Wikipedia:Featured article candidates/Amphetamine/archive4

The following is an archived discussion of a featured article nomination. Please do not modify it. Subsequent comments should be made on the article's talk page or in Wikipedia talk:Featured article candidates. No further edits should be made to this page.

The article was archived by Ian Rose via FACBot (talk) 8 October 2014 [1].

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Amphetamine

Nominator(s): Seppi333 (Insert 2¢ | Maintained) & Boghog (talk) 21:00, 16 August 2014 (UTC)

The initiation of this FAC marks eight months since the first FAC nomination was created...

Sources: this link contains all the WP:PAYWALLED papers cited in the amphetamine article. The file names reflect the ref name from the source (i.e., these papers were named according to <ref name="File name">).

Ian Rose, following your advice from the last FAC, I'm pinging everyone from previous FAC nominations except Shudde, since I have a strong aversion to interacting with that editor.

@Anypodetos, Aa77zz, Hamiltonstone, The Sceptical Chymist, and John: Do any of you have any comments on the current state of the article? The previous FAC nomination received minimal reviewer input, so the coordinators suggested I seek further input from you. Seppi333 (Insert 2¢ | Maintained) 21:00, 16 August 2014 (UTC)

@Ian Rose, Anypodetos, Aa77zz, Hamiltonstone, The Sceptical Chymist, John, and Nikkimaria: sorry if this is the second WP:ECHO notification you're receiving; AmericanLemming mentioned the notification didn't go through so I'm trying again. Seppi333 (Insert 2¢ | Maintained) 05:14, 17 August 2014 (UTC)

I received both notifications FWIW. Cheers, Ian Rose (talk) 05:16, 17 August 2014 (UTC)

@FAC coordinators: I imagine you don't receive this request very often, but would it be reasonable to ask that this nomination be archived tomorrow evening? I'd like to finish going through the article with AmericanLemming as he completes his review because he's being very thorough in his review and is, in my opinion, doing a fantastic job at improving language accessibility while retaining the technical content. I'm going to address his comments in this nomination tonight and tomorrow morning and then plan to continue working with him at Talk:Amphetamine/Archive 5#Informal peer review before my final renomination of this article.
Also (@Ian Rose), following up from my pings at the beginning of this FA nomination, of all the nominators in the previous echo notification list, only Anypodetos responded (see his section at the end of my talkpage). He went through and reviewed/edited the article section (Amphetamine#Overdose) that I pointed out - it was the only part of the article which was substantively changed since his review. Regards, Seppi333 (Insert 2¢ | Maintained) 21:15, 6 October 2014 (UTC).

Can action later today. Cheers, Ian Rose (talk) 01:02, 8 October 2014 (UTC)

Comments from AmericanLemming

@AmericanLemming: I've started the 4th FAC, so it may be best to continue the remainder of your review here. Seppi333 (Insert 2¢ | Maintained) 21:00, 16 August 2014 (UTC)

Sure thing. I'd like to apologize for disappearing for the past four days, but I flew from Wisconsin to Houston on Wednesday, drove eight hours to Oklahoma and moved into my dorm room on Thursday, and I've been catching up on sleep the past two days. By the way, User:Seppi333, I don't think you've actually pinged me or the other editors, because I didn't get a notification. While editor apathy may have had something to do with the total lack of comments the third time around, it may also have something to do with not pinging the past reviewers correctly. To get another editor's attention, you can leave a message on their talk page, or you can use [[User:Example]], I think. For more information on the matter, see Wikipedia:Notifications, especially the explanation of why they sometimes don't work. AmericanLemming (talk) 04:46, 17 August 2014 (UTC)

In other news, my semester starts on Monday, which may interfere with my ability to finish my review, but I'll do my best. You've put dozens of hours of work into this article, and I'd hate to see your efforts go unrecognized. Even if the article doesn't deserve the FA star right now, it's pretty close. AmericanLemming (talk) 04:46, 17 August 2014 (UTC)

It's actually closer to a couple hundred hours, especially if you include the time it took to make the annotated images.

In any event, I suppose the WP:ECHO feature didn't function since I used the feature while creating the page with several signatures. I'll go ahead and try it again... hopefully I'm not echo-spamming everyone though, hehe. Seppi333 (Insert 2¢ | Maintained) 05:13, 17 August 2014 (UTC)

Note to FAC delegates: Before I review this article at FAC, I should mention what I've already looked at during my informal peer review on the article talk page. I have proof-read the lead and the "Uses", "Contraindications", and "Side effects" sections for prose quality, comprehensiveness, and intelligibility to the non-expert (that is, me). I've made 14 comments, all of which Seppi333 has addressed, and I've made 18 edits to the article itself. I plan to slowly but steadily work my way through the rest of the article. AmericanLemming (talk) 07:19, 17 August 2014 (UTC)

Overdose

Apologies for my weeklong absence. Hopefully I'll be able to do a section a week; I might try to do two or three over Labor Day weekend. We'll see; my classes may get in the way of that. AmericanLemming (talk) 06:32, 25 August 2014 (UTC)

• “An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care.” What is “appropriate care”, exactly?

