Talk:Amphetamine

Abbreviations

Resolved

@Seppi333: It isn't clear if MOS:FIRSTABBR should apply to citations since they stand alone in their usage. For example, there is no problem with repeating the same link in many citations within an article MOS:REPEATLINK. Whywhenwhohow (talk) 06:22, 25 December 2019 (UTC)

@Whywhenwhohow: I'm familiar with the exception for links in citations; I simply dislike them. When I click something in a citation, I expect to navigate outside WP, not internally. Ignoring the guideline entirely, an abbreviation for a website or publisher entry is just extraneous markup; it doesn't serve any purpose like it does in the article text.

Anyway, can you restore the publisher parameters in the citations to the FDA website that you changed to DailyMed? It should be listed as the manufacturer; regardless of what website hosts the prescribing information, the publisher would still remain the same. I already restored a few, but there's others that need to be fixed. Seppi333 (Insert 2¢) 06:58, 25 December 2019 (UTC)

Yes, but why do you prefer the ones from the FDA website? They are PDF format and harder to navigate? The NIH DailyMed website is the official provider of FDA label information Whywhenwhohow (talk) 08:27, 25 December 2019 (UTC)

I don't have a fixed preference for DailyMed or the FDA's labels as a citation since both have an advantage over the other; the actual content is identical though. The PDFs have page numbers which makes verifiability easier when the prescribing information is rather long, but DailyMed is easier to navigate given its design. I'm just used to citing FDA labels since I've always used Drugs@FDA to search for drug information (e.g., the label itself, approval data, and information on current/actively marketed brands as well as discontinued drug products associated with the active ingredient I'm searching).

In any event, I just realized that I worded my earlier request about the publisher information very poorly; what I meant to say was to restore the publisher parameters from the FDA citations in the DailyMed citations. Databases like Drugs@FDA and DailyMed that host a drug label online should always just be listed in the website/work parameter of {{cite web}}, so you were doing that part correctly. The publishers are the entities that write/edit and produce a document, which in this case is the prescribing information − i.e., pharmaceutical companies like Shire Plc, Hoffmann-La Roche, Merck & Co, etc.. While the FDA approves prescribing information for drugs, the drug label for any given drug is the copyrighted intellectual property of the manufacturer/pharmaceutical company that produces the drug because they're the authors of the corresponding drug label; that's why they're listed as the publisher for drug labels. I've added the original citation templates below as an example. In any event, I'll go ahead and fix the DailyMed citations since you already spent time actioning my poorly worded request. Seppi333 (Insert 2¢) 09:59, 25 December 2019 (UTC)

They're all fixed now. If you want to change the 2 FDA drug label citations I added to DailyMed citations, feel free to do so. I don't really care which one we use. Seppi333 (Insert 2¢) 10:19, 25 December 2019 (UTC)

Drug label citation templates

{{cite web|title=Adderall IR Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2015/011522s042lbl.pdf|publisher = Teva Pharmaceuticals USA, Inc.|work = United States Food and Drug Administration|date=October 2015|accessdate=18 May 2016|pages=1–6}} {{cite web|title = Adderall XR Prescribing Information|url = www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf|page = 11|publisher = Shire US Inc.|work = United States Food and Drug Administration|date=December 2013|accessdate = 30 December 2013}} {{cite web|title=Evekeo Prescribing Information|url=www.evekeo.com/assets/evekeo-pi.pdf|publisher=Arbor Pharmaceuticals LLC|accessdate=20 July 2018|pages=1–2|date=September 2016}} {{cite web|title=Dyanavel XR Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2017/208147s003lbl.pdf|publisher= Tris Pharma, Inc.|work=United States Food and Drug Administration|accessdate=4 August 2017|pages=1–14|date=May 2017|quote=DYANAVEL XR contains d-amphetamine and l-amphetamine in a ratio of 3.2 to 1 ... The most common (≥2% in the DYANAVEL XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 108 patients with ADHD (aged 6–12 years) were: epistaxis, allergic rhinitis and upper abdominal pain. ... <br />DOSAGE FORMS AND STRENGTHS<br />Extended-release oral suspension contains 2.5 mg amphetamine base per mL.}} {{cite web|title=Vyvanse Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2017/021977s045,208510s001lbl.pdf|pages = 3–13, 17–21|website = United States Food and Drug Administration|publisher = Shire US Inc.|accessdate=10 July 2017|date = May 2017}} {{cite web|title=Mydayis Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2017/022063s000lbl.pdf|website=United States Food and Drug Administration|publisher=Shire US Inc.|accessdate=8 August 2017|pages=1–21|date=June 2017}} {{cite web|title=Adzenys XR-ODT Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2017/204326s002lbl.pdf|website = United States Food and Drug Administration|publisher=Neos Therapeutics, Inc.|accessdate=10 August 2017|page=16|date=January 2017|quote = ADZENYS XR-ODT (amphetamine extended-release orally disintegrating tablet) contains a 3 to 1 ratio of d- to l-amphetamine, a central nervous system stimulant.}}

