Talk:MDMA/Archive 5

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)

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

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

"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)

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)

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.

talk

) 12:39, 17 October 2014 (UTC)

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)

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)

Take a look at

talk

) 13:32, 17 October 2014 (UTC)

I'd also suggest taking a look at

talk

) 14:49, 17 October 2014 (UTC)

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)

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)

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

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

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)

Read the highlighted text.

If you feel we're overzealously enforcing

WT:MED#3,4-Methylenedioxymethamphetamine merge. Seppi333 (Insert 2¢ | Maintained

) 12:47, 18 October 2014 (UTC)

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)

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)

MEDRS is not just a policy of the Medicine Project, but of Wikipedia overall. Take a look at WP:RS

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)

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.

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)

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

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

This edit request has been answered. Set the |answered= or |ans= parameter to no to reactivate your request.

At the beginning of the section

) 23:49, 26 August 2014 (UTC)

Done

talk

) 03:00, 27 August 2014 (UTC)

term of mdma

This edit request to MDMA has been answered. Set the |answered= or |ans= parameter to no to reactivate your request.

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

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

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)

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)

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

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)

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)

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?!

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)

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)

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

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)

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)

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.

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)

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.

talk

) 13:30, 31 October 2014 (UTC)

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)

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)

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)

As long as it's encyclopedic and your source(s) satisfy

WP:paywalled one that I added, I can upload it for you. Seppi333 (Insert 2¢ | Maintained

) 05:26, 7 November 2014 (UTC)

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

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

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

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)

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)

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 v t e 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 nuclear factor kappa B), it induces an addictive state.[5][6]

References ^ 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 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. PMID 24939695 . ^ 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 ^ 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 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)

This anti-drug bigot

VMAT2, DAT

); the only thing that varies is affinities to targets, which means that pathway reflects MDMA at sufficiently high doses as well.

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)

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)

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

I have to agree with some of the sentiment that User:Seppi333 has taken over this article (and others besides), and imposed his/her opinions upon it. This edit, I think, is at the heart of the matter. If you are really as informed as you say you are, Seppi333, then you will know that any chemical can be neurotoxic at a high enough dose. I haven't had the time to look at all the studies you have brought to bear on this topic, but I am confident none of the studies showing histological evidence for MDMA neurotoxicity on particular receptor systems used human subjects. You should likewise know that the doses used in most animal studies are well in excess of typical recreational doses, and orders of magnitude above the subjective threshold dose. It's interesting that you disclose that you use amphetamines on a daily basis, and I can't help but thinking you might want to dial back the dose a bit. You are coming across as a bit manic. You keep insisting that you "don't give an iota of a fuck about MDMA's legality (or drugs in general)", but it is apparent that you care a lot about amphetamine drugs in general. I question your open-mindedness and scholarship. The pharmacodynamics of MDMA and pure amphetamine are not as similar as you make it sound. There is abundant evidence that MDMA is much more serotonergic than amphetamine. But that is another topic. I don't think "neurotoxic" should be the first descriptor of MDMA. As I've mentioned, the dose makes the poison. Furthermore, exitotoxiticy is mostly the result of glutamate, and even more proximally, Ca2+ ions. Now go change the article on Calcium to say: "Calcium is a neurotoxic element with atomic number 20." Cheers, -92.24.98.107 (talk) 16:49, 25 November 2014 (UTC)

Actually the animal toxicology studies are quite relevant and are comparable to those required by the FDA as part of prescription drug development and included in the package inserts of prescription drugs. And yes, they are always done at higher doses that human subjects would ever be exposed to in order to establish a margin of safety and pick up effects that would be too rare to pick up if the dose was limited to those actually encountered in people. The drug will be used by hundreds of thousands of people, and it is not practical to do animal toxicology in more than a few hundred animals. The physiological effects are observable on imaging studies, and the receptor studies you propose cannot be performed in human subjects (few are willing to volunteer for a study that requires donation of brain tissue). This is all pretty much standard toxicology.

An important difference between calcium neurotoxicity and MDMA neurotoxicity is that the calcium toxicity is secondary to head injury or stroke. And the calcium has to be there for function. MDMA is not required for function, and shows toxic effects in the absence of other insults. The comparison is really not even close.

We have asked for an outside opinion on this from an agreed upon neutral third party, and that person largely confirmed Seppi's conclusions. If you like, we can do an RFC at the Medicine Project, but I don't think it will go the way you want it to. The literature seems pretty clear on this issue.

talk

) 18:00, 25 November 2014 (UTC)

Er...I've pointed out MDMA is a direct neurotoxin; you're referring to an indirect neurotoxin (a toxin with a threshold). I've pointed out that I don't care about MDMA's legality exactly once, not repeatedly; although, in fact, I don't care about the legal status of drugs in general. If people want to be retarded and take a brain-borking substance, that's their prerogative IMO. (Now you can say I've said it repeatedly)

Btw: the obvious reason why MDMA has more affinity for serotonergic systems than amphetamine is that it has more affinity for SERT than DAT/NET relative to amphetamine, which allows it to access and bind to TAAR1 more readily within 5-HT neurons. You'd know that if you actually read TAAR1, in which I wrote an entire paragraph explaining that property of TAAR1 agonists. Seppi333 (Insert 2¢ | Maintained) 23:09, 25 November 2014 (UTC)

"I'm not even remotely interested in its legal status and don't even want to edit content on that". See, the problem is how sure you are of yourself, and I think, the literature. Most of the studies you cite are US government funded, obviously designed to show toxicity and other harm. Formerly 98 says human imaging studies can establish the specific neurotoxicity of a particular chemical! Ha. As Seppi333 would say "facepalm". There are so many confounds. People who use MDMA usually use a bunch of other drugs and typically don't have the healthiest lifestyles. Seeing volumetric or connectivity abnormalities in fMRI of some drug abusers is poor evidence. And, with respect, I know about the difference between direct and indirect toxicity, and the point that dosage is essential to that characterization still stands. Plus, the direct vs. indirect distinction is a bit messy anyway. Pure water is neurotoxic because it is extremely hypotonic. Inject a massive amount of pure H20 into someone's carotid artery and it will kill them very rapidly. Now is this effect direct or indirect? If it weren't for the high ion concentration inside the cells, the water wouldn't be toxic, this would imply indirect, the ions are directly responsible for the cell lysis. But wait, without the ions the cells don't function at all. And the same argument can apply to pH requirements of living cells, glutamate, calcium, ethanol, any chemical you can name. I'm fine with the article having neurotoxicity as a duly weighted section or subsection, it can even be mentioned in the lead. However placing the word neurotoxic as the first descriptor in the lead sentence is ridiculous. Personally, I don't think "empathogenic" should be in the first sentence either. What a joke. That term harkens to a day of alchemy and love potions. Just call it what it is, "...an amphetamine-class drug that acts primarily on serotonergic and dopaminergic neurotransmitter systems in the brain. It is used recreationally for euphoriant and empathogenic effects. Research has show that it can be neurotoxic and addictive." -92.24.81.232 (talk) 10:36, 26 November 2014 (UTC)

I've been watching this discussion. This is probably the last post like this that i'll allow to stand - future ones will be deleted. 1) Per the

wall of text. And please consider getting an account. There are several IP addresses active here and I for don't know if they are one person or several. Thanks. Jytdog (talk

) 11:57, 26 November 2014 (UTC)

