Talk:Amphetamine/Archive 3

Oral Bioavailability
Claimed oral BA for amphetamine was 25%, and for d-amphetamine wikipedia gives 75% oral BA. Regular amphetamine is 50% d-amp, and so even if l-amphetamine has 0 oral BA, the total would still be (0.75*50=32.5) 32.5% from d-amp alone. There is no reason a regular amine would have such low BA, but I can find no exact figures. Please cite a source if you decide to add this data again. Anareon (talk) 17:30, 2 December 2010 (UTC)

Uh?
"The European Monitoring Centre for Drugs and Drug Addiction reports the typical retail price of amphetamine in Europe varied between $60 and $100 a gram in half of the reporting countries.[4]" Right, we're talking normal amphetamine, not meth - we do not count in dollars in Europe, by the way. 5 to 15 euro should be more like it. --146.87.52.54 (talk) 00:40, 7 December 2009 (UTC)

Flying Jizz Monkey Pants
I don't know if I've ever heard them called that. Kids these days. Looks like vandalism to me. 220.248.62.50 (talk) 10:52, 22 November 2009 (UTC) That is a great name for it

"In children?"
In this sentence, I don't quite get what the "in children part" means: "The group includes prescription CNS drugs commonly used to treat attention-deficit hyperactivity disorder (ADHD) in children." It is factually true, but it implies it is not used in adults? Which is a factually wrong and bizzare assertion. So I'm removing it for now. Please explain your reasoning before reverting. —Preceding unsigned comment added by 87.121.52.97 (talk) 14:00, 13 December 2009 (UTC)

Unused picture
Through the Animusic talk page, I came across this image: Why is it still here if it is no longer needed? dogman15 (talk) 00:55, 2 March 2010 (UTC) Insert non-formatted text here Insert non-formatted text here

Norepinephrine mechanism expansion
I noticed that the "Major biological mechanisms" section begins with "Amphetamine exerts its behavioral effects by modulating several key neurotransmitters in the brain, including dopamine, serotonin, and norepinephrine" yet no where in that section is amphetamine's neuromodulation mechanism of norepinephrine discussed. The effects on dopamine, serotonin and even glutamate are discussed but I find it odd that this is the case because if anything, amphetamine primarily acts on DA and NE and its effects on 5-HT and glutametergic transmission is "secondary" at best.

It may seem like a nit-picky thing but I think it could do the article well if this subject was expanded beyond the last few lines of the section saying "Additionally, several studies demonstrate increased levels of norepinephrine, a neurotransmitter related to adrenaline, in response to amphetamine. This is believed to occur via reuptake blockage as well as via interactions with the norepinephrine neuronal transport carrier" as this is pretty vague. -Novaprospekt (talk) 22:36, 24 March 2010 (UTC)


 * I agree. The effect of amphetamine on the NE transporter (both as a releasing agent and as a reuptake inhibitor) is comparable to DA, and much stronger than on serotonin (5-HT). More generally, I think this article could be improved by combining the mechanism of action section and pharmacology section. The combined section should probably start (after the good chemical properties subsection) by summarising what effects amphetamine has on the DA, NE, and 5-HT transporter (i.e. that it is a releasing agent and a reuptake inhibitor, with less effects on the 5-HT transporter) and quantitative information drawing on the peer reviewed literature. I think it would make sense for more complex matters, such as the effect of amphetamine on the nucleus accumbens and addiction, to be discussed later (instead of first). I'll try to do some work on this page at some stage, if I have time. Woood (talk) 10:30, 3 December 2012 (UTC)

"Citation needed" For Music section
Considering: "Motörhead named themselves after the slang for an amphetamine addict.[citation needed]"

There is a source for this in Motörhead front man Lemmy Kilmisters Autobiography "White Line Fever" (2002). Kilmister notes this in passing somewhere in the first few pages of chapter six (built for speed). I only have access to a Swedish translation of the book though, but this citation should be easily found in an edition in english. —Preceding unsigned comment added by Tbruhn (talk • contribs) 00:15, 18 August 2010 (UTC)

Added some info about Amphetamine & music
I added information regarding Amphetamine's common use in the 80's punk scene and the "90's" punk band NOFX's tributes to the drug in song and as the suggestive title of an album. The information is 100% accurate, but I don't have the first clue how to go about citing a source. I'd suggest somebody link to a discography showing the album info for the song "Three on Speed" (it was first released on an EP titled "Surfer" in 2001). As for the intent behind the name "The Longest Line" -- during an interview in their "10 Years of F***ing Up" DVD, Fat Mike (nofx - vocals/bass) not-so-subtly hints at what the name of the record implies by pantomiming snorting a line of speed. Hopefully somebody can take this info and make it more suitable for Wikipedia's quality standards.71.10.74.4 (talk) 21:23, 5 January 2011 (UTC)
 * To be clear, I'm talking about actual Amphetamine not it's analogues.

71.10.74.4 (talk) 00:53, 17 January 2011 (UTC)

Unclear and irrelevant sentences in intro
From the article's lead section:


 * Amphetamine is chemically related to methamphetamine and lisdexamfetamine, a class of potent drugs that act by increasing levels of dopamine and norepinephrine in the brain, inducing euphoria.[2][3][4] The class includes...

What class are we talking about here? Does it have a name? And shouldn't the lead of the amphetamine article first and foremost talk about amphetamine, rather than about several members of a class of drugs chemically related to amphetamine? The lead as written doesn't tell me whether amphetamine increases dopamine and norepinephrine nor whether it induces euphoria. AxelBoldt (talk) 20:52, 9 January 2011 (UTC)


 * The class is amphetamine. Perhaps it should be worded "amphetamine is a class of drugs which includes methamphetamine & lisdexamfetamine" etc. Nagelfar (talk) 17:49, 26 January 2011 (UTC)


 * Ok, that makes sense. The box on the right suggests that this article is specifically about the substance (±)-1-phenylpropan-2-amine, not about the class of all amphetamines. Does (±)-1-phenylpropan-2-amine have a common name that we could use for this article's title? AxelBoldt (talk) 15:14, 4 February 2011 (UTC)
 * The intro should summarise the contents. This article is not about a class of drugs but about the specific chemical. However the intro seemed to be mainly about the class of drugs, and as such it did not do a good job of sumarising the article contents. I have moved some text from the intro to a new section about derivatives, the best place for this seemed to be after the Prodrugs section at the end. This leaves the intro rather short, if anyone feels like adding in a further summary of some parts of the article.--Pontificalibus (talk) 16:20, 4 February 2011 (UTC)
 * Thanks, it reads a lot better now. AxelBoldt (talk) 12:02, 6 February 2011 (UTC)

drawn synaptic image of amphetamine action
amphetamine acting between the axions & dendrites. Nagelfar (talk) 17:46, 26 January 2011 (UTC)

confusing line
From 1933 or 1934 Smith, Kline and French began selling the volatile base form of the drug as an inhaler under the trade name Benzedrine, useful as a decongestant but readily usable for non-rectal purposes Heh, something look wrong with this sentence? I'd fix this but I don't know what to change it to. Five- (talk) 19:53, 30 March 2011 (UTC)

Categories?
Should this really be categorised as "youth culture in the united kingdom"? 83.226.29.115 (talk) 19:57, 3 April 2011 (UTC)

Return of dopamine into transporter with amphetamine.
One aspect not really touched upon is that when amphetamine causes phosphorylation and releases more dopamine by widening the terminal, as it were, and additionally releases dopamine from the reuptake pump due to this. It however also allows dopamine to re-enter from the release pump which it does not normally do. This may explain the subjective difference in rush according to users when compared to cocaine, which blocks the occupied DAT's uptake fully, whereas amphetamine compromises the transporter in such a way that it allows dopamine back in and away from the receptors as well as releasing it; which cocaine does not in any way do. Nagelfar (talk) 00:23, 17 July 2011 (UTC)

