Talk:Methamphetamine/Archive 6

Latest comment: 2 years ago by Alexcalamaro in topic Ortography of Polish name, surname
Archive 1Archive 4Archive 5Archive 6Archive 7

Amendment to the first sentence

Hi, I think the first sentence should instead read like: "Methamphetamine[note 1] (pronunciation: /mɛθæmˈfɛtəmin/; contracted from N-methyl-alpha-methylphenethylamine) is a neurotoxin and potent psychostimulant of the phenethylamine and amphetamine classes, that is used medically, in some countries, to treat resistant cases of attention deficit hyperactivity disorder (ADHD) and obesity, but is better known for its role as an infamous drug of abuse."

Note: I have ignored much of the formatting in this sentence, the bolding and hyperlinking of the words and letters I think is fine the way it is.

Now my reasoning for this suggested change is that most people don't know it's used to treat ADHD or obesity, even there it's only used in some countries (mostly North American countries) and even then only in resistant cases, hence it might be more helpful to mention this and the fact it is well-known drug of abuse. I would just edit it myself, but I felt as this is a good article a consensus should be reached on something as important as the first sentence. Thoughts and opinions will be welcome by anyone. Even people I tend to ruffle the feathers of as I do still value their opinions as Wikipedia is still a democracy. Brenton (contribs · email · talk · uploads) 14:29, 20 July 2014 (UTC)

Seems a bit long. How's this? Seppi333 (Insert  | Maintained) 19:28, 20 July 2014 (UTC)
Sure, I think that's better than my suggestion due to my lack of concision.   Brenton (contribs · email · talk · uploads) 19:41, 20 July 2014 (UTC)

Levmetamfetamine as a USAN

@Fuse809: I'm fairly certain that levomethamphetamine doesn't have a USAN, since it has never been a pharmaceutical drug in the United States. I've read elsewhere that manufacturers (e.g., Vicks) use the INN on their packaging primarily to avoid the stigma associated with the term "methamphetamine". In any event, I'd normally just remove a clause I find dubious, but I figured I'd ask first: do you have a ref for the levmetamfetamine USAN? Nevermind, it's apparently in the very same ref I used to cite the INN... I'm clearly very perceptive. >.> Seppi333 (Insert  | Maintained) 23:45, 6 October 2014 (UTC)

Clarity on freebase vs salts

It's obvious to me why the melting point is listed as 3*C but that's likely to seem very weird for the majority of the population. Should it be made clearer that many of the chemical properties are referring to the freebase oil and not the more commonly seen hydrochloride salt?

Off-label use of prescription methamphetamine?

Is there any off-label medical uses for prescription methamphetamine other than ADHD and obesity? Probably narcolepsy, idiopathic hypersomnia and depression but without sources this is just a guess. Clr324 (say hi) 08:24, 19 February 2015 (UTC)

I imagine all of those are, but I doubt I can find a source that says that. Seppi333 (Insert  | Maintained) 01:55, 20 February 2015 (UTC)
That just sucks. :( I'll look for sources anyways just in case there is any. Edit: Easier than I thought. Clr324 (say hi) 03:55, 20 February 2015 (UTC)

New image

@Boghog: Hey, hope it's not too muxh to ask, but can you draw a new structure diagram for this article as well when you get a chance? I'd like to keep the Dbox images consistent across articles. Seppi333 (Insert  | Maintained) 02:51, 4 April 2015 (UTC)

No problem. I have updated the structure so that it is consistent with the one used in amphetamine. Boghog (talk) 09:28, 4 April 2015 (UTC)

Require sources

Recreationally, methamphetamine is used to increase sexual desire, lift the mood, and increase energy, allowing some users to engage in sexual activity continuously for several days straight.

Done although the entire recreational use section needs expansion. Sizeofint (talk) 16:21, 15 April 2015 (UTC)
The current ref for this sentence in the lead par is San Francisco Meth Zombies (TV documentary). National Geographic Channel. August 2013. ASIN B00EHAOBAO. Is this is an adequate source?? I know the sentence is prefixed with "Recreationally", but the inference is that meth enables continuous bonking for several days straight. So first qn is: is it true? 2nd qn: my body can be aroused that long much without any drugs (it can get to the state that the more we have sex, the more we want to have sex; my girlfriend's tendency to orgasm remains roughly constant, my frequency of ejaculation reduces with time and my refractory period grows), but we would not be capable of staying awake that long or being so obsessed for so long without drugs - this suggests to me that the most pertinent factor is not so much that meth enables extended sexual performance, but that it enables extreme wakefulness and obsession; is clarification along these lines appropriate? — Preceding unsigned comment added by 124.171.14.72 (talk) 12:51, 10 May 2015 (UTC)
Yes, this should be clarified. This section needs additional information and sources so everything is not based off a National Geographic documentary. Sizeofint (talk) 21:22, 10 May 2015 (UTC)
  1. Yes. It is a reliable source.
  2. No. You aren't a reliable source. Seppi333 (Insert ) 22:55, 10 May 2015 (UTC)
I agree that the section needs expansion though. Seppi333 (Insert ) 02:23, 15 May 2015 (UTC)

"UNLIKE AMPHETAMINE..."

LOL, who edited that one? Amphetamine of even garden variety is technically necrotic to neuron integrity DEPENDENT UPON MULTI-FACTORIAL CRITERIA - the statement "UNLIKE AMPHETAMINE..." simply stupidly fails to delve into these, unhelpfully and the simplism is brutal. As if your kid's Ritalin or Adderall was a magically different compound than Desoxyn... Someone state the facts more subtly and wisely here, rephrase things... Makes Wikipedia look retarded. Genetic polymorphisms of individuals and a million other factors determine whether amphetamine shall prove neurologically damaging, but the reality of its capacity above all these contingent factors, to obliterate Homo Sapiens axon-dendrite-ETC. connections necessary for cephalic functionality, is just a brute factum. — Preceding unsigned comment added by 2602:304:B34B:A940:F051:AB0F:3A76:DE48 (talk) 04:34, 19 June 2015 (UTC)