Page size

At 241,890 bytes of wiki markup, this page is far too large. That's particularly troubling for a page listed as a featured article. How can it best be divided? For example, splitting off the entire 'Pharmacology' section would remove over a fifth of that (less if a summary is kept here). Andy Mabbett (Pigsonthewing); Talk to Andy; Andy's edits 11:19, 2 January 2020 (UTC) @Pigsonthewing:

Document statistics:

File size: 989 kB

Prose size (including all HTML code): 123 kB

References (including all HTML code): 25 kB

Wiki text: 236 kB

Prose size (text only): 49 kB (6811 words) "readable prose size"

References (text only): 2506 B

User_talk:Dr_pda/prosesize.js

To quote WP:TOOBIG: These rules of thumb apply only to readable prose and not to wiki markup size (as found on history lists or other means), and each kB can be equated to 1,000 characters.

I'm not even going to consider splitting this article right now given that it's not even that long by the actual guideline metric. Seppi333 (Insert 2¢) 11:43, 2 January 2020 (UTC)

Wow, four bigs, and and underline? -- Mikeblas (talk) 19:56, 12 July 2020 (UTC)

"I'm not even going to consider..." That's OK, you're not required to participate. But in declaring that you're not participating, please don't selectively quite only parts of a guideline, as you do - unnecessarily garishly - above. The guidleline also says, near the top of the page (and so before the subsection you quote): "There are three related measures of an article's size: Readable-prose size [...] Wiki markup size [and] Browser-page size". Andy Mabbett (Pigsonthewing); Talk to Andy; Andy's edits 12:05, 2 January 2020 (UTC)

Yes, and the guideline says absolutely nothing about hard-limits on markup size like it does with the prose size, which you clearly are trying to use as a justification for splitting pages based upon their on markup size. The thing is, this page might have a markup size in the 200+kB range, but both this script and xtools indicate that the prose size is 49-50kB. No one is going to buy what you are selling if you keep trying to argue that this page needs to be split based upon markup size. And even if that was an issue, which it clearly is not, I could simply move this entire page's source code to a template and transclude it in, causing this page's markup size to drop to <10kB while the readable prose size remains the same. Seppi333 (Insert 2¢) 12:14, 2 January 2020 (UTC)

Not so; for example the guideline says: "The text on a 32 kB page takes about five seconds to load for editing on a dial-up connection, with accompanying images taking additional time, so pages significantly larger than this are difficult for older browsers to display. Some large articles exist for topics that require depth and detail, but typically articles of such size are split into two or more smaller articles. ". Andy Mabbett (Pigsonthewing); Talk to Andy; Andy's edits 12:21, 2 January 2020 (UTC)

I don't see a hard/fixed limit anywhere in the text you quoted. It appears to assert the incredibly obvious fact that shittier connections load webpages more slowly, and we're talking about two-tenths of one megabyte. Seppi333 (Insert 2¢) 12:26, 2 January 2020 (UTC)

Wikipedia talk:Article size is available, should you wish to dispute the contents of the guideline. Andy Mabbett (Pigsonthewing); Talk to Andy; Andy's edits 12:50, 2 January 2020 (UTC)

@Pigsonthewing: Dispute the guideline? Why would I do that? It supports my assertion and contradicts yours. I'm actually happy with it the way it is. Also, thank you again for the nomination. You're doing me a favor here. Seppi333 (Insert 2¢) 13:15, 2 January 2020 (UTC)

