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Page views for the last 12 months

Stashing this here. Has some new details about Clegg and corroborates some of the details of the Austin Chronicle article. http://www.playboy.com/articles/ecstasy-was-legal-in-1984-and-it-was-glorious

Has blurb on current usage. http://www.bbc.co.uk/newsbeat/article/36503623/danger-from-ecstasy-greater-than-ever-say-drug-experts Sizeofint (talk) 18:59, 8 November 2016 (UTC)[reply]

Additional source for history/spiritual uses to add if I can track down the original Guardian article. http://csp.org/practices/entheogens/docs/saunders-ecstasy_rel.html Sizeofint (talk) 20:29, 8 December 2016 (UTC)[reply]

Roger-Sánchez, Concepción; García-Pardo, María P.; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, María A. (April 2016). "Neurochemical substrates of the rewarding effects of MDMA". Behavioural Pharmacology. 27: 116–132. doi:10.1097/FBP.0000000000000210. Sizeofint (talk) 08:35, 18 December 2016 (UTC)[reply]

French, Larry G. (June 1995). "The Sassafras Tree and Designer Drugs: From Herbal Tea to Ecstasy". Journal of Chemical Education. 72 (6): 484. doi:10.1021/ed072p484. Sizeofint (talk) 02:48, 10 January 2017 (UTC)[reply]

Pasting here until the section can be expanded appropriately. Keep in mind that medical information needs to have WP:MEDRS content. Sizeofint (talk) 18:57, 8 November 2016 (UTC) ==Harm Reduction== Harm reduction, as stated by [[Harm Reduction International]], refers to policies, programmes and practices that aim to reduce the harms associated with the use of psychoactive drugs in people unable or unwilling to stop. <ref> What is harm reduction? https://www.hri.global/what-is-harm-reduction </ref> ===Supplementation=== ===Organizations===[reply]

Not accurate. Never was. The DEA scheduled it as a Schedule I substance without any basis in fact much like CPSC ruled on Buckeyballs (Which we now know was so deficient that the Judge had to "toss" most of Zen's arguments in their filing because they were only applicable (and hinted that most of them were) if the CPSC were...you know, competent, and did their jobs right...) It's classification by the DEA has flip-flopped twice and once of those was in defiance of court order. (See: https://www.drugpolicy.org/sites/default/files/DPA-MAPS_DEA_Science_Final.pdf) The "limited" trials were for patients and situations like PTSD where it could help patients to restructure their brains. In fact, in recent times there have been decisions to move the scheduling to III on things and they have now started the process on a Phase 3 clinical trial for PSTD wherein it actually has really high rates of success in major improvement for the patients, compared to the other regimens. The descriptions for this need to be changed, guys. False but "accurate" is only for the mainstream media. — Preceding unsigned comment added by 71.123.168.226 (talk • contribs)

MDMA currently has no accepted medical indications. We can't say otherwise until after the phase three trials finish. Sizeofint (talk) 10:29, 8 December 2016 (UTC)[reply]

Re: what Sizeofint said. Also, the phase 3 clinical trial doesn't start until sometime in 2017. Seppi333 (Insert 2¢) 00:43, 9 December 2016 (UTC)[reply]

What should we put as the class of this drug?

I propose psychoactive drug. User:Sizeofint proposes Empathogen-entactogen. Others thoughts? Doc James (talk · contribs · email) 22:25, 17 December 2016 (UTC)[reply]

Why? "Psychoactive drug" isn't a drug class. Seppi333 (Insert 2¢) 05:49, 18 December 2016 (UTC)[reply]

This book lists it as a "hallucinogen"[1] would be happy with that aswell. The DEA does not recognize "entactogen" Doc James (talk · contribs · email) 07:27, 18 December 2016 (UTC)[reply]

Causing hallucinations isn't really a primary effect of MDMA though. Even in this article we describe the hallucinatory effects as "mild". The primary effects of MDMA are on mood - not the modification of external stimuli. In that respect, it is more similar to an anti-depressant than a hallucinogen. Even "stimulant" would be a more accurate classification, though that also doesn't completely capture it. I'll look at a few reviews and see how they are classifying MDMA. Sizeofint (talk) 07:42, 18 December 2016 (UTC)[reply]

Even the authors of that book admit the term "hallucinogen" is misleading on page 289. Sizeofint (talk) 07:49, 18 December 2016 (UTC)[reply]

In the mid-1980s, based on the structure–activity relationships of MDMA-like molecules, Nichols (1986) proposed that the psychosocial effects of MDMA represented a novel pharmacological class, which he named “entactogens” to capture its apparently unique sensory and emotional effects. Data from rodent drug-discrimination paradigms (reviewed in Glennon, 1999; Nichols and Oberlender, 1989) suggested that MDMA was clearly distinguishable from hallucinogens, but shared many pharmacological, discriminative, and behavioral effects with prototypic amphetamine-like stimulants. Finally, in the 1990s, researchers began to conduct controlled studies to measure the psychosocial effects of MDMA in humans and to compare these to the effects of other stimulants.^[1]

MDMA has a stimulant, hallucinogenic effect, and is also known to enhance mental factors such as energy, empathy and euphoria (12).^[2]

Moreover, people can experience entactogenic effects and feel extremely connected with others and some even have mild hallucinations^[3]

MDMA has been called an entactogen, meaning literally “to produce touching within”, referring to its tendency to enhance inner awareness and distinguishing it from classic psychedelic drugs such as psilocybin^[4]

Because of this serotonergic component, MDMA exhibits some mental effects that differ qualitatively from other amphetamine-type stimulants (Schmid et al., 2014 and Schmid et al., 2015) and for this reason MDMA has been classified as an “entactogen”.^[5]

