Talk:Methamphetamine

Semi-protected edit request on 7 July 2023
Change A: Methamphetamine < Uses < Medical

"In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating ADHD and obesity in both adults and children;[24][25] however, the FDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use.[24] To avoid toxicity, FDA guidelines recommend methamphetamine at doses 25mg/day for ADHD in adults and children over six years of age.[5] Methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia.[26][27] In the United States, methamphetamine's levorotary form is available in some over-the-counter (OTC) nasal decongestant products.[note 3]"

To Change B: Methamphetamine < Uses < Medical

"In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating ADHD and obesity in both adults and children;[24][25] however, the FDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use.[24] To avoid toxicity and a risk of side effects, FDA guidelines recommend the initial dose of methamphetamine at doses 5-10mg/day for the treatment of ADHD in adults, and for the treatment of ADHD and obesity in children over six years of age. If a patient's therapeutic dose has not been reached, the dose may be increased by 5mg in weekly intervals until the optimum clinical response is found. The usual effective dose is around 20-25mg, however some people may find lower doses to be more therapeutic. "Methamphetamine should be administered at the lowest effective dosage, and dosage should be individually adjusted." [5] If required, a daily dose may be divided into 2 effective doses. Methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia in doses up to 60mg.[5][26][27] In the United States, methamphetamine's levorotary form is available in some over-the-counter (OTC) nasal decongestant products.[note 3]

'''The explanation for my edit request: '''

Contained within the "Uses" and "Medical" section for methamphetamine, there is a distressing error that claims, "To avoid toxicity, FDA guidelines recommend methamphetamine at doses 25mg/day for ADHD in adults and children over six years of age."

This is misleading, considering that a beginning dose, 25mg of methamphetamine, is NOT recommended by the FDA for the treatment of ADHD in adults, as well as the treatment of ADHD and obesity in children over six years of age without an observed clinical trial. A dose of 25mg is only "recommended" in the treatment of ADHD (Or a child's obesity) after testing a patient's dose-responsive relationship.

Reference [5] states that, "Methamphetamine is used as a secondary treatment for attention deficit hyperactivity disorder (ADHD) in children over the age of six and for the short-term management of exogenous obesity. Used in this context, the FDA has approved the administration of methamphetamine at doses of up to 25 mg/day."

Stated within the Desoxyn Prescribing Information PDF, reference 24, and according to "[Dailymed]",

"For treatment of children 6 years or older with a behavioral syndrome characterized by moderate to severe distractibility, short attention span, hyperactivity, emotional lability and impulsivity: an initial dose of 5 mg DESOXYN once or twice a day is recommended. Daily dosage may be raised in increments of 5 mg at weekly intervals until an optimum clinical response is achieved. The usual effective dose is 20 to 25 mg daily. The total daily dose may be given in two divided doses daily."

I suggest that we revise the Medical section of methamphetamine to become more informative and to ensure maximum risk prevention. Seventeenyearoldchemist (talk) 22:44, 7 July 2023 (UTC)


 * ✅ -- Wiki Linuz  { talk } 01:06, 8 July 2023 (UTC)
 * I appreciate the quick fix. Thanks for updating my talk page as well!
 * I also like how you improved the readability of the edit through the use of semicolons.
 * I was debating whether I should've included that Desoxyn can be prescribed for Narcolepsy at up to 60mg, but I later realized that it was unnecessary to include the maximum dosages because the clinical period is probably the same for somebody being prescribed methamphetamine for narcolepsy. Thanks for catching that and shortening up the edit! Seventeenyearoldchemist (talk) 07:25, 8 July 2023 (UTC)

Semi-protected edit request on 18 July 2023
'''Reason for edit: Small grammatical error. '''

Change A: In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating ADHD and obesity in both adults and children;[24][25] however, the FDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use.[24] To avoid toxicity and risk of side effects, FDA guidelines recommend initial dose of methamphetamine at doses 5-10mg/day for ADHD in adults and children over six years of age, and may be increased at weekly intervals of 5mg, up to 25mg/day, until optimum clinical response is found; the usual effective dose is around 20-25mg/day.[5][24] Methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia.[26][27] In the United States, methamphetamine's levorotary form is available in some over-the-counter (OTC) nasal decongestant products.[note 3]