Hippies critical?
The article claims that the 1960s hippie culture was very critical of speed, yet Ken Kesey and many of the Merry Pransters were frequent users of amphetamine — Preceding unsigned comment added by 24.144.222.22 (talk) 19:10, 16 August 2011 (UTC)

I also read that and there's the quote from Allen Ginsberg speaking out against amphetamines/speed yet Allen Ginsberg and his bisexual partner Peter Orlovsky both were known to take amphetamines both benezedrine and methedrine during periods of their life, as all of the beats were. There's a poem by Allen Ginsberg titled ""A Methedrine Vision in Hollywood".173.49.162.183 (talk) 08:38, 1 September 2012 (UTC)

"Toxicity" of clincal doses is a flawed interpretation of otherwise valuable research.
I read "Amphetamine Treatment Similar to That Used in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder Damages Dopaminergic Nerve Endings in the Striatum of Adult Nonhuman Primates" with interest; only to find that the study actually presents a mechanism by which adults can develop a tolerance to this sort of stimulant. When used by monkeys in levels comparable to the "reasonable doses" given by doctors for a month, changes in the count of binding sites observed in the post-sacrifice dissection of the monkey's brains can be measured. However, the paper makes no mention of outright toxicity to the neurons themselves, and as such, is best interpreted as an excellent way of quantifying facts long known medically about this drug, but at the neural level. Rather than presenting evidence of actual brain damage, the reference seems to show how the living brain responds to unnecessary administration of amphetamine. Rather than evidence of neural toxicity, this could be interpreted as a rock-solid example of the exact mechanism of physical addiction, and perhaps, even a way of quantifying the degree to which this has occurred.

To put it rather bluntly, if the research in question had not discovered these changes, the research would suggest that tolerance does not develop to amphetamine after repeated administration of doses considered to be within the therapeutic range - it is already very well known that this is not the case, and one would be hard-pressed to find any literature about medical use of amphetamine as a stimulant or anorectic that does not already mention that this occurs. This federally funded paper seems to present reliable data and uses language in a manner that is technically accurate when interpreted as a whole, but seems intended to incite fear in those who understand the meaning of some of the sentences, without grasping the whole of the paper itself.

Again, if such damage is actually considered evidence of neural toxicity, pharmaceutical companies have a lot to fear: changes in receptor counts are common with many drugs, and often, may even be the method by which intended effects occur! Zaphraud (talk) 18:47, 19 September 2011 (UTC)

"Recreational uses"
I realize wikipedia wants to be as neutral as possible, but i do know that they try to acknowledge the law in their articles. Someone may want to add that many amphetamines are not to be used for "recreation" according to US law, at least as far as i know... 98.127.72.61 (talk) 03:22, 28 January 2012 (UTC)

Physical effects - biased and distorted
The section on physical effects is inappropriately titled. It should be called effects of overdoes or effects of abuse. Or at least adverse effects. As it stands, the article portrays amphetamine as a dangerous substance with virtually no valid therapeutic value. This is simply not the case. If I find the time to learn how to tag an article as biased, I will do so. Hetware (talk) 19:16, 14 March 2012 (UTC)

Manufacture and destruction?
I think this article can greatly benefit from an analysis of the industrial and clandestine methods of manufacture. Also perhaps its detection, destruction and environmental effects (both primary and secondary)? — Preceding unsigned comment added by 2602:306:CD34:4EE0:21F:3AFF:FE10:1889 (talk) 06:29, 9 June 2012 (UTC)

For those who use the plural amphetamines incorrectly to refer to the chemical amphetamine
For your consideration and enjoyment: [http://bitnest.ca/external.php?id=%257DbxWfXSC%251B%2500%2501ryy%2501%2502Q%255BY%250B%255CAv%257Ee Editorial. Abuse of the term "amphetamines". - Alexander Shulgin; Clinical Toxicology 1976] C6541 (T↔C)  18:29, 29 August 2012 (UTC)

Religion
There was an anonymous IP-address-only edit which removed my references to use in religion. I consider David S. Touretzky a very reliable secondary source, and the two references I gave between them point directly to explicit (hearsay, but allegedly also now in court record) quotes about drug use from the user himself. I suspect given the edit history of that IP address that he will repeat his removal of the material with references. I would consider that vandalism, and the page may beed to be semi-protected.Fatphil (talk) 06:55, 31 August 2012 (UTC)

Are you saying that the writings of L Ron Hubbard have had no influence on society and culture in the 20th century? Amphetamine was as much a component of the generation of that writing as it was to any of the music of the musicians listed. Can you honestly say that Elliott Smith has had more influence on society than L.Ron Hubbard - why does the reference to him and one of his songs persist?Fatphil (talk) 12:52, 31 August 2012 (UTC)

Add Andy Warhol to film section.
Someone should mention how Andy Warhol also took Amphetamine pills. http://warholstars.org/chron/1963.html#awspeed WINTER 1963: ANDY WARHOL TAKES "SPEED."

Warhol got a prescription for pharmaceutical "speed" (Obetrol) from his doctor after seeing a picture of himself in a magazine in which he thought he looked fat.

Warhol told Bob Colacello in June 1972, during a trip to Mexico, that he took Dexamyl on a regular basis.

173.49.162.183 (talk) 08:42, 1 September 2012 (UTC)

Chembox Changed Values
Can someone take a look at the changed values in the chembox? It seems they weren't included in the verified revision, so the bots have marked them as "X." I'm not really sure about procedure regarding this, but the values seem correct. 173.170.255.211 (talk) 06:10, 28 October 2012 (UTC)

Long Term Effects Section
This article should have at least a subsection dedicated to the long-term effects of the substance. This is particularly significant because dopaminergic amphetamines are known to do profound damage to the dopamine system when abused, and the lasting effects of pharmaceutical use are still being debated. It's finals season, so I'm pretty busy at the moment, but I thought I should at least mention this. Here are the two most significant (conflicting) studies involving the lasting effects of pharmacological amphetamine use:

http://pharmacology.ucsd.edu/graduate/courseinfo/documents/ricaurteadhd.pdf

http://www.ncbi.nlm.nih.gov/pubmed/22805599

Exercisephys (talk) 16:39, 6 December 2012 (UTC)

Metabolism Information
The information about metabolism on the page is confusing, inadequately cited, and seems to be contradictory. The two sources given only give circumstantial mentions of the enzymes in question, and some claims are not cited at all. The information in the drug box at the top right and the information in the pharmacokinetics section seem to contract one another.

Exercisephys (talk) 02:03, 9 January 2013 (UTC)

Bias in effects sections
Can anyone think of a way to edit these sections to clarify the intended effects vs. the side effects, and to generally make it read as less of a horror show? It's quite biased and unnecessarily scary at the moment, and doesn't sufficiently mention the importance of dose. — Preceding unsigned comment added by Exercisephys (talk • contribs) 23:06, 9 January 2013 (UTC)

someone tried to add methyl to the compound
for more info see Electron_shell that H2 is closed. Lawstubes (talk) 18:56, 17 January 2013 (UTC)

Sorry, but you're wrong in that regard. The squiggly line is not an "unknown bonding group" or whatever you called it but rather a carbon atom. Amphetamine is not methyl amphetamine, you are correct, but it is alphamethylphenethylamine (AlphaMethylPHenEThylAMINE = amphetamine). The reason the line is squiggly is that it can be either "coming out" or "going in". This constitutes the two enantiomers, levoamphetamine and dextroamphetamine. I would suggest not making further edits without brushing up on organic chemistry and pharmacology a little.