Whereas phenethylamines without ring substitution usually behave as stimulants, ring substitution (as in MDMA) leads to a modification in the pharmacological properties. Ingestion of MDMA causes euphoria, increased sensory awareness and mild central stimulation. It is less hallucinogenic than its lower homologue, methylenedioxyamphetamine (MDA). The terms empathogenic and entactogenic have been coined to describe the socialising effects of MDMA.^[6]

A couple of books: Thought to be relatively save, in the mid-1970s it was proposed as an adjuvant to psychotherapy by Leo Zeff and other experimental psychiatrists who touted its ability to increase patient self-esteem, empathy and nondefensiveness and to facilitate therapeutic communication; thus its original classification as and "empathogen", though the term "entactogen" is now preferred.[2] Although entactogens and stimulants display similar stereoselectivity, when tested within their respective classes, the R isomers of MDA, MDMA, and MBDB substitute for MDMA and (+)-MBDB but not for (+)-amphetamine. [3]

Bolding mine. This is what I found on the first page of pubmed index reviews (at least from the ones I can access). The book results are admittedly more biased because I searched 'MDMA entactogen'. Most of the articles here emphasize how MDMA is different from typical stimulants and hallucinogens. Sizeofint (talk) 08:42, 18 December 2016 (UTC)[reply]

This says the term "entactogens" is not recognized by the DEA.[4] "Some authors proposed that MDMA represented a novel class of drugs, the entactogens that were not hallucinogenic. However, the DEA did not accept this new classification" Doc James (talk · contribs · email) 23:13, 18 December 2016 (UTC)[reply]

This book calls it a "stimulant" and a "hallucinogen"[5] Doc James (talk · contribs · email) 23:22, 18 December 2016 (UTC)[reply]

This paper calls it a stimulant and talks about how Nichols proposed the novel class "entactogens". I am not seeing that this is an officially accepted drug class. [6] Doc James (talk · contribs · email) 23:25, 18 December 2016 (UTC)[reply]

The DEA is a view - a potentially heavy weight one to be sure - but not the arbiter of what is and is not accepted classification for drugs. If the consensus in the scientific literature is that this is a valid classification - and that I think is what my initial survey of the latest reviews in PubMed suggest - then that is what we should go with regardless of the DEA's stance. To my knowledge, no scientist has the power to say, "this is now officially a drug class" so in that sense all drug classes are 'proposed'. It simply becomes accepted over time that this is indeed a valid drug classification. We can see this over at opioid. There isn't a single definition of opioid, only a set of 'proposed' definitions which are used until some more refined usage takes precedence. Notably, none of the reviews I read here disputed this classification. If they did dispute anything, it was the simple classification of MDMA with other hallucinogens and stimulants. Also, not all the sources I quote above use this 'proposed' modifier. Sizeofint (talk) 00:22, 19 December 2016 (UTC)[reply]

Additional sources:

Not MEDRS but shows traction of the term - MDMA is the prototypical empathogen and entactogen drug^[7]

Government agency - Drug Class: Mild CNS stimulant, empathogen, entactogen, mild hallucinogen and psychedelic, appetite suppressant.^[8]

Members of the entactogen class of psychostimulants (drugs that produce an “open mind state” including feelings of interpersonal closeness, intimacy and empathy) have been less frequently studied in self-administration models. The prototypical entactogen 3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”) supports self-administration but not with the same consistency nor with the same efficacy as structurally related drugs amphetamine or methamphetamine.^[9]

• FWIW: the |class= parameter takes & shows any text (unformatted). So one could use a list of classnames, or add a description/reference. I only hope it won't be too expanded, in an infobox. -DePiep (talk) 11:50, 19 December 2016 (UTC)[reply]

How about "stimulant (entactogen)"? Doc James (talk · contribs · email) 17:46, 19 December 2016 (UTC)[reply]

@Doc James and Sizeofint: Based upon the unique psychoactive effects of MDMA relative to other substituted amphetamines that lack a methylenedioxy ring, I think "Empathogen–entactogen" would be the most appropriate drug class for this compound. I've seen MDMA (as well as other methylenedioxy- derivatives of amphetamine) classified differently than amphetamine and methamphetamine in almost every paper that I've read on the class of substituted amphetamines. In most cases, MDMA and related derivatives were referred to entactogens and/or empathogens, which is in agreement with the references which Sizeofint provided. I imagine that the DEA doesn't "recognize" these two terms as drug classes because MDMA is the parent compound for all compounds in this class, none of them are licit substances, and none of them have any current medical uses. In any event, the DEA isn't an organization that is involved in the classification of drugs or other biologically active substances.

The two most common classification systems for drugs are the Anatomical Therapeutic Chemical Classification System (which assigns ATC codes) and Systematized Nomenclature of Medicine. MDMA has not been assigned a drug class in either of these systems. In some cases, these classification systems assign compounds to drug classes with rather technical names; for example, amphetamine's ATC code (N06BA01) assigns amphetamine to the class of "centrally acting sympathomimetics" (note: this class is a subcategory of psychoanaleptics and "psychostimulants, agents used for ADHD, and nootropics"), which essentially means "drugs which activate the sympathetic nervous system by stimulating the central nervous system". In lieu of this technical classification, I used "CNS stimulant" in amphetamine's drugbox, since it's almost the same classification.

I don't believe that listing "hallucinogen" alone is an accurate classification for MDMA or any other substituted amphetamine for that matter. "CNS stimulant" describes some of MDMA's drug effects, but does not encompass the pro-social, empathy-promoting (i.e., empathogenic) effects for which it is often used recreationally.