Change B: In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating ADHD and obesity in both adults and children;[24][25] however, the FDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use.[24] To avoid toxicity and risk of side effects, FDA guidelines recommend an initial dose of methamphetamine at doses 5-10mg/day for ADHD in adults and children over six years of age, and may be increased at weekly intervals of 5mg, up to 25mg/day, until optimum clinical response is found; the usual effective dose is around 20-25mg/day.[5][24] Methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia.[26][27] In the United States, methamphetamine's levorotary form is available in some over-the-counter (OTC) nasal decongestant products.[note 3] Seventeenyearoldchemist (talk) 02:55, 18 July 2023 (UTC)
 * ✅ - FlightTime  ( open channel ) 03:00, 18 July 2023 (UTC)

Dextroamphetamine stronger stimulant than levomethamphetamine
Accidentally said levoamphetamine instead of levomethamphetamine in my edit summary but I still don’t see how it’s relevant, particularly right there. Seems pretty random and I don’t see the point of comparing an isomer of methamphetamine to one of amphetamine when it’s not even comparing the same type of isomer. Comparing potency of dextroamphetamine to dexromethamphetamine would make exponentially more sense (in the intro). Dexedream (talk) 01:04, 22 July 2023 (UTC)
 * Hmm. I tend to agree; that seems like a weird comparison without additional context, especially given that it's in the lead. Ranked by psychostimulant potency, it's: dextromethamphetamine > dextroamphetamine > levoamphetamine > levomethamphetmaine. I know I've read this in a handful of sources before, so it shouldn't be difficult to cite. If a comparison between amphetamine and methamphetamine enantiomers is included at all, then all 4 should probably be mentioned. Otherwise, I think cutting it seems justified. Also, while levomethamphetamine technically is a CNS stimulant, it's a fairly weak one in comparison to the other enantiomers, particularly considering that it's sold OTC in the United States as a nasal decongestant.  Seppi  333  (Insert 2¢) 01:43, 22 July 2023 (UTC)
 * I think that information would be very useful for readers, so I think it should be included.Another editor recently moved the page levomethamphetamine to levmetamfetamine. It would benefit a review from you. -- Wiki Linuz  { talk } 15:14, 22 July 2023 (UTC)
 * I appreciate you being proactive about moving pages on drug articles to their INN pagename. There are, however, a handful of exceptions to the MOS:PHARM naming convention on drugs (see the first note), and you incidentally happened to come across one of those exceptions with levomethamphetamine. Just wanted to give you advance notice that I'll swap back the pagenames sometime in the near future. Since the page has fairly low traffic, this isn't a matter of any particular urgency.  Seppi  333  (Insert 2¢) 21:00, 23 July 2023 (UTC)
 * Where is the arbitration or discussion that determined this should be the case? I checked the Manuals of Style, but couldn’t find such a supposed exception. If you could let me know, that would be appreciated. JoeBo82 (talk) 01:17, 24 July 2023 (UTC)
 * I mean ... you could check the MOS:PHARM talk page archives and search for discussions about "INN" if you want to read the discussion about the use of the INN as the pagename and exceptions to this rule, but that's a bit unnecessary given what's actually written on MOS:PHARM. The exceptions to using the INN and when to use a different common name as the pagename is explicitly stated on the MOS page, and the particular exceptions for methamphetamine and several amphetamine derivatives are stated as examples on the MOS page as well. To quote MOS:PHARM directly: "A drug article should be titled according to its International Nonproprietary Name (INN), also known as recommended International Nonproprietary Name (rINN), if one exists, except in unusual circumstances where another common name is more appropriate."


 * As a convention, most substituted amphetamines that are also prescription drugs don't use the INN, as is evident from the tracking category entries below. Their INNs are much less recognizable than the names derived from the amphetamine contraction (i.e., the common names that are used instead) in English-speaking countries. As a rather extreme example, I doubt even 1% of the general population would even recognize MDMA by its INN.


