Talk:Amphetamine

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)

Re: 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.

Thanks for pointing this out. I've gone ahead and addressed that on the current revision of the methylphenidate article so that it's on par with this article.

For context, addiction/dependence liability parameters on drug infoboxes on Wikipedia are largely relative to other drugs that have a rating on their respective infoboxes. Without standardised reinforcement schedules for each drug that assess self-administration, the parameters are instead set based clinical evidence, the pharmacology of each drug, as well as the usage patterns and doses administered amongst the population. IMO it makes no sense to place methylphenidate and amphetamine at the same rating (i.e., "high") as heroin, cocaine, and methamphetamine because all three of those drugs are the most widely used recreational "hard drugs" globally, whereas methylphenidate and amphetamine administered at clinically relevant doses are not associated with an increased likelihood of developing substance use disorder, even though tens of millions of prescriptions are dispensed each year in the United States, Australia, and other countries where these medications are used as first-line treatments for ADHD. Professional Crastination (talk) 06:41, 25 September 2024 (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)

Those sections are cited by systematic reviews with meta-analysis of high-quality controlled trials, albeit with varying statistical designs. I don’t know what you consider to be a more scientifically rigorous methodology than meta-analysis for estimating effect sizes, but there’s no “better” scientific methodology than that to establish a drug effect, provided the inclusion of studies is unbiased/systematic and the included studies have adequate statistical designs (i.e., meta-analysis of RCTs with sufficient sample sizes and consistent, minimally-biased estimators is ideal).

If you’ve read different meta-analyses than the ones cited and they happen to have divergent/inconsistent conclusions, please link them here and I’ll edit the section(s) accordingly. Otherwise, the article isn’t going to change based on your opinion. Seppi333 (Insert 2¢) 00:27, 25 September 2024 (UTC)

Addressing the edit for lisdexamphetamine & CDS

In this edit, I included cognitive disengagement syndrome as a condition treatable by amphetamine. It was redacted here on the basis of an absent secondary source and it being lisdexamphetamine.

First, contrary to the statement, I believe I have cited a secondary source: the International Consensus Statement on CDS. It is a scientific consensus, analysis and evaluation/review of the scientific literature including the primary evidence of lisdexamphetamine as a treatment. As the WP:Secondary states: "A secondary source provides thought and reflection based on primary sources, generally at least one step removed from an event. It contains analysis, evaluation, interpretation, or synthesis of the facts, evidence, concepts, and ideas taken from primary sources".

Second, lisdexamphetamine is a valid derivative of amphetamine. As stated in the article: "currently, pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall, dextroamphetamine, or the inactive prodrug lisdexamfetamine".

Thus I fail to see the issue here. Please discuss. Thanks. Димитрий Улянов Иванов (talk) 01:25, 18 February 2024 (UTC)

WP:LEAD summarizes the body. There is no mention of cognitive disengagement syndrome in the body and it isn't prominent enough (see WP:UNDUE) to be added to the lead.

I know lisdexamphetamine formulation will be converted to dexamphetamine but the sources should mention amphetamine. Besides, the very source you cited is a proposal/study asking to recognize CDS as a distinct syndrome (which means it still hasn't been recognized). This is primary source, a clinical trial. And this doesn't even mention amphetamine and still is WP:UNDUE. --WikiLinuz (talk) 04:36, 18 February 2024 (UTC)

No, it is not a proposal for it to be recognised. It’s a consensus in changing terms. They concluded: “it is evident that CDS has reached the threshold of recognition as a distinct syndrome”. While the clinical trial itself does not mention the term CDS, it is cited as part of the international consensus and refers to the same syndrome as they make plain. Димитрий Улянов Иванов (talk) 10:55, 18 February 2024 (UTC)

CDS is not recognized yet. You can come back once standardized diagnostic manuals recognize it. Your source is a study and not a prominent one either. See what WP:WEIGHT says. --WikiLinuz (talk) 17:41, 18 February 2024 (UTC)

You also didn't address the fact the neither of your sources mention "amphetamine" at all, besides them being poor sources to be used here. You cannot add UNDUE material into lead when there is no mention of it in the body. --WikiLinuz (talk) 17:49, 18 February 2024 (UTC)

Not true! I have to reiterate, as the international consensus states: "it is evident that CDS has reached the threshold of recognition as a distinct syndrome". This is the consensus of all the world's leading experts. Since you are directly disagreeing with their robust conclusion, then I look forward to you citing a peer-reviewed rebuttal.

By the way, diagnostic manuals are not leading the research, but follows it and often a decade or two behind where the research is at the time. And the decisions made by the APA are also political, not just scientifically-based so its hard to know where this will go in the subsequent DSM version. Thus the condition not being recognised in diagnostic manuals does not preclude it from being a distinct syndrome and to claim otherwise is to contradict the scientific consensus. Plus, it objectively is prominent despite what you claim; all documented research since it's publication uses the CDS term on the basis of this consensus that I can locate. And, again, it is a scientific consensus which means it is prominent; consensus means the view is held by the majority of scientists in the field which therefore (from what I can read) does not violate WP:WEIGHT in the slightest. To imply otherwise here is to permeate a falsehood.