I think an adequate compromise would be to list "Empathogen–entactogen", "CNS stimulant", and possibly "Euphoriant" and/or "mild hallucinogen" as drug classes in the drugbox class parameter. Listing the first 2, and possibly one or both of the other classes as well, should adequately cover its classification. Seppi333 (Insert 2¢) 18:57, 19 December 2016 (UTC)[reply]

Maybe leave it blank than if it is not categorized by either ATC code or SNM Doc James (talk · contribs · email) 19:00, 19 December 2016 (UTC)[reply]

• I saw the note at WT:PHARM, and it's an interesting question. In a sense, it's really just "miscellaneous". I'd say the most precise description would be "euphoriant, empathogen–entactogen". I edit conflicted with Seppi333, and this suggestion is similar to his. --Tryptofish (talk) 19:06, 19 December 2016 (UTC)[reply]

These proposals seem reasonable to me. Simply saying MDMA is a stimulant or hallucinogen is, I think, misleading. That MDMA isn't present in a formal classification system is likely just due to its lack of medical indications. I don't think not having an ATC code is a persuasive reason to ignore how reliable medical/scientific sources are classifying it. Sizeofint (talk) 02:54, 20 December 2016 (UTC)[reply]

Section references

Petergstrom, is there a newer source for the claim of non-addictiveness? 1999 is rather old. Sizeofint (talk) 03:05, 8 January 2017 (UTC)[reply]

Agree

• Pentney, Alana (Sept 2001). "An Exploration of the History and Controversies Surrounding MDMA and MDA". Journal of Psychoactive Drugs. 33 (3): 213–221. {{cite journal}}: Check date values in: |date= (help)
• Jansen, K. L. (7 January 1999). "Ecstasy (MDMA) dependence". Drug and Alcohol Dependence. 53 (2): 121–124. ISSN 0376-8716.

This source says "may not induce classical manifestations of physical dependence"[7]

Which is not the same to as saying no risk of addiction. Doc James (talk · contribs · email) 07:57, 8 January 2017 (UTC)[reply]

Ref says "MDMA users may encounter problems similar to those experienced by amphetamine and cocaine users, including addiction. MDMA damages brain serotonin neurons. Serotonin is thought to play a role in regulating mood, memory, sleep, and appetite. Research indicates heavy MDMA may cause persistent memory problems in humans; however, a 2011 study has reported limited cognitive decline in users of MDMA.1"[8]

NIH says "Research results vary on whether MDMA is addictive. Experiments have shown that animals will self-administer MDMA—an important indicator of a drug’s abuse potential—although to a lesser degree than some other drugs such as cocaine."[9] Doc James (talk · contribs · email) 08:04, 8 January 2017 (UTC)[reply]

"With no reports of subjects who take large amounts of MDMA for long periods of time (Peroutka l 990a), indi­ cating that the drug is not addictive, " "It has been shown that MDMA is not addictive in humans (Beck & Rosenbaum 1 994; Peroutka 1 990a; Riedlinger 1 985),"

Petergstrom (talk) 08:35, 8 January 2017 (UTC)[reply]

All those sources are old and the never sources say something different. Doc James (talk · contribs · email) 09:13, 8 January 2017 (UTC)[reply]

I would disagree, saying that the sources are totally fine despite being over a decade old, but it smells to me like the consensus is on the other side so I guess thats that #RipmemesPetergstrom (talk) 09:19, 8 January 2017 (UTC)[reply]

I think both statements should be cited, with the context. The NIH statement is more recent, but it refers to animals and that animals self-administer MDMA does not by default entail that humans will as well (also noted WP:MEDANIMAL). The older statements refer to humans but are, well, older, and may have been superseded by later research. On their own, none out-WP:WEIGHT-s the other. Jo-Jo Eumerus (talk, contributions) 09:43, 8 January 2017 (UTC)[reply]

We have lots of other good sources that also comment on the addiction of MDMA include "There are no specific pharmacologic treatments for MDMA addiction" 2015 Nelson Textbook of Peds Doc James (talk · contribs · email) 10:04, 8 January 2017 (UTC)[reply]

We have a 2010 review that says "MDMA also modulates the activity of the dynorphinergic and enkephalinergic systems in several brain structures related to addiction, as it has been shown for other psychostimulants." Doc James (talk · contribs · email) 10:16, 8 January 2017 (UTC)[reply]

This 2013 review is even clearer "Users often consider ecstasy to lack the potential for dependence or addiction, but this is not the case." Doc James (talk · contribs · email) 10:26, 8 January 2017 (UTC)[reply]

per [10]it is a review and quite clear agree w/ Doc James--Ozzie10aaaa (talk) 11:44, 8 January 2017 (UTC)[reply]

I don't have access to that, but to me it smells primary. So right now we have two old sources saying it is not addictive and one new animal source and a new primary source that says it is. And we have this: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)60464-4/abstract source from the lancet that suggests its psychological dependence potential(addictive potential) is lower than cannabis.....Looks pretty clear cut, we can't say wether to not it is addictive. Better to keep it at None to moderate Petergstrom (talk) 10:36, 8 January 2017 (UTC)[reply]

Ah seriously? It is avaliable openly from PMC[11] and pubmed calls it a review article. Doc James (talk · contribs · email) 11:53, 8 January 2017 (UTC)[reply]

Petergstrom — making up facts is not a good way to go. You have access and it is marked as a review.... Carl Fredrik 💌 📧 11:58, 8 January 2017 (UTC)[reply]

Woah carl thats hostile. I googled the title and the sites i visited recquired purchase. I read the article on pubmed and it mentions dependence but i cant find it explicitly stating addiction. I still think we should list as none to moderatePetergstrom (talk) 13:03, 8 January 2017 (UTC)[reply]

Primary sources and dated sources are unacceptable. We stick to recent reviews. QuackGuru (talk) 17:45, 8 January 2017 (UTC)[reply]

• User:Petergstrom Pubmed abstracts include a classification. Click on this link for the 2013 review discussed above: PMID 24648791. Scroll down to where it says "Publication types". click the double downward arrowheads to the right, to reveal what is in the field. You will see it says "review" there. The abstract at pubmed also clearly displays links to the free version of the article, which anyone can reach by clicking the hyperlink where it says in bold and brown font "Free PMC Article", which is here.