Transclusion

This article is a source for transcluded sections in Adderrall. Its a real house of cards -- reference definitions must be in certain spots, different sections are tagged with <noinclude and one article or another is often broken because of problems. Is transclusion really the best way to build these articles? -- Mikeblas (talk) 16:48, 31 May 2020 (UTC)

Selective transclusion prevents information/content on multiple pages that cover the exact same topic from diverging over time. Yes, it does make it harder for unfamiliar editors to edit the source, at least initially when they're unfamiliar with the markup (see WP:SELTRANS for a primer). In this particular case, selective transclusions from amphetamine are used to ensure that this article, dextroamphetamine, lisdexamfetamine, and Adderall uniformly cover the same information in relevant sections. Seppi333 (Insert 2¢) 04:22, 17 November 2022 (UTC)

Reference to fraction bound by plasma proteins

1. I just corrected the value for the fraction bound to 20%, according to the already linked source. Maybe they changed the value at some point. At the moment the source is DrugBank; section Protein binding: https://go.drugbank.com/drugs/DB00182#pharmacology. For said parameter the reference on DrugBank is solely this article: https://link.springer.com/article/10.2165/00003088-200443030-00002. Would it not be better if this source was mentioned in the article instead of Drugbank?

2. I also cross-checked said 20% with other publications and it's about right. So I guess there is no point in adding additional sources to prove the same number?

PENDRAGON (talk) 11:23, 13 October 2020 (UTC)

Dopamine neuron should be changed to dopaminergic neuron

On of the image titles says "Pharmacodynamics of amphetamine in a dopamine neuron" there is no such thing as a dopamine neuron, it should be changed to dopaminergic neuron. — Preceding unsigned comment added by Ihazevich (talk • contribs) 16:22, 17 February 2021 (UTC)

Semi-protected edit request on 24 December 2021

The Safety of Stimulant Medication Use in Cardiovascular and Arrhythmia Patients - American College of Cardiology

yo, stimulants are in fact cardio protective. has anyone given careful thought to this? The heart is a muscle. Muscles become stronger the more they work, The faster the heart beats the more oxygen is delivered. Blood circulates faster. these are good things. w/out preexisting heart conditions theres no issue… do marathon runners die prematurely? … i’ve taken these medications for decades - its only Vyvanese that has brought premature aging up - the 80 years before Vyvanese no one conclusively proved stimulants shorten people’s life spans. The truth is probnly that the way Vyvanese is metabolizedin the live by whatever enzynmee is it is in the liver that activates it causes long-term live damage and when your liver is gone - its over. Lastly speaking from personal experience Real Dexedrine or Adderall make my heart beat WAY faste than Vyvanese so that simple fact tells me this is to put it politely, highly questionable and to put it bluntly, bullshit . and if you drive a car on on overdrive but give extra attention to maintainihg it it will last long - its only if you aren’t healthy or dont maintauin your car in the first place that a issuew MAY come up. and people if you don’t know for god’s sake, if your skin doesn’t look good drink more water until you’re drinking 6liters a day. I bet crackheads who drink 6 liters of water a day have great skin! 72.143.21.46 (talk) 07:39, 24 December 2021 (UTC)

 Not done: it's not clear what changes you want to be made. Please mention the specific changes in a "change X to Y" format and provide a reliable source if appropriate. Cannolis (talk) 07:43, 24 December 2021 (UTC)

Policy on chemical data

I am curious about what the policy is for including physicochemical data for pharmaceutical drugs. The box in this page gives the data for amphetamine base racemate, yet this is not a form that is available on the market, legal or illegal. There are of course many different salts and derivatives of the compound with different chemical structures and physical properties. Is it standard to give the base form of amines? How about tertiary amines, which have no stable base form and potentially different counterions? Would it make more sense to include all the common salts? Or perhaps have another page dedicated to it? Kilgore T (talk) 13:31, 26 October 2022 (UTC)

In the US, there are at least two brand names of amphetamine, EVEKEO ODT is the racemic sulfate salt, while DYANAVELXR is a 3.2 to 1 mixture of d- to l-amphetamine and is a mixed salt. I don't think it is practical to list all the avaiable salts, nor enantiomeric mixtures in the physicochemical properties section of the infobox, so I think it is appropiate to limit this section to the parent racemic free base. Tertiary amines are stable compounds that can be isolated. It is the quaternary amine which when isolated, must be complexed with a counter ion. Amphetamine is a primary amine. I would not object if someone wanted to create a seperate data sheet for the racemic sulfate, etc. Boghog (talk) 07:41, 27 October 2022 (UTC)