And on what basis are you suggesting sources cannot specify a derivative of amphetamine? The article states: "pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall, dextroamphetamine, or the inactive prodrug lisdexamfetamine". Please can you demonstrate that a source cannot be specifying an amphetamine derivative?

On a last note, contrary to your reversive edit on the lisdexamfetamine page, It is not an "advocacy study". The fact that CDS has reached the recognition and evidence threshold is not a promotive idea, it's a statement of fact, as the international scientific consensus makes plain. Димитрий Улянов Иванов (talk) 19:31, 18 February 2024 (UTC)

By the way, diagnostic manuals are not leading the research, but follows it and often a decade or two behind - WP:CRYSTAL, Wikipedia does not lead either. Wikipedia reports it if only it is recognized by mainstream standardized diagnostic manuals. You cannot use ongoing research as a fact, even if a group of researchers agree on a consensus. Until it is established, by that I mean, recognized by standardized diagnostic manuals, it cannot be included on Wikipedia as a distinct medical condition (like CRYSTAL says, Wikipedia does not predict future so you cannot write it in Wikipedia's voice).

Your own source states, Much work remains to further clarify its nature (e.g., transdiagnostic factor, separate disorder, diagnostic specifier) [...].

the condition not being recognised in diagnostic manuals does not preclude it from being a distinct syndrome - Yes it does, at least here.

since it's publication uses the CDS term on the basis of this consensus that I can locate - Anyone can go to Google Scholar and type in "cognitive disengagement syndrome" to get all. That's not the point.

does not violate WP:WEIGHT in the slightest - Did you even read the WP:LEAD I linked? UNDUE and WEIGHT I mentioned is related to this.

And on what basis are you suggesting sources cannot specify a derivative of amphetamine? - WP:SYNTH, you cannot combine one source and another and write a novel synthesis. The source must state amphetamines. I say this because the source itself is primarily dependent on the clinical trial source (it merely reports lisdexamphetamine trials).

I think you misunderstood by what I mean by advocacy. I meant, it is a conclusion of a working group proposing to replace the "SCT" with "CDS". Like I said, just because they say "it meets threshold of recognition as a distinct syndrome" does not mean it is yet a distinct syndrome (which your source states in the very next sentence). --WikiLinuz (talk) 22:07, 18 February 2024 (UTC)

"Wikipedia reports it if only it is recognized by mainstream standardized diagnostic manuals"

- May you please provide the relevant references or indicate precisely where this is stated? I do not see this specification in the WP:CRYSTAL you linked. Moreover, I can find a variety of conclusions maintained in related articles that contradict the standardised diagnostic manual (e.g. DSM). For example, emotional dysregulation being a core symptom of ADHD. Yet, per DSM diagnostic standards, it is not.

"Anyone can go to Google Scholar and type in "cognitive disengagement syndrome" to get all. That's not the point."

- Well, I was primarily contesting your point that it is "not prominent" and a "poor study". It's a scientific consensus, therefore it does not violate WP:WEIGHT that you referenced from what I can read. A scientific consensus objectively means it is prominent. To address your latter claim, no, it is not a poor study. It's a peer-reviewed international scientific consensus elucidating the mountain of research on CDS. There is nothing "poor" about it.

"Your own source states, Much work remains to further clarify its nature (e.g., transdiagnostic factor, separate disorder, diagnostic specifier) [...]." + "Like I said, just because they say "it meets threshold of recognition as a distinct syndrome" does not mean it is yet a distinct syndrome (which your source states in the very next sentence)"

- You are conflating the terms syndrome and disorder, and contextually, in extension. First, any notion that experts are self-refuting their own conclusion (specifying it is a distinct syndrome then not) is an absurd proposition at any surface-glance. It is also wrong, as they do not follow up by stating it is not a distinct syndrome as you claim; they're referring to differentiating it from ADHD in the context of certain organisations (e.g. APA). That's why the term syndrome was selected as "disorder" implies unanimous establishment by organisations. Yet, CDS is simultanously a distinct condition - hence their conclusion and terminology of syndrome.

"WP:SYNTH, you cannot combine one source and another and write a novel synthesis. The source must state amphetamines. I say this because the source itself is primarily dependent on the clinical trial source (it merely reports lisdexamphetamine trials)."

Ok, accepted. Still, a) this article maintains that amphetamine can be prescribed as lisdexamfetamine, an actual derivative (but I shan't belabour this point further but would appreciate any better clarification on that); b) this does not stand in the lisdexamfetamine article.

"I think you misunderstood by what I mean by advocacy. I meant, it is a conclusion of a working group proposing to replace the "SCT" with "CDS". Like I said, just because they say "it meets threshold of recognition as a distinct syndrome" does not mean it is yet a distinct syndrome..."

- No, it's an international scientific consensus, which the report group merely reports, nor is it a "proposition" or an "advocacy". This fact is evident by their conclusion which states; "To experts in the field, it is evident that CDS has reached the threshold of recognition as a distinct syndrome. Still, there is much more work to be done in further clarifying its nature, etiologies, demographic factors, relations to other psychopathologies, and linkages to specific domains of functional impairment". Proposition would imply it has not yet reached the threshold of recognition as a distinct syndrome, but instead are suggesting it should. That is not what was concluded.