The reference for that statement is reliable but is somewhat on the old side. If you have a newer WP:MEDRS compliant source feel free to provide it and we can update this section. Sizeofint (talk) 05:11, 19 June 2015 (UTC)
Lol. There's a link to the sections in the body right after that statement... the superscripted [i] and [iii], which explains one significant pharmacodynamic and associated toxicodynamic difference that has been identified between methamphetamine and amphetamine. Did you bother clicking that link before ranting here? A single methyl group is the difference between phenethylamine and amphetamine as well, so maybe the brain produces its own necrosis-inducing neurotoxins? Seppi333 (Insert ) 07:25, 19 June 2015 (UTC)

Page protection expired

Should this be extended? I note this page has a long history of vandalism and the first IP edit since protection was removed was vandalism. Sizeofint (talk) 18:45, 9 August 2015 (UTC)

Added a request at WP:RPP, though no clue if it'll go through. Seppi333 (Insert ) 20:20, 9 August 2015 (UTC)

Unclear

Hi. I think there is an editorial mistake in the lead - paragraph 4 - line five. Cheers Myrtlegroggins (talk) 08:52, 11 August 2015 (UTC)

Could you be more specific about the problem? What part of this looks like a mistake? Looie496 (talk) 14:54, 11 August 2015 (UTC)
Certainly - this is the part I found unclear: "the highest use of illegal methamphetamine occurs smokes most of it and parts of Asia, Oceania, and in the United States,". Myrtlegroggins (talk) 12:10, 14 August 2015 (UTC)
Fixed. Thanks for pointing this out. Sizeofint (talk) 18:40, 14 August 2015 (UTC)

Revisions needed in Lead / Medical sections

The following issues should be addressed. Comments please.

In the Lead section:

  1. Revise: "...in the United States, where both racemic methamphetamine and dextromethamphetamine are classified as schedule II controlled substances. In contrast, enantiopure levomethamphetamine is an over-the-counter drug which is marketed as a nasal decongestant in the United States." Sounds like isolated levomethamphetamine is not a controlled substance in the U.S. Very wrong. "Under 21 C.F.R. § 1308.12(d), methamphetamine or its isomers is a Schedule II controlled substance unless specially excepted."[1][2] Two exceptions exist for nasal inhalers made by Vicks and Classic Pharmaceuticals (now Aphena, who packages the product for others such as CVS and RiteAid).[3] Every other form or quantity of levomethamphetamine, even isolating it from the inactive ingredients in these inhalers makes it a Schedule II drug.[4]
    Could be revised to: "...in the United States, where all forms of methamphetamine are classified as schedule II controlled substances. However, decongestant nasal inhalers containing limited quantities of levoamphetamine are permitted as over-the-counter products in the United States." but a more comprehensive revision would be better. There is really no need to mention nasal inhalers in the lead since it is addressed in the Medical section of the article.
      Fixed - decongestant inhalers are currently the only products that contain "levmetamfetamine" per the FDA's drug directory, so I left that part alone. Seppi333 (Insert ) 08:06, 6 September 2015 (UTC)

In the Medical section:

  1. "Severe" should be deleted. "[M]ethamphetamine ... has been approved by the FDA for treating severe ADHD" Severe ADHD does not appear in the FDA monograph.[5] Compared to other stimulants, methamphetamine is rarely prescribed for many reasons: because of its profound illicit use and greater concerns of abuse, greater number/promotion of other stimulants/formulations, neurotoxic potential, high cost/exclusions from insurance formularies, extremely limited supply due to stingy/declining DEA issued Production Quotas[6], and lack of practitioner experience / lack of current therapeutic research / exclusion from medical reference guides. When used, methamphetamine is likely tried in persons with ADHD whose symptoms are not relieved by other ADHD medications. Some may be persons with severe ADHD but some might simply be persons with treatment resistant ADHD. Nonetheless the FDA indications do not specify severe ADHD. (Don't confuse American Society of Health-System Pharmacists' monographs with FDA monographs.)[7]
      Removed it. Seppi333 (Insert ) 08:06, 6 September 2015 (UTC)
  2. Wrong definition for exogenous obesity. "... and [for treating] exogenous obesity (obesity originating from factors outside the patient's control)" The phrase in parenthesis should be deleted (or corrected) because it is not the definition of exogenous obesity but is true for endogenous obesity. Exogenous obesity means consuming more calories than needed or used by the body[8] (as compared to endogenous obesity which means obesity resulting from endocrine or metabolic dysfunction).[9] To demonstrate, obesity may result from hypothyroidism and hypothyroidism is outside the patient's control but this would not be considered exogenous obesity.
      Removed the parenthetical note. Seppi333 (Insert ) 08:06, 6 September 2015 (UTC)
  3. I challenge this statement: "It is rarely prescribed due to concerns over toxicity." Accepting that A. methamphetamine is neurotoxic and B. methamphetamine is rarely prescribed does not prove the assertion. It is more likely that its recreational reputation (including violence and personal devastation) combined with the availability of other efficacious drugs (stimulants & non-stimulants) is the most prominent reason. Measures which were established to combat abuse/diversion such as the Controlled Substances Act, Prescription Monitoring Programs and state/DEA disciplinary actions against prescribers clearly are a major influence driving reduced methamphetamine prescribing. It would be much better to say, "It is rarely prescribed due to concerns over abuse and toxicity." or similar. ("Recreational use" is the MOS preferred term for abuse.) Otherwise please cite evidence for the prescription-toxicity assertion, not just A and B above. (Granted it isn't easy to find specific quality evidence about this.)
      Added summary of above + noted that it isn't an exhaustive list. Seppi333 (Insert ) 08:06, 6 September 2015 (UTC)
  4. Change "sometimes" to "also". "... methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia." "Also" would be more appropriate than "sometimes". "Sometimes" infers methamphetamine is a fringe therapy while the the drug has a long established history treating narcolepsy and the medical community considers narcolepsy a valid indication.
    • Off-label prescription of controlled substances is rather uncommon since treatment efficacy of a drug for off-label indications often isn't established in clinical trials (e.g., efficacy of amphetamine for depression isn't established, but it's an off-label use; by contrast, Adderall's efficacy in treating obesity is more-or-less established due to its relationship to racemic amph, which has established efficacy and is indicated for obesity). I don't have a problem with this proposed change; however, the descriptor "sometimes" is used in Dextroamphetamine#Medical, Amphetamine#Medical, and Lisdexamfetamine#Medical, so I left the sentence alone for now. Seppi333 (Insert ) 08:06, 6 September 2015 (UTC)
  5. The FDA black box warning should be deleted. The FDA requires a number of drugs to display black box warnings but I am aware of no others where it is copied verbatim into a Wikipedia article. It should be sufficient to mention the existence of the black box warning, cite the source and if needed, put the actual quoted warning in a footnote. The concerns raised in the warning should already exist elsewhere in the article.
      Removed quote + replaced w/ a 1 sentence summary - may be worth moving to another section though. Seppi333 (Insert ) 08:06, 6 September 2015 (UTC)
  6. Consider neuroprotective effects. While the article repeatedly mentions neurotoxicity, albeit preliminary, editors might consider methamphetamine's potential neuroprotective effects at low doses for stroke and CNS trauma.[10]