That was a language an author used to mean medical intervention at a hospital. Seppi333 (Insert 2¢ | Maintained)

• “High or low blood pressure” How can a moderate overdose cause “high or low blood pressure”? I sense a note in the making.

There's several cases where it can cause an elevation or reduction in some measure, e.g., blood pressure, pulse, and blood potassium levels. It depends upon the dose and initial conditions of the user. Seppi333 (Insert 2¢ | Maintained)

• When we talk about “moderate overdoses” and “extremely large overdoses”, could we give the approximate range for each?

Per WP:MEDMOS, I couldn't specify the range (this is indicated in a note in the source code), so I resorted to using those terms to give a relative magnitude for the range. The range is actually somewhat variable depending upon the user's tolerance as well, so it would've been hard to specify it in any case. Seppi333 (Insert 2¢ | Maintained)

• I don’t normally cite WP:SEAOFBLUE, but it seems to apply to the “extremely large overdose” sentence. You have no less than 16 blue links in a row. Can we find some way to reduce that number? Maybe only link the most unfamiliar ones? How else am I as the reader supposed to know what to click on? All of them? Maybe split them up into more common and less common symptoms?

The longest chain after my last edit is 6 comma separated blue links in a row. Let me know if you think it needs more revision. Seppi333 (Insert 2¢ | Maintained)

As I (finally) take another look at the sentence, I'm convinced that the number of things listed in a row is as much of a problem as the fact that so many of them are linked. To make it more reader-friendly, I would suggest grouping the symptoms into related categories and then having a sentence for each category. Perhaps you could do symptoms related to the brain/nervous system, symptoms related to the circulatory/pulmonary system, and then put whatever doesn't fit in those two categories in a third sentence. Breaking the sentence down will greatly increase readability, and grouping them by organ system affected will make it more logical. AmericanLemming (talk) 06:37, 5 September 2014 (UTC)

Ah, derp. Alright, I'll work on this today and follow up here once I'm done. I agree - the approach you're suggesting would make this read better. Seppi333 (Insert 2¢ | Maintained) 21:15, 5 September 2014 (UTC)

I've decided how to partition that section, though I had a quick question for you before going ahead with it. Do you think it would be better to keep the section as prose, or should I convert the OD symptoms list into a wikitable? If I convert it into a table, it would have a format that looks something like this:

I definitely would favor the table. It would help the reader to compare the severity of a moderate overdose and a extremely large overdose, and it would allow us to keep all the blue links without making the list of symptoms unreadable, like it is right now in prose form. The only difficulty I see is sandwiching text between the table and the giant annotated image we already have in this section; you may have to move that down a little. AmericanLemming (talk) 07:13, 14 September 2014 (UTC)

Example OD table

Overdose symptoms by system System Moderate overdose Extremely large overdose Cardiovascular Moderate Extreme Central nervous system Moderate Extreme Musculoskeletal Moderate Extreme Pulmonary Moderate Extreme Gastrointestinal Moderate Extreme Metabolic Moderate Extreme

I've made the table; I'm seeking feedback at WT:MED before pasting the completed table and updated section into the article. Seppi333 (Insert 2¢ | Maintained) 00:30, 8 October 2014 (UTC)

Seppi333 (Insert 2¢ | Maintained) 17:37, 6 September 2014 (UTC)

• Also, define metabolic acidosis, respiratory alkalosis, serotonin toxidrome, and sympathomimetic toxidrome in parentheses.

Done for three of these... I'll do the 4th once I can check the ref for more details. Seppi333 (Insert 2¢ | Maintained)

• Alright, one more comment on that sentence. How can the blood’s pH be too high and too low at the same time (respiratory alkalosis and metabolic acidosis, respectively)? Does this call for another note? AmericanLemming (talk) 06:32, 25 August 2014 (UTC)

I need to drop by my university library to check the book ref before I clarify this.