 * 3,4-Methylenedioxyamphetamine
 * 4-Hydroxyamphetamine
 * Aminophenazone
 * Amphetamine
 * Arylsulfatase B
 * Bempegaldesleukin
 * Blarcamesine
 * Butirosin
 * Cholecalciferol
 * Ciprofol
 * Copper (64Cu) oxodotreotide
 * CureVac COVID-19 vaccine
 * Cysteamine
 * Dextroamphetamine
 * Dibrospidium chloride
 * Fenethylline
 * Gosogliptin
 * Imidazole salicylate
 * Inosine pranobex
 * Isoprenaline
 * LSD
 * Lutetium (177Lu) oxodotreotide
 * Magnesium (medical use)
 * MDMA
 * Merestinib
 * Methamphetamine
 * Methicillin
 * Moderna COVID-19 vaccine
 * Niacin
 * Pecazine
 * Pfizer–BioNTech COVID-19 vaccine
 * Recombinant factor VIIa
 * Rifamycin
 * Savlon
 * Tenilapine
 * Tetrahydrobiopterin
 * Tetrahydrocannabinol
 * Trazium


 *  Seppi  333  (Insert 2¢) 02:09, 24 July 2023 (UTC)
 * That’s methamphetamine, racemic, not enantiopure levmetamfetamine which is being referred to. JoeBo82 (talk) 02:21, 24 July 2023 (UTC)
 * Uhm... I'm pretty sure if the racemate is common name, then the dextro and levo enantiomers have the same common name. If you want to make a big fucking deal about this and draw other editors in simply because you don't like being reverted, then we can go back through the motions all over again. But, there's virtually no way you're going to convince everyone to keep the INN of that page the way it is given previous discussions about these article names. Also, using an INN for an enantiomer and a different common name for the racemate in their respective articles is just weird.  Seppi  333  (Insert 2¢) 02:39, 24 July 2023 (UTC)
 * Where’s this supposed “big fucking deal” you’re whining about? I was nothing but polite to you. JoeBo82 (talk) 03:02, 24 July 2023 (UTC)
 * True, but I wouldn't expect to be immediately reverted by someone non-combative.
 * Not trying to be a dick, but you need to understand there has been a lot of discussion about these article names in the past. It's not like MOS:PHARM is just ignored on amphetamine, dextroamphetamine, methamphetamine, and levomethamphetamine. I mean, one of those is an FA and this page is a GA. Obviously, the pagenames have been discussed ad nauseum. I just don't remember if they primarily took place on this page, talk:amphetamine, WT:MED, WT:PHARM, or MOS:PHARM, and I don't particularly feel like searching through all 5 talk page archives right now. If you really want to read the relevant discussions, I'll link them for you later tonight or tomorrow. But again, I don't really see why you find it necessary given the fact that for basically any guidance to be written into a project MOS, it has to be discussed ad nauseum on the talk page first. So, you already know you'll find a consensus there.  Seppi  333  (Insert 2¢) 03:16, 24 July 2023 (UTC)

Methamphetamine Hcl =\= Crystal meth? Also physical dependence
Also while I’m here, is there actually a source that says methamphetamine hydrochloride (HCl) is the crystallized form of methamphetamine because that sounds sort of contradictory to me but maybe I just don’t know enough about chemistry. I thought hydrochloric salts were literally removed from certain drugs (such as cocaine) to make them “smokable” (unless it’s a case by case thing), and from what I understand crystallized methamphetamine was first introduced specifically to be smoked.

Admittedly I’m not sure on that one about the hydrochloride form but I do know for a fact that physical dependence saying “none” is undoubtedly incorrect. This notion that only downers cause genuine physical dependencies is getting pretty old. Not just on Wikipedia but in the drug/“scientific”/autodidact community in general. It really makes no sense and it treats neurological dependence like something which somehow isn’t “physical” merely because the symptoms are not somatic. The symptoms may not be “physical” but the dependency itself certainly is. Even coffee causes physical/neurological dependence. It seems to just be harping on the grossly outdated idea that stimulant dependencies are ‘fictive’ or just “in your head” with no palpable mechanisms which is clearly not the case. Meanwhile we have the other extreme going on with the cocaine article where people keep insisting on putting “high physical dependence” propensity which seems just as senseless. I can’t see any justifications for the meth/cocaine articles saying anything other than “moderate” in regards to the physical dependence sections. Maybe moderate - high at most. But just shamelessly saying straight up “high” or “none” is pretty ridiculous and essentially impossible to justify.Dexedream (talk) 01:20, 22 July 2023 (UTC)