The lead sentence has been the topic of both (the two more recent ip posts in this thread) my comments. It just happens that one contributor in particular seems to be very adamant that we eschew the style of basically all other articles on psychoactive drugs on WP and lead with "MDMA is a neurotoxin". Of course there are dozens of studies that show some neurotoxic effect from MDMA, and said contributor cited many of them, making critique of those studies an overly laborious task. But, for example, "Single oral doses of 125 mg and 75 mg of 3,4-methylenedioxymethamphetamine, 40 mg of amphetamine, and placebo were given." -Mas M et al; J Pharmacol Exp Ther 290 (1): 136-45 (1999). In this study, the control dose of amphetamine was half the size of the smallest MDMA dose. There are similar methodological problems with every paper cited about neurotoxicity. Is MDMA neurotoxic? Yes, I have no doubt that it is. Should neurotoxicity be discussed in this article? Absolutely. Does it make any sense to describe MDMA primarily as a neurotoxin, as if that is it's intended use? No. It doesn't. And that isn't 'just my opinion'. Look at the first sentence of the introduction of any paper ever published on MDMA and if one of them reads: "MDMA is a neurotoxin..." or "MDMA is a neurotoxic..." then you might have a point. As it is now, this is an advocacy essay, not an encyclopedia article. It diminishes the credibility of all the valuable info presented below when the lead is structured as it is. -92.24.81.232 (talk) 14:13, 26 November 2014 (UTC)

the article doesn't cite " J Pharmacol Exp Ther 290". Please discuss content and sources that are actually in the article. Thanks. Also, if your point is about the lead, let's discuss the lead. If your point is to claim that the content and sources don't support the neurotoxicity of MDMA, let's discuss that. Jytdog (talk) 13:26, 27 November 2014 (UTC)

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. --Fiveonfive (talk) 00:49, 15 November 2014 (UTC) @

@

Formerly 98:, OK, I hope you guys take it in the right direction --Fiveonfive (talk

) 01:55, 15 November 2014 (UTC)

The most recent and largest high-quality study from Harvard University[1], funded by the National Institute on Drug Abuse for $1.8 million dollars, found the following:

"Findings- We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic self-regulation, possibly reflecting increased impulsivity. However, this finding might have reflected a pre-morbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug."

"Conclusions- In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings—including our own—and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users."

This is the highest quality neurological/cognitive study of the subject to date.

--Fiveonfive (talk) 06:55, 15 November 2014 (UTC)

The two most common sources Parrott AC (2014)^[2] and Meyer JS (2013)^[3] cited in this article do not by themselves or together validate any theory that neurotoxicity arises from common mdma use. For the subject of neurotoxicity, the Parrott review focuses on a study of lower quality than that of the Harvard study, on interviewing poly-drug users whereas the Harvard study isolated sole ecstacy users, via hair testing and verbal confirmation. Unlike in prior studies- Both the control group and the ecstacy group attended raves and danced all night in the Harvard study as well (like I said, the highest quality study to date on the subject matter, commissioned by the National Institute on Drug Abuse). The Meyer review openly suggests that use associated with common dosages among users does not produce neurotoxic effects (Under "Neurotoxicity" in the review "the jury is still out"), which makes it an improperly-used and improperly-read source by he who put it there. This is on top of the fact that this review cites studies of lower methodological quality than that of the Harvard Study.

Here is the full excerpt from Meyer:

"Because animal studies of MDMA neurotoxicity have typically used large and/or repeated drug doses, we may ask whether one or a few modest doses of ecstasy are capable of exerting neurotoxic effects in users. This question has been addressed by several prospective studies of new ecstasy users participating in the Netherlands XTC Toxicity (NeXT) study. The results thus far have failed to show any serotonergic deficits in these low-dose users; however, other abnormalities were found related to brain vasculature and white matter structure. Thus, the jury is still out on whether damaging effects can be produced by consuming even a few ecstasy tablets"

I move to immediately remove language that suggests neurotoxic effects arise in humans from anything but near-death dosages, until any other high quality studies on humans come to light- that have not already been mentioned here.

--Fiveonfive (talk) 10:45, 15 November 2014 (UTC)

Why neutrality template is being constantly removed? Isn't it a vandalism? Neutrality is most definitely disputed. There is multiple persons against one (editor) that says that there is something wrong with this article (so much discussions in previous 2 weeks in the talk page). --217.24.68.165 (talk) 17:00, 15 November 2014 (UTC)

WP:MEDRS

requires us to assess the adherence among experts using secondary sources such as review articles published in peer reviewed journals. We don't assess the quality of primary research ourselves, but wait for review articles to see how the research is assessed by experts.

By these criteria, we probably cannot use the "Latest and Best Harvard Study" at all, let alone to establish consensus expert opinion. It is a primary research paper published in 2011. In the 2012 to 2014 interval, about 60 review articles were published on the subject of MDMA. As near as I can tell, the Harvard paper has not been cited in any of them. (Pubmed has a "this paper has been cited by" function in the lower right of the page).

For the functional tests, I'll leave that to Seppi as I believe those are his additions. But the imaging studies seems to clearly show a neurotoxic effect, and we know from studies of neurodegenerative diseases that frank symptoms often do not appear until neurological damage is fairly advanced. Tt seems very difficult to me to get away from describing this drug as neurotoxic in this article. ::

talk

) 18:30, 15 November 2014 (UTC)

At the very least, please remove the improperly cited source (Meyers JS). That source says the opposite of what it is being used for.

http://en.wikipedia.org/wiki/MDMA#cite_note-current_perspectives-13 --Fiveonfive (talk) 22:14, 15 November 2014 (UTC)

More from the Meyer's review (2013):

"Polydrug Use-

Ecstasy users are almost always users of other substances, including both licit (eg, alcohol and tobacco) and illicit (eg, marijuana, cocaine, methamphetamine, hallucinogens, and opiates). Polydrug use constitutes a major complication for interpreting studies of recreational ecstasy use, as it can be difficult to ascribe the results specifically to repeated MDMA exposure. Some investigators have attempted to deal with this confounding factor by statistically controlling for exposure to other substances of abuse. Another important approach, which is discussed below, is to perform experimental animal studies in which pure MDMA is administered to animal subjects with controlled dosing regimens. Laboratory studies have also permitted an analysis of the acute effects of MDMA in humans; however, simulation of heavy recreational ecstasy exposure cannot be performed for ethical reasons.

Several different patterns of ecstasy polydrug use have been identified. For example, analysis of data from the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) revealed three subtypes of ecstasy users: 1) extensive use of many different drugs of abuse (37% of ecstasy-using respondents); 2) heavy marijuana and cocaine use with moderate use of amphetamines, including ecstasy (29% of respondents); and 3) heavy marijuana use along with a low use of prescription drugs, primarily opiates (23% of respondents). The majority of category 1 respondents were found to suffer from multiple substance-use disorders involving tobacco, alcohol, cocaine, hallucinogens, and/or marijuana. The frequent co-occurrence of ecstasy and marijuana use has been confirmed in more recent studies and, therefore, is of particular concern, as chronic cannabis exposure has been associated with some of the same cognitive deficits and mood changes observed in heavy ecstasy users."

Fiveonfive (talk) 23:15, 15 November 2014 (UTC)

If you read the entire Neurotoxicity section of Meyer's it basically outlines the fact that most of the theories behind neurotoxicity are just that, theory. And yet to be proven. Given only that we have data from lab animals and not humans under the same conditions (with the exception of small samples of poly-drug users), he argues, no reliable conclusion can be made from the existing data. His own conclusion, cited by this article as a source of conclusive evidence, is that the debate is inconclusive, yet the article writes otherwise.. Fiveonfive (talk) 23:43, 15 November 2014 (UTC)

I know you're trying to be reasonable here and all, but I'm still having a hard time seeing your point. You quoted the section:

"Because animal studies of MDMA neurotoxicity have typically used large and/or repeated drug doses, we may ask whether one or a few modest doses of ecstasy are capable of exerting neurotoxic effects in users. This question has been addressed by several prospective studies of new ecstasy users participating in the Netherlands XTC Toxicity (NeXT) study. The results thus far have failed to show any serotonergic deficits in these low-dose users; however, other abnormalities were found related to brain vasculature and white matter structure. Thus, the jury is still out on whether damaging effects can be produced by consuming even a few ecstasy tablets"

I don't think that last sentence really rules out the idea that the drug is neurotoxic, just as the near zero likelihood of getting cancer from smoking 1 cigarette a week for 3 months is an argument that cigarette smoke is not carcinogenic. Its a little hard for me to follow the author's reasoning here: Isn't "abnormalities in white matter structure" a sign of toxicity? It certainly doesn't sound like something that I would want. I think this study could potentially be quoted to say that obvious cognitive deficits were not seen in a short term study of low dose users. I wouldn't want to go a lot further than that unless you find a better reference. Your second quote is a good one in that it points out the confounding issue (these almost always are present to some extent in any tox study other than a randomized clinical trial.) But there are other studies such as:

"A more refined 2010 meta-analysis by Nulsen et al differentiated between tests of short-term and working memory (verbal and visuospatial in both cases) and found that the ecstasy users performed more poorly in all memory domains. Results were significant regardless of whether the control group was composed of non-ecstasy polydrug users or individuals who had not been exposed to any illicit drugs."