Exercisephys (talk) 22:07, 17 January 2013 (UTC)

Real information from someone that knows:
As is usual, all the information regarding addiction, side affects, long term use or abuse and overdose fails to cover the opposite of the same. If one was to abuse the substance and use on a regular basis, what would cause things like drowsiness and loss of energy. Feelings of apathy and general calm and loss of libido instead of increase.

Many would like to know So if there is some studies or research on the opposites it would be good to see it posted.

Personally I have seen the reverse of most of the affects mentioned in the article and the user is of the opinion that they may be ADD or ADHD. Apparent medical or psychological checks have not determined this to be fact however and the mystery is still open.

Semi-Protected Request
This page is the target of constant vulgar vandalism, and it needs serious work as is. It could really benefit from semi-protection and a good revision (the latter of which I may be willing to provide). Exercisephys (talk) 20:34, 17 May 2013 (UTC)
 * You are welcome to be bold and give the article a "good revision", but semi-protection requests must be placed at WP:RFPP. Cheers, &mdash; KuyaBriBri Talk 21:43, 17 May 2013 (UTC)

Cleanup
This page is really a mess. I'm also working on revising long-term effects of cannabis, but I think I'm going to be doing a whole-page review of this article and I invite any willing individuals to help (I could definitely use it). Namely, this page essentially reads like a D.A.R.E. pamphlet, and needs separate discussion of pharmaceutical and recreational use, with a strong distinction made between the differing doses and risks. It should be a thorough empirical description of amphetamine as a chemical, a drug, and a medicine, not a tirade on everything that can go wrong with human use. This likely means a good number of new references are going to have to be introduced. Let me know if you want to help, it would be much appreciated. Exercisephys (talk) 03:26, 18 May 2013 (UTC)

Relevance and inheritance of notability
Have a look at notability verification

A. Person A is notable for his affiliation with mathematics. B. Person A used amphetamines. C. Therefore, his experience is worth of mention in amphetamine, because of premise A. Unless he was specifically notable in mathematics for his amphetamine use, I personally don't think inclusion is warranted. It's sort of like celebrity endorsement line of thinking.

I also find that relevance to amphetamine is quite low. Kind of like Dell Dude being in marijuana article, which I wouldn't find it relevant either. Cantaloupe2 (talk) 21:02, 23 May 2013 (UTC)


 * He is certainly notable for his amphetamine use; it's honestly one of the first things that is mentioned about him. He isn't analogous to some musician that smokes weed. Rather, he used amphetamine and methylphenidate daily for years and credited them with much of his success. Indeed, his productivity skyrocketed when he began using stimulants. This is the archetypal story of amphetamine in mathematics, the two of whom have a storied relationship. In this context, his story is definitely notable. Exercisephys (talk) 21:26, 23 May 2013 (UTC)

Claim that Amphetamine ADHD treatments stunt growth.
The paragraph right at the bottom of the opening section of Amphetamine is a claim that Amphetamine treatments stunt growth in children with ADHD. Dr. Russell Barkley is considered to be "the man that know the most about ADHD and its effects on the human brain" and he has been studying ADHD since 1977. In one of his most recent seminars on the advancements that we have seen in ADHD over the past 10 years, he states that "contrary to what Tom Cruise and the Scientologist's preach, stimulant therapies do no stunt brain growth. The slightly smaller brain growth and size seen in individuals with ADHD is actually one of the effects from having ADHD." The full seminar can be viewed here

I watched the full video a couple days ago so I'm not sure what the timestamp is, but I'll skim through it and see if I can find out. Other than that, can I use this video as a reference and a reason to remove something? --SwampFox556 (talk) 04:49, 7 June 2013 (UTC)
 * Rather than citing the video, I would suggest citing any studies that show if ADHD medicated/unmedicated is correlated with reduced brain growth in comparison to non-ADHD controls. One such study is mentioned here http://www.nih.gov/news/pr/oct2002/nimh-08.htm . (Castellanos, F.X., Lee, P.P., Sharp, W., Jeffries, N.O., Greenstein, D.K., and Clasen, L.S. (2002).Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit hyperactivity disorder. Journal of the American Medical Association, 288,1740–1748). However this field of research is criticized for methodology problems, see http://www.informath.org/apprise/a6402/b2342.pdf, I'm not sure how well regarded these criticisms are, but it may be better to present both sides of the argument. Woodywoodpeckerthe3rd (talk) 22:15, 7 June 2013 (UTC)

Thanks a lot for the source. For the time being, I won't remove anything as to not cause an uproar, however, I will add this information. SwampFox556 (talk) 05:47, 10 June 2013 (UTC)

What does the curve in the structural formula of amphetamine mean?
Can someone tell me the meaning of the crooked line (curve) in the structural formula of amphetamine?
 * Details of this type of chemical structure drawing are explained at Skeletal_structure. In this case, the wavy line indicates a methyl group attached to a carbon atom with mixed stereochemistry. (See specifically Skeletal_structure)  -- Ed (Edgar181) 21:50, 10 August 2013 (UTC)

Performance-enhancing use section
Shouldn't it be stressed that it is banned by WADA? And further, that it was heavily used by cyclist in 60s when it was responsible for couple of high profile death cases. — Preceding unsigned comment added by 89.142.191.37 (talk) 21:56, 17 August 2013 (UTC)


 * I added a clause stating that its use as a doping agent in competitive sports is typically prohibited.Seppi333 (talk) 20:14, 18 August 2013 (UTC)

Article split
The current page has information on amphetamine from a medical standpoint and a socio-cultural standpoint, so I think moving the latter material to a page titled something akin to (only a tentative name) "Amphetamine: History, Society, and Culture" is a good idea for the following reasons:


 * WP:SIZESPLIT suggests cutting an article when the size reaches 100k. As of writing this talkpage entry, the article is at 96.7k.
 * The content in the society and culture section (and smuggling section, which I've appended to it) is sufficient as a standalone article on that topic. Given that the amphetamine page is really about the drug from a medical standpoint, I think WP:CONSPLIT also provides guidance on dividing the article into its medical component and its cultural components.
 * I don't see this article achieving a higher rating from the chemicals/medicine/pharmacology wikiprojects without some action being taken to address the size and scope of the article.
 * Edit/Added bullet: I think it may be worth tacking the history section onto the split as well, since that section has a fair bit of context overlap with socio-cultural content on this page, or at least more overlap than it has with the medical portion of the article.Seppi333 (talk) 05:36, 15 September 2013 (UTC)

Thoughts? Seppi333 (talk) 22:22, 14 September 2013 (UTC)

I've made the split, so this proposal is now moot. New article at: Amphetamine: History, Society, and Culture. It may need to be renamed for better compliance with WP:MOS and a split proposal I've added at Talk:Methamphetamine.Seppi333 (talk) 05:05, 16 September 2013 (UTC)

Music section song references
This section uses a mix of quotations and italics when referring to the names of songs. I'm assuming there's probably similar issues throughout the society and culture section. Can anyone link me the WP policy on reference formatting for names of songs/books/albums/etc so that I can fix this section? Seppi333 (talk) 20:23, 15 September 2013 (UTC)

Section merger/rewrite: Mechanism of action and Pharmacology
The two sections, Amphetamine and Amphetamine, are somewhat redundant and should probably be merged. I also noticed that some of the material is outdated with papers being referenced from as early as 1997 (references 32-68 as of this revision https://en.wikipedia.org/w/index.php?title=Amphetamine&oldid=573088358), which predates the discovery of trace amine receptors, and most notably TAAR1 (the phenethylamine/amphetamine receptor). Some of the references are actually from even earlier, but don't pertain to DA/NE neurotransmission, and so aren't as likely to be invalid in light of that fact. Nonetheless, these older papers don't satisfy WP:MEDDATE, so they'd need to be replaced with newer secondary sources if possible. I plan to rewrite and resource the relevant material on DA/NE neurotransmission at the same time that I combine the sections.

