Wikipedia:Featured article candidates/Amphetamine/archive5


 * 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 promoted by Graham Beards via FACBot (talk) 12:34, 14 January 2015 (UTC).

Amphetamine

 * Nominator(s):  Seppi  333  (Insert 2¢ &#124; Maintained) & Boghog (talk) 00:25, 6 December 2014 (UTC)

I'd be surprised if anyone doesn't know what this article is about, based from the name alone, so I'll forego a description.  Seppi  333  (Insert 2¢ &#124; Maintained) 00:25, 6 December 2014 (UTC)

Comments from AmericanLemming
I'm renominating this now, though I assume you'll be busy until later in the month, so no worries. I've made this section for you in advance.  Seppi  333  (Insert 2¢ &#124; Maintained) 00:25, 6 December 2014 (UTC)


 * I quickly went through the Interactions subsection to give you some new comments to work with, but I need a few days to reread the first half of the article, both to refamiliarize myself with the material and tweak the prose further if need be. I also need to look at the "Overdose" section again and take a look at the changes you've made in response to my comments. Reviewing this is priority number one for my Christmas break, so I should be able to finish it before classes start up again. AmericanLemming (talk) 08:11, 15 December 2014 (UTC)

Lead Just finished reading through this part. It looks well-written, well-organized, and well-sourced. The first paragraph is a bit on the long side, as is the lead as a whole, but I'm not really sure you can cut anything out without losing something important. My four comments/questions are as follows:
 * “At therapeutic doses, this causes emotional and cognitive effects such as euphoria, change in libido, increased arousal, and improved cognitive control. It induces physical effects such as decreased reaction time, fatigue resistance, and increased muscle strength.” This wording implies to me that there aren’t any side effects at therapeutic doses, which probably isn’t the case.
 * After rereading it, I think I agree about the sentence on physical effects. The statement on psychological effects seems more or less neutral, since increased arousal can lead to insomnia or increased wakefulness. Similarly, changes in libido can be desirable or undesirable depending on the individual.  I'll tweak the the physical effects clause over the next day or so to address this.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * Now that I look at it again, just leave the sentence alone. Sometimes less is more, and I think making it any wordier would decrease the intelligibility to the general reader. Besides, it is correct as it stands.
 * Good point; I'm okay with that.  Seppi  333  (Insert 2¢ &#124; Maintained) 08:59, 10 August 2014 (UTC)


 * “Very high doses can result in a psychosis (e.g., delusions and paranoia) which rarely occurs at therapeutic doses even during long-term use.” First, “a psychosis” sounds awkward to me. If it’s consistent with medical terminology, then by all means keep it, but otherwise I would drop the “a”. Second, so it’s pretty difficult to die of an overdose of amphetamine? That’s the impression I’m getting here.
 * There's different types of psychoses, though I agree it sounds weird so I'd be ok with removing it. As for overdoses, it's pretty rare to die from an overdose when medical treatment is sought.  The doses that recreational users take are roughly 10-100 times higher than the maximum dose when its used medically.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * I've gone and removed the "a".


 * “Unlike methamphetamine, amphetamine's salts lack sufficient volatility to be smoked.” So if you can inhale amphetamine (see infobox), why can’t you smoke it? Or am I confusing smoking cigarettes and smoking other drugs?
 * The salts can't be smoked, but they can be snorted (insufflated) as a powder. That's really only a recreational route though.  The medical route involves inhaling small amounts of the freebase via an inhaler (e.g., File:Benzedrine_inhaler_for_wiki_article.jpg).  Unlike the salts, the freebase is a liquid at room temperature and CAN be smoked. Illicit amphetamine is almost never trafficked/sold as the freebase, which I'm assuming is due to its volatility.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “Amphetamine is also chemically related to the naturally occurring trace amine neurotransmitters, specifically phenethylamine and N-methylphenethylamine” Two questions here: 1. Does phenethylamine = trace amine neurotransmitters? 2. Is it that amphetamine is chemically related to trace amine neurotransmitters but is most closely related to phenethylamine and N-methylphenethylamine? That’s what it sounds like to me. AmericanLemming (talk) 06:26, 4 August 2014 (UTC)
 * Both phenethylamine and N-methylphenethylamine are trace amines; N-methylphenethylamine is the most closely chemically-related trace amine to amphetamine since it's an amphetamine isomer. If you can think of a better way to word it, feel free to change it!  Seppi  333  (Insert 2¢ &#124; Maintained) 19:06, 5 August 2014 (UTC)
 * I've taken a shot at that; please do double-check to make sure it's accurate.
 * Looks good.  Seppi  333  (Insert 2¢ &#124; Maintained) 08:59, 10 August 2014 (UTC)

I've made two edits to the lead, and I think that will do. The lead is meant to be the most accessible part of the article, and it really isn't the place to be explaining nuances and technicalities.