Ok, so apparently the ref for metabolic acidosis and respiratory alkalosis is this one (corresponds to the ref named "Acute amph toxicity" in the source code). Per this ref, the two can occur together. I'm not sure the relationship between metabolic acidosis and respiratory alkalosis can be easily explained in non-technical terms though; the parenthetical explanation for respiratory alkalosis is also a little more technical than that term (reduced partial pressure of blood carbon dioxide) as well. Seppi333 (Insert 2¢ | Maintained) 18:51, 1 September 2014 (UTC)

Update: I've been a little busier than I expected this past week, so I haven't worked on these issues yet. Sorry about that I'll get to this tomorrow since I've got some free time available now. Seppi333 (Insert 2¢ | Maintained) 07:54, 30 August 2014 (UTC)

I've been rethinking my review of this article; perhaps instead of shooting for a section a week I could try to do a paragraph a day. That might make going through the technical sections of the article a little less overwhelming. We'll see. And since we both seem to run into busy spells here and there, this might take a while. Hopefully I can finish before this gets to the bottom of the FAC list again, though. Ian might give us some extra time if progress continues to be made, but I'd rather not count on that. AmericanLemming (talk) 07:16, 5 September 2014 (UTC)

First off, I want to Thank you for all the hard work and effort you've put into this review so far. I really do appreciate it! Secondly, I'd prefer that you not burn out from doing this, so please go at whatever pace you're comfortable with! After all, WP:There is no deadline, and since you're being very thorough and making useful edit suggestions, I actually don't mind renominating it again if you happen to be too busy during the coming month. Take whatever time you need! Seppi333 (Insert 2¢ | Maintained) 21:15, 5 September 2014 (UTC)

• “Tolerance develops rapidly in amphetamine abuse, so periods of extended use require increasing doses of the drug in order to achieve the same effect.” If tolerance develops rapidly, that would imply the recreational user needs to rapidly increase the dose to achieve the same effect. Perhaps “require steeply increasing doses” would fit better here?

Just to keep the language simple/straightfoward, would you be okay with it worded this way? I think it reflects the idea you're suggesting (the "rate of change of dosage increase" increases with respect to time) if I understand it correctly, but I'd be okay with your version if you prefer it that way. Seppi333 (Insert 2¢ | Maintained)

I like your wording better than mine, actually. I think "increasingly larger" is slightly more objective and doesn't exaggerate the effect like "steeply increasing" does. AmericanLemming (talk) 07:20, 14 September 2014 (UTC)

• Note 11 doesn’t make any sense to me. What is “addiction treatment” (isn’t that the drug you’re taking, like imipramine?) and what is “adherence to addiction treatment”? Sticking to your withdrawal dosage schedule?

I actually have no clue about the intended definition of "adherence to addiction treatment". Cochrane used that phrase and didn't define it ANYWHERE in their paper (seriously, wtf?); I was very annoyed when writing this section because of this oversight on their part. I think what that term is supposed to mean is the amount of time which a person remains in a treatment program; so, in the context of that note, I'm assuming it's supposed to mean that imipramine increases the amount of time that a person continues to take imipramine (vs a placebo) as a treatment for amphetamine. I don't see how that makes imipramine useful as a treatment for amphetamine addiction, but that's the most logical meaning I could infer from that phrase and how it was used in the paper. This is a link to the complete Cochrane review on addiction treatment, hosted on my google site/file locker. I'm completely ok with either deleting the reference to imipramine entirely or trying to explain what that term means in the note; let me know which you think would be better. Seppi333 (Insert 2¢ | Maintained)

I'd suggest explaining the term in a note. I found a nice paper that defines treatment adherence succinctly: The impact of psychiatric diagnosis on treatment adherence and duration.... You could add "(Treatment adherence is sometimes defined as 'numbers of visits per month and treatment duration')" and then cite the above journal article. It agrees with you that treatment adherence isn't a very useful metric: "First, it must be acknowledged that measures of treatment adherence and participation duration are, at best, proxy measures for clinical outcomes and program effectiveness." AmericanLemming (talk) 07:33, 14 September 2014 (UTC)

• "no treatment has been demonstrated to be effective for the treatment of amphetamine dependence and abuse." This is a tad clunky. How about saying “there is no treatment for amphetamine dependence and abuse”?

I agree, that does seem a bit verbose. Would you be ok with it if I phrased this way - diff? It's a little longer than your version, but more direct and also less wordy than Cochrane's statement. Seppi333 (Insert 2¢ | Maintained)

Works for me. AmericanLemming (talk) 07:41, 14 September 2014 (UTC)

• “increased activation of dopamine receptors and co-localized NMDA receptors in the mesolimbic pathway” I think it would be helpful to have a note mentioning that the mesolimbic pathway is one of the brain’s main dopaminergic (dopamine-transporting) pathways. Context is key for the non-expert.

I think I've clarified it with this edit, but please let me know if anything is still unclear or could use additional clarification! Seppi333 (Insert 2¢ | Maintained)

I've kept what you've changed but added my tidbit about the mesolimbic pathway being one of the brain’s main dopaminergic (dopamine-transporting) pathways; changing "mesolimbic pathway" to "dopamine pathway connecting the ventral tegmental area to the nucleus accumbens" only made it more confusing to the non-expert (i.e., me). AmericanLemming (talk) 07:54, 14 September 2014 (UTC)

• “This review also noted that magnesium ions, which inhibit NMDA receptor calcium channels, and serotonin have inhibitory effects on NMDA receptors.” So serotonin doesn’t inhibit NMDA receptor calcium channels? If it did, we could reword this sentence to make it flow a lot better.