If anyone is comfortable with neuropharmacology and would be willing to either help rewrite/merge the sections or simply review what I've done afterward, I'd really appreciate the editorial support!

Regards, Seppi333 (talk) 05:57, 16 September 2013 (UTC)


 * Barring some minor citation updates to newer papers, this merge is complete. If anyone could review it for typos and/or the neuropharmacology, I'd appreciate it.Seppi333 (talk) 04:43, 19 September 2013 (UTC)

Article improvement
I'm going to attempt to improve this article to FA status by updating all of the outdated or inferior-quality references to current WP:MEDRS-quality reviews from the last 5 years while using the current FA-class articles, bupropion and sertraline, as a guide. If anyone has any suggestions on how to further improve the article at the moment or would like to help, please feel free to let me know or make the edits yourself! I don't WP:OWN this article by any means - I just edit it a lot. :)

Regards, Seppi333 (talk) 23:21, 21 September 2013 (UTC)


 * I started looking at Sertraline a few months back. It cites lots of primary sources. Most of those citations are based on a review cited somewhere in the article - but not all. This makes reviewing such an article for WP:SYN and WP:OR extremely problematical, particularly if the review is only cited at some point distant from the citation of the primary sources. I hope you will avoid that practice. If a claim has been made in a review based on the reviewer's synthesis of primary sources, feel free to reproduce the reviewer's synthesis if that's important, but don't cite the primary sources that reviewer cites - cite just the review itself. If you feel you must cite a primary source, please always cite the review that uses it alongside your citation of the primary source.


 * You about the sources for the Amphetamine. The source for the last sentence, "Furthermore, phenethylamine and its monomethylated derivatives, i.e. amphetamine and amphetamine isomers, all have comparable and notable antinociceptive properties, which manifest as increased pain tolerance.[17]" is supported by a paper on rat brain reuptake. I'd be very interested to read something on the antinociceptive effects of amphetamines, but isn't there a review addressing this factor? --Anthonyhcole (talk · contribs · email)  04:57, 11 October 2013 (UTC)


 * I'm glad you caught that. I didn't ask about that citation simply because I didn't think the claim was controversial, but I actually forgot I cited an animal study with the intent of finding a human study later on.  In spite of it being a primary study though, the claim actually references another paper (see quote/paper cited below) - so while technically a secondary source, it's still not a formal review (or MEDRS quality).  I'm not sure a systematic study on amphetamine induced increases in pain tolerance in humans exists, simply because it would necessarily involve causing pain to study participants.  However, I'd probably be able to find a review on the physiological effects of catecholamines that mentions an effect on pain tolerance in the context of fight-or-flight response or something similar.  I'll probably see if I can find that today.




 * Thanks again for bringing that to my attention. Seppi333 (talk) 13:13, 11 October 2013 (UTC)
 * Edit: That didn't take long... & . Seppi333 (talk) 13:23, 11 October 2013 (UTC)


 * Here's the particular part I've cited; if you'd like to check the articles yourself, I'll give you a download link.
 * And, the citation follows from the fact that noradrenaline is a potent agonist at alpha 2 adrenoceptors.Seppi333 (talk) 14:31, 11 October 2013 (UTC)
 * And, the citation follows from the fact that noradrenaline is a potent agonist at alpha 2 adrenoceptors.Seppi333 (talk) 14:31, 11 October 2013 (UTC)


 * Does Miller or Harteick  address the antinociceptive effect of amphetamine in animals or its effect on pain threshold or perceived pain intensity in humans? If so, can you quote what they say here, please? --Anthonyhcole (talk · contribs · email)  07:49, 12 October 2013 (UTC)

I'm hosting all three papers here until you've downloaded them. I don't really feel like quoting the relevant sections, but the cited material is literally what's in front of the citation. Cite 1 says they're TAAR1 agonists. Cite 2 says TAAR1 agonists induce NRI (5-HT and DA inhibition as well). Cite 3 says NRIs are analgesics. It's a fairly straightforward logical implication (technically, 2 of them), but if you have a legitimate concern, I'm open to suggestions. In any event, all three are documented NRI's, but it's just fewer cites to use the first 2 papers than an individual cite for each. Seppi333 (talk) 08:18, 12 October 2013 (UTC)


 * Got them. Thanks. Would you mind removing what you presently say about pain and amphetamines? Presently what you have is WP:SYN. If there is anything to say about the effect of amphetamines on nociception or pain perception (and I'll be surprised if there isn't) you'll need to find one source that says it, an authoritative secondary source - a scholarly review in a high-quality peer-reviewed journal or a chapter in a graduate-level textbook would be ideal. (Pain science tests the effect of compounds on pain perception and physiology in humans and animals all the time. There is never a problem in getting such studies through ethics committees provided they're not redundant, the premise makes sense and the researchers have demonstrated competency.) I haven't looked. If you can't find anything that addresses the point in one appropriate document, let me know and I'll do a search. --Anthonyhcole (talk · contribs · email) 10:20, 12 October 2013 (UTC)


 * I'll park it here for the moment I suppose. I don't think I've seen a primary source with a methodology like that, but I'll admit I haven't done a whole lot of article searching on the topic of nociception.  I did check a variety of pain-related search terms in pubmed a while back with really loose filters, but the most I found was the odd animals study.  In any event, that information isn't really particularly relevant to that section and I only thought it was noteworthy or interesting since the citation mentioned the entire class; consequently, I might just end up deleting it.  I'm more interested in finding secondary sources for the amphetamine induced alterations in endogenous phenethylamine biosynthesis that's currently on my user page.  That content is much more relevant to the article and in particular the pharmacodynamics.  I haven't had time to put much effort into looking for relevant sources because this article needs enough work as it is. Seppi333 (talk) 12:36, 12 October 2013 (UTC)


 * That said, I'm not too familiar with WP:SYNTH and I'm still sort of confused after reading What_SYNTH_is_not, so maybe you can help me understand the policy. Is it both a sequence of citations and the lack of inclusion of a specific object in a citation on its general class, together that create an issue?  I haven't really dealt with that kind of citation issue in this article since amphetamine is the most notable compound is it's structural class (the amphetamines) and its of its binding site (TAAR1).  If this were say, the fluoxetine article, and I wanted to cite a review on effects of 5-HT2 receptor antagonism which doesn't mention fluoxetine, would citing that study and the FDA's fluoxetine drug info or UNC's dissociation constant database (as in the linked table), constitute synth as well?  I'm using this example in particular because it's obviously an SSRI, but it's less "common-knowledge" neuropharmacology involves antagonizing those receptors.  If that's not synth, I'm not sure I understand the difference between the case here and that situation. Seppi333 (talk) 13:04, 12 October 2013 (UTC)

Moreover, phenethylamine, N-methylphenethylamine, and amphetamine are all potent TAAR1 agonists, and therefore norepinephrine reuptake inhibitors; consequently, they all produce analgaesic effects as a result of reduced nociceptive neurotransmission.