Medical
 * Question about this section in general: when we’re talking about medical uses of amphetamine, we’re almost always talking about Adderall, right?
 * Adderall (no generic name - i.e., a USAN/INN - even though it's almost always sold as a generic), dextroamphetamine (tons of brand names/generic forms), and lisdexamfetamine (brand:Vyvanse, still patented) are the currently available amphetamine-based pharmaceuticals; it covers this group of drugs.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “Magnetic resonance imaging studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function of the right caudate nucleus.” So it decreases abnormalities in brain structure and function in general and improves function of the right caudate nucleus in particular? If that’s so, I would suggest changing the second half to “ADHD; in particular, it improves the function of the right caudate nucleus.”
 * The caudate nucleus was one example that was highlighted in one of the reviews; there's improvement in function in more than one brain structure along the dopamine pathways that it acts upon.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “but high doses of dextroamphetamine in such people should be avoided.” Because of the side effects? Long-term damage to some part of the body?
 * It exacerbates motor tics in people with Tourette's, which is a harmless but undesirable/annoying side-effect.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “task saliency” this may warrant a quick note to define saliency; the Wikipedia article on the subject isn’t terribly helpful.
 * Good point; I'll go through later today and add this based upon the definition used in the textbook that cited that passage.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * - Diff  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “but this is prohibited at events regulated by the World Anti-Doping Agency.” From what I can gather, the World Anti-Doping Agency regulates just about every international and professional sporting event. I think this warrants another note/quick explanation in text, perhaps.
 * That's fine with me if you'd like to add this. Found a suitable ref, how's this look? Diff   Seppi  333  (Insert 2¢ &#124; Maintained)
 * Better and worse. On one hand, I think adding the "regulated by collegiate, national, and international anti-doping agencies" does a much better job of explaining that amphetamine is widely prohibited in sporting events; on the other hand, expanding the tidbit about the World Anti-Doping Agency (WADA) turned the sentence into a run-on. I've trimmed the part on WADA to fix the sentence, and I think you could cut it out entirely if you wanted to. Your fix (adding "regulated by collegiate, national, and international anti-doping agencies") was a lot better than the one I suggested, and we don't need both. AmericanLemming (talk) 06:30, 11 August 2014 (UTC)
 * the WADA mention - insisted I add it during the FAC review that he didn't finish. I didn't really want it to include it anyway - seemed like trivia.  Seppi  333  (Insert 2¢ &#124; Maintained) 16:00, 11 August 2014 (UTC)


 * “In healthy people at oral therapeutic doses, amphetamine has been shown to increase physical strength, etc.” It may be worthwhile mentioning that there are some minor side-effects, even in healthy people at oral therapeutic doses. Otherwise, why aren’t we all on amphetamine? :)
 * There's actually a lot of discussion among the academic community about the use of performance enhancing agents in the general population (e.g., this paper elicited quite a lot of responses). It was only recently determined that low doses of ADHD psychostimulants improve cognitive control in everyone via their effect on dopamine D1 receptors in the prefrontal cortex.
 * Back to the issue: I tried to keep this section disjoint from the side effects section to avoid redundancy and maintain neutrality when covering it. I think it'd be alright to mention that there are additional physical side effects in that paragraph; however, I'm not sure it's a good idea to re-list the physical side effects alongside these, since it's both redundant with the side effects section and isn't relevant to the performance enhancing effect. This list of physical enhancement effects isn't included in the side effects section for the same reason. That said, I'll go ahead and add a clause mentioning the presence of additional side effects if that's what you had in mind.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * I would suggest adding something along the lines of "At these doses, the side effects are minimal." That's enough to help the reader keep the existence of side effects in mind without the unnecessary repetition of listing them all in two places. AmericanLemming (talk) 06:47, 11 August 2014 (UTC)
 * –  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Also, with that same sentence, it does seem that this is one place where WP:OVERKILL might apply. I understand that the article’s on a fairly technical subject, but do you really need four inline citations of the exact same two sources for four words in a row? I suggest you put all three sources at the end of the sentence, like you do elsewhere. AmericanLemming (talk) 09:03, 6 August 2014 (UTC)
 * I'd be okay with grouping them at the end of the sentence, though the main reason I did this is because the performance enhancing use of these drugs has generated much controversy, and until recently there hasn't been much high quality research/review supporting these effects in humans. I imagine that some people reading this article might come into it with a bias, which is why I cited them by effect.  I'll go ahead and group the citations if you think it improves readability - let me know.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * I recommend doing that. Besides, you quote directly from the source in the inline citation, so if someone doubts whether the sentence is true they can just mouse over the citation and read it for themselves. And as it currently stands it's just hard to read. AmericanLemming (talk) 06:53, 11 August 2014 (UTC)
 * ✅ –  Seppi  333  (Insert 2¢ &#124; Maintained)

Sorry for the late follow-up; I've been pretty busy this past week. I'll address these points momentarily! Regards,  Seppi  333  (Insert 2¢ &#124; Maintained) 16:16, 9 August 2014 (UTC)

Contraindications
 * I don’t think there’s anything in the manual of style against a one-paragraph section, but it does look somewhat odd. What do you think about combining the “Contraindications” section with the “Interactions” section? The “Interactions” section does a nice job of explaining why people with certain conditions or on certain drugs (MAOIs, for instance) shouldn’t take amphetamine.
 * I actually agree that it would make sense to combine these, since serious drug interactions give rise to contraindications; however, the current layout of level-2 headers is indicated in MOS:MED, so I can't really deviate from the present state. Barring unusual or unique circumstances, there isn't much wiggle room in the section ordering.  Seppi  333  (Insert 2¢ &#124; Maintained) 14:19, 11 August 2014 (UTC)
 * After further thought, I think it may be better to keep these sections separate; most of the drug databases we link to in the drugbox don't provide this information together. The FDA uses distinct sections for the information as well.  Seppi  333  (Insert 2¢ &#124; Maintained) 18:17, 12 August 2014 (UTC)
 * I agree with you; you really can't go against the MOS, especially when you want to get the article to FA status. As the next best alternative, I've added explanatory hatnotes to each section that tell the reader what the section is about and that direct them to the other section if that's not what they were looking for. AmericanLemming (talk) 06:39, 13 August 2014 (UTC)
 * I think it might be best to use see also templates here, since some of the contraindications aren't substance-related. It seemed a bit difficult for me to summarize the relationship in a hatnote without it being really long. The first sentence of each section (I think) more or less implies how they're related though.  Seppi  333  (Insert 2¢ &#124; Maintained) 09:31, 13 August 2014 (UTC)