You have now had these extremely basic things about working with medical references explained to you

If you ever write things like this again (and I am recording the diffs): diff where you wrote: I don't have access to that, but to me it smells primary.. diff I googled the title and the sites i visited recquired purchase you will not be editing about health much longer in WP. Jytdog (talk) 04:26, 11 January 2017 (UTC)[reply]

User:Jytdog, woah, that that edit did not intent to discredit the source... I clicked on something and it asked for money, so I said I had no access. Someone could have just said, no you have access, its a review...and someone did, and I accepted it.Petergstrom (talk) 04:44, 11 January 2017 (UTC)[reply]

No. The diffs say what they say I don't have access to that, but to me it smells primary. when the pubmed abstract is free and obviously classifies the ref as a review. You demonstrated pure incompetence or tendetiousness and in the context of an edit war, and none of that is acceptable. I will not continue this discussion. I have warned you to behave and edit better and that is done. Jytdog (talk) 04:50, 11 January 2017 (UTC)[reply]

Dated sources?

The discussion is still underway. I don't see consensus for this. Is there a good reason to use dated sources? QuackGuru (talk) 22:39, 8 January 2017 (UTC)[reply]

(edit conflict) Petergstrom, there have been loads of reviews published the last five years. I would think there should be some that include this content if it is still the scientific consensus. If they don't then it is highly possible new research has altered the consensus. We want this article to reflect current scientific opinion which might be different from the scientific opinion from eight or sixteen years ago. Sizeofint (talk) 01:56, 9 January 2017 (UTC)[reply]

I don't own the book, but someone pointed out the source referenced WP:MEDANIMAL, and the quotation for the book does not mention addiction at all. I think both statements should be cited as someone mentioned above.Petergstrom (talk) 01:50, 9 January 2017 (UTC)[reply]

Which statement? Sizeofint (talk) 01:58, 9 January 2017 (UTC)[reply]

Updated the addiction liability with a newer source. Sizeofint (talk) 02:25, 9 January 2017 (UTC)[reply]

I don't see how changing

Impairments in multiple aspects of cognition, including memory, visual processing, and sleep have been noted in humans;<ref name=Current2013 /><ref name=Pharm2014 /><ref name="Abstinent MDMA fMRI review" /> the magnitude of these impairments is correlated with lifetime MDMA usage.<ref name=Current2013 /><ref name=Pharm2014 /><ref name="Abstinent MDMA fMRI review" /> Memory is impacted by ecstasy use, which is associated with impairments in several forms of memory.<ref name=Current2013 /><ref name=Pharm2014 />

to the following is an improvement.

However these findings have been inconsistent have have been of small significance,^[1][2][3] creating controversy surrounding the causal role of MDMA in long term cognitive impairment.^[4]

Assuming the text adequately summarizes the sources, the old version has references five to eight years more recent than this new text. Sizeofint (talk) 02:53, 9 January 2017 (UTC)[reply]

The article is slowing moving forward without the dated sources. Every 5 years we can do this again. QuackGuru (talk) 02:59, 9 January 2017 (UTC)[reply]

The addiction liability of MDMA is based upon this ref^[5] and the ratings of similar dopamine releasing agents on Wikipedia. I don't see a compelling reason to change this. Seppi333 (Insert 2¢) 03:03, 9 January 2017 (UTC)[reply]

If the newer source is as good quality we should prefer it. The desired effects of MDMA are mainly serotonergic so I would expect the usage patterns to be somewhat different from other dopamine releasing agents. Different usage patterns could affect the addiction liability. Consequently, I don't think we can necessarily expect MDMA to have the same liability. Sizeofint (talk) 03:18, 9 January 2017 (UTC)[reply]

I'm fine with leaving it at moderate though since that seems an acceptable reading of the source. Sizeofint (talk) 03:21, 9 January 2017 (UTC)[reply]

Petergstrom, why are you using older sources to overwrite content from newer sources? If the newer sources mention the evidence is low quality, why don't you just cite them? Also, you're over WP:3RR. Sizeofint (talk) 03:30, 9 January 2017 (UTC)[reply]

If i am over 3RR, so are you. Fine I will cite newer sources.Petergstrom (talk) 03:33, 9 January 2017 (UTC)[reply]

My count is I reverted twice, Quack another two times, and Seppi once. But in any case, thanks. Sizeofint (talk) 03:36, 9 January 2017 (UTC)[reply]

ill watchlist this article--Ozzie10aaaa (talk) 12:00, 9 January 2017 (UTC)[reply]

That's not enough to cite newer sources. We can expunge the older sources now rather than later. Is there a reason to use dated sources? QuackGuru (talk) 12:30, 9 January 2017 (UTC)[reply]

If there is a newer source cited with them I think the old sources are harmless to keep. They'll eventually disappear by attrition. Actively hunting them down is more effort than it is worth I think. Sizeofint (talk) 12:36, 9 January 2017 (UTC)[reply]

In my drafts if a newer source is just two years and cites the same or similar claim I use the newer source. If the claim is similar with the newer source I make a slight tweak to the text. I always keep things fresh. Its that simple. QuackGuru (talk) 12:43, 9 January 2017 (UTC)[reply]

This 2011 review supports the NIH source and discusses research in human subjects:

All three drugs [methamphetamine, d-amphetamine, and MDMA] have addictive potential and can lead to varying degrees of drug dependence...approximately 15% of routine MDMA users recently fit the diagnostic criteria for MDMA dependence...Comparable results have been reported following MDMA abuse in the United Kingdom (McCambridge et al., 2005). Furthermore, MDMA and D-AMPH were reported to have similar reinforcing effects in people during a controlled laboratory study (Tancer and Johanson, 2003). Thus, there is some epidemiological evidence to support the addictive potential of MDMA as described in animal studies, although to a much lesser extent than that of either METH or D-AMPH.^[6]

—PermStrump(talk) 00:32, 10 January 2017 (UTC)[reply]

Dependence and addiction are used together in this study...it doesnt seem very good.Petergstrom (talk) 00:54, 10 January 2017 (UTC)[reply]

It seems more useful for quantifying the dependence liability than addiction liability. Haven't finished reading it yet though. Sizeofint (talk) 01:06, 10 January 2017 (UTC)[reply]

The current classification of MDMA puts it on par with amphetamine and (and phenethylamine when it's coadministered with a MAO-B inhibitor) in terms of its addiction and dependence liability, while being less addictive and less prone to induce psychological dependence than methamphetamine or cocaine. This is in part based upon usage demographics (i.e., usage patterns and the doses administered), in part based upon clinical evidence, and in part based upon the molecular neuropharmacology of each drug. I'm not aware of any substituted amphetamines that have been shown/documented to induce physical dependence. Cocaine, which is a nonselective MA reuptake inhibitor, doesn't do this, so I wouldn't expect a nonselective MA releasing agent to cause this either. It is worth pointing out that amphetamine, MDMA, and methamphetamine directly affect glutamate neurotransmission in some cell types in the brain via internalization of neuronal and/or astroglial EAATs in addition to monoamine neurotransmission via several mechanisms that affect VMAT2/DAT/NET/SERT. Alterations in synaptic glutamate concentrations in the NAcc, which is one region where these drugs affect EAATs, directly affects the development and maintenance of an addiction as a result of changes in postsynaptic glutamate receptor signaling (case in point: altered NMDA receptor signaling in the NAcc is strongly implicated in the development of addiction to ketamine and phenylcyclidine). Seppi333 (Insert 2¢) 21:15, 10 January 2017 (UTC)[reply]

So, in a nutshell, I don't see a point in trying to look for refs to change this. These "liability" parameters are really just rather subjective ratings of how likely a drug is to induce addiction or dependence relative to other drugs which have addiction/dependence liability ratings on Wikipedia. Individual liability ratings IMO are fairly meaningless without context (i.e., comparison to other drugs which induce addiction or dependence). Seppi333 (Insert 2¢) 21:19, 10 January 2017 (UTC)[reply]

Firstly, phenethylamine with an MAO is not anything that is researched. I have only hear anecdotes related to it so I don't know why you mentioned it. Secondly, "The current classification of MDMA puts it on par with amphetamine". Source? We have found sources that say a variety of things, some say addictive(no magnitude), and others say not addictive. Currently, there is no quantitive data on addictiveness, the 15% is meaningless (of what population? Context of use?). The only real good way to measure addictiveness is with progressive ratio self administration break point in the same lab setting, which hasn't been done with MDMA to my knowledge, I have only found studies comparing cocaine, nicotine, cathinone, morphine and methamphetamine. Given the inconsistency, I think that low would be the best classification for addiction liability on this page, a sort of compromise/average given the sources we have. It's really the best we can do, or we can remove the statistic from the chart overall....because its kinda of hard to quantify and kinda dumb.Petergstrom (talk) 00:31, 11 January 2017 (UTC)[reply]

Firstly, phenethylamine with an MAO is not anything that is researched. You're correct.

I have only hear anecdotes related to it so I don't know why you mentioned it. - re: "...in part based upon the molecular neuropharmacology of each drug"

Secondly, "The current classification of MDMA puts it on par with amphetamine". Source? - amphetamine. I was referring to the current classification on Wikipedia.

I agree that studies with each drug which utilize a standardized reinforcement schedule which is appropriate for studying self administration would be the ideal sources to use set these parameters and cite them. I'm not aware of any body of research like that though.

I don't see any reasonable justification to set the addiction liability of MDMA lower than all other dopamine releasing agents based upon the current evidence. The only ref that we have which compares it to other drugs states that its liability is "relatively small", and "moderate" is "relatively small" compared to "high", which drugs like cocaine, methamphetamine, and heroin are rated. Seeing as how those are the three most widely used recreational "hard drugs" globally, I have no clue what else the term "relatively" in the phrase "relatively small" would be referring to in that reference. Seppi333 (Insert 2¢) 01:02, 11 January 2017 (UTC)[reply]

Well you cant base addiction liability on pharmacology on structure. Firstly, it is well known that the speed DA activity heavily influences the euphoria experienced, and therefore the addictive potential. Secondly, given that MDMA is largely a serotonergic drug, this should prevent addiction, as 5-HT acting drugs have a tendency to create a satiation of desire-kind of like having too much of a food you like. That is why although mildly euphoric, drugs like LSD and psilocybin are not addictive. So, no. You cant say "because MDMA is a phenethylamine, it is moderately addictive". Thats way too far of a jump, not in biology. Maybe in math, maybe in physics(although probably not), but not in biology.Petergstrom (talk) 01:49, 11 January 2017 (UTC)[reply]