 * Gaaa. Please don't make me read that example. My reading of synth is, only say what a review or scholarly overview has said. Above you're saying Source A says 1 Source B says 2 Source C says 3 ergo 4 We need to find that deduction (or a simple assertion of the conclusion, "amphetamines have a nociceptive effect") in one strong source. I want to know the answer. I would be very surprised if the amphetamines do not raise the pain threshold (or diminish perceived pain intensity) in humans, and very disappointed if that's not in a textbook or review somewhere, so I'll add it to my list of things to do, and let you know how I get on. --Anthonyhcole (talk · contribs · email) 13:43, 12 October 2013 (UTC)
 * , I've seen numerous mentions in POV reviews on "performance enhancing drugs (of abuse)" (as opposed to "ergogenic aids"), but I'd rather not cite one of those simply because they present it in an entirely POV manner - ie, the only mention is in the context of masking pain and putting a user at risk of greater injury, along with the presentation of adverse effects without any (or very minimal) review of ergogenic literature. The abstracts of such papers are usually very obviously promoting a certain position on stimulants in general.   This is in spite of the fact that there's no systematic reviews that pure stimulants, like caffeine and amphetamine, at therapeutic doses are dangerous to use while exercising.  Meanwhile, there IS systematic evidence that there's no relationship/association between therapeutic dose stimulant (amphetamine, methylphenidate, etc) use and adverse cardiac events for people with normal cardiac function (see the physical side effects section - 3 reviews there for different population subgroups state that).  So, I'm not sure those reviews actually qualify as MEDRS-sources due to apparent POV/bias.
 * In any event, let me know if you'd like any other sources from the article. Any issues are sure to arise in FA-review later on if they aren't addressed beforehand. Seppi333 (talk) 06:02, 13 October 2013 (UTC)

Synthesis in Pharmacology...
...states that amphetamine was a secondary amine. This it true for e.g. methamphetamine, but afaik nitrogen which has two hydrogens usually tends to be (part of) a *primary* amine. Correct? 2.244.235.3 (talk) 14:15, 9 October 2013 (UTC)
 * Thanks for catching the typo. This section needs more work. I will do so when I have time.  Boghog (talk) 14:32, 9 October 2013 (UTC)

Excretion
In Amphetamine, percentages have been confused with fractions. The suggested excreted proportion should be recognized to be implausible. 30-40% of the drug is typically excreted unchanged in urine, not .30-.40%. The observed range is 1-75%.  98.208.32.105 (talk) 09:03, 26 October 2013 (UTC)

Thank you for pointing that out. Seppi333 (talk) 20:30, 26 October 2013 (UTC)

Statement that Amphetamine is not Neurotoxic
I just removed a statement from the intro that stated that amphetamine is not neurotoxic. This is a massive error and I'm not sure how it made it into the article. It is extremely well established that, at large doses and likely in small/moderate doses, amphetamine is neurotoxic. It can be neurotoxic to the point of causing serious permanent debilitation. The mechanisms of this toxicity have been extensively studied, and are universally accepted. Just search "amphetamine neurotoxicity" on any article database. Exercisephys (talk) 16:25, 29 October 2013 (UTC)


 * It's well established that amph is neurotoxic at high doses - I won't debate that for a second. There is an important (although subtle) difference between saying that a substance is neurotoxic (or not neurotoxic) and causing neurotoxicity at high doses though.  Every substance is a toxin (neurotoxin) in sufficient quantities - even water and sodium can cause permanent brain damage (see the wikilink on sodium) far worse than what amphetamine could cause (mainly because amph doesn't demyelinate neurons).  The main difference between saying a substance is neurotoxic and being toxic at high doses is that a neurotoxin has a direct, toxic effect on a cell - i.e. exposure at any (technically, very low) quantities induces cytotoxicity.  Amphetamine doesn't have that quality at low doses on neurons, whereas methamphetamine is a direct neurotoxin to midbrain dopamine neurons. Hope that clarifies things.  Seppi333 (talk) 18:19, 29 October 2013 (UTC)


 * I thought mentioning this might help illustrate the point. Phenethylamine isn't a neurotoxin, but it does literally the same thing as amphetamine by activating TAAR1.  And, in spite of its short half life and first-pass metabolism, it's still an active compound when consumed orally.  As a result, sufficiently high quantities of oral phenethylamine will very likely induce the same dopaminergic neuronal degeneration that a rather large dose of amph would cause.  Seppi333 (talk) 19:14, 29 October 2013 (UTC)


 * I think that your source is incorrect. There isn't any known difference between methamphetamine and amphetamine that would cause this discrepancy; they have the same method of action. Also, remember that some people have a vested interest in differentiating the two drugs because of pharma sales. Additionally, if methamphetamine were significantly neurotoxic at all doses (and I don't think that has been established either) it wouldn't be a prescription medication. Exercisephys (talk) 19:48, 29 October 2013 (UTC)


 * Yeah, I just read that quote and it's factually incorrect. You have to remember that neurotoxicity isn't a binary; even very toxic substances can be neutralized in small levels. There is no demonstrated fundamental difference between the activity or toxicity of amphetamine and methamphetamine, and it is the medical consensus that amphetamine is termed a "neurotoxin". Saying it isn't (much saying that it isn't while methamphetamine is) would be drawing a line in the sand that doesn't exist, and would in the end be factually wrong. A more reasonable statement would be, "Amphetamine is known to be neurotoxic in high doses. It's neurotoxicity in small and moderate doses in humans is still a matter of debate." Exercisephys (talk) 19:55, 29 October 2013 (UTC)


 * In general, beware of medical textbooks for facts on drugs, particularly on their toxicity and chronic risks. That research is continually developing and is best reviewed on a case-by-case basis. Also, there's an awful status quo that allows professionals to be willfully ignorant and uninformed when it comes to illegal drugs. Exercisephys (talk) 20:02, 29 October 2013 (UTC)


 * Amph and meth do not do the same thing. See Template:Amphetamine and Template:methamphetamine.  Also note that meth does not have any activity on CART activity or receptors, which isn't reflected in those templates.  Nonetheless, I'm not going to throw out a grad/professional MEDRS-compliant text in molecular neuropharm simply because you disagree with it.  You'd need to show me a MEDRS-compliant secondary source that states your claim before I'm willing to remove it from the article.  Also, email the authors if you feel it's factually inaccurate - this text is used in many graduate courses as it is.  Author names/affiliations are here: http://www.mhprofessional.com/product.php?isbn=007164119X
 * I'm just going to point out that your argument is literally that amph MUST be a neurotoxin because N-methyl-amph is a neurotoxin - that's no different than saying dopamine MUST be a neurotoxin because alpha-methyl-dopamine is a neurotoxin (a potent one). Seppi333 (talk) 20:16, 29 October 2013 (UTC)


 * Making the argument that AMPH is not a neurotoxin is absolutely ridiculous. Do just a bit of research, there are thousands of studies exploring all niches of amphetamine neurotoxicity. I don't really know where you come up with these really strong opinions. I reverted it with sources. I really wish you'd be more cautious with your editing, it takes a lot of time and effort to police all of your changes. Exercisephys (talk) 00:37, 30 October 2013 (UTC)

(Outdent) Your book source says meth is a neurotoxin and doesn't even mention amphetamine. It explicitly says "AMPH" refers to substituted amphetamines. Your second source says nothing about amphetamine neurotoxicity. The explicit mention of neurotoxicity in humans is methamphetamine induced degeneration in this quote - the source says absolutely nothing about amphetamine neurotoxicity in humans.

Amusingly, your source corroborates my source's statement about meth vs cocaine neurotoxicity:

Also, neither of these are MEDRS sources because neither is a review of literature or professional medical source from the past 5 years. See WP:MEDDATE. Seppi333 (talk) 03:41, 30 October 2013 (UTC)


 * I'll quote the FDA on this one - this is the 2013 adderall XR label.
 * You won't find a single MEDRS-quality source stating amphetamine is a neurotoxin in humans simply because it's not neurotoxic to humans. Seppi333 (talk) 03:46, 30 October 2013 (UTC)
 * You won't find a single MEDRS-quality source stating amphetamine is a neurotoxin in humans simply because it's not neurotoxic to humans. Seppi333 (talk) 03:46, 30 October 2013 (UTC)

Neurotoxicity Content 1
It is chemically related to methamphetamine; however, unlike methamphetamine, amphetamine is not a neurotoxin, and its salts lack sufficient volatility to be smoked.

Neurotoxicity Content 2
It is very closely chemically related to methamphetamine, and the two drugs have very similar methods of action and effects. High doses of amphetamine are known to be neurotoxic; the neurotoxicity of small and moderate doses in humans is a subject of debate. However, unlike methamphetamine, its salts lack sufficient volatility to be smoked.