Comments please. Box73 (talk) 14:14, 1 September 2015 (UTC)

Touched up, 2x Box73 (talk) 14:24, 1 September 2015 (UTC) Box73 (talk) 14:34, 1 September 2015 (UTC)
These changes seem reasonable. However, the addition neuroprotective effects would require a MEDRS source such as a review article. Sizeofint (talk) 14:34, 1 September 2015 (UTC)
Most of these sound fine. The lead statement I think you're reading too much into, but if you want to clarify its US schedule, feel free to append a statement on that. If you can find a statement in a review that directly supports neuroprotective effects in humans, go ahead and add it. Seppi333 (Insert ) 14:52, 1 September 2015 (UTC)

References

  1. ^ "949 F2d 1065 United States v. R Youngblood | OpenJurist". openjurist.org. Retrieved 2015-09-01.
  2. ^ "Title 21 CFR - PART 1308 - Section 1308.12 Schedule II". www.deadiversion.usdoj.gov. Retrieved 2015-09-01.
  3. ^ "Title 21 CFR - PART 1308 - Section 1308.22 Excluded substances". www.deadiversion.usdoj.gov. Retrieved 2015-09-01.
  4. ^ "FindLaw's Supreme Court of Mississippi case and opinions". Findlaw. Retrieved 2015-09-01.
  5. ^ "DESOXYN® Methamphetamine Hydrochloride Tablets, USP [Monograph]" (PDF). U. S. Food and Drug Administration. Retrieved September 1, 2015.
  6. ^ "Government Report Slams DEA for Oversight of Drug Production Quota System | RAPS". www.raps.org. Retrieved 2015-09-01.
  7. ^ "Methamphetamine Hydrochloride Monograph for Professionals - Drugs.com". www.drugs.com. Retrieved 2015-09-01.
  8. ^ "exogenous obesity". Retrieved 2015-09-01.
  9. ^ "endogenous obesity". Retrieved 2015-09-01.
  10. ^ Rau, Thomas; Ziemniak, John; Poulsen, David (2015-02-25). "The neuroprotective potential of low-dose methamphetamine in preclinical models of stroke and traumatic brain injury". Progress in Neuro-Psychopharmacology & Biological Psychiatry. doi:10.1016/j.pnpbp.2015.02.013. ISSN 1878-4216. PMID 25724762.

neurotoxicity

I like how it says that meethamphetamine is much more toxic than ritalin and amphetamine. This makes no sense. At low doses toxicity would be absolutely the same. I am not even saying that it compares meth additcs to schoolers on ritaline by 18mg. Higher toxicity is achievable only at large doses due to more powerful output capabilities of meth. Extreemator (talk) 06:45, 31 July 2014 (UTC)

The article states that meth is neurotoxic even at low doses in humans – and amphetamine and methylphenidate are not – because that's what the citations say. The article compares the neuroplastic effect of high dose meth to those of low dose amph because that's as much as could be said from neuroimaging reviews wrt those drugs in humans.
I'd suggest reading the sources if you want an explanation about a statement. Seppi333 (Insert  | Maintained) 00:06, 2 August 2014 (UTC)
Looks like they are trying to keep meth as a bad stuff due to it's common illicit use and keep amphetamine, no one will sponsor a study which says ritalin and adderal are toxic. It seems that you use your sources more than common sense. Btw give the exact citations if you can of what you found so everyone can see your clear research evidence of why amphetamine is so good and so different and not toxic and meth is completly different.
Extreemator (talk) 01:18, 16 January 2016 (UTC)
Amphetamine#Medical - end of the 1st paragraph, all 3 sources. This review – specifically, the section "2.2. Long-Term Damage of Low Dose" – covers long-term methamphetamime use at similar doses. Seppi333 (Insert ) 11:07, 16 January 2016 (UTC)

Semi-protected edit request on 27 December 2014

"Unlike amphetamine, methamphetamine is directly neurotoxic to dopamine neurons.[39]" Source 39 is bogus, the authors do not cite any research to support this statement, it seems to be no more than an opinion. "Methamphetamine also inhibits VMAT1, has agonist activity at all alpha-2 adrenergic receptor and sigma receptor subtypes, and is directly toxic to dopamine neurons in humans, whereas there is no evidence of acute amphetamine toxicity in humans.[39][44][57][63]" None of the cited sources support the statement that there is no amphetamine toxicity in humans. That statement should be removed or supported by valid sources. 70.80.73.24 (talk) 00:47, 27 December 2014 (UTC)

See WP:MEDRS for what constitutes a valid medical source. Seppi333 (Insert  | Maintained) 01:00, 27 December 2014 (UTC)

The guy who wrote this seems to work for pharm company, this Seppi333 is so confident and know what source is good and what is bad. Extreemator (talk) 01:21, 16 January 2016 (UTC)

MEDRS-compliant sources are good. Non-MEDRS sources are bad.   Seppi333 (Insert ) 11:03, 16 January 2016 (UTC)


Neurotoxicity evidence in patients?