 * The distinction between physical dependence and psychological dependence is literally just based on whether withdrawal symptoms are physical/somatic or cognitive. Drug dependence - the more general concept - can entail either or both, depending on the drug. Physical/somatic withdrawal symptoms are easily observable/measurable. E.g., ethanol can induce delirium tremens and opioid withdrawal involves "restless legs, nausea, vomiting, diarrhea, sweating, and an increased heart rate", per the lead of that article. All of those symptoms reflect a withdrawal syndrome associated with physical dependence. The symptoms I didn't quote from the lead - given that they're cognitive in nature - reflect psychological dependence. That being said, I don't see where in this article or cocaine the occurrence of physical dependence is mentioned. They shouldn't state this because neither one - nor virtually any other psychostimulant drug - induces physical/somatic withdrawal symptoms after repeated use.  Seppi  333  (Insert 2¢) 02:03, 22 July 2023 (UTC)
 * Addendum: here's a source for the name reflecting the HCL salt.  Seppi  333  (Insert 2¢) 02:09, 22 July 2023 (UTC)
 * Well I don’t see what that link has to do with dependence since that word isn’t even mentioned, nor do I see how it’s even a remotely reputable source. I bet I could scour that site and find dozens of bits of misinformation. I’ve found worse from “better sites” after all. At the end of the day many “professionals” don’t even care about the details or the technical nuances, they’re just doing a job and want to finish and get home like everybody else. Dexedream (talk) 16:49, 29 July 2023 (UTC)
 * yeah that makes no sense because obviously the mechanisms which cause psychological symptoms are still very physical regardless, therefore the dependence itself is still clearly physical. I don’t understand why people have such a problem accepting that drug dependencies are either neurological or somatic (or even both) but there’s literally still no such thing as a “non-physical drug dependency”. That’s a pretty contradictory notion. I mean somebody can say what they want about the symptoms themselves but the dependence.. like the actual dependence is ALWAYS physical and that’s an inescapable fact. So this is clearly a misnomer.
 * Also not that it really matters and it’s certainly not a competition but.. Those “opioid withdrawal symptoms“ you listed sound like some pretty rookie shit to me. I’ve had weed withdrawals that make those symptoms you listed look like a freaking trip to Disneyland. And I mean restless leg syndrome? Really? I mean come on lol, I know RLS sucks but people get that from SO many drugs. You do know RLS is mostly correlated with deficient dopamine levels right? Also no offense but virtually everything you said here pretty much goes without saying, it’s kind of just a reiteration of the same stuff people have said for a while now but it still doesn’t reconcile how the dependence is not physical. It’s still physical. We already know the presentation symptoms between these drugs. Like we know dude lol but come on you can’t really think that actually changes this issue. We don’t have to be experts to discern this. And I would gladly change or look into changing the “psychological dependence” article to a title such as “neurological dependence” but the terminology as of now makes no sense and is CLEARLY outdated. And yes credentialed people have pointed this out. But either way it’s a pretty obvious thing. I mean the title and what it implies is like straight out of the 80/90s or something. I even kinda wish there was even room for debate on this topic there really isn’t.. Sorry but there’s just no debatable angles to this. All drug dependencies are physical. There’s no way around that. Dexedream (talk) 16:43, 29 July 2023 (UTC)
 * If you want to conflate the two, that’s your prerogative. Everyone else in the world is still going to make the distinction.  Seppi  333  (Insert 2¢) 20:36, 3 August 2023 (UTC)
 * Everyone else in the world? Nobody believes neurological doesn’t mean physical Dexedream (talk) 18:13, 4 August 2023 (UTC)
 * People think “psychological dependence” means a fictive craving or just a mental desire. They don’t realize that it has neurological foundations and if they did they would admit that it’s physical, which it is. This is one of the things that’s not debatable. Dexedream (talk) 18:18, 4 August 2023 (UTC)
 * It doesn't matter what your opinion is. Wikipedia articles are based on reliable sources that meet WP:MEDRS criteria. If you want to disseminate your personal opinion, you should do that in your own blog or somewhere else, and not infiltrate into every medical article pushing your personal opinion. -- Wiki Linuz  { talk } 18:24, 4 August 2023 (UTC)