Semi-protected edit request on 8 April 2023

Má huáng 1015 (talk) 22:25, 8 April 2023 (UTC)

i think it would be better if the image that shows the structure of amphetamine in 2D would be replaced with the image that Wiktionary uses the reason why i think this change should be made is the image from wiktionary shows that there are two enantiomers i do want to make it clear that i don't know a lot about chemistry unfortunately https://en.wiktionary.org/wiki/amphetamine#/media/File:Amphetamine-2D-skeletal.svg

 Not done for now: the image doesn't look line an improvement, though you're welcome to seek consensus for the alteration. M.Bitton (talk) 19:33, 9 April 2023 (UTC)

Removal of lack of neurotoxicity in humans statement due to serious misinterpretation of the sources

Please either remove "There is no evidence that amphetamine is directly neurotoxic in humans" or change to "The neurotoxicity in humans under therapeutic doses is currently not understood" as there is no basis to sustain the current sentence using current citations.

"Amphetamine". United States National Library of Medicine – Toxicology Data Network. Hazardous Substances Data Bank. Archived from the original on 2 October 2017. Retrieved 2 October 2017. Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation.

This citation is talking about vascular toxicity in the brain, rather than neurotransmitter toxicity (neurotoxicity), thus can't sustain the above statement.

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. p. 370. ISBN 9780071481274. Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.

This citation is a secondary source with no basis on research.

Throughout my search for alternative sources, I have not found any concrete research into neurotoxic effects in humans rather than lab animals at all. Review of the existing literature links to effects in humans being not understood

Thus I believe that the sentence as it is currently written in the article leads readers to false conclusions that it's safe to take amphetamines in therapeutic doses as there is research with no evidence, rather than that there is no research at all. Ritave (talk) 16:30, 24 April 2023 (UTC)

@Ritave: The Toxnet source does indeed talk about neurovascular damage. It's still a form neurotoxicity. The molecular neuropharmacology textbook is a graduate-level text written by three researchers who read, perform, write, and synthesize research in this field. In fact, one of them is heavily cited throughout this article. In any event, it is a WP:MEDRS-compliant source.

That being said, Amphetamine has been a pharmaceutical drug with an ongoing medical use for 80 years; in spite of the large population size of active medical amphetamine users, researchers have not identified neurotoxicity in the brains of individuals who take amphetamine pharmaceuticals at therapeutic doses and published a paper about it. You can't "prove" a negative finding with the vast majority of statistical hypothesis tests employed in statistical models; that's just not how statistical inference works. Hence, why nobody publishes papers saying "hey, we did all these brain scans and found that amphetamine is not neurotoxic". What you can say is, "we failed to detect evidence of neurotoxicity", but literally no one publishes research papers with a negative result like that because it's not a research finding (seriously, I challenge you to find one); rather, it's a lack of one. If you expect a stronger statement to be made based on more research, you'll be waiting a while because that will never happen. Seppi333 (Insert 2¢) 04:50, 7 May 2023 (UTC)

Thank you for the explanation, it helped me understand a different view.

Regarding the first citation, I'd say using data showing no dangers in a subset of a category by extending it to a whole category is misleading. Especially when the main mechanism of action of the drug is based on a nervous system rather than the vascular system.

I understand that Amphetamine was not found to be neurotoxic and I don't expect research stating negative result to exist. I tried to find one before asking for a change.

The sentence I'm asking to change is making deductions rather than inductions from the data to a general audience, creating a sense of security about a topic. That sense of security might be well based from unwritten experience of doctors over the world, but as a layman, I could not find more data outside of this single book that would either confirm or deny such statement.