I've clarified the point in the contraindications section. diff These are the references cited: see P125-127, see page 2-4, see P546.  Seppi  333  (Insert 2¢ &#124; Maintained) 18:17, 12 August 2014 (UTC)
 * “Due to the potential for stunted growth, the USFDA advises monitoring the height and weight of children and adolescents prescribed amphetamines.” This contradicts the statement in the first paragraph of the “Medical uses” section that “humans experience normal development and nerve growth”. Do humans experience normal development when using amphetamine or not? AmericanLemming (talk) 07:20, 11 August 2014 (UTC)
 * It's technically a transient effect due to a rebound growth spurt associated with a temporary cessation of treatment. IIRC, all dopaminergic stimulants suppress growth hormone release in adolescents (see page 4, paragraph 2 in this ref), so it's not unique to amphetamine.  See section 5.3 of this ref for more detail.  Seppi  333  (Insert 2¢ &#124; Maintained) 14:19, 11 August 2014 (UTC)
 * Follow-up: After rereading the sentence I wrote in medical uses, I noticed there isn't actually a contradiction here. The full statement in medical uses is:"Long-term amphetamine exposure in some species is known to produce abnormal dopamine system development or nerve damage,[35][36] but humans experience normal development and nerve growth." The "normal development" is in reference to the development of neural systems (not just dopaminergic systems) and the brain, as opposed to the body and physical development.  All the citations included in that sentence are confined to this context as well.
 * I've changed "normal development" to "normal brain development" and similarly tweaked the note added in the "Contraindications" section. AmericanLemming (talk) 06:54, 13 August 2014 (UTC)

Side effects
 * “Amphetamine may reduce gastrointestinal motility (i.e., intestinal peristalsis) if intestinal activity is high, or increase motility if the smooth muscle of the tract is relaxed.” I have no idea what this sentence means. You do a really nice job explaining what “contraction of the urinary bladder sphincter” means in plain English earlier in this paragraph; I would use that as a model here. AmericanLemming (talk) 07:20, 11 August 2014 (UTC)
 * clarification earlier - I forgot to reply here after I did this. Please let me know if the current section is understandable! The current version:"If intestinal activity is high, amphetamine may reduce gastrointestinal motility, i.e., the rate at which content moves through the digestive system; however, amphetamine may increase motility when the smooth muscle of the tract is relaxed." Seppi  333  (Insert 2¢ &#124; Maintained) 18:19, 12 August 2014 (UTC)
 * Much better. I've put the definition in parentheses. Personally, I'm curious to know what causes the smooth muscle of the gastrointestinal tract to relax, but I'm not sure if the average reader shares my interest. :) AmericanLemming (talk) 07:02, 13 August 2014 (UTC)
 * I'm not entirely sure to be honest. The enteric nervous system isn't well understood at the moment.  Seppi  333  (Insert 2¢ &#124; Maintained) 20:47, 15 August 2014 (UTC)

Overdose 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)


 * Most of that section is arranged according to MOS:MED and a current proposal on MOS:MED's talkpage. Addiction is in that section because the phenomenon only develops with chronic high-dose use; it literally requires a pathological overactivation of the mesolimbic DA pathway (either directly through DA receptors or indirectly through a possibly complex mechanism, e.g., alcohol).  Toxicity is an indicated subsection of overdose, so it kind of needs to be there.  I could merge toxicity and psychosis into one section if you'd prefer.  Seppi  333  (Insert 2¢ &#124; Maintained) 03:37, 11 October 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?
 * I'm not sure this would be easy for me to define succinctly... e.g., see Cognitive behavioral therapy. I could probably define it in a note, I'd be more or less be restating parts of that section.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “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?
 * Cochrane's review was just pharmacological therapy. Seppi  333  (Insert 2¢ &#124; Maintained)


 * 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?
 * I'm just deleting that clause because its explanation is a lot longer than the clause itself. I'm not sure it affects reward perception necessarily; psychostimulant sensitization involves an increased of dopamine response in the nucleus accumbens from psychostimulant use, which increases the likelihood of developing an addiction.


 * 3. “reduces the reinstatement of drug-seeking behavior” So you’re less likely to relapse?
 * Yep, I've noted this.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * 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?
 * I think I've addressed this. Let me know.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “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”?
 * ✅  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “The most important transcription factors” I would suggest adding a note explaining the role of transcription factors in gene expression.
 * I need to find a MEDRS-quality source first, but I intend to do this.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * ✅ Added this as a note next to the first use of the "transcription factor" phrase.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “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.
 * I meant to link to necessary and sufficient; I did it in other articles, but oddly enough, I missed it here. Essentially it means that the plasticity of addiction and ΔFosB overexpression always occur together, never alone.  It's necessary and sufficient because it's been observed to produce this plasticity with viral overexpression (using viral vector gene transfer) and their occurrence doesn't occur with a viral block of ΔFosB expression (i.e., viral overexpression of ΔJunD opposes ΔFosB and hence this plasticity with concurrent drug use). This is rather technical - the reference that quotes that sentence explains it more. As for the plasticity, some of it is indicated in the psychostimulant column of the table below, which I've transcluded to several articles from FOSB.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “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?
 * It means it increases gene expression of ΔFosB. I've clarified this and linked to inducible gene with a pipe as "Since natural rewards induce expression of ΔFosB..."  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “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.
 * I clarified the text a little and added the appropriate quote to the reference ("In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex"). It's simply compulsive sexual behavior as a result of amphetamine use.  There is a notable interaction between reward perception with sexual behavior and amphetamine use, and an overactivation of DA networks involved in reward perception and reinforcement mediate that phenomenon.  I actually rewrote sex addiction recently to try to explain that concept better (and because I got into an edit war with another editor...). Let me know if you think it needs more work in the article.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “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?
 * I'll look through the Cochrane review soon and see if I can add more material. Most of the content in the amphetamine psychosis section either isn't particularly relevant (e.g., first paragraph) or isn't cited by a MEDRS-quality source.  Seppi  333  (Insert 2¢ &#124; Maintained) 03:47, 11 October 2014 (UTC)


