I - at the moment - have no time to cite (INCLUDING Parrott ;)) the sh** out of the topic and rewrite the paragraph towards a more balanced representation. Neither do I have time to write and publish a review during the next few days. ;)

Right now the lay reader will read the paragraph and think "some hippie organization is doing pseudo science to find a reason to do drugs. And drugs make holes in your brain." Which is a misrepresentation.

ad "limited efficacy": I wouldn't call an effect size of 1.24 in treatment resistant patients "limited efficacy".

ad "didn't examine [...] functional impairments": Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Paced Auditory Serial Addition Task (PASAT) and Rey-Osterrieth Complex Figure (RCFT)were applied with no significant differences between the 2 experimental conditions. This is in line with every other clinical RCT applying MDMA in a way that would be therapeutically useful.

Examining "the presence of neurotoxicity" in vivo is not possible (afaik!).

ad "unblinded" (as in the paragraph): the Mithoefer studies had a gold standard design. Because this is what you have to do in phase II clinical research. Blinding did not really succeed because there is no way [smart people spent a lot of time thinking about that problem] to conduct a study like that in a methodologically bullet proof fashion.

...there are no "safe medical treatments" btw. MDMA is no wonder drug and no silver bullet and it comes - like any other (psychiatric) medication/intervention - not without risks and side effects - but quite a few experts in the field came to the conclusion that the benefits outweigh the risks. Increasing evidence shows that, as an adjunct to psychotherapy, it can be applied effectively and without detectable harm to the patients. More research is indicated.(<- this is also a valid position, but some might not want to hear it because of reasons that are not to be found in the realms of science&medicine...unfortunately the field is as complex as it is biased. :/ Things would be fundamentally different if MDMA would have been developed - say - last year.)

I hope my position is clearer now. I'm bowing out.

5.168.234.124 (talk) 19:13, 30 October 2014 (UTC)[reply]

Human in vivo neuro-toxicity/plasticity studies are performed via neuroimaging, often as functional- and/or structural-MRI. Based upon the names of those tests, I gather none of them examine functional impairments in memory. I'm not entirely sure an uninformed lay-reader is going to take such a general interpretation about all psychoactive drugs from that paragraph. The only thing one can logically infer from reading this article is that MDMA is a direct neurotoxin to human 5-HT neurons and has no current approved medical uses. That fact doesn't necessarily mean it's not suitable for some form of medical use in the future - e.g., methamphetamine is a direct human DA neurotoxin, yet it's a US schedule 2 prescription drug (and its levorotatory enantiomer is actually OTC...).
Nonetheless, I suppose I'll rework the language of that section over the weekend to make this clear. Seppi333 (Insert 2¢ | Maintained) 02:31, 31 October 2014 (UTC)[reply]

217.200.150.57 (talk) 11:23, 31 October 2014 (UTC) scnr. 1. Sorry, maybe I misunderstood, but I question your competence if you honestly think the neurotoxic effects of 3 [or make it 300..] doses of MDMA can be seen via any form of functional [let alone structural...seriously?!] imaging in a sample of 20 clinical patients. That's a massive misjudgement of both the capabilities of MRI and the damage associated with even tremendous MDMA-abuse. Maybe I should introduce a few numbers here: MDMA-psychotherapy is conducted with 3 doses of 125mg/~2mg/kg (at Max.; this would be the 'full dose' in regards to psychoactivity) with weeks between doses; 5-HT neurotoxicity in pre-clinical studies can be demonstrated with regimens in the range of 10-20mg/kg [sic] IV, twice a day for 4 to 10 consecutive days; functional impairments in humans have been shown in users with hundreds to even thousands of expositions with Ecstasy (which can be pretty much anything) in completely uncontrolled settings - and with associated lifestyles. It is an obvious fact that Ecstasy-abuse (high dose and high frequency) is detrimental to mental health - no doubt. However the rationale of "this medicine is not safe because it is neurotoxic and must not be applied" completely disregards the basic principle of toxicology: "dosis facit venenum." Given the apparently high efficacy of the intervention, this rationale is unscientific and immoral (!) in my opinion.[reply]