"Comparison to amphetamine pharmacodynamics": compares meth abuse with amphetamine prescription. Claims that amphetamine is good for the brain even. Since this article explicitly states that meth is neurotoxic, implying that doctors are prescribing neurotoxic medication to 6 year olds with the approval of the FDA, it should at least include evidence that patients incur methamphetamine-induced neurotoxicity?
Not impressed by Malenka RC, Nestler EJ, Hyman SE (2009). "15". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. btw, a tertiary source that doesn't list a single reference. Ssscienccce (talk) 08:21, 5 October 2015 (UTC)

Here's "low dose" for you.[1]
Personally, I couldn't care less if a reader (i.e., you) is "impressed" or not with sources. That section's sentences are all cited by MEDRS-quality references and that book's refs are at the end of the chapters. Neurotoxicity from a prescription drug isn't unique to meth. Some FDA-approved drugs (e.g., phenylbutyrate) literally list neurotoxicity as adverse effects in their prescribing information. Seppi333 (Insert ) 08:29, 5 October 2015 (UTC)
FWIW, I do think that section needs to be rewritten. Seppi333 (Insert ) 09:01, 5 October 2015 (UTC)


Minor spelling edit to third paragraph

This is just a small catch, in the last line of the third paragraph:

"this damage includes adverse changes in brain structure and function, such as reductions in grey matter volume in several brain regions and adverse changes in markers of metabolic integrity.[19]"

Should read:

"This damage includes adverse changes in brain structure and function, such as reductions in grey matter volume in several brain regions and adverse changes in markers of metabolic integrity.[19]"

I'm unable to make this change myself, since this account has too few edits on Wikipedia

Rushingseas8 (talk) 03:15, 16 November 2015 (UTC)

  Fixed Seppi333 (Insert ) 06:41, 16 November 2015 (UTC)

Section on recreational use problematic, misleading, possibly homophobic

i'll address the specifics on the Talk Page to the main article this is copied from ("History and culture of substituted amphetamines"), but essentially this text is problematic. It is misleading, biased, lacks flow or organization, and doesn't work well as an introduction to a complex topic. This should be a general intro with a projected organization that cites primary sources, not a TV documentary focusing on a particular aspect of the phenomenon. Issues with specific communities and demographics should be addressed as separate sub-topics in the main article on meth history and culture. TheArcane03 (talk) 10:31, 1 December 2015 (UTC)TheArcane03

Agreed. It makes it seems like the only or major manifestation of illicit methamphetamine use is for chemsex, whcih is actually a relatively recent phenomenon. It seems this angle was only introduced in early 2014. Nick Cooper (talk) 17:27, 1 December 2015 (UTC)
Regarding chemsex, we have an article on the topic, under "party and play". We should also have a mention of the associated phenomenon of "crystal dick", which leads to concurrent use of eretile dysfunction drugs with methamphetamine to diminish that side effect. -- The Anome (talk) 15:52, 11 December 2015 (UTC)
There's just 2 recreational uses for methamphetamine: it's an aphrodisiac/orgasm-enhancer in both sexes, but which can also cause ED in males; it's a euphoriant. The latter effect isn't context specific and it's an identical psychological affect for all euphoriant drugs, so it doesn't really merit coverage (I don't know how to cover that anyway). As for the former, that could just as well be stated in the side effects section; but, as has been stated above, there's sociocultural aspects to its libido/pleasure-enhancing effects. The current section on recreational use is obviously not comprehensive, so I agree that's an issue; however, I don't see how it's misleading or homophobic. The section states facts in a neutral manner. Seppi333 (Insert ) 23:10, 11 December 2015 (UTC)

Enantiopure — less is more

What is the difference between dextromethamphetamine and enantiopure dextromethamphetamine? Dextromethamphetamine is assumed to be enantipure. When I read "two dextrorotary and levorotary enantiomers" it sounds like four isomers; it is sufficient to say "two enantiomers". IMO once we say methamphetamine is a racemate with enantiomers dextro- and levomethamphetamine, we can let go of the extra baggage unless it resolves obvious ambiguity in some sentence.

Consider the difference: While enantiopure dextromethamphetamine is a more potent drug, than racemic methamphetamine, the racemic form is sometimes produced and sold instead of dextromethamphetamine due to the relative ease of its synthesis by certain methods and the limited availability of associated chemical precursors. (I probably should have added "illicitly" before produced.)

There was an old George Carlin piece that went, "They divided the class into two halves... I think it was two halves... Uh, yea, definitely two halves." We don't need to state the obvious. Hence my edits. — Box73 (talk) 14:27, 2 January 2016 (UTC)

Looks fine. Seppi333 (Insert ) 21:03, 3 January 2016 (UTC)

Semi-protected edit request on 2 February 2016

In Pharmacology->Pharmacodynamics it incorrectly says that "Activation of TAAR1, via adenylyl cyclase,". We know that GPCRs activates a effector protein like adenylyl cyclase, but the sentence says that effector protein(in this case adenylyl cyclase) activates TAAR1. So it must be "Activation of adenylyl cyclase, via TAAR1,". Ref: Lodish Molecular Cell Biology-> Chapter 15-> Last sentence of page 689. Morteza1440 (talk) 11:59, 2 February 2016 (UTC)

  Fixed Seppi333 (Insert ) 14:00, 2 February 2016 (UTC)

No longer for sale as a nasal decongestant

Levomethamphetamine is available as an over-the-counter drug for use as an inhaled nasal decongestant in the United States.[note 3] - Vicks has discontinued this product. 199.46.199.232 (talk) 10:37, 25 February 2016 (UTC)DLM

  Fixed. Worth noting that Vicks wasn't/isn't the only manufacturer of levomethamphetamine-containing decongenstants. Virtually every Walgreens in the United States sells it. [2] Seppi333 (Insert ) 13:59, 7 March 2016 (UTC)

wrong image

The image is wrong and someone must have vandalised the page — Preceding unsigned comment added by 61.69.118.118 (talk) 10:32, 12 December 2016 (UTC)

Semi-Protected edit request: mechanism of action

This article seems to attribute the psychoactive effects of methamphetamine primarily to TAAR1 activation, which has not been shown. In fact the reverse transport hypothesis is still important in explaining DAT releaser mechanism of action. While there is clearly a role for TAAR1, it is not entirely well-defined, and may be involved more in sensitization than in acute psychostimulant effects. There are also other modulatory proteins involved in this process. [1] [2] (Watchthestorm (talk) 04:13, 7 November 2015 (UTC))