 * “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.
 * There really isn't much to say about amphetamine toxicity in humans. Direct toxicity simply does not occur.  I could probably write a whole paper on direct DA toxicity in rats, but including that in the article would be sort of POV because it's misleading.  The mechanics of indirect toxicity are mediated entirely through oxidative events related to excessive dopamine release. I could probably add a sentence or two on its mechanics, but these are necessarily going to be fairly technical descriptions compared to the text currently in that section.   Seppi  333  (Insert 2¢ &#124; Maintained) 03:47, 11 October 2014 (UTC)


 * 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?
 * Due to the the MOS indications that I mentioned in a bullet, and the points I raised in the above two bullets, it may be best to simply combine the two sections if you'd prefer to have fewer subsections under the Overdose heading.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “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)
 * This actually refers to the prescribing information from all manufacturers of amphetamine pharmaceuticals. The prescribing information is under copyright, and they vary in format, but they're pretty much standardized in the information in they provide (I can link you to a few examples for amphetamine pharmaceuticals on pubchem if you'd like to see what I mean), even though it is copyrighted.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * I've pasted this from the review so that I can address/reply the points by issue here. I've added the table for the symptoms - let me know what you think. There was a small addition of content in the behavioral treatments section since you last checked it as well.  Seppi  333  (Insert 2¢ &#124; Maintained) 01:25, 11 October 2014 (UTC)

Seppi wanted an "edit source" button here
Lead through Side effects Reading through these first few sections again I made a few tweaks to the prose, but I have a lot fewer comments than I did the first time around. Rather than 30-40 I've only got five. AmericanLemming (talk) 03:37, 23 December 2014 (UTC) As for performance and cognitive enhancing use, anyone who is prescribed amphetamine pharmaceuticals can technically "misuse" it for such a purpose by taking it when it's needed for such a purpose as opposed to taking it a fixed number of times every day around the same time. It's also possible to acquire a prescription for an amphetamine without actually having a relevant medical condition... I'm not sure how common this is, but healthy individuals (often students) can feign symptoms of ADHD to acquire a prescription for amphetamine or methylphenidate for use as a cognitive enhancer. This technically is legal in spite of being a nonmedical use for a highly controlled (US schedule 2) substance.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * Lead: “Amphetamine is also used as a performance and cognitive enhancer” So while using it as “a performance and cognitive enhancer” is almost always illegal, such use is not considered recreational?
 * Recreational use is really just using a drug for the pleasure it provides. Virtually all drugs that are used recreationally (except certain hallucinogens/deliriants) are rewarding and consequently produce some form of high or desirable feeling. That property unfortunately also makes them addictive drugs.

That is, are “illegal drug use” and “recreational drug use” usually but not always synonymous?
 * Dextromethorphan (brand: Robitussin - where the phrase "robo tripping" comes from) is an OTC recreational drug, so uncontrolled/OTC recreational drugs do exist. This example is actually covered in detail at Recreational use of dextromethorphan.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Lead: “which includes prominent substances such as bupropion, cathinone, MDMA (ecstasy), and methamphetamine.” Can all these compounds be synthesized from amphetamine and/or are they commonly synthesized from amphetamine? We might want to mention that.
 * They're not really synthesized, per se. They represent a compound which contains amphetamine in its skeletal structure (i.e., if you look at a structure diagram of one of these chemicals, the amphetamine skeletal structure is contained within it as a substructure.  You can think of substituted amphetamines as any chemical that can be formed ("described" might be a better term) by adding chemical groups onto the amphetamine compound. I don't think it's even possible to synthesize methamphetamine from amphetamine - Boghog expanded the chemistry section since I'm really not chem-savvy.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Lead: “Unlike methamphetamine, amphetamine's salts lack sufficient volatility to be smoked.” What exactly is the significance of this statement? That is, why is it in the lead? Does it make amphetamine less practical for recreational use than methamphetamine?
 * IIRC, smoking methamphetamine is the most common route of administration for taking methamphetamine recreationally. This basically says amphetamine salts can't be smoked, only the volatile liquid freebase can be (amphetamine is almost never stored as the freebase), making it much more difficult to smoke.  If you think it's not worth including, we can delete it.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * I've removed it. The general reader isn't going to be able to make sense of it without context, and given space constraints in the lead, we don't have room for that context. It's also somewhat off-topic; the article's about amphetamine, not methamphetamine. AmericanLemming (talk) 09:32, 9 January 2015 (UTC)


 * Medical: “Therapeutic doses of amphetamine improve cortical network efficiency,” as in the mesocorticolimbic pathway?
 * The ref indicates that it improves efficiency in the dorsolateral prefrontal cortex (which is part of that pathway) and the posterior parietal cortex (which isn't part of that pathway). These are included in the reference's quote parameter, so I imagine if someone is curious about which cortices become more efficient, they'd probably look there and see the quote.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Contradictions: Um, aren’t hypertension and elevated blood pressure the same thing? I ask because the whole “These agencies also state that anyone with…elevated blood pressure, etc.,” makes it sound like there’s some difference between them.
 * Fixed that by changing it to hypertension.  Seppi  333  (Insert 2¢ &#124; Maintained)

Overdose I just finished going through all of my old comments from this section and looking at your changes and responses. I'm now satisfied with the organization and comprehensiveness of the section, but the prose still needs some tweaking, some of which I can take care of and some of which I'll need to ask you about. I really like the table, by the way; it does a much better job of presenting the same information. Also, I think you should reread the section to make sure I haven't oversimplified anything in my relentless quest to make the article accessible to the general public. AmericanLemming (talk) 08:41, 25 December 2014 (UTC)
 * I’m not comfortable with the second paragraph. I think it does a pretty good job of summarizing the section, but I wrote almost all of it, so I’m not sure how accurate it is.
 * I tweaked it a tiny bit when I added some detail on how ΔFosB expression affects addictive behavior, but it looked fine.   Seppi  333  (Insert 2¢ &#124; Maintained)