CDS meets validity as a distinct syndrome as established by said scientific consensus. The syndrome is considered valid because: 1) well-trained professionals in a variety of settings and cultures agree on its distinction plus presence or absence using well-defined methods and scientific findings and 2) the diagnosis is useful for predicting a) additional problems the patient may have (e.g., difficulties learning in school); b) future patient outcomes (e.g., risk for unemployment; c) unique pattern of response rates to treatment (e.g., medications and psychological treatments); and d) features that indicate a consistent set of causes for the condition (e.g., findings from genetics, twins or brain imaging). They also concluded: ". This constellation of symptom dimensions is considered to be a syndrome because of the higher co-occurrence (inter-correlation) or coherence of these symptoms with each other and inter-relatedness of its dimensions relative to their relationship with symptoms/dimensions of other psychopathologies (ie, internal validity) and unique association and prediction with functional outcomes when covarying other psychopathologies (ie, external validity)". Димитрий Улянов Иванов (talk) 22:02, 19 February 2024 (UTC)

The working group conclusion/consensus citation isn't apt here. Neither is a clinical trial. If you cannot find a secondary, high-quality, peer-reviewed WP:MEDRS review articles, medical textbooks, or meta-analysis that states amphetamines (or their derivates) is indicated or can be used to treat/manage "cognitive disengagement syndrome," you cannot add it here.

And the sources in question do not meet this criteria. --WikiLinuz (talk) 22:53, 19 February 2024 (UTC)

Semi-protected edit request on 6 June 2024

This section “ The oral bioavailability of amphetamine varies with gastrointestinal pH;[74] it is well absorbed from the gut, and bioavailability is typically 90%.[93] Amphetamine is a weak base with a pKa of 9.9;[94] consequently, when the pH is basic, more of the drug is in its lipid soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut epithelium.[94][74] Conversely, an acidic pH means the drug is predominantly in a water-soluble cationic (salt) form, and less is absorbed.[94]” under the sub heading “Pharmacokinetics” is not relevant to Lisdexamphetamine. The pro drug is almost completely absorbed from the gastro system into the blood stream, and the majority of conversion from Lisdexamphetamine to Dextroamphetamine + Lysine happens in the blood stream. The pH is therefore not a factor in bioavailability for this drug. Please see here for evidence:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873712/

The section in Jimmymozzer (talk) 15:09, 6 June 2024 (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. Lightoil (talk) 17:09, 11 June 2024 (UTC)

@Jimmymozzer Re: "The oral bioavailability of amphetamine [...]" under the sub heading “Pharmacokinetics” is not relevant to Lisdexamphetamine.

This wiki article is on amphetamine, which "is about mixtures of levoamphetamine and dextroamphetamine", per the italicised text in the first line of the article. Additionally, the top of this talk page has a "frequently asked questions" banner that solely covers whether LDX is covered an amphetamine, in which the answer that LDX is "chemically distinct from the amphetamine enantiomers (i.e., levoamphetamine and dextroamphetamine)" is provided. So, the content covered in the pharmacokinectics section of this article (i.e., the bioavaliability of amphetamine and its enantiomers) is entirely appropriate given that this is the amphetamine article and not the LDX article.

In any event, your concern regarding the coverage of LDX's unique conversion to dextroamphetamine by a rate-limiting enzyme in blood is actually addressed both in the first paragraph of the pharmacology section of the LDX article and in the third paragraph of the PK section in this very article (i.e., amphetamine). Despite the heavy reliance on transcluding content from this article (i.e., amphetamine), all of the wiki articles covering different pharmaceutical amphetamines/dose-formulations (e.g., Adderall, dextroamphetamine, lisdexamfetamine) have unique content added to address notable characteristics where applicable; case in point: when I wrote the binge eating disorder section for the LDX article, I purposefully wrote the source code in a way that only allows the coverage of that content to be rendered in the medical uses section of the LDX article - and not, say, the Adderall article - if only because LDX is the only amphetamine-dosage formulation to have its clinical use and efficacy in BED covered in systematic reviews and meta-analysis'.

With all that said, I do agree that it's a bit odd that the PK section of the LDX article has the passage about oral absoprtion and gastrointestinal pH included in the transclusion from this article. Though, I suppose that may just be a limitation of wikipedia's source code. In any event, I'll take a look the source code when I have some free time later today and see if there's anything that can be done about it. If it can be removed without breaking the other articles that use the same transclusion, then I'll likely see to it. Professional Crastination (talk) 08:42, 16 July 2024 (UTC)

Protected page edit request

Hello. Requesting that the following category be added to this semi-protected page:

[[Category:Monoaminergic activity enhancers]]

See the monoaminergic activity enhancer page for details and sources. Thank you. 98.191.202.231 (talk) 19:57, 25 July 2024 (UTC)

 Done Professional Crastination (talk) 06:46, 25 September 2024 (UTC)