It's probably best to ask me what I have in mind when I said "in part based upon the molecular neuropharmacology of each drug" than to assume you know what I'm referring to. Just like other dopamine releasing agents, and as stated verbatim in the article: MDMA has been shown to induce ΔFosB in the nucleus accumbens.^[7] MDMA and amphetamine induce DA/glutamate release into NAcc D1-type MSNs, which necessarily triggers the exact same signaling cascade into those neurons to induce ΔFosB expression. Those neurons don't even express serotonin receptors, so the notion that it being a serotonin releasing agent somehow changes things is asinine. The fact that MDMA and amphetamine are structural or even functional analogs is also irrelevant - the only relevant neuropharmacological aspect of these drugs in relation to addiction is how they affect neurotransmission at synapses between glutamate/dopamine neurons and D1-type NAcc medium spiny neurons. And, FWIW, the ref above that states that MDMA induces NAcc ΔFosB expression also examined MDMA, cocaine, nicotine, and amphetamine on a progressive ratio reinforcement schedule and measured their break points:[12] [13]. There's a fairly clear consensus on this talk page not to change the addiction liability, so stop edit warring. Seppi333 (Insert 2¢) 02:13, 11 January 2017 (UTC)[reply]

What is asinine is think think of addiction solely from a biochemical viewpoint. Yes FOSB expression is related to addiction, but you are forgetting addiction is at its core a behavioral phenomenon. If 2 refs explicitly state MDMA is not addictive in humans, although old, they outweigh a newer ref that suggests it induces FOSB expression in the NAcc. That is ridiculous. Stop reverting to moderate. Best to remove it during this discussion, and I think if we cant come to a conclusion, given how it is impossible to quantify addictiveness potential and the stat is stupid as is, we should remove it.Petergstrom (talk) 03:06, 11 January 2017 (UTC)[reply]

"DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS" - very first words of PMID 24459410; no emphasis was added - that all caps is from the source.

This very recent review on the role of ΔFosB in addiction states outright that the degree of ΔFosB induction by a drug is a biomarker that can be used to measure the addictiveness (i.e., addiction liability) of a drug.^[8] I'd suggest that you not offhandedly disregard a field of addiction research which is extremely relevant to this conversation simply because you don't know much about it. The notion that addiction isn't a brain disorder is simply outrageous to me; seriously, what do people who advocate otherwise actually think "thought" and "behavior" comes from if not neurons within the brain? The foot? Vacuum? A magical pink bunny in the sky? Nowhere - that it just simply happens without a mechanism? Seppi333 (Insert 2¢) 03:21, 11 January 2017 (UTC)[reply]

LMAO. I never said FOSB expression should be discounted entirely, nor did I say addiction wasn't a neurological disorder. I agree FOSB is an important in addiction. However, addiction is diagnosed by behavioral traits, not FOSB expression. The reason that FOSB expression is not used as a diagnosis tool is because there are more components to addiction than FOSB expression(that an measurement). If you want to put FOSB expression in the page, then do so, however dont use that as support for putting "Addiction liability:Moderate" down. That is pure ignorance. Don't discount how complex biology is because you don't have a good understanding. Petergstrom (talk) 03:49, 11 January 2017 (UTC)[reply]

Incidentally, if you put a colon before a paragraph the paragraph is indented. Adding a colon for each "level" of the discussion helps to keep the discussion organized. Last I heard, the reason FOSB isn't used as a diagnosis tool is because they'd have to do a biopsy of your brain tissue. This is somewhat difficult to do when the subject wants to remain alive/functional. The current diagnostic criteria are a bit screwed up at the moment if you've seen our DSM-5 article. FOSB is necessary and sufficient for addiction. The relationship between the two is so close that researchers are looking into medication that will treat addiction by reducing FOSB expression. In any case, I think all the current sources support a 'moderate' rating for addiction liability. Sizeofint (talk) 04:05, 11 January 2017 (UTC)[reply]

Petergstrom, my issue with your 2007 sources is that you were using them to overwrite newer sources. WP:MEDDATE is a rule of thumb, not a hard rule. I don't think your recent edits are improving this article. Sizeofint (talk) 04:10, 11 January 2017 (UTC)[reply]

The FOSB article would need a secondary source stating that this is equivalent to an indication of moderate addiction liability-an editor cant make that decision. The addiction liability stat needs to go, as the only sources that specifically state addiction liability in humans(which happen to be stated as zero) are too old to be used. Either a newer source specifically stating that the addiction liability in humans in moderate needs to be found, the older sources need to be used, or the stat needs to go.Petergstrom (talk) 04:09, 11 January 2017 (UTC)[reply]

We use the best available sources for any claim. There are multiple factors that determine quality - age is only one of them. Sizeofint (talk) 04:12, 11 January 2017 (UTC)[reply]

Sizeofint Lots of research has been done in the last 10 years. We need to find those sources to implement them in the article. I am currently compiling some.Petergstrom (talk) 04:13, 11 January 2017 (UTC)[reply]

Then why don't you wait until you have them before you start removing content? Sizeofint (talk) 04:18, 11 January 2017 (UTC)[reply]

I was referring to the addictiveness. If there is no viable source for "moderate" rating, then why is it there????. It should be gone until we have a good source for it. An study on FOSB does not allow an editor to conclude "Moderate addiction liability". A study on FOSB, can go in the effects section, not in the side bar under addiction liability. We have older sources explicitly stating no addiction liability in humans, but they are too old, however we have no newer studies explicitly contradicting them. There is of course the study on dependence, but thats not enough. In the dependence section, that should be stated, but not in the side bar under addiction lability. I don't even see where the source on MDMA decision making states it is addictive. I see a mention that decision making may play a role in addiction, and that it(addiction to another drug) was an exclusion criteria for a study. Did I miss something. Furthermore, the quotation from the book only mentions neurotoxicity, did I miss something again? Also the FOSB study used rats...I mean if the studies suggesting addiction(albeit never saying "Moderate") are rat studies, or studies using old criteria and the term dependence, then I really don't think there is enough evidence to put down "Moderate" and "15%"Petergstrom (talk) 05:21, 11 January 2017 (UTC)[reply]

I see these quotations from the 15% study

These observations further question the relevance of animal experiments that rely on self-administration to gauge the addictive properties of MDMA. As outlined earlier, MDMA is not readily self-administered, indicating that its rewarding properties are modest in comparison to d-AMPH or cocaine.