 * I’ve reworded every sentence in this section (it feels like I have, anyway), and I’m worried that I’ve traded accuracy for readability in some places. You may want to read over the whole thing to make sure the facts are still straight.
 * I looked over the whole section. Most of the revisions were accurate; I added a little more detail in some cases.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “Increases in nucleus accumbens ΔJunD expression using viral vectors can reduce many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the changes caused by ΔFosB); large enough increases may block these changes altogether.” So it sounds like we have/could have a drug that cures addiction, more or less. I suppose it’s still in animal trials/has extremely severe side effects?
 * Basically, yes. It's almost correct to say that ΔFosB overexpression alone causes addiction, though it's a little more technical because ΔFosB interacts with other proteins differently and different addictive drugs/behaviors have variable effects on those interacting proteins. It is crucial for an addiction though, so repressing ΔFosB in the nucleus accumbens will result in marked reductions in compulsive reward-seeking/addictive behavior.   Seppi  333  (Insert 2¢ &#124; Maintained)


 * About these sex addictions again. So they only happen if you’re addicted to amphetamine? That is, these are highly unlikely at typical therapeutic doses?
 * It's more likely to occur than an amphetamine addiction if an individual engages in both frequent sexual activity and frequent amphetamine use. It's still uncommon though. That said, because the rewarding effects of sex and amphetamine cross-sensitize bidirectionally, it's technically possible to see a "sex-induced amphetamine addiction", though I haven't read about one in humans.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “chronic acquisition of these rewards can result in a similar pathological state of addiction.” Most people eat every day, but very few of them become addicted to food. By “chronic acquisition” do you mean excessive/abnormal/more than usual?
 * ΔFosB isn't normally produced upon acute (a single) exposure to an addictive stimulus; it requires repeated exposure at some minimum intensity (e.g., frequent drug use a above some threshold dose or the amount/frequency of food intake). The more excessive and more frequent the exposure to an addictive stimulus, the more likely it is that ΔFosB will begin to be expressed. This actually is the reason why it's not possible to become addicted to anything upon a single exposure to it, no matter how "intensely" (e.g., the severity of an overdose) it is experienced. Back to food though, only sweet and fatty foods are addictive, since these are perceived as being palatable/tasty (rewarding). You'd have to frequently consume a lot of these types of foods to start eating them compulsively; I can't imagine most people have that type of diet anyway. :P  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “increased activation of dopamine receptors and co-localized NMDA receptors” So these receptors are located in the same cells?
 * Same neurons to be more precise, but yes. I actually illustrated this on template:psychostimulant addiction.  Their occurrence together along that plasma membrane makes them co-localized.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Diagram and caption: “trigger internal signaling events through a cAMP pathway and calcium-dependent pathway that ultimately result in increased CREB phosphorylation.” So I take it these are two different pathways?
 * It's basically referring to the signaling that starts at the dopamine receptors (the cAMP pathway) and the signaling that originates from the calcium channel/NMDA receptor (calcium-dependent pathway). These pathways intersect/merge once they reach/signal to CREB (as shown in the diagram).  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Diagram and caption: “Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-fos gene with the help of corepressors.” What does repressing the c-fos gene do? I understand it’s implicated in many types of cancer and plays an important role in the cell, but what is its importance here?
 * Well... because c-fos is an immediate early gene, it does a lot of things. ΔFosB actually has other immediate targets (unlike c-fos, it increases the expression of some of them); I just didn't have a lot of drawing room to show more. The primary diagram I used as a reference simply stopped at that point anyway, so it's probably not losing anything significant by omitting all of them except c-fos. :P  Seppi  333  (Insert 2¢ &#124; Maintained)
 * Edit: this is a more useful answer to your question: accumbal ΔFosB targets/effects table.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Psychosis and toxicity: “as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.” What exactly does this mean? Does amphetamine indirectly cause oxidative stress by increasing synaptic dopamine levels, which then increases the production of free oxygen radicals? AmericanLemming (talk) 07:00, 1 January 2015 (UTC)
 * That's exactly what it means. A direct toxicity would mean that amphetamine itself is toxic to neurons.  This form of indirect toxicity means that the toxic compounds are the reactive oxygen species and autoxidized dopamine radicals. The main difference between a direct and an indirect toxicity is that an indirect toxicity has a threshold dose for when the compounds begins to produce toxicity.  All substances, including salt and water, are indirect neurotoxins.  Seppi  333  (Insert 2¢ &#124; Maintained)

Interactions
 * “Inhibitors of the enzymes that metabolize amphetamine…will prolong its elimination half-life” What the clinical significance of having amphetamine in your system longer? Does that make it easier to overdose on it?
 * Eh... an increased elimination half-life doesn't do much more than extend the amount of time the drug is active (going about its business). It could contribute to an overdose if it is used frequently enough, though I've never read of an unintentional amphetamine overdose arising solely from half-life manipulations.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * “increase plasma catecholamines” I know we’re mentioned it in the lead, but adding “(i.e. norepinephrine and dopamine)” after catecholamines may be helpful for the general reader. AmericanLemming (talk) 08:11, 15 December 2014 (UTC)
 * I added this in.  Seppi  333  (Insert 2¢ &#124; Maintained)

I support promotion of this article on the basis of its prose, comprehensiveness, and intelligibility to the non-expert (that is, people like me). I've only copy-edited the lead and the Uses, Contraindications, Side effects, Overdose, and Interactions sections, but considering I've spent 40-60 hours doing so, the prose in those sections is now flawless and highly intelligible to the general reader. I've spent a lot of time mulling over awkward wordings that aren't necessarily grammatically incorrect and that take a long time to come up with a better way to say them. I've also spent a lot of time familiarizing myself with rather technical medical/biochemical information in order to be able to say things in a clearer and more accessible manner.