Finally, he concludes with

"Although it is not yet clear whether a few MDMA doses are harmful to the user, heavier use has been associated with significant mood changes and cognitive deficits. Another major concern is possible serotonergic dysfunction produced by repeated and/or high doses of the drug."

Thank you for bringing those points up. The first section you referenced, is the last paragraph of the Meyer's review for neurotoxicity as well as it's conclusion on the topic of neurotoxicity. Neither the Meyer study nor the other excerpts you brought up rule out the possibility of neurotoxicity from the subject. They both however say "it is not yet clear" (to quote one of your excerpts) whether it harms the user, for lack of sufficient data to prove one way or the other. This is why I have held that the current scientific consensus is that the topic is "inconclusive". Fiveonfive (talk) 00:07, 16 November 2014 (UTC)

I'm sorry, I didn't see the part about heavier users in your second excerpt. These excerpts are taken from the "Neuropsychological deficits" section however, and related conclusion about neuropsychological deficits specifically, which are separate from the "Neurotoxicity" section. The cognitive deficits described are also discussed in the Neurotoxicity section under that section's context.

--Fiveonfive (talk) 00:53, 16 November 2014 (UTC)

No worries, we'll sort it out.

I must admit I find the organization of the paper odd. If you use a drug and get cognitive deficits as a result, is that not neurotoxicity?

I believe the "unclear" remark you refer to is limited to the case of "a few doses".

In this case we have several lines of evidence of toxicity, including the meta analysis which found a significantly higher level of cognitive dysfunction in MDMA users compared to a control group of non-MDMA polydrug users; 2 prospective studies of new MDMA users; and boatloads of animal toxicology studies. Meyer concludes his article by saying that heavy use is associated with cognitive defects.

If you want to add the sentence I suggested about no cognitive defects seen in short term, low dose users, that is fine with me. Beyond that I think we need to do an RFC and get broader community input. If you want to go that way, I suggest the simple (and I think neutral) wording: "Do reliable medical sources show MDMA to be neurotoxic?" Your thoughts?

talk

) 01:05, 16 November 2014 (UTC)

I do not believe that cognitive deficits are necessarily always equivalent to neurotoxicity, but they are not a positive either.

I like both of your ideas, and agree that an RFC would be a good way forward. I like the wording you chose: "Do reliable medical sources show MDMA to be neurotoxic?".

Out of sheer curiosity, is caffeine considered to be a neurotoxin? I know that it causes cognitive deficits with regards to its effects on dopamine.

Also, some more interesting text from the Meyer review which i'm sure is to complicate the picture even further (finding from animal studies):

"Finally, prior exposure to low-to-moderate doses of MDMA can blunt or even prevent the neurotoxic effects of a subsequent high-dose treatment regimen. It is not yet known whether this effect, which has been termed “MDMA preconditioning,” applies to human recreational ecstasy users."

--Fiveonfive (talk) 05:19, 16 November 2014 (UTC)

Crazy stuff. I think that caffiene would be considered neurotoxic only if there were effects that persisted after the drug was cleared from the system. The RFC process is here https://en.wikipedia.org/wiki/Wikipedia:Requests_for_comment#Before_starting_the_Request_for_comment_process but I am going to bed. If you want to start it great, otherwise I'll do so tomorrow.

Sounds good. I'll let you handle it. As far as neurotoxicity in animals, we should also avoid attributing results of animal studies onto humans as conclusive. See Olney's lesions. Fiveonfive (talk) 05:48, 16 November 2014 (UTC)

We should pick some references to cite in the RFC to make it easy for people. I suggest Myer and Parrott.

talk

) 12:22, 16 November 2014 (UTC)

Do with it as you see fit. I still think that saying it's neurotoxic is jumping to conclusions, as even the bearish medical reviews avoid saying outright that neurotoxicity happens in humans, and only can be proven in animals (with completely different biology) at ultra-high mg/kg doses. There are valid questions to contradictory data- a lot with low methodological quality. The National Institute for Drug Abuse website (government run) avoids mention of the word 'neurotoxicity' anywhere in accordance- normally the most hawkish entity of all and a sure sign the debate is still undetermined. --Fiveonfive (talk) 12:02, 18 November 2014 (UTC)

Alright, I have to admit that I'm feeling a lot less strongly about this than I was a few days ago. If you agree, maybe I'll just ask jytdog to give us a third opinion. He's a medical editor who is very fact oriented, and to the best of my knowledge has no history of editing recreational drug articles or any strong opinions on the subject. You can look at his editing history and let me know what you think.

talk

) 13:26, 18 November 2014 (UTC)

I haven't had much time over the past few days to get on WP, but my thoughts are to just get a 2nd opinion from the uninvolved as suggested. Seppi333 (Insert 2¢ | Maintained) 20:51, 18 November 2014 (UTC)

Jytdog looks solid, and impartial Fiveonfive (talk) 00:38, 23 November 2014 (UTC)

I left a note on his page.

talk

) 02:08, 23 November 2014 (UTC)

hi, i am all flattered. i will do my best to help you! i read the article and its sources, and then I read the discussion above, and it is not clear to me exactly what is being disputed. Is there some particular content that somebody wants to change? if so what and how? thx Jytdog (talk) 02:44, 23 November 2014 (UTC)

Since Seppi edited this, there have been several complaints about the prominent description of MDMA as neurotoxic and/or the extent of its putative neurotoxicity and the weight put on the issue in this article. So we put to you: Is MDMA neurotoxic? Is the toxicity, if present, severe enough to merit the weight put on it in this article?

talk

) 03:58, 23 November 2014 (UTC)

I think it should be expanded to (possibly with it's own section)--- The exact characterization of neurotoxicity in distinctions between animals, humans vs. low, moderate, and high dose users and vs. low, moderate, and high dosage frequencies. The scientific consensus and conclusiveness of the various distinctions described in regards to general and long-term neurotoxicity. What Formerly 98 said also, this is a complicated issue as revealed by our discussion Fiveonfive (talk) 04:25, 23 November 2014 (UTC)

fiveonfive you should have a look at

WP:MEDRS for sourcing (it also talks about style). granted they are both thin for toxicity content, but they nonetheless inform how we write about all health-related matter. we read the best and most recent secondary sources we can find and paraphrase what they say. we do not go at this like it a scientific review article and rehearse all the data - we write for the general reader and we provide the consensus of the field. based on my review of the sources in this article (and i checked to see if there were any newer or better ones), neurotoxicity is probably the most important risk of this drug. (btw it is a powerful drug. there is no drug that isn't toxic and generally the higher the dose and the longer you take it, the more toxic any drug is). based on what i read, there have not been the kind of rigorous phase I/phase II studies you need to get a good handle on the "therapeutic window" (if we can even discuss that for a recreational drug) so we don't know the dosing at which the side effect profile (short term and long term) would be acceptable. and btw, many toxicities are short-lived. the brain is plastic, somewhat. anyway, it is a ~little~ too harsh and too detailed now but not by a lot. if i were to get active on this article i would reduce the size of the adverse section which is laundry-listy and I would get rid of the discussion of animals in the neurotox section too. Jytdog (talk

) 04:56, 23 November 2014 (UTC)

i see. still learning about wikipedia's processes. thanks for the assistance.

looking forward to seeing your balancing of the article and I appreciate your dedication to being impartial, as well as Formerly 98's.