Rather than strengthening the statement on more data, I'm asking to relax the statement to a more ambiguous one, more in line of the intent of "it should be safe to administer based on previous experience" rather than "it's safe to administer and here's proof of such". Ritave (talk) 20:39, 21 May 2023 (UTC)

@Seppi333: I've dug into this subject a bit (131 MEDRS refs in the last decade) and found a few interesting ones which I suggest you check out. A 2020 review states that the neurotoxicity of amphetamine increases the risk of Parkinon's severalfold after exposure, but is silent about dose. Some of the cited sources in the review apply this to therapeutic doses as well. Anything of substance in your opinion? Wretchskull (talk) 17:18, 16 July 2023 (UTC)

@Wretchskull: Really busy off-wiki right now, so I'll follow up on this by Friday. There's a lot to unpack on this topic, so I'll probably give you a more comprehensive/detailed response on the concordant and inconsistent evidence of direct neurotoxicity by amphetamine vs certain substituted amphetamines (meth & MDMA) in humans of which I am aware; I wrote/cited virtually all the pharmacology and neurotoxicity-related content in these articles, so I'm familiar with the similarities and differences between them. FWIW, that review makes a fairly weak assertion about the strength of the association with PD relative to the relationship mentioned in methamphetamine#Neurotoxic_and_neuroimmunological. Seppi333 (Insert 2¢) 06:26, 19 July 2023 (UTC)

Seppi's wall-of-text response

I don't have time to proofread right now, so I apologize in advance for any butchered sentences I might have written here. Just to define some terms first: the phrase "directly neurotoxic" implies that a substance exerts pharmacological/toxicological activity directly in neurons that results in some form of toxicity that impairs their structure/function. The phrase "indirectly neurotoxic" implies that a substance induces neural toxicity through its pharmacological activity in neurons or other cells through secondary mechanisms. A good example of indirect neurotoxicity would be how methamphetamine induces excitotoxicity in neurons via its action on EAAT2 in astrocytes, which increases synaptic glutamate concentrations. Asserting that something is a direct neurotoxin is a pretty strong statement; it implies that a drug is toxic to neurons with a sufficient level of exposure (i.e., dose), which in turn implies that it will cause neurodegeneration with repeated use. This can be measured, and several studies cited in the article have examined this (NB: they're not cited in the neurotoxicity section because they didn't happen to find evidence of that). Regarding the ToxNet source and the implications of a drug damaging neural vasculature, keep in mind that the pathophysiology underlying "subcortical vascular dementia" involves neurodegeneration caused by damage to small blood vessels in the brain. If a drug is directly toxic to neural vasculature, it would inevitably induce neurodegeneration and cognitive impairment similar to subcortical vascular dementia at a sufficient level of exposure because it damages/destroys blood vessels in the brain, in turn compromising cerebral blood supply. While a drug that directly damages neural vasculature is not technically a direct neurotoxin, it is an indirect neurotoxin because it leads to the same outcome at a sufficient level of exposure: marked neurodegeneration. Regarding amphetamine neurotoxicity, I've actually spent an inordinate amount of time looking for research on this, and concerns about potential amphetamine neurotoxicity have been a recurring issue on this talk page over the past decade. The last time I did a comprehensive literature search on amphetamine neurotoxicity for this article was in 2019 or 2020. So, any research published since then wouldn't be covered in this article's current revision. Even so, it's important to point out that amphetamine, meth, and MDMA have both common and distinct biomolecular targets and that there is an abundance of brain imaging studies published about the effects of methamphetamine and MDMA use in humans; both methamphetamine and MDMA are directly neurotoxic to dopamine and serotonin neurons, respectively. Given the abundance of evidence published about these drugs, it seems extremely unlikely that amphetamine could also be a direct neurotoxin without inducing any measurable degree of neurodegeneration with long-term exposure. The serotonergic effects of MDMA are a major contributor to its neurotoxic effects (NB: it directly damages serotonin neurons through an unidentified mechanism, and its serotonergic activity at moderate-high doses induces hyperpyrexia, which markedly increases BBB permeability, thereby promoting neurodegeneration). Amph and meth do not share MDMA's serotonergic pharmacology if only because they're shitty SERT substrates by comparison, which limits their ability to access TAAR1 and VMAT2 in serotonin neurons. Amph and meth share many biomolecular mechanisms within dopaminergic and noradrenergic neurons and have similar affinities as substrates for DAT and NET, so their pharmacology in those neurons is very similar. Even so, there are important differences that strongly impinge upon neurotoxicity. E.g., meth is an agonist for sigma receptors 1 & 2 and inhibits EAAT1/EAAT2, and these mechanisms induce neurotoxicity and excitotoxicity, respectively. Amph isn't a sigma receptor agonist and only inhibits EAAT3, which isn't associated with glutamatergic neurotoxicity because EAAT3 is responsible for only a tiny fraction of glutamate uptake compared to EAAT2. There are undoubtedly many other mechanisms involved in METH/MDMA neurotoxicity, but I doubt they'll all be identified anytime soon. Regardless, amphetamine lacks many of the known pharmacological mechanisms responsible for meth/MDMA toxicity, though amphetamine is obviously still capable of inducing neurotoxicity if only because it can induce cerebral hyperpyrexia at high doses; but, beyond that, there's a relative lack of evidence of neurotoxicity from amphetamine abuse (in humans) compared to the amount of evidence published on MDMA/meth-induced neurotoxicity from long-term or high-dose use of these drugs. There have been a number of studies that have used MRI methods to examine the effects of long-term amphetamine use on brain structure and function. Unlike methamphetamine, which induces neurodegeneration in dopaminergic neurons with long-term/high-dose use, long-term low-dose amphetamine use normalizes the structure and function of several brain structures with dopaminergic innervation (NB: this is covered in the first paragraph in Amphetamine#Medical). If amphetamine is indeed directly neurotoxic to dopamine neurons, then it would cause measurable dopaminergic neurodegeneration with chronic use a la methamphetamine/MDMA; however, the findings mentioned in the studies cited in that section would appear to contradict this. If amphetamine actually does induce neurodegeneration through direct neurotoxicity, those MRI-based brain imaging studies are perfectly capable of measuring and detecting it (NB: compare the methods employed in these studies to the methods employed in the brain imaging studies on methamphetamine & MDMA neurotoxicity); however, neurodegeneration wasn't what they found. Given this clinical evidence on the effect of chronic amphetamine use on ADHD brain structure/function and the lack of any published evidence on amphetamine-induced monoaminergic neurodegeneration (relative to the plethora of evidence on meth/MDMA-induced neurodegeneration), I don't see how amphetamine could possibly be directly neurotoxic to any monoamine neurons. IMO, it seems absurd to me to expect that amphetamine can exert direct neurotoxicity given the findings in these studies and the lack of findings compared to MDMA/meth. It's not like researchers haven't looked, so I don't see how people with this expectation can reconcile their beliefs with the available evidence and lack thereof. Taking everything I wrote above into consideration, without clear evidence of direct neurotoxicity by amphetamine, it seems highly misleading to me - and poses an WP:NPOV issue - to suggest that it's unclear whether amphetamine-mediated direct neurotoxicity occurs in humans, particularly since we don't even have a source that unambiguously asserts this. Regardless, I really don't see how it's possible for amphetamine to cause direct neurotoxicity AND long-term amphetamine use to normalize brain structure/function; the former should induce marked neurodegeneration with long-term use, not seemingly therapeutic neuroplasticity. Seppi333 (Insert 2¢) 20:18, 19 July 2023 (UTC)