However, the results of animal behavioural and toxicity studies cannot be readily extrapolated to patients. This is particularly true for MDMA where major pharmacokinetic differences exist between commonly used laboratory animals. Thus, extensive longitudinal research in clinical settings is necessary to dissect confounding environmental factors such as polytoxicomanic drug use and pre-existing mental conditions from amphetamine-induced toxicity in the future. It is safe to predict that the availability of good data and reliable epidemiological evidence will also allow for a more temperate approach to the abuse and therapeutic use of amphetamines in the future.

Studies on ‘MDMA dependence’ in humans are often confounded by mixed sample populations of poly-drug users and typically rely on subjective user reports.

Few direct correlations exist between MDMA abuse and human disease states other than addiction.

All three drugs have addictive potential and can lead to varying degrees of drug dependence.

MDMA is clearly a reinforcer in animal studies, but the mechanism of MDMA-induced drug dependence is still under scrutiny.

You have to read through the information about limitations and pick out the nuggets of information the authors feel have conclusive support. The quote in the book is used to support a statement on neurotoxicity above. I'll see if I have access to the book. If there is no viable source for "moderate" rating, then why is it there???? Well the sources so far support a low or moderate rating. Seppi believes the molecular biology source is more in line with moderate. I don't have a strong feeling on this so I'm inclined to follow his judgement on this. Sizeofint (talk) 05:38, 11 January 2017 (UTC)[reply]

Petergstrom that quote is talking about neurotoxicity which is not the same thing as cognitive impairment. Sizeofint (talk) 06:00, 11 January 2017 (UTC)[reply]

So then why is it listed as a source for moderate addiction? Also, the reason Seppi gave for a biological support of moderate is only FOSB expression in rats, and an editor cannot make that jump. The sources we have don't support anything...except the old sources which support none. Petergstrom (talk) 06:07, 11 January 2017 (UTC)[reply]

The source with that neurotoxicity quote supporting the addiction liability is used in multiple places, one of which is the discussion of neurotoxicity. That is why the quote is there. Why do you think the 2017 source doesn't support at least a low rating? The best approach is to gather good recent sources (or at least sources as good or better than what we already have) to make a case. If sources conflict we may be able to compromise with Low / Moderate or similar. This reference, for example, states MDA and MDMA are less reinforcing than amphetamine...^[9] Sizeofint (talk) 06:24, 11 January 2017 (UTC)[reply]

I completely support a low rating, but I support even more a none-low rating or removal of the rating in the sidebar, and rather a discussion below in effects. Petergstrom (talk) 06:31, 11 January 2017 (UTC) Im gonna sum up source[reply]

It's laughable that you think my comments on a talk page have to adhere to WP:MEDRS. This source has supported the addiction liability statement ever since I added it over two years ago.^[5] The statement that it makes isn't vague/ambiguous or open to interpretation. The parameter is set to "moderate" because this is the default rating that I've given to any addictive drug unless there's a reason to set it lower or higher based upon the sources that I've used to cite addiction-related content in the article or any relevant clinical evidence that I subsequently become aware of. In other words, if a drug is addictive, it's probably going to be rated moderate. Seppi333 (Insert 2¢) 09:30, 11 January 2017 (UTC)[reply]

Arbitrary break

For addictiveness liability

• https://www.drugs.com/illicit/mdma.html drugs.com is not MEDRS

I'm actually not sure whether or not we consider drugs.com MEDRS. I think in general we try to use better sources which are almost always available Sizeofint (talk) 08:41, 11 January 2017 (UTC)[reply]

• http://www.eurekaselect.com/71315/article/cannabinoids-opioids-and-mdma-neuropsychological-interactions-related-addiction this source which pubmed provide two external links for, both costing 50-60 dollars. It does not state anything other than MDMA being concurrently used with other drugs may affect addiction

Doesn't look like I have access. Sizeofint (talk) 08:46, 11 January 2017 (UTC)[reply]

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931692/ this source which as stated above uses the DSM 4, conflates addiction and dependence, and never explicitly states that MDMA is addictive, although does infer it.

Despite having a compulsive use factor, ecstasy dependence is not typically as profound as the dependence that can occur in heavy users of alcohol, cocaine, methamphetamine, opioids, and tobacco. Compulsive use corresponds to addiction. I think this supports a low to moderate rating. Sizeofint (talk) 08:56, 11 January 2017 (UTC)[reply]

• https://www.drugabuse.gov/publications/drugfacts/mdma-ecstasymolly which refers to animal self administration WP:MEDANIMAL, and not to addiction

Yes, they just waffle. Not too helpful for our purposes. Sizeofint (talk) 08:57, 11 January 2017 (UTC)[reply]

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497800/ this which, again, never explicitly states MDMA's addictive potential, although does conflate and indicate dependence
• Seppi claiming that FOSB expression in rats is sufficient to jump to a magnitude of addiction, which firstly relies on WP:MEDANIMAL and is an inference an editor cannot make