References

  1. ^ Cotter, Rachel; Pei, Yue; Mus, Liudmila; Harmeier, Anja; Gainetdinov, Raul R.; Hoener, Marius C.; Canales, Juan J. (13 February 2015). "The trace amine-associated receptor 1 modulates methamphetamine's neurochemical and behavioral effects". Frontiers in Neuroscience. 9. doi:10.3389/fnins.2015.00039.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  2. ^ Sitte, Harald H.; Freissmuth, Michael (January 2015). "Amphetamines, new psychoactive drugs and the monoamine transporter cycle". Trends in Pharmacological Sciences. 36 (1): 41–50. doi:10.1016/j.tips.2014.11.006.
@Watchthestorm: Can you please be specific about the change you would like (something akin to, change sentence X to read Y)? I could take a look and compose alternate wording myself, but if you have something in mind please specify it here. -- Ed (Edgar181) 11:37, 7 November 2015 (UTC)
I don't have anything specific in mind but thought that reference to multiple theories of transporter function would be appropriate, including the reverse transport hypothesis as well as the role of TAAR1. I can try to write something in the next couple of days. Watchthestorm (talk) 18:57, 9 November 2015 (UTC)
Sorry for not following up earlier. I'm not sure what you're referring to when you say the article attributes psychoactive effects to TAAR1. The pharmacodynamics section only covers TAAR1-related signal transduction in neurons. I added content that was missing w.r.t. its inhibitory effect on neuron firing rate and the unidentified TAAR1-independent efflux mechanism which occurs through DAT phosphorylation by CAMKIIα. It's well established that amphetamine and methamphetamine both phosphorylate DAT via PKA, PKC, and CAMKIIα in vivo, which trigger reuptake inhibition or reverse transport, depending upon the phosphorylating kinase. A comprehensive model (this diagram) involving in vivo, ex vivo, and in vitro evidence supports the role of TAAR1 as the triggering mechanism for the PKA and PKC-mediated signaling cascades, as per this review which is entirely about the role of TAAR1 in DA/monoamine neurons. Xie and Miller (note that Miller wrote the review I've linked) conducted much of the research on TAAR1 in monoamine neurons and they frequently utilized methamphetamine and specific trace amines as ligands in their experiments, as is evident from the review.
The review you cited (2nd paper) omits nearly all the evidence on this simply because the authors believe these compounds bind to the transporters (IIRC from when I read it a while back). That said, the 2011 model is still consistent with the current limited evidence of TAAR1's in vivo pharmacology, although the actual effect of meth on neurons via TAAR1 signaling can't be considered in isolation: the receptor requires co-localization with both a monoamine transporter and VMAT2. It's worth noting that TAAR1 activation without effluxing neurotransmitters from VMAT2 produces a much weaker releasing effect. In contrast, TAAR1-mediated GIRK signaling can reduce dopamine neurotransmission, but this effect doesn't actually appear to occur through TAAR1 in dopamine neurons (current evidence suggests that it arises through TAAR1-mediated GIRK signaling that originates from TAAR1 which is expressed in adjacent+inhibitory or presynaptic neurons).
For several technical reasons (TAAR1-DRD2 functionally/physically interact in such a way that TAAR1 KO actually significantly changes presynaptic DRD2's neuron expression and function compared to WT; TAAR1 is only expressed intracellularly w/ very poor membrane expression; TAAR1 in different species has highly variable sequence similarity with human TAAR1; and other reasons) it's not easy to conduct in vivo research on TAAR1's signaling cascades. Seppi333 (Insert ) 22:02, 7 November 2015 (UTC)
I apologize, I didn't mean to put psychoactive in my earlier post, I think I meant to put pharmacodynamic. In any case, I don't argue that TAAR1 is important in methamphetamine mechanism of action, but there are other mechanisms that are worthy of discussion in this article. In the review I cited, which is more recent than your reference, they do discuss the role of TAAR1 and don't discount it as important. But they maintain that reverse transport is the predominant mechanism of action, wherein the releaser doesn't remain bound to the transporter as you may have thought they said, but passes through it backwards disrupting the ion gradient, and causing reverse transport of the neurotransmitter. It does this at both DAT and VMAT. To completely leave out any discussion of reverse transport in this article doesn't adequately represent the current diversity of understanding of this topic, regardless of any user's interpretation of the strength of one particular argument over another. Watchthestorm (talk) 18:57, 9 November 2015 (UTC)
I'll see about adding something on reverse transport hypothesis over the next day or two to address your concern; to ensure comprehensive coverage, I'll need to do a literature and pharmacology database search first. I've been really busy this week so I haven't had much time for wikipedia. Seppi333 (Insert ) 22:02, 12 November 2015 (UTC)
I went through the evidence-based literature I could find on the topic; at the moment, there doesn't appear to be any evidence that amphetamine or methamphetamine trigger reuptake inhibition or efflux in the absence of transporter phosphorylation. It's apparently well established now that the TAAR1-signaling model from the 2011 review is in fact the in vivo function of TAAR1 in dopamine neurons; the TAAR1-mediated effects on release/reuptake and neuronal firing from the model are listed in IUPHAR's TAAR1 entry (physiological function subsection), which is based primarily on in vivo data. This doesn't necessarily mean there isn't another PKA/PKC phosphorylation mechanism in meth's reuptake/releasing effects though. That said, TAAR1 isn't fully responsible for methamphetamine-induced reverse transport, since there's still the issue of the CAMKII phosphorylation cascade which is TAAR1-independent.
Based upon very recent findings (literally this month) involving DAT-coupled L-type calcium channels, it appears that monoamine transporter/Ca2+ channel coupling mediates DAT phosphorylation by CAMKII and dopamine release by amphetamine as well as CAMKII-mediated SERT phosphorylation and serotonin release by MDMA; it was shown that transporter depolarization activates the coupled calcium channel and triggers calcium influx. Calcium influx putatively triggers CAMKII phosphorylation of DAT as a downstream effect (see [1][2]).
Excluding one mechanism involving sigma receptors, that's all I could find on potential mechanisms of CAMKII signaling and subsequent DAT phosphorylation by meth. That said, I couldn't find any current literature on a release mechanism mediated by the process you described (reverse uptake of a transporter substrate against an ion gradient). From rereading the review you mentioned initially, I gathered that the author was arguing primarily in favor of a release model involving transporter oligomers to explain observed phenomena; the model described in that review is currently just a hypothesis though.
I intend to add something on the CAMKII signaling mechanism described above once there's corroborating evidence (in which case I'd cite a database) and/or it's adequately covered in a medical review. Seppi333 (Insert ) 21:39, 14 November 2015 (UTC)