NMDA receptors have rather esoteric pharmacology... there are numerous different binding sites for different compounds. See this commons image and caption for reference of the binding sites - I'm not sure which location serotonin binds at, though I know it doesn't directly block or "plug" the channel like magnesium does. That said, I'm completely ok with simplifying the sentence. I'll see if I can think of a less wordy and more direct way of stating it and then follow up here. Seppi333 (Insert 2¢ | Maintained)

I've gone ahead and reworded it myself. I think it's still correct, but you might want to make sure. AmericanLemming (talk) 08:01, 14 September 2014 (UTC)

• “It also suggested that, based upon animal testing, pathological amphetamine use significantly reduces the level of intracellular magnesium throughout the brain” In this case, is “pathological” a synonym for “unsafe” or “heavy recreational”? If so, I’d recommend switching to one of those two terms; for a second I thought that excessive amphetamine use was caused by another disease, which didn’t seem right.

Pathological use is essentially a form of use that will result in addiction (or more generally, any form of substance-use disorder associated with amphetamine). Off the top of my head, "addiction-inducing use" or some equivalent variant of that would be a suitable replacement for that term if "pathological use" seems to jargony/technical. Let me know! Seppi333 (Insert 2¢ | Maintained)

I like the definition in parentheses, but I've removed the Wiktionary link because it's the specific definition of "pathological" that's confusing here, not the general definition. The average reader will know that "pathological" means of or related to a disease/disease-causing, but the way it's used in this specific case that's potentially misleading. We laypeople usually think of pathogens (bacteria, viruses, parasites, etc.) when we hear the word "pathological", not illicit drugs. AmericanLemming (talk) 08:10, 14 September 2014 (UTC)

• “supplemental magnesium” if this is a possibly effective treatment, why don’t we mention it with fluoxetine and imipramine above?

The main reason is that it was from a different review. WP:MED has a thing for Cochrane reviews in particular (the one that mentioned fluoxetine/imipramine) because they're extremely rigorous evidence-based systematic reviews (their reviews are arguably the highest quality medical sources). Since the magnesium review wasn't systematic (i.e., the evidence quality wasn't quite as high), I figured I should separate them. That said, the magnesium review also mentioned fluoxetine, which is why I noted that it agreed/corroborated with the Cochrane review. Seppi333 (Insert 2¢ | Maintained)

• “as been shown to reduce self-administration in both humans and lab animals” meaning that they give themselves smaller doses of amphetamine/give themselves amphetamine less often? I’m not sure exactly what “self-administration” means. AmericanLemming (talk) 07:16, 5 September 2014 (UTC)

Self-administration in a lab animal is essentially the of a drug by an animal that has free access to large quantities of the drug. So in this context, it means the amount of freely accessible drug that an animal in the treatment group uses is reduced compared to an animal in the control group. Seppi333 (Insert 2¢ | Maintained)

Life keeps getting in the way of Wikipedia; I'm going to be really busy until Friday morning this week, but after that I should be able to power through a section or two. Between two essays and my Friday biochemistry test, I don't have much time to spare until the weekend. AmericanLemming (talk) 04:40, 9 September 2014 (UTC)

Update: I've finished going through the prose of the Overdose section, though I do plan to go through it again, as it's hard to catch everything the first time around. One general note: I have some issues with the organization of the section, particularly with the beginning and ending and with the subheadings. See the suggestions below. I would like to log in every day and keep an eye on developments here, but in reality we're probably looking at middle to end of next week or possible next weekend; I'm kind of busy through Wednesday. AmericanLemming (talk) 09:09, 14 September 2014 (UTC)

1. This section is technical enough that I think a introduction paragraph is warranted. Give the general reader the bottom line about the most effective treatments, give a simplified description of the bimolecular mechanism of addiction, ditto with psychosis, toxicity, and withdrawal. Don't make them go digging for what they're looking for, especially when some of the content is highly technical.

2. Also, I don't think the "Psychosis" and "Toxicity" sections are long enough to warrant their own level 3 headings when "Dependence and addiction" is a level 3 heading with five paragraphs and those two are half-paragraphs. I suggest either significant expansion, consolidation of the two into one level 3 heading subsection, or addition to the top of the section with the rest of the overdose symptoms.

3. Put the Overdose symptoms into a chart as we talked about above and then move the giant annotated image further down so we're not sandwiching text between images.