At the end of the day, 40-60 hours is a long time to spend on someone else's article, and given that Seppi hasn't edited this page since 14 December and my first comment was on 15 December, he has yet to respond to a single comment I've made the past three weeks. I'm sure he has his reasons: work, school, family obligations, sickness/personal issues, or simply exasperation with the often frustrating process that is FAC. Anyway, I took a look at the peer review, GA review, and all five FA nominations and came to the conclusion that this article was fairly close to FA status by the end of the second FAC (and possibly earlier.) Essentially it failed because Shudde opposed promotion, and Shudde essentially opposed promotion on the basis of prose (and layout, but he was going against WP:MED guidelines on that).

I have significantly improved the prose in the sections the average person is going to read (the average Joe isn't going to care about amphetamine's pharmacology or chemistry). Those two sections are likely of interest only to those who already know a fair amount about medicine/chemistry, so improving the prose for the general reader isn't especially important. My remaining reservations (though "suggestions for further improvement not necessary for FA status" might be a better description) are as follows:
 * 1. I would like to see Seppi take a look at the new comments I've made during the fifth and current FAC.
 * 2. I would personally like to see the current pharmacodynamics subsection expanded and moved into its own article; I get the sense from reading it that the subject matter is complicated enough that its current treatment here doesn't do it it justice. Also, I believe that the equivalent section in the Adderall article is much more intelligible to the general reader (me) and thus should be transcluded here.
 * 3. I would also like to go through the second half of the article with as much care and diligence as I did with the first half, but I'm not going to put any more work into the article until Seppi addresses the comments I've already made (see #1).

That being said, I'm not really sure that the prose in the second half is really in need of that much improvement, especially given its highly technical nature. The prose in the first half is, in my opinion, impeccable and goes above and beyond the requirement for FA status, if such a thing were possible. (Perhaps I feel that way because I've spent so much time on it.) Reading through all the previous FACs I got the impression that the prose was at a pretty good level already. (John, who is incredibly picky about prose, supported promotion on the basis of prose during FAC #2. Who am I to oppose on the basis of prose, now that I've made it even better?)

Other editors have supported on the basis of the article's medical and biochemical/pharmacological accuracy, quality of sourcing, comprehensiveness, etc., during previous FACs. Perhaps one reason why I'm making the argument for promotion is because I've invested so much of my own time into the article and want that work to be recognized with a shiny gold star. Perhaps another is that I want to see Seppi recognized for all the hard work that he's put into the article. Anyway, sorry for the overly long support with reservations post, but I thought it best to let the FAC coordinators understand exactly why I'm supporting, particularly given that said support might not be entirely objective in nature. AmericanLemming (talk) 05:34, 2 January 2015 (UTC)
 * Quick update: Seppi responded to a message I left on his talk page; it appears he was taking an unannounced wikibreak during the holiday season but will start looking at my comments promptly. If he does, there is no need to action this FAC just yet. :) AmericanLemming (talk) 10:51, 2 January 2015 (UTC)

Also, I added 2 new reviews to the biomolecular mechanisms section and tweaked the explanation on the necessary/sufficient relationship (I put it in a note) while restoring these edits; feel free to revise the text I added if you feel it can be improved!  Seppi  333  (Insert 2¢ &#124; Maintained) 00:04, 4 January 2015 (UTC)
 * I've been travelling, though I'm back home now. I'll be WikiOgring (RAWR!) the article and a few others shortly.    Seppi  333  (Insert 2¢ &#124; Maintained) 22:19, 2 January 2015 (UTC)
 * I had to temporarily revert to a december 20th revision of the article due to a large problem with the selective transclusions to adderall, dextroamphetamine, and lisdexamfetamine; it wasn't readily apparent to me where the parsing error was in the source, so I decided to manually restore the edits since the 20th. So far, I've reduced the differences between the past and current revision to this point: special:diff/640446238/640869098 (the improved diff gadget - Special:Preferences, "wikiEdDiff" in the gadgets tab - helps a lot in highlighting where there are substantive difference between these revisions). I figured I should mention here that I intend to add the remaining text revisions back into the article by tomorrow morning - I don't want you to think that I'm just massively reverting all the work you put into the article.   I'll start addressing these FAC comments once I've restored the edits you made over the past 2 weeks. Sorry for the delay!


 * It's more or less back to how it was (diff of original vs restored versions) - I made a few tweaks for accuracy in some places and expanded the mechanism section while I was going through the page. The transclusion issues are sort of my fault since I made the source code of the page so complicated; I noticed there were 3 transclusion syntax errors in different sections, which is why I had trouble finding the problem. In any event, if I missed restoring an edit or there's any other issues you see in the article, feel free to fix them! You might want to reread the main overdose section and the mechanism subsection again since I added new content and revised some existing content while restoring the page. I added a collapsed version of Addiction glossary above the diagram as well to help with accessibility in the addiction section.  Seppi  333  (Insert 2¢ &#124; Maintained) 10:38, 4 January 2015 (UTC)

Forgot to ping you when I finished the edits/replies. Btw, do you think I should put in the collapsed addiction-related plasticity table at the bottom of the addiction section? I figure it might add some context for the statement about exercise therapy for amph addiction and amph-sex addiction interactions. Also, for spending a huge amount of time working on this article with me. I really appreciate your help and hard work on it!  Seppi  333  (Insert 2¢ &#124; Maintained) 02:10, 8 January 2015 (UTC)

This line fixes a reference formatting error.

Five more comments

I've looked over both your responses to my comments and all the changes you've made, and I've made a few more tweaks of my own. I've also come up with five more comments from the Lead through the Overdose section. After these are all taken care of we'll just have three sections left in the article to look over.