Fiveonfive (talk) 05:47, 23 November 2014 (UTC)

I think that Formerly 98's characterization of the issues presented in this article, are accurate in depicting what most people expressing issues with this article feel. There is also a very small section dedicated to immediate risks,

such as mdma's heat-trapping effect which produces hyperthermia in hot environments that leads to liver failure, kidney and organ failure and possibly death (which is not thoroughly explained as well as understated). These are the conditions most people taking this drug are found in (raves). That same line (hyperthermia) connects low sodium/water intoxication to hyperthermia which should be better clarified to explain how the two phenomenon are connected in layman terms. Water intoxication and low electrolyte balance is another immediate risk in itself, that should also be given greater weight as it is attributable to a few deaths and more sicknesses during recreational use. Lastly, not enough emphasis is put on adulteration of the substance within the article, which is implicated in almost every overdose that occurs and is the single greatest threat with recreational mdma use, especially when substances are combined with mdma. These are all the things people die from related to its use. As well, Mdma's psychadelic effects are most closely associated with the effects of mescaline, in the general section. I'll post more as I find, will edit with sources when i have time.

-Fiveonfive (talk) 07:07, 23 November 2014 (UTC)

Even though Parrott AC offers a rebuttal to this (to save his reputation), his very review is being disputed in the medical community. Is this the best source to base the majority of the article on?

http://www.ncbi.nlm.nih.gov/pubmed/24590541 Fiveonfive (talk) 10:37, 23 November 2014 (UTC)

ill let you guys have it. Too painfully boring for my taste. Fiveonfive (talk) 07:55, 24 November 2014 (UTC)

Source on retrospective quality issues http://www.nature.com/npp/journal/v37/n4/full/npp2011202a.html#bib2 Fiveonfive (talk) 01:59, 29 November 2014 (UTC)

Underneath the pretty graph with the 20 bubbles, it says, "Addiction psychiatrists were polled regarding 20 popular recreational drugs; ecstasy was ranked 16th in addictiveness and 12th in harmfulness." However, that's not what the graph says. It says it was ranked 16th in both categories. If the graph is right, E is not as harmful as the words say.

174.92.77.189 (talk) 03:48, 17 November 2014 (UTC)

It looks like you are right. The raw data is here http://commons.wikimedia.org/wiki/File:Rational_scale_to_assess_the_harm_of_drugs_(mean_physical_harm_and_mean_dependence).svg and the paper is here http://www.antoniocasella.eu/archila/NUTT_2007.pdf. Sorting the mean dependency, physical harm, and social harm columns shows ecstasy to be ranked 16th in all categories. I'll change this when the edit lock is lifted unless someone else does so before me.50.106.202.195 (talk) 06:47, 19 November 2014 (UTC)

somebody has put HUGE quotes in references. In my view several of those go way way beyond fair use. please cut them down and keep them down to a (non-German) sentence or two. Jytdog (talk) 04:58, 23 November 2014 (UTC)

Examine this page. Note that the entire page is composed of excerpts from research papers and hosted on a US government website. Seems a bit heavy handed to call the use of quote parameters for text exactly like they do a

WP:COPYVIO. Seppi333 (Insert 2¢ | Maintained

) 05:09, 23 November 2014 (UTC)

yes, otherstuff exists. and who is going to sue the US government for infringing copyright of work they probably paid for? Please don't include long excerpts from copyrighted texts in WP. You know this is not OK. Jytdog (talk) 06:17, 23 November 2014 (UTC)

Actually my point is it is OK to quote excerpts from copyrighted sources in the context of a review. You should probably familiarize yourself with this aspect of copyright law if you're going to delete content on those grounds. FYI, the US government doesn't pay authors to write for pharmacology textbooks. Seppi333 (Insert 2¢ | Maintained) 13:20, 23 November 2014 (UTC)

While you all are discussing, in good faith, whether this material is suitable, I've removed it and locked the article in that state because

WP:EW is unacceptable behavior on its face. There's no damage to having it not-there for a few days while you sort it out, and it's visible in the history so everyone can see what's being discussed. But it's less damaging to leave it out for now (annoying absence vs licensing policy violation), and I'm surprised that someone would edit-war to include a potential policy violation. DMacks (talk

) 13:38, 23 November 2014 (UTC)

My 2¢: I could a list of a few dozen articles with said "copyright violation", some of which have gone through thorough reviews; this is an asinine tangential road we're going down. Seppi333 (Insert 2¢ | Maintained) 13:45, 23 November 2014 (UTC)

seppi, i suggest you strike the "asisine" comment. I get it, that you think, in good faith, that your use of lengthy quotes is totally fine. I don't, and ask that you respect my good faith. I've not been in a dispute before, about whether or not something violates copyright. It appears that the only option for bringing in other voices is to post

WP:COPYQUOTE, where it says that in an extreme case, a quote of 400 words from a 500 page book was found in court to be infringement. in this dif i removed a quote of about 500 words. . Can we come to agreement on a reasonable length limitation? Jytdog (talk

) 16:54, 23 November 2014 (UTC)

I didn't revert that deletion because I agree that it was exceptionally long. We probably can come to a limit agreement given that I agree with you on that style point. Seppi333 (Insert 2¢ | Maintained) 18:25, 23 November 2014 (UTC)

thanks for the strike, and for compromising  :) Jytdog (talk) 19:50, 23 November 2014 (UTC)

I cut the following and am pasting here. we need to find

An unblinded, single center pilot study of MDMA therapy in 20 post-traumatic stress disorder (PTSD) patients performed by the staff of MAPS – an organization advocating medical uses for psychedelics and marijuana – reported positive results that persisted in an open-label follow-up study performed several years later.^[1][2] A second study with 12 participants marginally failed to demonstrate a statistically significant effect.^[3]

parking here for now. Jytdog (talk) 19:34, 24 November 2014 (UTC)

I doubt there are any reviews out considering the limited amount of research done so far. Perhaps we should just comment that there is PTSD research in progress as NIDA does here http://www.drugabuse.gov/publications/drugfacts/mdma-ecstasy-or-molly. 50.106.202.195 (talk) 01:51, 25 November 2014 (UTC)

Some, possibly all, of those are covered in Parrott's and Meyers' reviews IIRC. I'll check tomorrow. You want me to email you any papers btw? Seppi333 (Insert 2¢ | Maintained) 03:43, 25 November 2014 (UTC)

thanks seppi i have access to pretty much any medical article. Jytdog (talk) 05:32, 25 November 2014 (UTC)

No direct dehydration

As far as I can tell, the existing literature, including the references cited, do not support the idea that MDMA causes dehydration. It seems that dancing causes dehydration and MDMA may mask thirst. I suggest we remove dehydration as an effect of MDMA.