"Amusingly, your source corroborates my source's statement about meth vs cocaine neurotoxicity" How is this amusing? Cocaine is in a completely different family of drugs and was never the topic of discussion. This is not some elaborate debate; you're wrong. You'd realize that within two minutes if you did any research outside of your single source. I'm getting really irritated because of your arrogance, your WP:Kingship, and the amount of my time that you're wasting. Here's yet another source for you (this one is a review and is five years old):http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769923/ It is quite comprehensive and continually supports my points. Additionally, instead of being a sentence haphazardly thrown into a textbook, it focuses solely on the subject at hand. Please lay down your sword and let us get back to improving this article. Exercisephys (talk) 03:56, 30 October 2013 (UTC)

Long quote from the paper "Abuse of amphetamines and structural abnormalities in the brain." - see bolded text about neurotoxicity of amphetamine in humans

Please, don't make personal attacks - stick to the content. Seppi333 (talk) 04:04, 30 October 2013 (UTC)

I never personally attacked you, I only criticized the way you're handling this article. Are you still in dispute, or can I add my quoted text back to the intro? Exercisephys (talk) 04:11, 30 October 2013 (UTC)


 * None of the sources you've cited have said amphetamine is a neurotoxin *in humans.* All of them have said it is a neurotoxin *in rodents.*  If you want to explicitly state that it is a neurotoxin in rodents, I'm fine with that.  I'm not ok with even implying it's a neurotoxin in humans though, because it's not, and none of the above sources suggest this. Seppi333 (talk) 04:16, 30 October 2013 (UTC)


 * What about the first sentence? "We review evidence that structural brain abnormalities are associated with abuse of amphetamines." The entire review operates on the basis that both AMPH and MAMPH are neurotoxic in humans. Read it. Exercisephys (talk) 04:29, 30 October 2013 (UTC)


 * Or this: "Most of the evidence for amphetamine-induced human brain damage comes from examination of current and former amphetamine and methamphetamine abusers." The fact that they do approximately the same thing is so basic it's just assumed that the reader already knows it. Exercisephys (talk) 04:32, 30 October 2013 (UTC)


 * "Amphetamine ... is a drug of abuse with neurotoxic potential" -http://jad.sagepub.com/content/11/1/8.full.pdf+html Let's stop now. Exercisephys (talk) 04:38, 30 October 2013 (UTC)


 * I removed the collapse tab around the neurotoxicity quote from that paper that was above this. I bolded the section that discussed neurotoxicity in humans.  If I recall correctly, for humans, it's been established that Meth is a dopaminergic neurotoxin and MDMA is a serotonergic and dopaminergic neurotoxin, but Amph isn't known induce neurotoxicity.Seppi333 (talk) 04:40, 30 October 2013 (UTC)


 * That last source says this about neurotoxicity in humans: (Paper hosted here temporarily)


 * Here are my main points:


 * all the quotes you're pulling from my sources refer to long-term therapeutic use, not binge use
 * binge use counts as use
 * binge use causes neurotoxicity (you yourself acknowledged this above: "It's well established that amph is neurotoxic at high doses - I won't debate that for a second."); this is immediately apparent in the clinical problems faced by AMPH abusers
 * I won't find a source that actively observes neurotoxicity in AMPH abusers because that's considered unethical
 * your sources for METH's neurotoxicity aren't any strong than mine for AMPH
 * it is a general consensus that binge use of AMPH causes neurotoxicity
 * AMPH neurotoxicity is more pronounced in primates than it is in rodents
 * most modern research is on METH because it's a larger societal problem
 * it is hard to do studies on AMPH-only users because METH is more available and they are largely interchageable; they are therefore generalized to "METH users"
 * current research like the stuff I'm citing operates on the consensus that binge AMPH causes neurotoxicity; the question is whether therapeutic use does
 * the believed mechanism of neurotoxicity generalizes to both METH and AMPH (see http://www.annualreviews.org/doi/full/10.1146/annurev.pharmtox.47.120505.105140?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&, "All of these mechanisms have potential implications for both amphetamine- and methamphetamine-induced neurotoxicity, as well as dopaminergic neurodegenerative diseases.")
 * therefore, saying AMPH is not a neurotoxin is ridiculous


 * To clarify, I was making the point that *any* substance is neurotoxic in excess (and that obviously includes amph). That's why I mentioned the water intoxication (also known as water poisoning) link and Central pontine myelinolysis (sodium-induced neurotoxicity) link.  If you quote a paper directly that states amphetamine is a neurotoxin in humans, then I wont contest this anymore.  I'm not doing this to give you a hard time.  I know a lot more about this drug than I've put into this article or let on due to the absurd number of research papers I've read on it.  I've literally not found a single piece of research indicating that amph is a neurotoxin in humans.  Based upon what I've read, the reason neurotoxicity in rodents doesn't translate to humans is due to the fact that rodents metabolize amphetamine entirely differently than we do. Seppi333 (talk) 05:07, 30 October 2013 (UTC)

"I know a lot more about this drug than I've put into this article or let on due to the absurd number of research papers I've read on it." Trust me, same here.

"Based upon what I've read, the reason neurotoxicity in rodents doesn't translate to humans is due to the fact that rodents metabolize amphetamine entirely differently than we do." Source? Also, this is refuted by the fact (shown in sources above) that AMPH is more toxic in primates than it is in rodents. Also, your sources for METH aren't any stronger than mine for AMPH, so I could make the same argument. And: "Amphetamine ... is a drug of abuse with neurotoxic potential" -http://jad.sagepub.com/content/11/1/8.full.pdf+html There's your quote, I already posted it. Done. Exercisephys (talk) 05:15, 30 October 2013 (UTC)


 * Nevermind my statements - I'm not trying to make an argument - I was simply stating what I remember without citation. The point of this thread is for you to provide a MEDRS-quality source which explicitly states (i.e. not an implication or your inference) that amphetamine is a neurotoxin in humans.  I need a quote, not a link to an entire paper or website that supposedly says this, before I stop contesting your claim.  In any event, I'm going to sleep, so I'll check this thread sometime tomorrow. Seppi333 (talk) 05:26, 30 October 2013 (UTC)


 * ...I just supplied a quote in the previous post. Exercisephys (talk) 14:01, 30 October 2013 (UTC)


 * Here's another: "Repeated high doses of amphetamines (in particular methamphetamine) can also induce partial cell loss in substantia nigra." p. 873 Encyclopedia of Psychopharmacology (2008)


 * I can't seem to find the words (or a slight variation of) "neurotoxicity" and "humans" in those quotes. Seppi333 (talk) 17:03, 30 October 2013 (UTC)

"Amphetamine ... is a drug of abuse with neurotoxic potential" At this point I feel like you're trolling me. Do you think they're talking about mice using amphetamine as a drug of abuse? Let's also note that your quote doesn't use the word "human". Additionally, the Encyclopedia of Psychopharmacology, from which I quoted "Repeated high doses of amphetamines (in particular methamphetamine) can also induce partial cell loss in substantia nigra.", is about human psychopharmacology. They don't bother to use the word "humans" in every sentence. Exercisephys (talk) 19:17, 30 October 2013 (UTC)

I'm willing to settle on this conclusion: “amphetamine[, referring to both METH and AMPH,] neurotoxicity for humans is not yet proven, but it is highly likely.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923/ Despite this compromise, I would like to point out two things:
 * your initial sentence that started this debate is dead wrong in two regards (METH being proven a neurotoxin in humans, AMPH being disproven a neurotoxin in humans; if we are talking humans only then neither are proven, if we're talking mammals in general then both are proven)
 * this article is not your WP:Kingdom because you are willing to waste more time than me
 * on the note of WP:Kingship, please stop aggressively refuting things instead of starting an open discussion. It starts these tiffs and causes the article to suffer. If you hadn't vehemently defended that ridiculous quote for so long I would have been a lot less staunch in supporting the opposite point and we would have compromised sooner. Exercisephys (talk) 19:42, 30 October 2013 (UTC)