References

  1. ^ Cameron KN, Solis E, Ruchala I, De Felice LJ, Eltit JM (2015). "Amphetamine activates calcium channels through dopamine transporter-mediated depolarization". Cell Calcium. 58 (5): 457–66. doi:10.1016/j.ceca.2015.06.013. PMID 26162812. One example of interest is CaMKII, which has been well characterized as an effector of Ca2+ currents downstream of L-type Ca2+ channels [21,22]. Interestingly, DAT is a CaMKII substrate and phosphorylated DAT favors the reverse transport of dopamine [48,49], constituting a possible mechanism by which electrical activity and L-type Ca2+ channels may modulate DAT states and dopamine release. ... In summary, our results suggest that pharmacologically, S(+)AMPH is more potent than DA at activating hDAT-mediated depolarizing currents, leading to L-type Ca2+ channel activation, and the S(+)AMPH-induced current is more tightly coupled than DA to open L-type Ca2+ channels.
  2. ^ Ruchala I, Cabra V, Solis E, Glennon RA, De Felice LJ, Eltit JM (2014). "Electrical coupling between the human serotonin transporter and voltage-gated Ca(2+) channels". Cell Calcium. 56 (1): 25–33. doi:10.1016/j.ceca.2014.04.003. PMC 4052380. PMID 24854234. S(+)MDMA (ecstasy) and 5HT (serotonin) induce Ca2+ mobilization in cultured muscle cells expressing hSERT. ...
    The electrical coupling between hSERT and CaV1.3 takes place at physiological concentrations of 5HT.
    hSERT-mediated depolarization activates voltage-gated calcium channels.

Semi-protected edit request on 20 April 2016

Hello,

I respectfully propose the following changes under the Emergency treatment section.

Sincerely,

John R. Richards, MD, Professor, Department of Emergency Medicine, University of California, Davis Medical Center, Sacramento, CA

______________________________________

Replace the last two sentences "Chlorpromazine may be useful in decreasing the stimulant and CNS effects of a methamphetamine overdose.[21] The use of a nonselective beta blocker may be required to control increased heart rate.[7]"

with

Antipsychotics such as Haloperidol are useful in decreasing the stimulant and CNS effects of methamphetamine overdose.[new reference 1] Beta blockers with lipophilic properties and CNS penetration such as Metoprolol and Labetalol may be useful for treating CNS and cardiovascular toxicity.[new reference 2] The mixed beta/alpha blocker Labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine.[new reference 3] The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta-blockers for treatment of methamphetamine toxicity.[new reference 3]

1) Richards JR, Derlet RW, Duncan DR. Methamphetamine toxicity: treatment with a benzodiazepine versus a butyrophenone. Eur J Emerg Med. 1997 Sep;4(3):130-5. PubMed PMID: 9426992.

2) http://emedicine.medscape.com/article/820918-treatment#d10

3) Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015 May 1;150:1-13. doi: 10.1016/j.drugalcdep.2015.01.040. Epub 2015 Feb 18. Review. PubMed PMID: 25724076.

Jrrichards (talk) 13:10, 20 April 2016 (UTC)

  Done. These changes appear constructive and well sourced, so I have made your suggested edit. However, I would suggest in the future making any potential conflict of interest clear (citing your own publications, as appears to be the case here; see WP:COI for details). Regards, -- Ed (Edgar181) 15:20, 20 April 2016 (UTC)
@Jrrichards: Despite the conflict of interest issue with self-referencing, your contributions to this article are appreciated; it's nice to have a subject expert review article content. Seppi333 (Insert ) 21:20, 20 April 2016 (UTC)

Bias in Research

I believe it is important to factor in the influence of confirmation bias, media campaigns, politics, public perception and the influence of pharmaceutical companies when vetting sources for this article. In the last ten to fifteen years in the USA there has been a push by anti-drug advocates to vilify methamphetamine versus drugs of similar percieved danger, ie heroin or cocaine. At the same time pharmaceutical stimulants have had their risks minimized in public perception, despite many having nearly identical pharmacological profiles.

The "Faces of Meth" campaign is a good example. These "before and after" photos used were hand picked out of hundreds of choices, and no attempt was made to control for poverty, homelessness, malnutrition, other diseases or polysubstance usage, and many other factors. As well "meth mouth" and "meth bugs" have been popularized as a common occurrence when in reality they are rare.

Even on wikipedia, methamphetamine's dependence likelihood is "very high" versus a tame "moderate" for its extremely close pharmacological cousin, lisdexamphetamine. There is even a claim that methamphetamine is neurotoxic, while amphetamine is not. This claim is outrageous. To suggest any psychoactive substance does not have potentially toxic properties is extremely misleading.

One might argue that self-reports by users are sufficient evidence of meth's greater danger, but sadly users are notoriously unreliable, are as vulnerable to public perceptions, media bias and the placebo effect as the rest of us, and have relatively small overlap between those who use illegal versus prescription stimulants.

Lastly I want to point out that other developed countries, the UK and Nederlands especially, only recognize that meth is only slightly more addictive than amphetamine. — Preceding unsigned comment added by Toomanybigwords (talkcontribs) 07:14, 14 May 2016 (UTC)

Just butting in here, there is some rigorous analysis of these very issues in this paper : "https://www.opensocietyfoundations.org/sites/default/files/methamphetamine-dangers-exaggerated-20140218.pdf" The comparison of neurotoxicity between methamphetamine and amphetamine may be generally accepted, but it may also be wrong. I too am only pro-truth- check out the citation.