4. I have some more ideas for rearranging and adding/moving subsection headers, but I'll wait on those until we've decided what to do with the above three proposals. AmericanLemming (talk) 09:09, 14 September 2014 (UTC)

And now for the prose comments for the rest of the section:

• “Cognitive behavioral therapy” Could we give a brief definition in-text?
• “Cognitive behavioral therapy is currently the most effective clinical treatment for psychostimulant addiction” So even though it’s the most effective clinical treatment, isn’t that based on extremely limited evidence? Or does the Cochrane Collaboration review from the “Pharmacological treatments” subsection only refer to drugs?
• The last sentence in the “Behavioral treatments” paragraph is pretty much unintelligible to the general reader. While I think the whole sentence is in need of some improvement, the very last part is the worst offender: I’ll start from the beginning of the sentence and take it by parts:

  1. “aerobic exercise decreases psychostimulant self-administration” I added a definition of self-administration in the above paragraph, so this is good.

  2. “attenuates sensitization to the rewarding effects of psychostimulants” So basically you don’t feel as good when you take the drug?

  3. “reduces the reinstatement of drug-seeking behavior” So you’re less likely to relapse?

  4. induces opposite effects on striatal dopamine receptor D2 signaling to those induced by pathological stimulant use.” What are the “opposite effects” on striatal dopamine receptor D2 signaling caused be aerobic exercise, and what are the effects caused by pathological stimulant use?

• “Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain.” Based on what I read later, I take it that “certain parts of the brain” really means the nucleus accumbens. How about “in certain parts of the brain, especially the nucleus accumbens”?
• “The most important transcription factors” I would suggest adding a note explaining the role of transcription factors in gene expression.
• “since its overexpression in the nucleus accumbens is necessary and sufficient for many of the neural adaptations seen in drug addiction” I assume you’re referencing necessary and sufficient cause here, but the fact that you neither mention the word “cause” nor link to Necessary and sufficient causes is cause for confusion. Also, why is ΔFosB considered a “necessary and sufficient cause” of these neural changes? And what are these neural adaptations, anyway? If the neural adaptations are talked about in the caption to the giant annotated image, you should add “(see caption below image to the right)” so people can read up on that if they want to.
• “Since natural rewards induce ΔFosB just like drugs of abuse do” What does it mean that they “induce” ΔFosB? They cause the body to make more of it?
• “and amphetamine-induced sex addictions.” Do these amphetamine-induced sex addictions occur frequently at therapeutic and/or recreational doses? How does amphetamine cause sex addictions? Does an amphetamine-induced sex addiction mean that you’re addicted to both amphetamine and sex? I’m not harping on this just because it mentions sex; I feel that the sentence as is introduces a condition/disease without really explaining it.
• “Psychosis” subsection: I feel that the current length of this section doesn’t do the topic justice. We don’t need four full paragraphs about it, but how about 8-10 sentences instead of the current four?
• “Toxicity” subsection: Same concern as with the Psychosis subsection. Again, I’d feel much more comfortable with the article’s comprehensiveness with 8-10 sentences here instead of three.
• Actually, as I come to think about it, how about we expand the above two subsections slightly, delete the subsection headings, and then move them to the topic of the section where the other overdose side-effects are found?
• “Manufacturer prescribing information does not indicate the presence” Which manufacturer? Or are we talking about US FDA prescribing regulations? I’m confused. AmericanLemming (talk) 09:09, 14 September 2014 (UTC)

I've been stupidly busy the past two weeks, but I'll have some spare time this week to work on this. Sorry for the delay! Seppi333 (Insert 2¢ | Maintained) 18:53, 28 September 2014 (UTC)

No worries. Considering how long it's been taking us to go through the article, it will probably be archived before we finish, but we can just continue the review on the talk page and renominate when we're good and ready. AmericanLemming (talk) 00:14, 29 September 2014 (UTC)

I've finally managed to create the OD symptom table (I'm seeking feedback on it before adding it to the article - a tentative version is in my sandbox at the moment), though I probably won't get to these recent points you've added until tomorrow. I'm a bit behind on my editing, but I'll address these issues soon enough. Seppi333 (Insert 2¢ | Maintained) 00:30, 8 October 2014 (UTC)

Comments for Nikkimaria

@Nikkimaria: I believe I've addressed your three bulleted concerns from the previous review, though I'm not entirely certain what you were referring to when you mentioned the italics; was this present in the refs, the article, or both? I made a few cuts in the article where the added stress wasn't completely necessary. Seppi333 (Insert 2¢ | Maintained) 21:00, 16 August 2014 (UTC)

Forgot to mention: I followed the ref formatting for the medication guide work/publisher fields as used on Bupropion, since it's the only current pharmaceutical FA and it recently went through a FAR. Most of the citations from accessdata.fda.gov used on amphetamine are drafted/published by a pharmaceutical company and hosted on that site. Consequently, I ended up placing the pharmaceutical company that copyrighted the medication guide in the publisher field to maintain concordance with bupropion's formatting. Seppi333 (Insert 2¢ | Maintained) 10:51, 17 August 2014 (UTC)