In addition, the following sentence is incoherent, self-contradictory, and badly needs revision: "The most serious short-term physical health risks of MDMA are hyperthermia and dehydration;[25][29] this is due to a life-threatening complication – hyponatremia (excessively low sodium concentration in the blood) – associated with drinking large quantities of water without replenishing electrolytes.[25][29][30]"

173.228.54.200 (talk) 07:23, 25 November 2014 (UTC)

I'm still confused after reading this section several times. Does MDMA somehow prevent users from sweating when their body temperature rises? (Hint: The answer is no). All the refs quite clearly support that statement. What exactly do you think is wrong with the sentence on hyponatremia? Seppi333 (Insert 2¢ | Maintained) 05:50, 26 November 2014 (UTC)

The main issue with the hyponatremia sentence is that dehydration cannot be caused by hyponatremia, which the sentence claims, since the two clinical states are opposites. 173.228.54.200 (talk) 06:11, 26 November 2014 (UTC)

That sentence says hyponatremia is the result of responding to dehydration by drinking a lot of water. It's referring to

dilutional hyponatremia. Seppi333 (Insert 2¢ | Maintained

) 06:16, 26 November 2014 (UTC)

CYP2D6

The page currently says that CYP450 is important, "especially CYP2D6". But clinical studies by de la Torre and colleagues show that MDMA inhibits CYP2D6, which greatly limits its contributions to MDMA metabolism. What justification is there for the word "especially"? I suggest we change it to "including". 173.228.54.200 (talk) 07:36, 25 November 2014 (UTC)

"CYP2D6 is the major enzyme involved in the oxidative metabolism of MDMA that in turn produces metabolites of recognized toxicity." –

PMID 22392347 Seppi333 (Insert 2¢ | Maintained

) 22:40, 25 November 2014 (UTC)

That sentence isn't responsive, as the sentence states that 2D6 is the major enzyme producing toxic metabolites. The sentence does not say 2D6 is the major enzymne. In any case, see, for example, http://www.ncbi.nlm.nih.gov/pubmed/23162568 and http://www.ncbi.nlm.nih.gov/pubmed/23112822 I think the review is probably too old to reflect current knowledge. 50.250.213.37 (talk) 23:50, 25 November 2014 (UTC)

Substituted amphetamines are generally both inhibitors (even if only competitive) and substrates of CYP2D6. In any event, I don't have a problem with the proposal, so I'll change it as requested. Seppi333 (Insert 2¢ | Maintained) 00:04, 26 November 2014 (UTC)

Why was melting point removed from box?

I added a melting point range for MDMA, which was removed by another user, because it did not have a reference. I then added it back with a reference. Then the entire section was removed. I suggest we add melting point back into this page. It is a little disheartening to have objective, referenced information arbitrarily removed. 173.228.54.200 (talk) 07:39, 25 November 2014 (UTC)

remove the information you

edit warred into the article and i will be happy to talk with you. i am dealing with too many crazy people tonight. Jytdog (talk

) 07:48, 25 November 2014 (UTC)

I'm not certain what you mean? I am trying to add referenced information and improve uncited and incorrect information. What do you want removed, please discuss here instead of reverting good faith edits. 173.228.54.200 (talk) 08:02, 25 November 2014 (UTC) I propose adding melting point back into the box with a reference to Shulgin's work and using the lowest and highest numbers he gives while specifying that mp varies depending on hydration. 173.228.54.200 (talk) 05:03, 26 November 2014 (UTC)

Unsupported claim of 'safer' unapproved and unproven treatments

This statement does not appear to be supported by the reference: "The author noted that oxytocin and D-cycloserine are safer co-drugs in PTSD treatment" I did a search of the paper for both drugs and did not find them mentioned. Moreover, neither drug has been approved as safe and efficacious. I suggest we reword to something like: "While oxytocin and D-cycloserine are potentially safer co-drugs in PTSD treatment, they have not been approved for this indication by any regulatory body." 173.228.54.200 (talk) 07:54, 25 November 2014 (UTC)

...Look at the abstract. See also the content under the heading "SAFER DRUGS FOR POST-TRAUMATIC STRESS DISORDER THERAPY". Seppi333 (Insert 2¢ | Maintained) 22:37, 25 November 2014 (UTC)

Ohhh, you're right. I was looking at the wrong pdf! Thanks for the correction. In any case, I think my point stands that the page should not appear to endorse a non-clinician's untested opinion about the safety of unapproved drugs. D-cycloserine has serious neurological and psychiatric side effects, not clearly better than MDMA or amphetamines. Neither drug that author mentions has been shown to be efficacious. I think it would be best to remove the reference to D-cycloserine and oxytocin. Failing that, I suggest clarifying that they have unknown safety and efficacy and are not approved for this indication. 173.228.54.200 (talk) 04:39, 26 November 2014 (UTC)

That's fair. I'll tweak the language as suggested. Seppi333 (Insert 2¢ | Maintained) 05:12, 26 November 2014 (UTC)

No evidence of experiments as interrogation tool

This sentence is not supportable: "The Army experimented with MDMA as an interrogation tool in Project MKUltra." The Army did preclinical toxicity studies with MDMA (Harman et al) after they killed someone in research with MDA. But there is no evidence in the literature that they experimented with MDMA as an interrogration tool. Moreover, the book being cited explicitly says this in the chapter co-written by Grob. The citation seems to use irrelevant page numbers. I suggest changing this statement and, in general, when books have different authors for each chapter, the chapter should be cited. 173.228.54.200 (talk) 08:24, 25 November 2014 (UTC)

I never edited this section, but if it can't be verified, it should be deleted. Seppi333 (Insert 2¢ | Maintained) 05:30, 26 November 2014 (UTC)

Done.173.228.54.200 (talk) 06:06, 26 November 2014 (UTC)

Lack of appropriate reference for MDA as "direct neurotoxin"

I noted a citation was needed for the claim that MDA is a "direct neurotoxin". The reference added by Seppi333, actually a compendium of abstract-style summaries of primary literature, does not seem to support the claim. The first appearance of the word MDA claims to be a peer reviewed citation, but it's actually an unreviewed government website and the word "MDA" appears to be a typo:

"Research shows that MDA destroys serotonin-producing neurons in the brain, which play a direct role in regulating aggression, mood, sexual activity, sleep, and sensitivity to pain. It is probably this action on the serotonin system that gives MDMA its purported properties of heightened sexual experience, tranquility, and convivality. [National Institute on Drug Abuse (NIDA) Infofax on ECSTASY. Available from http://www.nida.nih.gov/Infofax/ecstasy.html on Wednesday, May 17,2000] **PEER REVIEWED* "

This is obviously not peer reviewed. The linking of MDA in the first sentence with "this action" in the second makes it clear that MDA is a typo and that they meant to write MDMA. Moreover, the sentence about MDA does not appear on the website, as far as I can tell. I suggest that Toxnet be deprecated in favor of more reliable refernces. The vast majority of the papers it mentions seem to be about MDMA and many describe NIH-funded studies where volunteers were given MDMA. The only other mention relevant to MDA toxicity I see seems to state the opposite of the original claim:

"Direct injection of either 3,4-(+/-)-methylenedioxymethamphetamine (MDMA) or 3,4-(+/-)-methylenedioxyamphetamine (MDA) into the brain fails to reproduce the serotonergic neurotoxicity seen following peripheral administration."

I propose adding in the citation needed tag or removing the sentence, which has only peripheral relevance since it isn't about MDMA. 173.228.54.200 (talk) 04:56, 26 November 2014 (UTC)

I corrected the issue with species earlier which had been incorrectly stated. The current version is in accordance with the source, so I'm not going to revise this further. Seppi333 (Insert 2¢ | Maintained) 05:10, 26 November 2014 (UTC)

I'm sorry, can you clairify what you mean by "the issue with species"? I have pointed out that the references you gave do not support the claim the MDA is a neurotoxin. Do you believe they do? 173.228.54.200 (talk) 05:16, 26 November 2014 (UTC)

https://en.wikipedia.org/w/index.php?title=MDMA&diff=635435983&oldid=635414760 - notice the timestamp relative to your post. I'm not sure what the issue with the current revision is. Seppi333 (Insert 2¢ | Maintained) 05:22, 26 November 2014 (UTC)

Actually, given that this is nonhuman animals, I'm just going to delete the clause. Neurotoxicity in animals doesn't necessarily reflect upon humans by any means. Seppi333 (Insert 2¢ | Maintained) 05:37, 26 November 2014 (UTC)

The issue was that the reference does not support any neurotoxicity from MDA, only MDMA. And I have a secondary concern that the reference is unreliable since it claims un-reviewed goverment websites were peer reviwed and it has important typos. I suggest Toxnet be depricated as a reference. 173.228.54.200 (talk) 05:38, 26 November 2014 (UTC)

Toxnet satisfies

WP:MEDRS. Trying to argue this point is going to get you nowhere. Seppi333 (Insert 2¢ | Maintained

) 05:40, 26 November 2014 (UTC)