@Wretchskull: Just read through the review you linked. I think the only thing really worth adding to an article from that paper is the involvement of α-synuclein as a mechanism of methamphetamine-induced direct neurotoxicity within the nigrostriatal pathway.

This statement - The molecular studies show that amphetamine upregulates α-syn in substantia nigra which accumulates leading to aggregation, which in turn damages neurons [191] contributing to the Parkinson’s-like behavior [199]. - seemed like a bombshell until I looked at the citations and realized the authors are discussing evidence involving methamphetamine; I'm not sure how the authors and peer reviewers missed this. The only evidence they actually provided about amphetamine from a research paper is that amphetamine and methamphetamine both bind to N-terminus of intrinsically unstructured α-synuclein, which induces a folded conformation; in turn, this increases the likelihood of protein misfolding and aggregation. The fact that amphetamine and methamphetamine have similar effects on body temperature and similar mechanisms for causing it would seem to suggest that amphetamine would also increase α-synuclein expression through cerebral hyperpyrexia. Taken together, it seems plausible that amphetamine neurotoxicity could increase PD risk. The relationship between methamphetamine and PD is well-established in humans, but, the evidence supporting this relationship for amphetamine is entirely based on in vitro evidence of α-synuclein protein binding and its shared mechanisms of neurotoxicity with methamphetamine. So, there's basically no evidence in humans from a retrospective study to support that claim; it's just a well-founded suspicion at this point. Seppi333 (Insert 2¢) 15:12, 20 July 2023 (UTC)