Comments from Axl

• From the lead section, paragraph 1: "Based upon the quantity of seized and confiscated drugs and drug precursors worldwide, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine; however, in some parts of Europe, amphetamine is more prevalent than methamphetamine." It is unclear to me why the lead section specifically draws a comparison with the prevalence of methamphetamine. This comparison is only helpful if the reader already has an idea of the usage of methamphetamine. (I certainly don't know that.) Why not mention cannabis, MDMA, or cocaine? Axl ¤ [Talk] 18:35, 17 August 2014 (UTC)

@Axl:The lead statement was a summary of Amphetamine#History, society, and culture, specifically the statements "Amphetamine is still illegally synthesized today in clandestine labs and sold on the black market, primarily in European countries.[23] Outside Europe, the illicit market for amphetamine is much smaller than the market for methamphetamine.[23]" The comparison to meth in that section was included for two reasons: the first is the amalgamation of amphetamine and methamphetamine's society and culture sections into the history and culture of substituted amphetamines article (they have a fair amount of overlapping historical/sociocultural aspects, hence the merge). The second reason is that amphetamine, MDMA, and methamphetamine were grouped together in a very large section with detailed analysis/comparison in the World Drug Report ref, e.g., see pages 123-135(they share very similar synthesis methods and precursor compounds). Cocaine/cannabis were covered in different sections with no comparisons to amphetamine-type stimulants. Seppi333 (Insert 2¢ | Maintained) 20:28, 17 August 2014 (UTC)

Forgot to mention: MDMA was also included in the lead comparison a while ago, but Exercisephys removed it. The illicit production of MDMA is much less prevalent than amphetamine/methamphetamine production though (it's harder to make and the precursors are more difficult to acquire than amph/meth). I can re-add it to the lead and body if you think it's worth including. Seppi333 (Insert 2¢ | Maintained) 20:41, 17 August 2014 (UTC)

I don't think that it is helpful to the reader to include a comparison with methamphetamine and/or MDMA in the lead section. It would be far more useful to indicate how many people use amphetamine illegally. This source might be helpful. Perhaps you could provide some sort of ranking among the illicit drugs (in terms of prevalence of use)? Also, there should be an indication somewhere in the article of the amount of money (street value?) of amphetamine sold per year.

All of this information doesn't necessarily need to be in the lead section, but it certainly should be in the article. Axl ¤ [Talk] 10:31, 18 August 2014 (UTC)

Per your suggestion, I've added the usage statistics of "amphetamines" (amph/meth) over the past year in the EU member states. Since price for amph varies locally in the EU (6-38 euros/g), I used the total confiscated mass instead of total average street value. Diff Seppi333 (Insert 2¢ | Maintained) 13:41, 18 August 2014 (UTC)

I'm not sure why you rounded 0.9% up to "roughly 1%". Otherwise, the information that you have added is helpful. However that source has more information available. It includes an estimate of price (either €6–38 or €9–23 per gram) and variation in purity. Ideally, I would like to see an estimate of total usage rather than seizure. Also, I would like to see a ranking of prevalence among the other illicit drugs.

I note that you did not remove the comparison with methamphetamine from the lead section. Axl ¤ [Talk] 18:00, 18 August 2014 (UTC)

Diff - Better? Seppi333 (Insert 2¢ | Maintained) 19:32, 18 August 2014 (UTC)

Yes, thank you! Although I am a little surprised that the source separates opiates from opioids. My understanding is that opiates are directly derived from opium, while opioids also include the synthetic/semi-synthetic drugs. Axl ¤ [Talk] 20:26, 18 August 2014 (UTC)

• From the lead section, paragraph 2: "Presently, it is typically prescribed as Adderall." "Presently" is often used to mean "Soon". Perhaps "Currently" would be better? Also, "it" could be inferred to mean "Benzedrine" on the basis of the preceding sentence. It may be better to spell out "pharmaceutical amphetamine". Axl ¤ [Talk] 17:06, 19 August 2014 (UTC)

Done. Seppi333 (Insert 2¢ | Maintained) 04:11, 20 August 2014 (UTC)

Thanks. Axl ¤ [Talk] 10:48, 20 August 2014 (UTC)

• From "Uses", subsection "Medical", paragraph 1: "Long-term amphetamine exposure in some animal species is known to produce abnormal dopamine system development or nerve damage, but, in individuals with ADHD, stimulants appear to improve brain development and nerve growth." The term "stimulants" is rather vague. Perhaps change this to "amphetamine" or "stimulants such as amphetamine"? Axl ¤ [Talk] 10:57, 21 August 2014 (UTC)

Diff - this is more or less how it was written a week or two ago. Lots of edits to this section recently. Seppi333 (Insert 2¢ | Maintained) 11:59, 21 August 2014 (UTC)