2. Dude, /any/ of those tests measure some sort of memory function. That's why they were performed. How stupid do you think those researchers are? (like: "Hey our paradigm is controversial because there is evidence it could impair memory - let's just not measure that...^-^")

3. The question why MAMP and a whole range of other well-known neurotoxic amphetamines (along with Benzodiazepines) with no curative value whatsoever, are widely prescribed (especially) in the US is quite interesting; also the question on why ethanol, which is toxic to pretty much any structure in the human body (including and especially neurons), is freely available; or the questions regarding SSRIs' efficacy, side effects and withdrawal syndrome; and so on........those questions have nothing to to with the current topic besides pointing to the fact on how hypocrite this controversy is led. 217.200.150.57 (talk) 11:23, 31 October 2014 (UTC)[reply]

User 217:

Please restrict your comments to the content of the article if you want to be taken seriously here. Personal remarks are not appreciated, are against policy, and do not foster consensus development.

I am inclined to agree with you regarding the non-significant toxic effects of limited MDMA dosing. But I disagree strongly with your statement about high efficacy. What we have in this case is a result that is a priori unlikely, obtained by biased investigators in a small, unblinded trial. As a biotech investor, this is the kind of thing that I actively seek out in publicly traded companies as a prime shorting opportunity, as such results hold up in larger, better designed trials less than 5% of the time. Realistically I don't think this trial even belongs in the article. Formerly 98 (talk) 13:30, 31 October 2014 (UTC)[reply]

I stopped reading after the first two sentences of your reply; I've changed my mind - I'm not going to waste my time this weekend reworking that section. The article is fine as is; must feel great knowing such an incompetent editor rewrote an article on a topic near and dear to your heart, right? Seppi333 (Insert 2¢ | Maintained) 16:18, 31 October 2014 (UTC)[reply]

2001:62A:6:1:0:0:0:13 (talk) 22:56, 31 October 2014 (UTC) I should have bowed out, when it was time. ;) Sorry for going over the top Seppi! Seriously. @Formerly: Thanks for your comment! There are huge and unsolved methodological problems in this field. The problem is that those studies neither follow a pharmacological paradigm nor can they be investigated with the means of classic psychotherapy research (you see the results). The very nature of the paradigm brings with it that there are numerous confounders that cannot be controlled, that investigators must necessarily be biased [as in: /believe/ that the intervention is working. We're talking about psychotherapy here and the biggest factor of efficacy is still the therapist.] to do this kind of therapy at all and that blinding is simply impossible. However there is a lot of anecdotal evidence of unlikely or sometimes even miraculous results (acquired in formal settings), which is scientifically absolutely useless but motivates many. I suggest that we let this cool down for some time. If I find time to rewrite the paragraph I will post a proposal here. 2001:62A:6:1:0:0:0:13 (talk) 22:56, 31 October 2014 (UTC)[reply]

I might over the next few days add stuff like bits of research and a few paragraphs in regards to MDMA's perceived risk level here and there to 'balance' this article out, since, for the most part, it seems to cherry-pick negative research a bit too much. The actual knowledge we have of MDMA seems to be for the most part uncertain since (to my understanding) there's not enough research being done with it due to its prohibited status.

What I'm trying to say is that most researchers are not certain about what MDMA's effect on the body truly is as of yet... while its neurotoxicity is undeniable, the actual harm that the drug poses to users is less well known and basing the whole article on a few bits of negative research here and there (when there's other research contradicting the research cited in this article) seems to violate the expected neutrality of this article.

The truth is that we don't know how much MDMA harms users and in what way, as other users have mentioned in this talk page, and for the article to say with certainty that MDMA is absolutely known to be harmful is just as fallacious as an article saying that MDMA is absolutely known to not cause any lasting harm: after all, there's not enough research to prove things either way (and the truth probably lies somewhere in the middle).