This article needs mentions and definitions of "super meth" and "P2P meth"
"Super meth" and "P2P meth" are getting a lot of discussion in the popular press lately but are not mentioned here. Could someone please add some information? Mondebleu (talk) 20:39, 13 November 2023 (UTC)
 * See History_and_culture_of_substituted_amphetamines. -- Wiki Linuz  ( talk ) 01:54, 14 November 2023 (UTC)

Death from Overdose
This section is well reference by many reliable sources including the CDC. Reknihtdivad (talk) 13:48, 22 November 2023 (UTC)
 * reliasmedia.com, nchrc.org, amegroups.org, consultant360.com, and chooser.crossref.org are not reliable sources.Interpreting WP:PRIMARY sources (such as stats, invidual case reports, etc.) is WP:OR. Overdose information should be sourced from WP:SECONDARY sources that meet WP:MEDRS criteria. -- Wiki Linuz  ( talk ) 19:04, 22 November 2023 (UTC)
 * Thank you for your help. That is greatly appreciated. Reknihtdivad (talk) 20:10, 22 November 2023 (UTC)

Reknihtdivad (talk) 15:09, 22 November 2023 (UTC)

Methamphetamine overdose deaths often involves polydrug abuse, involving various drug classes, not just methamphetamine. This nuance should be included if we write a section on overdose deaths. It should be tailored to incidents of only methamphetamine overdose. -- Wiki Linuz  ( talk ) 13:16, 27 November 2023 (UTC)


 * Although these statistics are reported as deaths involving a particular drug, I made that change, the CDC implies that these numbers represent the number of deaths with a particular drug, at least with opiates. See Understanding the Opiate Epidemic. https://www.cdc.gov/opioids/basics/epidemic.html
 * It might be that opiates are perceived to be more lethal than methamphetamine or cocaine which is probably true. Reknihtdivad (talk) 03:40, 28 November 2023 (UTC)

Semi-protected edit request on 7 March 2024
Change “Addiction liability” from Very High to Moderate (10-15%).

There is no evidence that Methamphetamine addiction potential is ‘very high’, and there is no source linked to back up that claim on this page.

Meanwhile, studies show Methamphetamine to have moderate addiction potential, 10-15%, which is the same addiction liability as Alcohol which has “Moderate (10-15%)” on its wiki page.

This information should also be added to the pharmacology section on the page.

Here is a link to one such study that shows Methamphetamine’s 10-15% addiction liability:

https://www.researchgate.net/publication/232545123_Comparative_Epidemiology_of_Dependence_on_Tobacco_Alcohol_Controlled_Substances_and_Inhalants_Basic_Findings_From_the_National_Comorbidity_Survey

Thank you. 24.5.117.157 (talk) 22:06, 7 March 2024 (UTC)


 * ❌: Methamphetamine have established addiction liability. Methamphetamine. That linked paper doesn't say methamphetamine has 10-15% addiction liability. -- Wiki Linuz  ( talk ) 00:05, 8 March 2024 (UTC)

Methamphetamine "direct" neurotoxicity validity
This article refers to methamphetamine as a neurotoxin, aka a direct neurotoxin. Before I continue, I just want to state that it's very clear that methamphetamine will induce neurodegeneration with chronic exposure to high doses. Not only is this evident from the generous amount of brain imaging studies avaliable on meth recreational (high) and binge (very high) users, but also from the neurotoxic mechanisms methamphetamine has at high doses via EAAT inhibition and hyperthermia/BBB permeability.