Interesting. Can you explain how Toxnet fits that WP? It isn't clear to me that it does. And it appears to me that its value is questionable. The first thing you/they cited mentioned the wrong drug through a typo and claimed an unreviewed web article was peer-reviewed. How can this be alleged to be reliable? And there seems to be no recourse for correcting it: In the FAQ, Toxnet says that non-Pubmed parts cannot be corrected because they are not produced by the NLM. Regards, 173.228.54.200 (talk) 05:51, 26 November 2014 (UTC)

I'm not going to argue over this. Ask about the source here if you actually want to push the issue:

WT:MED. Seppi333 (Insert 2¢ | Maintained

) 05:56, 26 November 2014 (UTC)

Done. Thanks for the pointer. 173.228.54.200 (talk) 06:05, 26 November 2014 (UTC)

I agree that Toxnet is not a reliable source per WP. It obscures the actual sources. SaltyRide (talk) 04:54, 11 March 2015 (UTC)

Addiction section is too narrowly focused on one lab's theories of a single mechanism

The research on addiction with MDMA that I have seen primarily documents sign and symptoms in users. It therefore seems strange to direct the reader to a "main page" about ΔFosB. This appears to be a strong endorsement of Nestler lab theories about addiction. If anything, a section on MDMA addiction should send users to a more broad article about addiction that addresses clinical issues. It appears to be a theory of this section that clinical issues with MDMA are analogous to those of psychostimulants. This seems to me to be unproven and possibly original research. It's well established that MDMA release of DA is largely indirect (which is why SSRI treatment reduces it in in vivo microdialysis), which distinguishes it from methamphetamine or amphetamine. I suggest that discussion of ΔFosB should be limited to one sentence and the diagram removed because it has not been demonstrated that the Nestler lab theories are correct or that these mechanisms explain clinical phenomena in MDMA users. 173.228.54.200 (talk) 05:34, 26 November 2014 (UTC)

Rofl. Seppi333 (Insert 2¢ | Maintained) 05:38, 26 November 2014 (UTC)

I suspect your Rofl violates WP:NoRofl But seriously, I think that section has big issues. Regards, 173.228.54.200 (talk) 05:57, 26 November 2014 (UTC)

Oh...you weren't joking were you? Seppi333 (Insert 2¢ | Maintained) 06:03, 26 November 2014 (UTC)

semi-protection

I've had it with the tendentious editing from IP addresses. I've requested semiprotection. Jytdog (talk) 07:13, 8 December 2014 (UTC)

 Done. I made it indef not because I think it should be infinite, but because it's a long-term problem and the good-faith editors need an uncertain amount of breathing room to see if there are any improvements at hand. No objection (== "need not consult with me first") to other admins converting to indef/long-term pending-changes or setting an endpoint to the semi. DMacks (talk) 07:24, 8 December 2014 (UTC)

thank you! Jytdog (talk) 08:59, 8 December 2014 (UTC)

Thanks DMacks. I was about to request this myself - both methamphetamine and amphetamine are permanently semi-protected anyway, so there is a precedent for an indefinite lock here. Seppi333 (Insert 2¢ | Maintained) 09:36, 8 December 2014 (UTC)

Synthetic routes

Its fine to have a sentence or two about how organic compounds are synthesized, but we generally do not provide the level of detail that was added here per

WP:NOTAGUIDE

. In the case of referring to specific named organic reactions and reagents, this sort of thing goes way over the head of 99% of our readers in any case. And as one of the 1% who does understand this material, I'd generally go to other sources and not Wikipedia when looking for synthetic information.

Yes, you can find examples of fairly detailed synthesis descriptions in some articles, but these are generally removed within a day or so of being added as I have here, for the above reasons. See for example the diffs below.

https://en.wikipedia.org/w/index.php?title=Tetracycline&diff=639920650&oldid=639815940 https://en.wikipedia.org/w/index.php?title=Benzoctamine&diff=prev&oldid=640281520 https://en.wikipedia.org/w/index.php?title=Lometraline&curid=35642404&diff=640281098&oldid=640264636

talk

) 08:42, 1 January 2015 (UTC)

I don't personally care as long as we are consistent with similar articles. Methamphetamine also has a pretty substantial synthesis section which should be pared down under this reasoning.Sizeofint (talk) 09:45, 1 January 2015 (UTC)

Well, I tried to trim that out and got slapped down, as it has been designated a "Good Article". So I am going to back off a little bit here and just ask that you try to keep a cap on the technical details and name reactions. Thanks for the discussion.

talk

) 13:53, 1 January 2015 (UTC)

Alright, I will add it back in and see if I can simplify the section. Sizeofint (talk) 23:56, 1 January 2015 (UTC)

I added my thoughts on synthesis sections in articles like MDMA here: Special:Permalink/640752702#Synthesis section. I personally don't really care if such a section is included in a few articles like this, but it may be worth starting the dialogue I mentioned to establish a concrete policy on the coverage of synthesis routes in articles on US/UN schedule 1 controlled substances (globally banned chemicals). Seppi333 (Insert 2¢ | Maintained) 04:05, 3 January 2015 (UTC)

Image in header

There seems to be an edit war over which image this article should use. The top one shows the double bonds but the bottom one shows some hidden atoms. Anyone have comments regarding this.

File:MDMAPNG2.png

Sizeofint (talk) 19:45, 8 January 2015 (UTC)

I don't want to say a lot to sway public opinion on this. I appreciate the call to discuss. If you look at the top picture, the hidden atoms are not entirely hidden. You have to view the larger resolutions to see them clearly but they are at least partially visible, it's because of the angle of the image that they're not as obvious in the thumbnail. Lazord00d (talk) 16:58, 9 January 2015 (UTC)

The top image does not accurately depict the bonding in a benzene ring, showing alternating single and double bonds. The bottom image, which I made some years ago, shows the the C-C bonds in the ring are more or less equivalent in length and strength. I would strongly encourage those without a strong chemistry background not to get involved in making molecular models, as it leads to inaccuracies like this. --Ben (talk) 18:32, 10 January 2015 (UTC)

I agree with Ben. I have no objection to using normal single/double-bond styling for regular skeletal diagrams (the top), even though the bonds are not truly like that. But if one were to use them in any sort of more sophisticated style that includes geometry, every bond-length in that ring must be equal and the presence of the "second" bond of a double bond should not displace the position of the "first" bond (note that these detail is true even in the single/double diagram). It's okay not to know that this ring is not actually single and double bonds, and it's okay in some contexts to illustrate it that way, but anything built on top of that factually flawed detail becomes increasingly incorrect--and visibly so--in many ways. See benzene and aromaticity to learn more. The double-bonds really approximately do circulate around the ring, as the lower diagram illustrates, and the perspective is better in that the back atoms are more readily visible even at thumbsize. DMacks (talk) 20:12, 10 January 2015 (UTC)

Okay, if there aren't any objections in the next day or so I'll switch the image to the bottom one. Sizeofint (talk) 00:19, 11 January 2015 (UTC)

The bond lengths in the images I've submitted are determined by the software's built-in algorithm and the size settings for the atom diameter.. as I didn't write it I can't speak for it's accuracy, however jmol is well known and I trust its programmers much more than any reference in this thread I can say that for sure. Also, even though the points about aromaticity are factual, my position is that the fact that the stick and ball models I've submitted are closer to the 2d model makes them more easily understood. I can't support reverting based on that criteria but this is a public forum so it's not up to me what happens ultimately and honestly constantly defending edits gets old and boring when there is no real challenge and life is passing by. I'd rather enjoy it than argue back and forth about stuff that essentially boils down to opinion of people who have zero credibility that I have seen in real life. Have any of you posted your diplomas anywhere lol? Really I would expect much more substance in your rebuttals (which would of course take optical phenomena caused by different shaped structures on each side of connected spheres into account now wouldn't they? ;-) the concept is as old as the circle & square illusion) but hey it's whatever.. Y'all have fun now! I mean that too. Enjoy life! :-)