The burden of proof is on you, not me, since the text I cited explicitly addresses neurotoxicity in humans and is a MEDRS source written by experts in their field from top research universities (e.g. Stanford and Harvard). Your kingship argument is a logical fallacy, since it's off-topic and a straw man, so please stay on topic. You still have not provided a single source stating its a neurotoxin. Citing any of them to make your claim is WP:SYNTH because they don't directly support your claim. If you'd like, we can request a third party from WP med to weigh in on this issue, based upon the sources raised in this thread. Seppi333 (talk) 20:49, 30 October 2013 (UTC)

Please remind me how your source/claim passes any of the challenges you asked of me. Can you find a single other source supporting the idea that amphetamine is proven not to be neurotoxic in humans, or that methamphetamine is proven to be neurotoxic in humans? You found a mistake in a textbook and have defended it to the bitter end. There is absolutely no other evidence that that statement is true; every review we have looked at supported the following conclusion: "amphetamine[, referring to both METH and AMPH,] neurotoxicity for humans is not yet proven, but it is highly likely." Additionally, give me one other MEDRS source that supports your conclusion. We have unquestionably discussed this at sufficient length for you to know that sentence is wrong. No research has proven (or even suggested) that high-dose amphetamine is not neurotoxic in humans, nor is methamphetamine proven to be neurotoxic in humans.

What? The last claim I offered was a direct quote from a source.

Here's from one MEDRS source:

And another:

And another:

And another:

I'm waiting to see a single source supporting your conclusion that isn't that single sentence. Exercisephys (talk) 00:26, 31 October 2013 (UTC)


 * Your justification for removing the molecular neuropharm citation is that it's wrong - that's the claim you need to cite with reliable medical sources, w.r.t. humans. I frankly don't need more than 1 MEDRS source to make the case, which is why I'm not going to bother looking for another one.  This isn't about who is right, it's about WP:PROVEIT.  All four of the sources above are either talking about nonhuman animals (1st, 3rd, 4th) or are talking about the class of (substituted) amphetamines (1st, 2nd (note the word "they"), 3rd, 4th).  None of these sources unambiguously state that amphetamine (alpha-methylphenethylamine, as opposed to (substituted) "amphetamines") is a neurotoxin in humans like the molecular neuropharm quote, i.e. "unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons."  You're getting ahead of yourself by arguing about text you want to put in when you *first* need to make your case for removing the cited text that was already there. Seppi333 (talk) 00:58, 31 October 2013 (UTC)

I've already said this twice, but the point I'm supporting is: “amphetamine[, referring to both METH and AMPH,] neurotoxicity for humans is not yet proven, but it is highly likely.”, which was pulled from one of my sources.

Nope. The first: "effects of repeated therapeutic doses of amphetamine on DAT density in living human brain are unknown" (explicitly about humans) and "Amphetamine (AMPH) is therefore, unusual among the psychostimulants (and most psychoactive agents) in that it is a drug of abuse with neurotoxic potential" (In rodents? Is it a drug of abuse for mice?). The third: "This neurotoxic potential of the drugs may be relevant for humans.", "MDMA and amphetamine neurotoxicity for humans is not yet proven, but it is highly likely." uses the word "humans" twice. The fourth: "It is not known if there are similar alterations in the dopaminergic system of humans" Again, supporting my point using the word "humans".

I would also like to point out that your quote is ambiguous, not mentioning which species it refers to.

All of my sources discuss amphetamine directly (first), mention medical amphetamines (which include only amphetamine and secondarily methamphetamine, and therefore must refer to both if they use the plural) (second, fourth), or repeatedly discuss AMPH and explicitly group into into the category "amphetamines" (the fourth states "Amphetamine was initially synthesized in Berlin in 1887 as 1-methyl-2-phenethylamine. It was the first of several chemicals, including methamphetamine and methylenedioxymethamphetamine, which have similar structures and biological properties, and are referred to collectively as 'amphetamines”'"). As for directly mentioning definitive neurotoxicity, the second ("with important neurotoxic consequences when abused") and fourth ("can be neurotoxic") both refer to neurotoxicity directly and without the mention of it being possible nonexistent. I'm not even trying to argue that, though. I'm just arguing that it isn't proven not to be a neurotoxin, which is what your source suggests.

When I can find a whole slew of contradictory ones, you do.

I'm proving that the text already there was wrong. It should therefore be removed.

By the way, I posted this here. Exercisephys (talk) 01:23, 31 October 2013 (UTC)


 * Since you've just ignored my argument and reaffirmed your position with stating the same points, I'm going to ask for an external opinion on wp:med. It's unlikely this will be resolved by agreement. Seppi333 (talk) 02:27, 31 October 2013 (UTC)

What exactly I didn't respond to? I addressed each of your points individually. Exercisephys (talk)


 * See bolded sections. I am literally repeating my refutation from above.


 * Above, the author uses amphetamines and amphetamine interchangeably. They also explicitly state there is no proof.


 * This doesn't state amph is a neurotoxin. Is bupropion a neurotoxin too?  That's a keto-amph.  This quote also has almost no context and you didn't provide a link.


 * This source is also inconclusive and doesn't support your point. Also note the non-specific/plural "amphetamine stimulants"

I'm strongly considering just merging the text/citations and providing 2 viewpoints on this, as I don't see how else to resolve it. Seppi333 (talk) 04:14, 31 October 2013 (UTC)

I'll just point out now that minoxidil is extremely toxic to cats. That's obviously not reflective of human toxicity because that's the key component of rogaine. So, in a nutshell, toxicities to nonhuman animals do not necessarily reflect toxicity to humans. Evidence of neurotoxicity in rats and nonhuman primates is meaningless (and not WP:MEDRS, which indicates avoiding the use of animal studies). Seppi333 (talk) 04:21, 31 October 2013 (UTC)
 * Toxicity is difficult. Many studies cannot be done on humans due to it being unethical. But none human data is not as accurate / reliable. Thus the statement we should have is that their is limited human date with some tentative animal data associated with harm (that is if we can find appropriate secondary sources). Doc James  (talk · contribs · email) (if I write on your page reply on mine) 10:02, 31 October 2013 (UTC)

Third opinion
This seems to me to be mainly a pointless argument about whether amphetamine is neurotoxic or not. It seems fairly clear to me that the answer to that question depends in the dose, circumstances, and the exact meaning given to 'neurotoxic'.

I cannot believe that it is not possible to agree a form of words that accurately describes the current state of scientific knowledge on this subject and is acceptable to all. Let me know if you would like me to help. Martin Hogbin (talk) 09:45, 31 October 2013 (UTC)

It explicitly defines "amphetamines": "stimulant amphetamines (METH and AMPH)". I am also stating that there is no definitive proof, so this supports my point. You are arguing that there is definitive proof against it.

You're right, but it does state that it may be: “effects of repeated therapeutic doses of amphetamine on DAT density in living human brain are unknown”. Also, I did provide a link.

As I already quoted in my previous response, this source explicitly defines "amphetamine stimulants" to include AMPH at the beginning of the article. Based on your arguments at this point, I suspect that you aren't reading my responses. Most of what I'm saying at this point is just repeating things for you that I've already stated. I no longer understand what you're arguing. Are you still trying to suggest that amphetamine has been proven not to be neurotoxic, like you did initially?

This is what I have been suggesting for a while now.

Propositions for compromise
How about this?