 * Lead: “amphetamine” versus “amphetamines”: I know there’s the note and all, but I think we should avoid using the term “amphetamines” because it’s potentially ambiguous. Whenever I see the term I’m never quite sure whether it means “amphetamine” or “substituted amphetamines”. There’s three instances in the “Medical” subsection and one at the very end on the “Contraindications” section.
 * I'll remove these and use the singular. Edit: I thought that using the singular term would be slightly odd in those places since racemic amphetamine isn't a pharmaceutical - though I think using "amphetamine pharmaceuticals" instead clarifies the point, especially considering that we have a section which covers the types of these pharmaceuticals.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Side effects/Overdose: Sorry about the Cardiac dysrhythmia/tachycardia mix-up; I’m not quite sure what happened there. By the way, does that mean that the Overdose symptoms table should read “Increased heart rate” and link to tachycardia instead of reading “Abnormal heart rhythm” and linking to cardiac dysrhythmia as it does now?
 * I'll need to double check.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * The current article language/wikilink is slightly generalized, but still consistent with the citations.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Overdose: “since repeated overdoses continually increase the level of accumbal ΔFosB” Would “gradually” fit better here? Otherwise I think we can drop “continually” because “repeated overdoses continually increase” is kind of wordy and having “continually” there doesn’t really add any new information.
 * Gradually would be fine here.  Seppi  333  (Insert 2¢ &#124; Maintained)


 * Overdose: “Once nucleus accumbens ΔFosB is sufficiently overexpressed, it begins to directly influence the severity of addictive behavior (e.g., compulsive drug-seeking).” By “directly influence” you mean “make worse”, right?
 * Yes, essentially increased ΔFosB expression exacerbates an addiction.


 * Overdose: “Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression.” Is this a cycle where sufficient ΔFosB overexpression leads to an addictive state, which leads to further ΔFosB expression, which induces an even more addictive state, etc.? AmericanLemming (talk) 12:30, 9 January 2015 (UTC)
 * Yeah, it's a pretty retarded positive feedback loop in the brain...  Seppi  333  (Insert 2¢ &#124; Maintained)

Comments from Jfdwolff
This is a very good article. Balanced in an area where there's information from numerous domains to compare and weigh. Using every way possible to clarify difficult concepts using notes and tooltips etc.
 * While almost all sections are supported heavily by secondary sources, I still find a number of primary sources in some sections. I found one of these to be over 20 years old (e.g. Imperato et al 1993). They may not have been reproduced or included in the current paradigm.
 * A number of references currently contains a message that the "chapter" parameter is being ignored. Can this be fixed?

I will see if any other concerns arise from reviews by others (as I cannot claim much expertise in the subject matter) but I have a low threshold for support provided the primary sources concern is addressed. JFW &#124; T@lk  22:18, 6 December 2014 (UTC)


 * Don't bother with doing so - I replaced it with a new review. I don't mind cutting primary sources because any that are included are unnecessary for WP:V, so if any others are a concern, let me know. The few primary sources covering medical content in humans are all coupled to WP:MEDRS-quality reviews, as far as I'm aware. I'm quite pedantic about citing anything medical regarding humans with medical reviews or high-quality pharmacology references. In any case, I replaced it with a new medical review covering preclinical evidence (I assume this means "lab animals", so I kept that phrase). That sentence was just meant to provide context to indicate that dopamine and acetylcholine interactions from amphetamine are not unique to humans.
 * In the few other cases that I included the primary sources with reviews, I did so because: (1) I found it hard to find the information in the review when re-checking (the review on flavin-containing monooxygenase, where it's in a table instead of the article) or (2) I thought the material was important, but not widely covered in reviews in a relevent context or relevant databases (e.g., the dopamine beta-hydroxylase references).  Seppi  333  (Insert 2¢ &#124; Maintained) 23:53, 6 December 2014 (UTC)
 * Edit: Forgot to note, I'm discussing the citation error issue on the CS1 module talkpage. Will probably have them fixed by tomorrow.  Seppi  333  (Insert 2¢ &#124; Maintained) 00:35, 7 December 2014 (UTC)
 * Everything should be fixed now; let me know if anything is still amiss. Citation errors were really just an error in the module script.  Seppi  333  (Insert 2¢ &#124; Maintained) 03:51, 8 December 2014 (UTC)


 * Thanks, happy to support for FA. JFW &#124; T@lk  07:32, 1 January 2015 (UTC)

Comments from Axl
If you'd prefer different wording, feel free to edit that line to your liking. I very seldom revert a reviewers changes to an article in the event you're concerned about it.  Seppi  333  (Insert 2¢ &#124; Maintained)
 * This is a point that I made at previous FACs: 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." Should high doses be avoided in children with tic disorders more so than in children without tic disorders? Axl ¤ [Talk] 10:51, 8 December 2014 (UTC)
 * Sorry, I hadn't realized my previous comment didn't address your concern - I reworded the sentence to how I interpreted what Cochrane was essentially saying: "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 could exacerbate tics in such individuals."
 * No, not in "such individuals", in "some" individuals. Stimulants do not exacerbate tics.  *SOME* people may have issues, though. Here are the words from the Cochrane review:
 * To evaluate evidence for this reported phenomenon we searched for clinical trials of medications for ADHD used specifically in children with tic disorders. The trials indicate that a number of stimulant and non-stimulant medications are safe and effective treatments for ADHD symptoms and do not worsen tics. High dose stimulants may transiently worsen tics in some children, and worsening tics may limit dose increases of stimulants in some children, but in the majority of children both tics and ADHD symptoms improve with use of stimulant medications.
 * And, surprise, that is correct :) "Some" is the correct word. Sandy Georgia  (Talk) 22:09, 10 December 2014 (UTC)
 * I don't mind how the statement is worded, though I think this is worth noting: Cochrane's samples were entirely upon individuals with ADHD and some form of tic disorder, so they technically can't generalize the population outside that group without it producing biased statistical inference (i.e., the samples are nonrespresentative of individuals with ADHD in general with or without tic disorders). That's why I assumed their analysis was always in context of the sample and consequently worded that sentence with "such"; in any event, I actually agree completely that dopaminergic-related movement side effects are not specific to individuals with tic disorders.  Anyone can develop abnormal involuntary movements and hypersensitive locomotor responses using dopaminergic stimulants because, as in the nucleus accumbens, dopamine (and hence DA stims like amphetamine) induces nigrostriatal ΔFosB in response to chronic sufficiently high dosing.( - epigenetics/pharmacogenomics of involuntary motor activity from chronic high-dose L-dopa therapy) Nigrostriatal ΔFosB overexpression, coupled with high-dose amphetamine/methamphetamine, would necessarily produce abnormal motor function and dysregulated motor responses (e.g., substituted amphetamine induced stereotypies). This may or may not contribute to tics though, depending upon which neural pathways give rise to tic disorders.  Seppi  333  (Insert 2¢ &#124; Maintained) 01:11, 11 December 2014 (UTC)
 * Thank you. The current text is fine. Axl ¤ [Talk] 09:48, 12 December 2014 (UTC)