Lazord00d (talk) 05:02, 11 January 2015 (UTC)

To be blunt, that you have only been able (thus far) to find settings that make chemically incorrect results or only fed it chemically incorrect input is not our problem. Every molecular modelling package (even the heavy-weight quantum computing ones) and every attempt to do something blindly/automatically from a skeletal structure (such as PubMed or related indexing) can and often does give wrong (sometimes wildly wrong) structural results if the initial parameters are not correct--we've seen examples on wikipedia of tangled rings, atomic collisions, and bonds intersecting each other. I would tolerate a single/double 3D diagram and certainly value making something clearer, but not at the expense of amplifying other incorrect aspects. Readers have a funny habit of putting trust in what they read; I think it's a horrible choice to make something more incorrect (with no other aspect being made more correct to compensate) just to be more understandable (especially when what's being made "more understandable" is not correct in the first place). What matters on wiki is what's on-wiki and what's citeable (

GIGO. DMacks (talk

) 10:53, 11 January 2015 (UTC)

Note that Jmol has a feature for measuring atomic distances, so you can measure for yourself whether the C–C and C=C are actually equal lengths (and just displayed with optical illusions). There's some science: I made an observation about your results, you proposed an alternate hypothesis to explain it; but you have the actual underlying data, so go prove it one way or another. Though why one would think that an image subject to optical illusions that suggest there are factual mistakes is better than one that doesn't is beyond me (especially if your claim is that this all is to better-illustrate it!). DMacks (talk) 10:59, 11 January 2015 (UTC)

Ahh there you go! Substance. Congratulations you're the first. Yay for you! But I'm still not waving my white flag :-)...

My interest in uploading images in the first place was to try to standardize some of the hodgepodge that's out there in terms of molecular visualization, so I thought about what variation would be the most beneficial to the most users and this is what I ended up with.. pretty much zero% of users will have thought about this as much as you or I have which is the reason I ended up with that result not to muddy the waters. If anything they're muddied by the randomness of the models that currently exist IMO. I have a feeling that a lot of them are inaccurate in far worse ways than mine with their double-bonds showing (oh myyyy).. this isn't a Chemistry textbook, it's an Encyclopedia. There is a difference in scope..

Lazord00d (talk) 11:31, 11 January 2015 (UTC)

Water intoxication

At Wikipedia:Articles for deletion/Sasha Rodriguez, about an article which reports several cases of death from water intoxication after consuming MDMA, I have proposed that information about that subject be merged to this article under "Adverse effects". The sourcing at that article is not satisfactory, but a scan of Google Scholar suggests that adequate sourcing can be found. Any input to that AfD is welcome, as is any comment here about whether such a merge would be appropriate. --MelanieN (talk) 23:03, 18 January 2015 (UTC)

Hyponatremia is discussed under Adverse effects. I don't think we'd need any sources from that article, particularly since they would need to comply with MEDRS for inclusion here. I would say just delete it; a merge is probably not necessary. Sizeofint (talk) 20:00, 19 January 2015 (UTC)

It's true that "life threatening hyponatremia" is mentioned in the article. That doesn't convey much to the casual reader. I was thinking it might be important to add that death can occur and has occurred under these circumstances. I don't see any mention of death, in plain English, in the article; people reading this article might need it stated a little more clearly that you can die from this course of action. Of course the references would have to meet MEDRS (which the ones in the AfD article don't, so you're right, merge is not an appropriate suggestion), but there are articles about this in the literature. Naturally I would propose any such addition and references here before adding anything to the article. --MelanieN (talk) 21:08, 19 January 2015 (UTC)

I don't think anyone would be opposed if you want to clarify or expand on water intoxication here. Sizeofint (talk) 01:24, 20 January 2015 (UTC)

Edits of January 29, 2015

@

talk

) 00:24, 1 February 2015 (UTC)

@

Formerly 98: I understand your concerns. I've reviewed the sources that claim the DEA was unaware of the therapeutic use of MDMA in 1984. All eventually link back to a Newsweek article published in April 1985 in which the DEA pharmacologist makes his statement. I have changed the text so it indicates the information originates from this single pharmacologist. Thanks for taking time to discuss. Sizeofint (talk

) 03:08, 1 February 2015 (UTC)

Primary source usage

The paragraph I added the primary source to already has two primary sources citing neurotoxic effects; I do not understand why a primary source citing the cause of neurotoxicity would not be relevant. If secondary sources must be used, then the whole section should be deleted. This rule should either apply across the board or not. Please review

WP:MEDRS; secondary sources are not a requirement. — Preceding unsigned comment added by Morrowfolk (talk • contribs

) 00:47, 13 February 2015 (UTC)

@

WP:MEDRS

states: " Primary sources should generally not be used for medical content. [Bolding in original]. Many such sources represent unreliable information that has not been vetted in review articles, or present preliminary information that may not bear out when tested in clinical trials."

Further down this message is repeated. "Primary sources should generally not be used for health related content, because the primary biomedical literature is exploratory and not reliable - any given primary source may be contradicted by another, and the Wikipedia community relies on the guidance of expert reviews, and statements of major medical and scientific bodies, to provide guidance on any given issue."

If there are other statements in the paragraph that are supported solely by primary sources, I will fully support their removal.

talk

) 01:34, 13 February 2015 (UTC)

talk

) 01:34, 13 February 2015 (UTC)

I forgot to sign my last post, my apologies. Anyway, I am referring to this quote:

"If the conclusions of the research are worth mentioning (for instance, publication of a large, randomized clinical trial with surprising results), they should be described as being from a single study, for example:

"A large, NIH-funded study published in 2010 found that selenium and Vitamin E supplements increased the risk of prostate cancer; it was thought they would prevent prostate cancer." (citing

PMID 20924966

)

After enough time has passed for a review in the area to be published, the review should be cited in preference to the primary study. Using a secondary source often allows the fact to be stated with greater reliability:

"Supplemental Vitamin E and selenium increase the risk of prostate cancer." (citing

PMID 23552052

)

If no review on the subject is published in a reasonable amount of time, then the content and primary source should be removed."

The citation in question was published in a journal that does not promote an agenda, and certainly had surprising results. However, it is from 2011 and does not have a review that I can find. There are a few comments, but that is essentially it. I do not see refutation of the data... Is three years too long? "Reasonable amount of time" is vague.

Thank you for the clarification of your views; I was initially very annoyed because many users post rules as a means of maintaing a certain view in an article, but you make it clear that you are simply attempting to improve the quality of medical articles. Morrowfolk (talk) 18:33, 13 February 2015 (UTC)

The main reason we're not going to include that is because it refutes what the reviews conclude, where most of those neurotoxicity reviews are 2-3 years more current than that primary source. Seppi333 (Insert 2¢ | Maintained) 21:06, 13 February 2015 (UTC)

Edit: btw, there are a couple newer primary sources like

PMID 24177245 which suggest MDMA also produces dopamine neurotoxicity through its metabolites. We don't include these either simply because they're primary sources. Seppi333 (Insert 2¢ | Maintained

) 21:10, 13 February 2015 (UTC)

Molly gets two definitions?

In the text it both says molly means the pure form and other things - this is directly in contradiction with each other. It can't mean the unadulterated form if it also means other drugs! "The UK term "Mandy" and the US term "Molly" colloquially refer to MDMA in a crystalline powder form that is relatively free of adulterants.[5][6] "Molly" can sometimes also refer to the related drugs methylone, MDPV, mephedrone or any other of the pharmacological group of compounds commonly known as bath salts.[12]" This pair of sentences would probably be better to say that the name was given to one but has expanded on the street to mean any of these such as:"The UK term "Mandy" and the US term "Molly" colloquially refer to MDMA[5][6], however "Molly" can sometimes also refer to the related drugs methylone, MDPV, mephedrone or even any other of the pharmacological group of compounds commonly known as bath salts.[12]" ...which then wouldn't contradict itself by saying it was the colloquially pure when it can mean all the others which are colloquially not pure. A statement that the street form is usually a tablet or encapsulated powder probably should be in a different sentence not contradicting itself. 76.21.107.77 (talk) 19:55, 23 February 2015 (UTC)

A couple of points here:

• The first statement says "colloquially", which implies that it is vernacular and/or slang, and therefore not always or even generally accepted;
• The second statement says "'Molly' can sometimes refer to (object)"; the word "can" is not the same as the word "must", which implies that it doesn't always refer to (object).
• (edit) What, pray tell, does "colloquially pure" mean?