Anyway, I was looking through the citations to better understand how and why methamphetamine is neurotoxic even at the doses indicated for ADHD, because they aren't as direct and straight forward as the imaging meta-analysis on ADHD amphetamine use in that article. I found two citations that seem to be the most relevant for claims of low dose/direct neurotoxicity. The first one is" Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.)" which states

"unlike cocaine and amphetamine, methamphetamine is directly neurotoxic to midbrain dopamine neurons."

However, I have read the third edition from 2015, which has revised this claim to

"Unlike cocaine and amphetamine, methamphetamine is directly toxic at higher doses to midbrain dopamine neurons."

Granted, this kind of feels contradictory. If something is directly toxic, surely it should cause toxicity upon exposure. Say, if a 5mg Desoxyn tablet were given.

Secondly, the source "Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology". has a section in the paper titled "2.2. Long-Term Damage of Low Dose" That seems very direct. However, reading the content of the section, they don't quantify dose. They mention damage related to "chronic use" and "meth abusers", but never quantify the "low dose" part of the title. Maybe there was some confusion during editing and that sentence got cut? They must have got that from somewhere though, so I read the cited papers and see to see what dose is considered low dose methamphetamine. There are eight papers cited in the section,


 * 1) Cognitive Performance of Current Methamphetamine and Cocaine Abusers No mention of dose - Users recruited into the study came from treatment programs. MA and COC using participants were recruited from people treatment clinics in San Bernardino and Los Angeles counties in California. All of the participants for either drug group met DSM-IV criteria for abuse or dependence. I think it's safe to assume that most users in treatment for addiction were not low dose users.
 * 2) Association of Dopamine Transporter Reduction With Psychomotor Impairment in Methamphetamine Abusers. The subjects were included in the study if their average methamphetamine use involved at least 0.5 g/day, at least 5 days per week,for at least 2 years. No low doses here
 * 3) Reflection Impulsivity in Current and Former Substance Users. A UK study, zero meth use. All Amphetamine for the stimulant users. All amphetamine users took street amphetamine daily; 7 were also receiving a dextroamphetamine prescription (dose36.421.9[15–70] mg); none reported methamphetamine use. I'm not sure why the authors cited this. They do know that amphetamine and methamphetamine are different drugs right?
 * 4) Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence. The study specifically recruited high dose users.
 * 5) Incidence of Parkinson’s disease among hospital patients with methamphetamine-use disorders. Individuals aged at least 50 years were assigned to the methamphetamine group only if they had the following characteristics: (1) an ICD-9 diagnosis, in any diagnostic position, of 304.4 (amphetamine and other psychostimulant dependence), 305.7 (amphetamine or related acting sympathomimetic abuse), 969.7 (psychostimulant poisoning) or E854.2 [accidental/unintentional psychostimulant poisoning] The study was based on a review of hospital records, so the doses used cannot be determined. People admitted into the study had to have been medically treated for either dependance, abuse or poisoning related to stimulants. What do you think the low dose vs high dose breakdown is for each of those categories?
 * 6) Brain serotonin transporter in human methamphetamine users  Based on autopsies, 11 out of 16 were reported to have methamphetamine intoxication as cause of death. I think we can all agree that a lethal dose of methamphetamine would not be considered a "low" dose?.
 * 7) Loss of Dopamine Transporters in Methamphetamine Abusers Recovers with Protracted Abstinence.  Not low doses. The minimum dose to be admitted into the study is at least 5-10 times the therapeutic dose range. "METH abusers fulfilled Diagnostic and Statistical Manual of Mental Disorders IV criteria for METH dependence (average METH use of at least 0.25 gm /d, at least 5 d per week for at least 2 years, at least2 weeks of METH abstinence).:
 * 8) Perseverative behavior in rats with methamphetamine-induced neurotoxicity. Oh hey, a rat study.  "The next day, rats received 4 injections at 2-hr intervals of either 0.9% saline or METH (10 mg/kg, s.c.). The rats were repeatedly injected with high doses (the LD50 of meth for rats is ~50mg/kg)."   So after reading every single citation in the section, the lowest dose mentioned is 250mg a day. I don't think anyone could call that a "low dose". I have no idea why the section was named the way it was when there is zero evidence to support it. It's unfortunate that seems to have confused a number of individuals.