I therefore think it's important to cite more research that has been done with MDMA and to make it clear in the article that we just don't know what's going on as far as permanent harm goes with this substance, to state otherwise is misleading. It seems to me like there's a lot of cherry picked data here. --Ugriffin (talk) 17:52, 6 November 2014 (UTC)[reply]

As long as it's encyclopedic and your source(s) satisfy WP:MEDRS, you can add whatever you like. Most of the new refs are free; although if you don't have access to a new WP:paywalled one that I added, I can upload it for you. Seppi333 (Insert 2¢ | Maintained) 05:26, 7 November 2014 (UTC)[reply]

What's wrong with this article now? It seems so biased in the negative way. It's more negative than heroin, MDA and many other articles about more dangerous psychoactive substances. Previous versions wasn't perfect but much better. According to this article, those my friends, who has taken this substance, would be permanently retarded and addicted to it. If MDMA has neurotoxicy, it's subtle and more theoretical, and it's addiction in reality is nowhere the same as amphetamines because of serotonin depletion (users are unable to get high taking MDMA 3 days at row). Yes, MDMA can be addictive, but in completly different way. There is a reason, why Lancer ranked ecstasy as less dangerous substance than amphetamine and cannabis.

Why overdose effects section looks so large in comparision to recreational effects section? Overdose is a result of uncommon use of substance and is very rare.

--217.24.78.169 (talk) 10:56, 8 November 2014 (UTC)[reply]

Completely agree with you. MDMA is a panacea for all known human diseases. Seppi333 (Insert 2¢ | Maintained) 05:01, 9 November 2014 (UTC)[reply]

No, but MDA is. In MDA article neurotoxicity isn't even mentioned. --217.24.78.169 (talk) 10:15, 9 November 2014 (UTC)[reply]

Maybe, at least, there should harm reduction section. For example, that taking MDMA no more than 4 times a year user can greatly minimize neurotoxicy. Most people don't even now this and try to abuse this drug as amphetamine. Especially, that you in Wikipedia article compare it so much to other stimulants (that dopamine diagram, uh). Who, in reality, snort this drug like cocaine day after day? That is definitely the way to gain some permanent disabilities.

This article is all about pharmacology activity and how it SHOULD affect people. But there is no psychological, behavior information, how actually people are affected. Of course, social researches isn't valid for you, because most people is stupid in pharmacology, they are tricked and they just don't know, how they should react to this substance. Especially, in this case, where pharmacology and neurotoxicy isn't fully understand. --217.24.78.169 (talk) 10:15, 9 November 2014 (UTC)[reply]

There's no information in the article on its psychological and behavioral effects in a clinical setting because research into its medical use is still in its infancy; there have been a handful of relatively small trials with this drug. That's why medical reviews are calling for more clinical trials to determine its degree of efficacy and effects. On another note, everything in this article on neurotoxicity and neuroplasticity cites observational evidence in humans, not a theoretical model or animal studies. Seppi333 (Insert 2¢ | Maintained) 15:10, 9 November 2014 (UTC)[reply]

Millions of people take MDMA every weekend and somehow very few of them are harmed -- but the Wikipedia page is all about harm, harm, and more harm. Perhaps it's because a US agency with a complete drug-war bias has funded hundreds of millions of dollars' worth of studies into potential harms of MDMA -- thus lots of published papers are all about harms -- thus there are lots of ways to cite many different studies about harms. But harm is by far the abnormal situation with MDMA; the vast majority of its users are never harmed.

It would be as if the Aspirin page spent 4/5ths of its text on bad side effects of Aspirin. But it doesn't. Or if the page on Stairs was all about injuries. But it isn't; in fact, it barely mentions them despite stairs being the cause of millions of injuries and 12,000 deaths per year in the United States. (see 2012 NEISS Highlights and search for Stair).

And why does the page include an almost completely irrelevant and overdetailed huge colorful diagram of some kind of brain chemistry, apparently coming out of this "psychostimulant addiction" template that doesn't even reference MDMA? MDMA is generally not considered an addictive drug! Alta Mira Recovery's list of most addictive drugs does not even include MDMA; various citations about addictive drugs see it as low in addictive risk.