 * From "Contraindications": "It is also contraindicated in people currently experiencing... severe hypertension." The FDA reference states "Moderate to severe hypertension". The Inchem reference just states "hypertension". Axl ¤ [Talk] 11:07, 8 December 2014 (UTC)
 * That was probably pruned during previous copyediting - I've cut the word "severe" and left it at hypertension.  Seppi  333  (Insert 2¢ &#124; Maintained) 13:46, 8 December 2014 (UTC)
 * I am wary of adding "elevated blood pressure" in parentheses after "hypertension". Hypertension is more than simply elevated blood pressure. Also, elevated blood pressure is subsequently noted as a cautionary feature that should be monitored. (This statement is in line with the references.)


 * I am inclined to delete the "clarification" of the meaning of hypertension from the text. (I note that the subsequent cautionary features such as bipolar disorder, psychosis and Raynaud's phenomenon do not have associated short definitions.) If you insist that a short definition should be included for hypertension, perhaps change it to "persistent blood pressure"? Axl ¤ [Talk] 09:56, 12 December 2014 (UTC)
 * Deleted it; I don't care for the parenthetical clarification - I only added them in cases where they were requested. In this case, it was redundant anyway.  Seppi  333  (Insert 2¢ &#124; Maintained) 09:12, 14 December 2014 (UTC)
 * The clarification seems to have been changed to "high blood pressure". Axl</b> ¤ <small style="color:#808000">[Talk] 21:40, 16 December 2014 (UTC)
 * I deleted every parenthetical descriptor next to hypertension and hypotension in the article. diff.  Seppi  333  (Insert 2¢ &#124; Maintained) 10:22, 4 January 2015 (UTC)
 * I forgot to ping you when I updated this. Sorry about that. :p  Seppi  333  (Insert 2¢ &#124; Maintained) 07:03, 7 January 2015 (UTC)


 * From "Side effects", subsection "Physical", paragraph 1: "Cardiovascular side effects can include irregular heartbeat (usually an increased heart rate)." Not all arrhythmias are irregular. Indeed atrial fibrillation is the only common arrhythmia that is irregular. I am aware that the linked article, "Cardiac dysrhythmia", states that "irregular heartbeat" is a synonym. The statement is inaccurate. The reference seems to be inaccessible at the moment. <b style="color:#808000">Axl</b> ¤ <small style="color:#808000">[Talk] 10:15, 12 December 2014 (UTC)
 * I tweaked this as such. Let me know if that works.  Wasn't sure how you wanted it.  Seppi  333  (Insert 2¢ &#124; Maintained) 09:12, 14 December 2014 (UTC)
 * No! I recommend "cardiac dysrhythmia (abnormal heart rhythm)." <b style="color:#808000">Axl</b> ¤ <small style="color:#808000">[Talk] 21:45, 16 December 2014 (UTC)
 * I've changed it to "abnormal heart rhythm". I feel somewhat responsible for the inaccurate parenthetical explanations because I'm the one who requested and/or added them. Per Make technical articles understandable, I've been trying to explain technical terms, here, since the article's unintelligibiilty to the general reader was one of the main reasons it wasn't promoted before. At the same time, we don't want to oversimplify things, either. AmericanLemming (talk) 10:42, 18 December 2014 (UTC)
 * Thank you. <b style="color:#808000">Axl</b> ¤ <small style="color:#808000">[Talk] 12:11, 19 December 2014 (UTC)

We somehow ended up linking to a concept which isn't an adverse effect of amphetamine, so I went ahead and made this edit (reasoning in the edit summary) to reestablish concordance with the citations. Let me know of any concerns.  Seppi  333  (Insert 2¢ &#124; Maintained) 10:22, 4 January 2015 (UTC)

Comments from Abductive

 * I feel that the lead is a bit overlong.
 * The lead certainly is too technical, and jumps around between the historical, medical, chemical, abuse, and legal aspects of the topic. I'll break this down by coding each sentence or part of sentence: 1st paragraph; m,hc,c,c,m,ma,la. Second paragraph; h,hm,m,m,m. 3rd; a,am,am,a. 4th; c,ca,m,c. Abductive  (reasoning) 04:36, 18 December 2014 (UTC)
 * Er... I'm not really sure what you just said in the second bullet. If there's a particular sentence that you think is too technical or unnecessary, just let me know and we can address it.  Seppi  333  (Insert 2¢ &#124; Maintained) 10:00, 4 January 2015 (UTC)

Graham Beards (talk) 12:34, 14 January 2015 (UTC)
 * The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.