That doesn't help. What are "ADHD stimulants"? These could be inferred to mean environmental factors that provoke ADHD. Actually, on second thoughts, my second suggestion would be better as "stimulant drugs such as amphetamine". Axl ¤ [Talk] 17:05, 21 August 2014 (UTC)

Diff - this better? Little more succinct. Seppi333 (Insert 2¢ | Maintained) 17:26, 21 August 2014 (UTC)

Yes, thank you. Axl ¤ [Talk] 17:40, 21 August 2014 (UTC)

• From "Uses", subsection "Medical", paragraph 1: "Magnetic resonance imaging studies suggest that long-term treatment with amphetamine ... improves function of the right caudate nucleus and other parts of the brain involved in dopamine transmission." I am not sure that "involved in dopamine transmission" is the best phrase. This seems to imply that dopamine transmission is an aim in itself. How about "that utilize dopamine transmission". Axl ¤ [Talk] 10:04, 27 August 2014 (UTC)

I figured it might be simpler to just word it like this: Diff. How's that look? Seppi333 (Insert 2¢ | Maintained) 07:59, 30 August 2014 (UTC)

Thanks. Axl ¤ [Talk] 18:57, 31 August 2014 (UTC)

• In "Uses", subsection "Medical", paragraph 3 includes note 6, which describes the anatomical locations of dopamine & norepinephrine neurotransmission. Could this information be worked into the body of the text rather than as a note? Axl ¤ [Talk] 19:33, 6 September 2014 (UTC)

If I recall correctly, the only reason that note was made was because Shudde complained that it was unnecessarily technical, but he's not reviewing the article anymore. The article text is basically just a simplified version of the text in the note; the note was originally the text in the article. I can just replace the article text with the note text if you'd like. Seppi333 (Insert 2¢ | Maintained) 20:14, 6 September 2014 (UTC)

I would be happy with that. I have invited Shudde to comment here. Axl ¤ [Talk] 19:54, 8 September 2014 (UTC)

Diff Seppi333 (Insert 2¢ | Maintained) 21:19, 8 September 2014 (UTC)

In the absence of any comment from Shudde, that is fine. Axl ¤ [Talk] 18:28, 10 September 2014 (UTC)

• From "Uses", subsection "Medical", paragraph 4: "A Cochrane Collaboration review on the treatment of ADHD in children with tic disorders indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine in such people should be avoided." I think that we may have discussed this point during a previous FAC. Does the statement imply that it is acceptable to give high doses to ADHD children without tics? Why should high doses be avoided? I am only able to view the abstract of the reference. It does not seem to examine children without tics at all. From the reference's abstract, it seems that high doses might exacerbate tic disorder, but the evidence is not that strong. Axl ¤ [Talk] 20:19, 8 September 2014 (UTC)

Paywalled journal source link. Link to that Cochrane review. The statements in the Cochrane review are only relevant for children with ADHD and comorbid tic disorders, so that statement isn't relevant to child ADHD without comorbidity. High dose dextroamphetamine use in that study increased the risk of exacerbated tic symptoms without additional treatment benefit compared to low doses (see page 11), hence their conclusion to avoid high doses. Seppi333 (Insert 2¢ | Maintained) 21:19, 8 September 2014 (UTC)

I guessed that that was the intended meaning. However the current text could be inferred to mean that high doses of dextroamphetamine could be useful in people without tics. Axl ¤ [Talk] 18:34, 10 September 2014 (UTC)

• From "Medical", subsection "Enhancing performance", paragraph 1: "Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform a task) and increase arousal." Could you clarify the meaning of "arousal" in this context please? (Perhaps "wakefulness"?) Axl ¤ [Talk] 21:52, 14 September 2014 (UTC)

• Arousal has a perfect description. Wakefulness is a suitable simplified substitute for the term. Seppi333 (Insert 2¢ | Maintained) 07:27, 16 September 2014 (UTC)

Can you incorporate this into the article please? Axl ¤ [Talk] 09:10, 16 September 2014 (UTC)

Thanks. Axl ¤ [Talk] 12:03, 30 September 2014 (UTC)

• From "Contraindications": "People who have experienced allergic reactions to other stimulants in the past or are taking monoamine oxidase inhibitors (MAOIs) are advised not to take amphetamine." The FDA reference indicates that hypersensitivity to sympathomimetic amines or use of MAOIs are contraindications. Axl ¤ [Talk] 19:50, 2 October 2014 (UTC)

Sympathomimetic amines are actually a chemical subclass of stimulants (sympathomimetics are drugs which increase activity of the sympathetic nervous system; sympathomimetic amines are those which also possess an amine group, e.g., catecholamines), so I just simplified the language and used the broader term "stimulants" instead. I did this mainly to keep the section accessible for the layperson. I imagine anyone prescribing an amphetamine pharmaceutical isn't using wikipedia as their primary reference for contraindictions, so I wasn't worried about making this section very precise/technical when I wrote it. I can specify this with "stimulants (specifically, sympathomimetics)" if you prefer though. Seppi333 (Insert 2¢ | Maintained) 23:24, 6 October 2014 (UTC)