This is basic English grammar, and I'm tired of this silly argument over "MDMA" vs "Molly". "MDMA" clearly and unambiguously describes the chemical which is the subject of this article. Street names are relevant to the discussion but ultimately a distraction. If you don't like it, you're free to change it, but please don't do it from an anonymous IP. Simishag (talk) 22:42, 23 February 2015 (UTC)

INACCURACIES

MANDY was ENGLISH name for a prescribed drug with the TRADE NAME MANDRAX ( a sedative containing METHAQUALONE & DIPHENHYDRAMINE HYDROCHLORIDE ). The GERMAN ARMY was EXPERIMENTING with MDMA in 1934 . — Preceding unsigned comment added by 134.2.64.114 (talk) 18:46, 2 March 2015 (UTC)

I can tell you that the sources I have read do not mention experimentations with MDMA in 1934. It is possible they were experimenting with MDA however. Sizeofint (talk) 18:51, 2 March 2015 (UTC)

I am not sure about Mandy as a slang term, however Urban Dictionary lists powdered MDMA as the most popular definition of Mandy. Granted, UD is not a reliable source but it indicates the term is plausible. Sizeofint (talk) 18:57, 2 March 2015 (UTC)

A quick Google News search turns up numerous references that indicate "Mandy" is indeed a slang term for MDMA, particularly in the UK. -- Ed (Edgar181) 19:05, 2 March 2015 (UTC)

Semi-protected edit request on 8 March 2015

Addiction and dependence glossary[1][2][3]
biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake) drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose drug withdrawal – symptoms that occur upon cessation of repeated drug use physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens) psychological dependence – dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome) reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach sensitization – an amplified response to a stimulus resulting from repeated exposure to it substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose
v t e

This edit request to MDMA has been answered. Set the |answered= or |ans= parameter to no to reactivate your request.

Please change "has potential adverse effects, such as neurotoxicity and addiction" to "has potential adverse effects, such as neurotoxicity and transient addiction" as that is what the source claims.

Although these findings may not apply to all groups of ecstasy users, they suggest that ecstasy abuse and dependence may be transient phenomena in many, if not most, instances. - Meyer, J. in 3,4-methylenedioxymethamphetamine (MDMA): current perspectives

Boddika (talk) 15:28, 8 March 2015 (UTC)

Dependence is not addiction. Seppi333 (Insert 2¢ | Maintained) 22:43, 8 March 2015 (UTC)

But isn't dependence required for addiction? Either way, seems like the main issue is the lack of the word "transient", which was not addressed. SaltyRide (talk) 16:24, 15 March 2015 (UTC)

Not done: please establish a consensus for this alteration before using the {{edit semi-protected}} template. — {{U|Technical 13}} (e • t • c) 22:06, 15 March 2015 (UTC)

Dependence and addiction are 2 entirely different concepts. The ref makes no statement at all about addiction. Seppi333 (Insert 2¢ | Maintained) 23:26, 15 March 2015 (UTC)

References

1. ISBN 9780071481274
   .
2. PMID 24459410
   . Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.⁴¹. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
3. PMID 26816013
   . Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
   Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.

Lack of appropriate reference for MDA as "direct neurotoxin"

I noted a citation was needed for the claim that MDA is a "direct neurotoxin". The reference added by Seppi333, actually a compendium of abstract-style summaries of primary literature, does not seem to support the claim. The first appearance of the word MDA claims to be a peer reviewed citation, but it's actually an unreviewed government website and the word "MDA" appears to be a typo:

"Research shows that MDA destroys serotonin-producing neurons in the brain, which play a direct role in regulating aggression, mood, sexual activity, sleep, and sensitivity to pain. It is probably this action on the serotonin system that gives MDMA its purported properties of heightened sexual experience, tranquility, and convivality. [National Institute on Drug Abuse (NIDA) Infofax on ECSTASY. Available from http://www.nida.nih.gov/Infofax/ecstasy.html on Wednesday, May 17,2000] **PEER REVIEWED* "

This is obviously not peer reviewed. The linking of MDA in the first sentence with "this action" in the second makes it clear that MDA is a typo and that they meant to write MDMA. Moreover, the sentence about MDA does not appear on the website, as far as I can tell. I suggest that Toxnet be deprecated in favor of more reliable refernces. The vast majority of the papers it mentions seem to be about MDMA and many describe NIH-funded studies where volunteers were given MDMA. The only other mention relevant to MDA toxicity I see seems to state the opposite of the original claim:

"Direct injection of either 3,4-(+/-)-methylenedioxymethamphetamine (MDMA) or 3,4-(+/-)-methylenedioxyamphetamine (MDA) into the brain fails to reproduce the serotonergic neurotoxicity seen following peripheral administration."

I propose adding in the citation needed tag or removing the sentence, which has only peripheral relevance since it isn't about MDMA. 173.228.54.200 (talk) 04:56, 26 November 2014 (UTC)

I corrected the issue with species earlier which had been incorrectly stated. The current version is in accordance with the source, so I'm not going to revise this further. Seppi333 (Insert 2¢ | Maintained) 05:10, 26 November 2014 (UTC)

I'm sorry, can you clairify what you mean by "the issue with species"? I have pointed out that the references you gave do not support the claim the MDA is a neurotoxin. Do you believe they do? 173.228.54.200 (talk) 05:16, 26 November 2014 (UTC)

https://en.wikipedia.org/w/index.php?title=MDMA&diff=635435983&oldid=635414760 - notice the timestamp relative to your post. I'm not sure what the issue with the current revision is. Seppi333 (Insert 2¢ | Maintained) 05:22, 26 November 2014 (UTC)

Actually, given that this is nonhuman animals, I'm just going to delete the clause. Neurotoxicity in animals doesn't necessarily reflect upon humans by any means. Seppi333 (Insert 2¢ | Maintained) 05:37, 26 November 2014 (UTC)

The issue was that the reference does not support any neurotoxicity from MDA, only MDMA. And I have a secondary concern that the reference is unreliable since it claims un-reviewed goverment websites were peer reviwed and it has important typos. I suggest Toxnet be depricated as a reference. 173.228.54.200 (talk) 05:38, 26 November 2014 (UTC)

Toxnet satisfies

WP:MEDRS. Trying to argue this point is going to get you nowhere. Seppi333 (Insert 2¢ | Maintained

) 05:40, 26 November 2014 (UTC)

Interesting. Can you explain how Toxnet fits that WP? It isn't clear to me that it does. And it appears to me that its value is questionable. The first thing you/they cited mentioned the wrong drug through a typo and claimed an unreviewed web article was peer-reviewed. How can this be alleged to be reliable? And there seems to be no recourse for correcting it: In the FAQ, Toxnet says that non-Pubmed parts cannot be corrected because they are not produced by the NLM. Regards, 173.228.54.200 (talk) 05:51, 26 November 2014 (UTC)

I'm not going to argue over this. Ask about the source here if you actually want to push the issue:

WT:MED. Seppi333 (Insert 2¢ | Maintained

) 05:56, 26 November 2014 (UTC)

Done. Thanks for the pointer. 173.228.54.200 (talk) 06:05, 26 November 2014 (UTC)

I agree that Toxnet is not a reliable source per WP. It obscures the actual sources. SaltyRide (talk) 04:54, 11 March 2015 (UTC)
Cite error: There are <ref group=Color legend> tags on this page, but the references will not show without a {{reflist|group=Color legend}} template (see the help page).