  It's probably best to ask me what I have in mind when I said "in part based upon the molecular neuropharmacology of each drug" than to assume you know what I'm referring to. Just like other dopamine releasing agents, and as stated verbatim in the article: MDMA has been shown to induce ΔFosB in the nucleus accumbens.[7] MDMA and amphetamine induce DA/glutamate release into NAcc D1-type MSNs, which necessarily triggers the exact same signaling cascade into those neurons to induce ΔFosB expression. Those neurons don't even express serotonin receptors, so the notion that it being a serotonin releasing agent somehow changes things is asinine. The fact that MDMA and amphetamine are structural or even functional analogs is also irrelevant - the only relevant neuropharmacological aspect of these drugs in relation to addiction is how they affect neurotransmission at synapses between glutamate/dopamine neurons and D1-type NAcc medium spiny neurons. And, FWIW, the ref above that states that MDMA induces NAcc ΔFosB expression also examined MDMA, cocaine, nicotine, and amphetamine on a progressive ratio reinforcement schedule and measured their break points:[12] [13]. There's a fairly clear consensus on this talk page not to change the addiction liability, so stop edit warring

  "DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS" - very first words of PMID 24459410; no emphasis was added - that all caps is from the source.

This very recent review on the role of ΔFosB in addiction states outright that the degree of ΔFosB induction by a drug is a biomarker that can be used to measure the addictiveness (i.e., addiction liability) of a drug.[8] I'd suggest that you not offhandedly disregard a field of addiction research which is extremely relevant to this conversation simply because you don't know much about it. The notion that addiction isn't a brain disorder is simply outrageous to me; seriously, what do people who advocate otherwise actually think "thought" and "behavior" comes from if not neurons within the brain? The foot? Vacuum? A magical pink bunny in the sky? Nowhere - that it just simply happens without a mechanism? Seppi333 (Insert 2¢) 03:21, 11 January 2017 (UTC)

Sources indicating no addiction

• Pentney, Alana (Sept 2001). "An Exploration of the History and Controversies Surrounding MDMA and MDA". Journal of Psychoactive Drugs. 33 (3): 213–221. {{cite journal}}: Check date values in: |date= (help)

• Although old explicitly states ""It has been shown that MDMA is not addictive in humans (Beck & Rosenbaum 1 994; Peroutka 1 990a; Riedlinger 1 985)"

Riedlinger 1985 is some of the very earliest research on MDMA. I've use Beck & Rosenbaum extensively in the history section. It is a fascinating read but I don't know why the author would cite them for medical information. In any case, we have newer and higher quality sources so this doesn't hold much weight. Sizeofint (talk) 09:00, 11 January 2017 (UTC)[reply]

• Jansen, K. L. (7 January 1999). "Ecstasy (MDMA) dependence". Drug and Alcohol Dependence. 53 (2): 121–124. ISSN 0376-8716. describes rare cases of addiction criteria being met with a drug that is generally considered non-addictive, evidence for at least a low rating.

  Methylenedioxymethamphetamine (MDMA) is generally described as non-addictive. However, this report describes three cases in which criteria for dependence were met.

Yes, we have newer better sources now. Sizeofint (talk) 09:04, 11 January 2017 (UTC)[reply]

There is a mountain of sources cited for addictiveness, but none of them are substantial...The two(old) sources that we have that actually explicitly mention addictiveness in humans as addictiveness, not dependence, mention none potential. Petergstrom (talk) 08:09, 11 January 2017 (UTC)[reply]

This is a good start. I'm still looking through some Google Books entries. So far the sources state the liability is less than amphetamine and alcohol - substances we currently rank as moderately addictive. Sizeofint (talk) 09:04, 11 January 2017 (UTC)[reply]

MDMA's addictive liability appears to be lower than that of other drugs of abuse....^[10] Here the authors are mostly comparing MDMA to cocaine and methamphetamine, drugs we currently say have a high addiction liability. Sizeofint (talk) 09:56, 11 January 2017 (UTC)[reply]

In terms of evidence for dependence-syndrome-like patterns of use, and thus diagnosability of MDMA use, historically there has been little evidence for it; the drug is typically used weekly or less at a scale inconsistent with traditional notions of drug dependence....^[11] I can't tell if they are conflating dependence with addiction or not. Sizeofint (talk) 10:20, 11 January 2017 (UTC)[reply]

Any ref that covers diagnosis will have that issue. Seppi333 (Insert 2¢) 10:25, 11 January 2017 (UTC)[reply]

The APA really screwed the proverbial pooch on this one. Sizeofint (talk) 10:36, 11 January 2017 (UTC)[reply]

It seems to present a smaller addiction potential than cocaine or methamphetamine.^[12] Sizeofint (talk) 10:36, 11 January 2017 (UTC)[reply]

• PMID 23627786 (already cited in the article, from 2013) says (extended quote since it is paywalled): "While MDMA appears to be a promising treatment for at least one psychiatric disorder when combined with psychotherapy, it also possesses moderate abuse potential. Rodents and primates will self-administer MDMA [75-77]. For instance, monkeys will regularly self-administer MDMA, though they will pay a higher cost in lever presses for amphetamine or methamphetamine [78, 79]. The mood elevation produced by MDMA can be experienced as rewarding [see for instance 64, 65, 74, 80]. A national survey found that an estimated 2.5% of youths aged 12-17 and 12.4% of young adults aged 18 to 24 report using ecstasy at least once in their lives [81] and 9.1% reported use upon a second follow-up. Of those, 0.6% of this representative sample of young people, [82] and a higher percentage of polydrug users [83], report developing ecstasy dependence, though estimates vary between nations and over time, with polydrug users reporting more abuse of ecstasy. Regular and heavy users will take ecstasy once or twice a week or once every two weeks rather than on a daily basis. However, some people report problems arising from their use. Hence, like psychostimulants and unlike classic psychedelics, MDMA is associated with some abuse liability." Jytdog (talk) 10:59, 11 January 2017 (UTC)[reply]

Section references