 * I think this is going in the right direction, but should be more specific. Amph will cause neuronal degeneration in excessive doses in humans, because every substance has a toxicity threshold (this may also be worth stating in the OD section).  The studies don't indicate that there is any (consistent) evidence of  direct neurotoxicity in humans, and arguments in these papers are made by extrapolation to humans from animal studies.  Per MEDRS, the latter point is moot, or former is what we have left to summarize.  I'd propose:

Note for above - I'm using neurotoxicity and cytotoxicity interchangeably. Seppi333 (talk) 17:00, 31 October 2013 (UTC)

I feel like it would be preferable to stick to one term (leaving out cytotoxicity). Do you have any reason for the use of synonyms aside from spicing things up? Can you link me to the systematic evidence (or description thereof) of METH neurotoxicity? I don't remember that being discussed, and some of the MEDRS sources I supplied stated that the toxicity of both METH and AMPH is still unproven. I believe that is the case, largely because of the same limitations and confounding factors that prevent a definitive conclusion on AMPH. By the way, I recently added the third primate ADHD treatment study (which showed neurotoxicity) to the article, which wasn't mentioned in your above suggested passage. I just assumed below that the current block about primate ADHD treatment studies will be used. Perhaps the best option would be to leave out discussion of METH's neurotoxicity altogether. Or, we could just mention that due to sociological reasons almost all human-related research has focused on METH. So, how about this?

Anecdotally, this page could probably use more discussion of long-term psychological/cognitive effects along with the neurological effects that we've spent so much time on. Exercisephys (talk) 19:25, 31 October 2013 (UTC)

EDIT: Removed the word "binge" from the above suggested passage. Exercisephys (talk) 19:32, 31 October 2013 (UTC)


 * My only reason for using cytotoxicity is that I don't like using the same word over and over again. Any suitable synonym would be fine.  I saw your edit and I'm fine with it because you stated the conclusion of the review.  My only issue with animal studies is using them to draw conclusions about humans, which you didn't do with that edit, so it's fine.  Some of the papers cited above address methamphetamine dopaminergic neurotoxicity directly, but there's a whole bunch of recent reviews on pubmed on just meth neurotox, so to cite a few sources:

Edit: This is an older review, but it's probably the most dire abstract I've seen so far on meth neurotox:  (note: includes animals)

Edit again: I just noticed these 2 reviews while editing the meth page (the article also contains all the MEDRS-quality sources above) - both of these satisfy MEDRS, but both include animals (unlike the first 2 quoted reviews above this).


 * It's probably better to discuss this in another thread since it's off topic, but the only review I'm currently aware of on long term histological/cognitive changes with amphetamine & ADHD psychostimulant use: (edit: just noticed  was a meta-analysis).  I haven't done a thorough literature search on that topic though.  Seppi333 (talk) 20:08, 31 October 2013 (UTC)


 * Edit: Just for the record, I think that every edit you've made so far today on this article has been very helpful/constructive. Seppi333 (talk) 20:44, 31 October 2013 (UTC)

Sounds like we're in agreement. I'll add the final version. Let me know if you have any further concerns. Exercisephys (talk) 23:36, 31 October 2013 (UTC)

I'm not sure its wise to elaborate on animal neurotoxicity from those studies simply because I suspect most people will erroneously draw the conclusion that animal neurotoxicity is indicative of human neurotoxicity. Seppi333 (talk) 00:25, 1 November 2013 (UTC)

Can I at least remove the quote from that additional source you provided (the one you've been referencing from the start)? All other evidence we have suggests that its conclusions are unwarranted or simply wrong, and it contradicts our consensus conclusion (that amphetamine neurotoxicity is unknown). Exercisephys (talk) 02:46, 1 November 2013 (UTC)

That review just states that it's not a direct neurotoxin, not that it doesn't induce neurotoxicity. That's more or less consistent with what's written on the page, because amphetamine itself isn't (known to be) what causes (its) dopaminergic neurotoxicity, dopamine itself causes that (as odd as it sounds, in excess, dopamine really is a radicals are direct neurotoxins to dopamine neurons). That wouldn't present if an inhibitor of dopamine metabolism were administered at the same time. Seppi333 (talk) 03:56, 1 November 2013 (UTC) Edit/Clarify: amph induces this form of neurotoxicity by maintaining high synaptic dopamine concentrations, which is where autoxidative dopamine neurotoxicity occurs.Seppi333 (talk) 05:37, 1 November 2013 (UTC)

I haven't seen any evidence supporting the statement that amphetamine definitely isn't directly neurotoxic, but I don't have time to get into it now. I'll check back soon. Exercisephys (talk) 01:04, 2 November 2013 (UTC)

I needed to tweak the wording of that section to better fit the source quotes above. I've got a whole lot more ref-checks to make, so I'm not trying to spend a lot of time on any particular section. If you notice or know of a ref that supports a clause I remove, it'd be a big help if you could replace the text and add that ref (also, it's not necessary, but adding the relevant quote to the quote parameter would be better still). I'll take care of the citation formatting afterward if you add something. The article needs to have all the refs checked/verified for text-source integrity for the GA/FA-prep review. All the refs need to be consistently formatted as well. Seppi333 (talk) 03:02, 2 November 2013 (UTC)

, I figured you'd be interested in this...this book states meth is a direct neurotoxin (a good definition/explanation of that term is on the 2nd page of the free preview of this book chapter) with citations to papers. Also, this review states it as well, but it also lists proposed indirect neurotoxic mechanisms of meth, all of which are relevant to amphetamine (except BBB disruption which I haven't read about being associated with it anywhere):

Regards, Seppi333 (talk) 00:39, 6 November 2013 (UTC)

Nonhuman primates
Long-term exposure to amphetamine throughout adolescence in non-human primates has been observed in three studies. The animals were given daily doses of amphetamine that caused blood plasma levels of amphetamine equivalent to or slightly greater than those observed in adolescent humans prescribed the drug. Two of these studies found no discernible adverse effect on their physiology, behavior, or dopamine system development, while one observed long-term damage to dopaminergic nerve endings.

The second ref is a secondary source for the first ref, so there's technically only two studies on this. Only ref [3] needs a secondary source. Needs to be reworded to reflect only two studies.

✅

I just fixed this. There were in fact three studies; I added new citations. Exercisephys (talk) 01:20, 3 November 2013 (UTC)
 * Thanks! I noticed the Volkow one referenced two when I added it a while back, but the second study in his paper has a title reflecting only MPH, so I never read that paper.  I also only skimmed the Volkow paper to see if it satisfied MEDRS – and in particular to see if it was an independent source – so I don't remember what it said about either paper besides being "high quality" or something of the sort.  Does it cover amphetamine as well? Seppi333 (talk) 01:29, 3 November 2013 (UTC)


 * I just checked again and I guess you're right. I could have sworn that Volkow conducted a study on this herself, but I guess not. I'll re-edit to change it back to two. Exercisephys (talk) 17:15, 3 November 2013 (UTC)


 * (In hindsight, it's probably because I was focusing on methylphenidate at the time.) Exercisephys (talk) 17:16, 3 November 2013 (UTC)

JonesKornblum
The activity of amphetamine throughout the brain also appears to be site-specific. Specifically, certain receptors that respond to amphetamine in some regions of the brain tend not to do so in other regions. For instance, D2 receptors in the hippocampus, a region of the brain associated with forming new memories, appear to be unaffected by the presence of amphetamine.

I haven't removed this content yet, but this needs a new ref. I'm going to edit it when I reach that section. I think The first 2 sentences *could* be referenced by the Miller ref on TAAR1, but I'd need to check when I get there.

TrevorKatzung
Need a replacement ref for this sentence (and a couple variants of it), since the source doesn't state this:

"Dangerous physical side effects are exceedingly rare in typical pharmaceutical doses."


 * I would assume that you could just cite the FDA side effects sheet. Exercisephys (talk) 05:03, 3 November 2013 (UTC)