I appreciate the thorough reply! Makes a lot of sense now. By the way, I've also discovered a review stating that ADHD may be neuroprotective later in life due to the effects of stimulation-seeking behavior, and that amphetamine may strip that. Would you consider this notable in any way? Wretchskull (talk) 22:55, 20 July 2023 (UTC)

Interesting hypothesis. I don't think it's worth covering research topics that are under investigation on Wikipedia, though. Better to wait until there are published research findings, as it avoids misleading readers whenever results differ from expectations and precludes the need to update the information later on when findings are published. Seppi333 (Insert 2¢) 00:33, 22 July 2023 (UTC)

Seppi I have been waiting for another amphetamine infodump from you for literal YEARS. Like, holy shit. Reading the archives of this talk page and the FA reviews back in the day taught me a ridiculous amount and happened to benefit my own Dexedrine treatment plan overall. Why don't you start a blog or something? It'd be great to read your insight on a number of things in greater detail regarding this compound without it being necessarily an exercise in improving the composition of this article. I know I don't just speak for myself on this. Like, you're the man, man! 103.51.113.44 (talk) 16:09, 22 July 2023 (UTC)

Hahaha, I appreciate the sentiment. I've been a bit preoccupied with work at my company since mid-2020, so I've been much less active on Wikipedia for the past 3 years compared to the preceding 7-ish. For the same reason, I haven't really have much time available for other activities like blogging either. That being said, my workload recently decreased, and I'll likely be reasonably active on Wikipedia at least until the end of the year. Seppi333 (Insert 2¢) 06:49, 23 July 2023 (UTC)

Amine

Shouldn’t “amine”, located in the very first paragraph, be transformed into a link?

Is there a reason it hasn’t? HockeyCowboy (talk) 09:31, 28 April 2023 (UTC)

I did. Hope that’s ok. HockeyCowboy (talk) 05:54, 30 April 2023 (UTC)

Lead content

@Dexedream: I apologize for undoing what you wrote, but a lot of the content you introduced to the lead section is way too technical per MOS:INTRO. Also, the article originally had a 4-paragraph, 20-sentence lead section, which was already above average for a featured article, per MOS:LEADLENGTH. The lead looks to be about ~50% longer (24 vs 16 line breaks) on my screen with your changes relative to the original version, which pushes it well outside the guidelines.

I don't see a problem with introducing this content with citations in the body of the article, though. Seppi333 (Insert 2¢) 00:27, 22 July 2023 (UTC)

Semi-protected edit request on 11 September 2023

Change dependance/abuse liability from "moderate" to "high" as per the cited reference (Stahl) P3nt0th41 (talk) 04:59, 11 September 2023 (UTC)

@P3nt0th41: I am able to access a copy of the source - it doesn't seem to state that the dependence liability is high. The source states:

•High abuse potential, Schedule II drug
•Patients may develop tolerance, psychological dependence

While I agree it clearly states that abuse potential is high, dependence liability is not listed in the same way. Is there some reason to interpret "may" as a high rather than moderate risk? I've closed the edit request to get it out of the queue but am completely open to discussion. Tollens (talk) 02:12, 14 September 2023 (UTC)

The text does not indicate the abuse liability is "moderate" either? That is your interpretation.

The prescribing information for amphetamine explicitly states the same fact.

The dependence liability of amphetamine is widely known with a plethora of literature supporting the fact - including any prescribing information published after 1980.

T

The fact that it's listed as moderate on the page is discrediting the veracity of the article.

Furthermore, it is baffling as to why methylphenidate is listed as "high", and yet amphetamine is listed as "moderate". Anyone with a basic understanding of psychostimulant pharmacology would be dismayed by how ridiculous this is.

I assumed this would have been obvious edit and not something that required discussion. P3nt0th41 (talk) 05:01, 14 September 2023 (UTC)

Multiple Effect Citations Needed

Why does this page list increased cognitive performance and increased muscle strength as effects? There have been no specifically conclusive, academically acceptable or even scientifically reasonable studies done to show that either of these effects occur in a significant enough portion of the general population to include them as "effects". There have, however, been studies to the contrary. 74.140.151.89 (talk) 20:43, 16 January 2024 (UTC)