Comments from Tezero

Support; haven't read through it in detail but everything looks to be in order. I suppose if I had one complaint, it'd be that the page is unclear at points as to what specifically amphetamine is, but that can be explained by the ambiguity of the term in common use as mentioned in the intro, so I don't have a problem with it. Tezero (talk) 04:30, 25 August 2014 (UTC)

Comments from Anypodetos

Seppi told me the Overdose section has changed considerably since my last review, so I'm focusing on this.

• "hyperthermia" → "elevated body temperature" or "elevated body temperature" or "hyperthermia (elevated body temperature)"?

Pasted "hyperthermia (elevated body temperature)" per your suggestion. :) Seppi333 (Insert 2¢ | Maintained)

• Does addiction/withdrawal belong here? MOS:MED says withdrawal belongs into the side effects section.

Amphetamine withdrawal (technically a misnomer) only occurs in response to excessive binges, so it makes more sense to place this under overdose; the phenomenon is essentially a rebound effect from a drug binge as opposed to an actual episode of withdrawal associated with physical dependence though. Withdrawal is actually a concept related to addiction (clinically: substance dependence), so it would normally be appropriate to place it as a subsection of addiction or dependence, but as I mentioned before, amphetamine withdrawal is less a case of true withdrawal than a rebound effect.
I actually plan to bring this section ordering issue up on the MOS:MED talkpage soon since the current MOS ordering is unusual. Seppi333 (Insert 2¢ | Maintained)

• Behavioral treatments:

• "adjunct treatment (supplemental treatment)" → simply "supplemental treatment"? Does the word "adjunct" add anything here?

I'm ok with removing adjunct if you'd prefer. An adjunct treatment is basically one which is used together with a primary treatment and never by itself. It's a little more exact than "supplemental", though its meaning is probably only apparent to clinicians. Seppi333 (Insert 2¢ | Maintained) 22:08, 6 October 2014 (UTC)

• "and induces opposite effects on striatal dopamine receptor D2 signaling to those induced by pathological stimulant use" → "and induces effects on striatal dopamine receptor D2 signaling opposite to those induced by pathological stimulant use" would save the reader the question "opposite to what?"

I'm planning to reword this by the end of the day; that paragraph is essentially a summary of the "psychostimulants" and "exercise" columns in the table at ΔFosB#Summary of addiction-related plasticity. I'll reply here when I'm done. Seppi333 (Insert 2¢ | Maintained)

• Image: (cool one)

Thanks! It took a lot of time to make. Seppi333 (Insert 2¢ | Maintained)

• Wikilink the words in "Color legend 1"? (ion channel etc.)

Done. Seppi333 (Insert 2¢ | Maintained)

• NMDA receptor co-agonist: This is amphetamine (or a similar drug) to judge from the text? Could you clarify this in the image?

The co-agonist would be one of the body's endogenous ligands (e.g., D-serine or glycine); there's a few, so I didn't specify one. I'm not sure which molecule is the primary agonist is in this region, assuming there is one. I noted glutamate as the co-agonist at the first binding site (which also binds aspartate) since amphetamine promotes glutamate release in the nucleus accumbens. I could note these two agonists (D-serine & glycine) in the legend instead of "NMDA receptor co-agonist" if you think it's a better substitute. Seppi333 (Insert 2¢ | Maintained)

• "Following presynaptic dopamine and glutamate co-release by a drug" → "Following presynaptic dopamine and glutamate co-release by such psychostimulants / by one of these psychostimulants"?

Fixed - I've used the first statement you've suggested in the caption. Dopamine and glutamate function as cotransmitters in the nucleus accumbens (essentially, neurotransmitters which co-release), so any drug which promotes mesolimbic dopamine neurotransmission will indirectly increase/promote glutamate neurotransmission in that pathway. Seppi333 (Insert 2¢ | Maintained)

Sorry for any duplicates; I admit I haven't read all of the above comments.

No problem, and thank you again for doing this! :) Seppi333 (Insert 2¢ | Maintained) 22:08, 6 October 2014 (UTC)

Otherwise, and given that the rest of the article hasn't changed significantly since my last review, I support promotion to FA status. --ἀνυπόδητος (talk) 09:29, 29 September 2014 (UTC)

• Closing note: This candidate has been withdrawn, but there may be a delay in bot processing of the close. Please see WP:FAC/ar, and leave the {{featured article candidates}} template in place on the talk page until the bot goes through. Ian Rose (talk) 11:16, 8 October 2014 (UTC)

The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.