Is there anymore evidence that asserts that methamphetamine is toxic at low doses? I understand that there's going to be a greater prevalence of evidence covering high-dose users because methamphetamine is primarily a recreationally used drug. But, surely there needs to be some direct coverage of low dose/therapeutic dose range to be stating outright that methamphetamine is directly neurotoxic in the article. I feel like if anyone would know, it would be @Seppi333, as they've been very active throughout this article over the years. Given the scope of contributions you've made here, I trust you wouldn't have made such an assertion lightly.

2001:388:6080:84:44D5:6AD6:DCAC:9235 (talk) 09:31, 5 May 2024 (UTC)


 * Apologies in advanced for any grammatical errors; I finished writing this some time after my medication wore off and I pretty much lost all interest in proof reading by the end of it.
 * I'm not Seppi, but I feel the need to point that this article doesn't actually quantify the threshold exposure (i.e., dose) of methamphetamine that's necessary for DA neurotoxicity. The only mention of dose "range" is in the lead with the statement that "methamphetamine is neurotoxic to human midbrain dopamine neurons and, to a lesser extent, serotonin neurons at high doses." This is entirely consistent with the sources mentioned.
 * Re: However, I have read the third edition from 2015, which has revised this claim
 * As for the revised wording RE: meth nTox across the 2nd and 3rd editions of the Molecular Neuropharamcology textbook, that likely happened as a result of increasing questions of whether methamphetamine at lower doses is actually toxic to DA neurons, especially in humans. It clearly is at higher doses, but the toxicity of lower doses has been challenged. So the field does not have a definitive answer to that question.
 * In any event, all direct neurotoxins have a threshold dose they must meet in order to exert their relative toxic effect on the brain. What makes them direct neurotoxins is the fact that the substance engages in a direct pharmacological interaction with some aspect of a neuron that results in toxicity. Methamphetamine is a direct neurotoxin if only due its high lipophilicity which allows it to permeate mitochondria in DA neurons and inhibit complexes II and III of the electron transport chain to trigger mitochondria depolarisation. Inhibition of those complexes from sufficient concentration of methamphetamine disrupts oxidative phosphorylation and ATP production (i.e., mitochondrial dysfunction) which confers increased susceptibility to apoptosis. This is a direct pharmacological effect of the methamphetamine molecule in DA neurons and DA neurotransmission is not necessary and sufficient for this to occur. Increases of sufficiently high DA via meth's participation in TAAR1- and CAMKII-mediated signaling cascades that phosphorylate DAT - and subsequent DA autoxidation can definitely amplify the neurotoxic effects of meth due DA quinones also having the capacity to mess with electron transport chain enzyme subunits. I think it's also worth pointing out that any neurotoxicity is also potentiated by meth's activity at Sigma 1&2 receptors in human DA neurons, which increases DA release and elevates body temperature (NB activation of sigma receptors aren't inherently neurotoxic, but they potentiate meth's neurotoxicity because of severalGPCR s that they interact with; sigma-2 receptor activation can also trigger apoptotic cascades). That being said, the biggest contributor to neurodegeneration when using methamphetamine at relatively high doses is cerebral hyperpyrexia.
 * With all that said, I doubt we're going to get a clear answer on whether methamphetamine is neurotoxic or neuroprotective at the USFDA-approved dose range for Desoxyn pharmaceuticals through meta-analytic reviews of neuroimaging studies of low-dose users, a la amphetamine, any time soon. Methamphetamine is a direct neurotoxin to DA neurons and current reviews of neuroimaging studies show that methamphetamine use correlates with neurotoxicity/neurodegeneration. Obviously, given (1) the common dosage patterns amongst methamphetamine users worldwide and (2) how irrelevant Desoxyn is relative to other USFDA-approved ADHD psychostimulants, meth use correlates with high-dose meth use in general. So, again, methamphetamine is clearly directly toxic at higher doses in humans, but that finding cannot be extended to lower (i.e., ~25 mg) doses. Professional Crastination (talk) 14:31, 28 June 2024 (UTC)