Image+refs

Signaling cascade in the nucleus accumbens that results in psychostimulant addiction Note: colored text contains article links. Nuclear pore Nuclear membrane Plasma membrane Cav1.2 NMDAR AMPAR DRD1 DRD5 DRD2 DRD3 DRD4 Gs Gi/o AC cAMP cAMP PKA CaM CaMKII DARPP-32 PP1 PP2B CREB ΔFosB JunD c-Fos SIRT1 HDAC1 [Color legend 1] This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methamphetamine, and phenethylamine. Following presynaptic dopamine and glutamate co-release by such psychostimulants,[1][2] postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP-dependent pathway and a calcium-dependent pathway that ultimately result in increased CREB phosphorylation.[1][3][4] Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-Fos gene with the help of corepressors;[1][5][6] c-Fos repression acts as a molecular switch that enables the accumulation of ΔFosB in the neuron.[7] A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for 1–2 months, slowly accumulates following repeated high-dose exposure to stimulants through this process.[5][6] ΔFosB functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.[5][6]

References ^ a b c Renthal W, Nestler EJ (September 2009). "Chromatin regulation in drug addiction and depression". Dialogues in Clinical Neuroscience. 11 (3): 257–268. doi:10.31887/DCNS.2009.11.3/wrenthal. PMC 2834246. PMID 19877494. [Psychostimulants] increase cAMP levels in striatum, which activates protein kinase A (PKA) and leads to phosphorylation of its targets. This includes the cAMP response element binding protein (CREB), the phosphorylation of which induces its association with the histone acetyltransferase, CREB binding protein (CBP) to acetylate histones and facilitate gene activation. This is known to occur on many genes including fosB and c-fos in response to psychostimulant exposure. ΔFosB is also upregulated by chronic psychostimulant treatments, and is known to activate certain genes (eg, cdk5) and repress others (eg, c-fos) where it recruits HDAC1 as a corepressor. ... Chronic exposure to psychostimulants increases glutamatergic [signaling] from the prefrontal cortex to the NAc. Glutamatergic signaling elevates Ca2+ levels in NAc postsynaptic elements where it activates CaMK (calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5. Figure 2: Psychostimulant-induced signaling events ^ Broussard JI (January 2012). "Co-transmission of dopamine and glutamate". The Journal of General Physiology. 139 (1): 93–96. doi:10.1085/jgp.201110659. PMC 3250102. PMID 22200950. Coincident and convergent input often induces plasticity on a postsynaptic neuron. The NAc integrates processed information about the environment from basolateral amygdala, hippocampus, and prefrontal cortex (PFC), as well as projections from midbrain dopamine neurons. Previous studies have demonstrated how dopamine modulates this integrative process. For example, high frequency stimulation potentiates hippocampal inputs to the NAc while simultaneously depressing PFC synapses (Goto and Grace, 2005). The converse was also shown to be true; stimulation at PFC potentiates PFC–NAc synapses but depresses hippocampal–NAc synapses. In light of the new functional evidence of midbrain dopamine/glutamate co-transmission (references above), new experiments of NAc function will have to test whether midbrain glutamatergic inputs bias or filter either limbic or cortical inputs to guide goal-directed behavior. ^ Kanehisa Laboratories (10 October 2014). "Amphetamine – Homo sapiens (human)". KEGG Pathway. Retrieved 31 October 2014. Most addictive drugs increase extracellular concentrations of dopamine (DA) in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), projection areas of mesocorticolimbic DA neurons and key components of the "brain reward circuit". Amphetamine achieves this elevation in extracellular levels of DA by promoting efflux from synaptic terminals. ... Chronic exposure to amphetamine induces a unique transcription factor delta FosB, which plays an essential role in long-term adaptive changes in the brain. ^ Cadet JL, Brannock C, Jayanthi S, Krasnova IN (2015). "Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: evidence from a long-access self-administration model in the rat". Molecular Neurobiology. 51 (2): 696–717 (Figure 1). doi:10.1007/s12035-014-8776-8. PMC 4359351. PMID 24939695. ^ a b c Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews Neuroscience. 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the c-fos gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression. Figure 4: Epigenetic basis of drug regulation of gene expression ^ a b c Nestler EJ (December 2012). "Transcriptional mechanisms of drug addiction". Clinical Psychopharmacology and Neuroscience. 10 (3): 136–143. doi:10.9758/cpn.2012.10.3.136. PMC 3569166. PMID 23430970. The 35-37 kD ΔFosB isoforms accumulate with chronic drug exposure due to their extraordinarily long half-lives. ... As a result of its stability, the ΔFosB protein persists in neurons for at least several weeks after cessation of drug exposure. ... ΔFosB overexpression in nucleus accumbens induces NFκB ... In contrast, the ability of ΔFosB to repress the c-Fos gene occurs in concert with the recruitment of a histone deacetylase and presumably several other repressive proteins such as a repressive histone methyltransferase ^ Nestler EJ (October 2008). "Transcriptional mechanisms of addiction: Role of ΔFosB". Philosophical Transactions of the Royal Society B: Biological Sciences. 363 (1507): 3245–3255. doi:10.1098/rstb.2008.0067. PMC 2607320. PMID 18640924. Recent evidence has shown that ΔFosB also represses the c-fos gene that helps create the molecular switch—from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure

Is some anti-drug bigot getting paid to manipulate Wikipedia articles? Gnuish (talk) 23:57, 10 November 2014 (UTC)[reply]

This anti-drug bigot uses amphetamine on a daily basis (so all substituted amphetamines are bad, mmkay?) and drew that image, which is based upon amphetamine's signal transduction. If you don't know why accumbal ΔFosB induction by MDMA (as noted in PMID 16957076) makes it an addictive drug, perhaps you should read ΔFosB (would also be worth knowing the definition of an "addictive drug"). Amphetamine and MDMA have common pharmacodynamics in DA neurons (actions at TAAR1, VMAT2, DAT); the only thing that varies is affinities to targets, which means that pathway reflects MDMA at sufficiently high doses as well.

If MDMA didn't have a mountain of evidence on its adverse neurocognitive effects, the article wouldn't have a section on that. In any event, I frankly really don't care about the "harm potential" of any drug; papers on that topic are basically subjective rants for or against drugs that try to push a policy position for legalization or regulation. I don't give an iota of a fuck about MDMA's legality (or drugs in general), but I do about the accuracy of medical information on MDMA. Nothing is going to change in the adverse effects or overdose sections, because that content is accurate and non-subjective.

I'm not going to bother arguing about this - I've said all I have to say. Seppi333 (Insert 2¢ | Maintained) 01:32, 11 November 2014 (UTC)[reply]

Most MDMA use habits happen because of MDMA activity on serotonin receptors. MDMA affects dopamine receptors, but dopamine role is onlf secondary. if amphetamine and MDMA is so similiar so why exactly EMCDDA annual reports shows that each year there is 20 times more amphetamine users in drug addiction treatment than MDMA users? You don't even mention that kind of data. This article is just your pharmacological interpretations. I won't argue more, because there will definetly be other people who will do this, and this article will be changed. --91.188.45.39 (talk) 17:35, 12 November 2014 (UTC)[reply]

Facepalm Seppi333 (Insert 2¢ | Maintained) 18:09, 12 November 2014 (UTC)[reply]

Recently flagged this for Neutrality issues. This article cites reviews from psychiatrists and psychologists cherry-picking many sources of medical data to present specific worldview, and are not ordinarily qualified to interpret such vast quantity of data outside of their respective fields as experts. Most of the data they look at has been agreed to be inconclusive within the scientific community. Furthermore, it appears that legitimate data has been erased from the article. The article itself seems to cherry-pick studies without the corresponding follow-ups and reviews to those studies in order to paint a specific agenda. The overall quality of many drug and health sections on wikipedia have since been, consequently, negatively impacted. The drug sections seem to incite panic and do not provide a rational understanding of the current available data. In order for Wikipedia articles to be taken seriously over the future, a more balanced approach is needed on these hot-topic issues as many are featured as the lead article on Google, even if they are not featured on Wikipedia.
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