Apologies for the current lack of references, though a quick google search can verify the majority of my claims. I will try to add them in the future, and feel free to ask for any particular one. I am not pro-meth only pro-truth, and am open to criticism. — Preceding unsigned comment added by Toomanybigwords (talkcontribs) 05:10, 14 May 2016 (UTC)

Have you bothered searching this page's archives? Seppi333 (Insert ) 09:10, 14 May 2016 (UTC)


Sorry rather new to editing wikipedia, appreciate any pointers!§

Please cite sources that meet WP:MEDRS for your claims. I don't dispute that the dangers of certain drugs have been somewhat overemphasized, but I disagree strongly with many of your claims. In particular, I want to highlight the neurotoxicity claim - methamphetamine has been demonstrated to be nerotoxic and this is a strongly accepted medical consensus, while amphetamine itself has not been demonstrated to be neurotoxic (along with methylphenidate) and this is also a strongly accepted medical consensus. There is a significant difference between the substances in terms of pharmacological properties, and methamphetamine's addiction/abuse potential is higher than amphetamine (which is still high, just not as high). I'm not quite sure why we classify amphetamine's as "moderate" rather than "high", I need to look into that policy before I can give you an informed response on the reason for that. I'm on a mobile device right now, but I will reply with a longer comment when I get back to my desktop. Garzfoth (talk) 19:26, 14 May 2016 (UTC)
Sepi333 has modified the addiction_liability parameter to "High", which is in line with how addiction_liability is used on Wikipedia. On Template:Infobox_drug, there is some explanation about addiction_liabiliy (it can be Low/Medium/High/Extremely high). The parameter dependency_liability is separate.
So I said I'd reply in greater detail, and here you go:
  • "I believe it is important to factor in the influence of confirmation bias, media campaigns, politics, public perception and the influence of pharmaceutical companies when vetting sources for this article" -- This is not WP:NPOV, nor is it WP:MEDRS compliant.

Apologies for any breach of protocol, I'm new to editing wikipedia.

  • "In the last ten to fifteen years in the USA there has been a push by anti-drug advocates to vilify methamphetamine versus drugs of similar danger" -- Please specify what drugs you are referring to.
  • "At the same time pharmaceutical stimulants have had their risks minimized in public perception," -- Arguable.
  • "despite many having nearly identical pharmacological profiles" -- Nearly identical != identical. 2H2O is nearly identical to H2O, but if I started drinking 2H2O instead of H2O, I'd gain a new appreciation for the term "nearly". I'm sure there are better/wittier examples out there, I just chose a simple and quick one to illustrate the differences.
  • "and no attempt was made to control for [...] and many other factors [...] "meth mouth" [...] [has] been popularized as a common occurrence when in reality [it is] rare" -- PMID 18992021, PMID 17134084, and PMID 12271905?
  • "There is even a claim that methamphetamine is neurotoxic, while amphetamine is not. This claim is outrageous. To suggest any psychoactive substance does not have potentially toxic properties is extremely misleading" -- The claim is accurate. Amphetamine is NOT neurotoxic, and that property has no influence on the nasty side effects of amphetamine overdose, which are clearly explained in every article about an amphetamine-based drug (usually transcluded from amphetamine), as well as in the methylphenidate article.
There you go. Garzfoth (talk) 22:01, 14 May 2016 (UTC)

Hi, thank you for responding. I am new at this (editing wikipedia) so please forgive me for breaking any decorum. Thank you for the formidable and well thought out response. §

First and foremost I think I should emphasize my comments were aimed at "desanctifying" the value of scientific references (which are more or less the gold standard) as evidence in support of one's position, especially on controversial topics like this one. §

Anyone who has ever done any sort of lab work knows that often the slightest mistake in an experiment's process may lead to different results, and as well a perfectly executed experiment that yields unexpected results may be discounted by a researcher. Lets not forget the influence of a scientist's own theories, as well as the interests of his or her benefactor, in determining what actually gets published.§

Now the "scientific consensus" argument, this one is tricky because on one hand this is usually how "facts" ie global warming, are determined, but on the other hand the number of false ideas held in scientific consensus is historically enormous and thanks to man's hubris will likely continue as such.

As for your comments on chemical similarity, I agree completely with what you said (and I think propylene glycol vs. ethylene glycol might be a better example). But notice I said "pharmacological profiles" not "structural profiles". I was referring to the similarity in receptor interactions between meth and amphetamine, ie that with DAT, SERT, TAAR1 blah blah blah. Though if you know a key difference please share.§

The last issue I'd like to presently cover is that of neurotoxicity. Presently this is not a well defined term. "The death of neurons/synapses" might be a good starting place, but how does this reconcile with the fact that, in terms of numbers of neurons and synapses, and adult human has far LESS than a toddler. Clearly killing brain cells isn't all bad. "Toxicity" in this case too often means a change the researcher views as bad. E.g., a researcher might see a loss of DA neurons and immediately think "anhedonia" when really the result could be "increased caution" or another potentially positive or neutral result.§

Thank you for your time§ — Preceding unsigned comment added by Toomanybigwords (talkcontribs)

The pharmacodynamic differences between amphetamine and methamphetamine relevant to neurotoxicity include sigma-1 receptor binding and EAAT1 + EAAT2 vs EAAT3 inhibition.
The death of adult neurons is almost always bad, as there is generally no turnover in most regions of the brain. A neuron doesn't have to die for a drug to exert a neurotoxic effect though (e.g., a drug can permanently and adversely affect protein function/distribution in the axon terminal/dendrites). Neurotoxicity is detectable via functional, chemical, and structural neuroimaging; if you know of a review article that says there is clear evidence of this in humans taking amphetamine, please post it here.
The reason I asked if you checked the archives is that you are not the first person to ask about this and I'm getting annoyed with repeating myself. Seppi333 (Insert ) 05:48, 16 May 2016 (UTC)

Allow me to bring an interesting analogy to your attention, one that cuts to heart of what I'm getting at. It is that of the "colorblind scientist who studies color:" she knows virtually all there is to know about color, ie wavelengths and other light properties, how the brain perceives colors etc etc. What she lacks is the experience of actually seeing color. Since there is virtually no overlap between scientists who study meth and individuals who take it we are stuck with research produced by individuals much like the colorblind scientist. Other good analogies might be, "a mechanic who has never driven a car," "a doctor who has never been sick." Or consider all of all the positive findings on the health effects of coffee; considering most scientists like coffee, I be willing to bet if meth was their drug of choice, we'd be seeing all kinds of articles extolling meth. §

Lolz for the last part, I'm not surprised. Thanks for the references will definitely check them out. — Preceding unsigned comment added by Toomanybigwords (talkcontribs) 22:24, 16 May 2016 (UTC)

The article on dentistry I have seen before (abstract only, too poor for the whole thing), if it has a statistic on the prevalence of "meth mouth" I would appreciate if you could post it perhaps along with the methods used to determine that statistic. I know the phenomenon is real, and likely caused by a combination of dry mouth, vasoconstriction, bruxism, poor hygiene, etc. Most of these can be offset with regular hydration, gum chewing, holding the mouth piece past one's teeth/exhaling through the nose. §

I take it that these glutamine transports you reference are indirectly affected by dopamine release, causing excitotoxicity. EAAT3 corresponds to amphetamine, yes? As to why 3 would lack cytotoxic effects, I am not sure I understand. I would guess your theory is 3 is only expressed in glia while 2 and 1 are expressed in neurons? Correct?§

You might want to post at the meth mouth article talk page for the references. I never bothered downloading those sources. The mechanism by which amph/meth differentially affect glutamate transporters isn't known. EAAT2 is responsible for over 90% of glutamate clearance in the brain,[1] so I imagine this is how meth could induce excitotoxicity. EAAT3 is expressed in DA neurons. EAAT1/EAAT2 are expressed in glia. Seppi333 (Insert ) 17:12, 18 May 2016 (UTC)
Edit: My bad, I didn't answer your question about EAAT3. Yes, amphetamine alters the trafficking/expression of this transporter at the plasma membrane.[2] Seppi333 (Insert ) 22:24, 29 May 2016 (UTC)


References

  1. ^ Holmseth S, Scott HA, Real K, Lehre KP, Leergaard TB, Bjaalie JG, Danbolt NC (2009). "The concentrations and distributions of three C-terminal variants of the GLT1 (EAAT2; slc1a2) glutamate transporter protein in rat brain tissue suggest differential regulation". Neuroscience. 162 (4): 1055–71. doi:10.1016/j.neuroscience.2009.03.048. PMID 19328838. Since then, a family of five high-affinity glutamate transporters has been characterized that is responsible for the precise regulation of glutamate levels at both synaptic and extrasynaptic sites, although the glutamate transporter 1 (GLT1) is responsible for more than 90% of glutamate uptake in the brain.3 The importance of GLT1 is further highlighted by the large number of neuropsychiatric disorders associated with glutamate-induced neurotoxicity.

    Clarification of nomenclature
    The major glial glutamate transporter is referred to as GLT1 in the rodent literature and excitatory amino acid transporter 2 (EAAT2) in the human literature.
    {{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG (July 2014). "Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons". Neuron. 83 (2): 404–16. doi:10.1016/j.neuron.2014.05.043. PMC 4159050. PMID 25033183. The dependence of EAAT3 internalization on the DAT also suggests that the two transporters might be internalized together. We found that EAAT3 and DAT are expressed in the same cells, as well as in axons and dendrites. However, the subcellular co-localization of the two neurotransmitter transporters remains to be established definitively by high resolution electron microscopy.

Metabolism diagram

Note to self: add a direct pathway for methamphetamine → phenylacetone (FMO3).   Added Seppi333 (Insert ) 22:25, 18 September 2016 (UTC)

Edit: should probably also update File:Meth Pathway.png so that the recent revisions to the {{amphetamine pharmacokinetics}} image file are reflected in the image file for this template; the associated enzyme/reaction type annotations from the amphetamine template could then be easily adjusted for use in the meth template. Seppi333 (Insert ) 03:46, 25 September 2016 (UTC)

Neurotoxicity update

 
CC-by-2.5 neurodegeneration image from this ref.[1]

Reviews to add (at some point)...

  1. [2] - includes coverage of human low-dose methamphetamine-induced neurotoxicity
  2. [3] - 2nd human neurotoxicity review

Seppi333 (Insert ) 03:45, 13 July 2015 (UTC); Updated: 13:09, 16 January 2016 (UTC)

Neuropsychological effects review

Section reflist

References

  1. ^ a b Beardsley PM, Hauser KF (2014). "Glial modulators as potential treatments of psychostimulant abuse". Adv. Pharmacol. 69: 1–69. doi:10.1016/B978-0-12-420118-7.00001-9. PMC 4103010. PMID 24484974.
  2. ^ Yu S, Zhu L, Shen Q, Bai X, Di X (March 2015). "Recent advances in methamphetamine neurotoxicity mechanisms and its molecular pathophysiology". Behav. Neurol. 2015: 103969. doi:10.1155/2015/103969. PMC 4377385. PMID 25861156.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ Salamanca SA, Sorrentino EE, Nosanchuk JD, Martinez LR (January 2015). "Impact of methamphetamine on infection and immunity". Front. Neurosci. 8: 445. doi:10.3389/fnins.2014.00445. PMC 4290678. PMID 25628526.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ Saha K, Sambo D, Richardson BD, Lin LM, Butler B, Villarroel L, Khoshbouei H (August 2014). "Intracellular methamphetamine prevents the dopamine-induced enhancement of neuronal firing". J. Biol. Chem. 289 (32): 22246–22257. doi:10.1074/jbc.M114.563056. PMID 24962577. The primary target of psychostimulants such as amphetamine and methamphetamine is the dopamine transporter (DAT), the major regulator of extracellular dopamine levels in the brain. However, the behavioral and neurophysiological correlates of methamphetamine and amphetamine administration are unique from one another, thereby suggesting these two compounds impact dopaminergic neurotransmission differentially. ... The intracellular application of methamphetamine, but not amphetamine, prevented the dopamine-induced increase in the spontaneous firing of dopaminergic neurons and the corresponding DAT-mediated inward current. The results reveal a new mechanism for methamphetamine-induced dysregulation of dopaminergic neurons.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  5. ^ Steinkellner T, Freissmuth M, Sitte HH, Montgomery T (2011). "The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine". Biol. Chem. 392 (1–2): 103–15. doi:10.1515/BC.2011.016. PMC 4497800. PMID 21194370. d-AMPH and METH vary considerably in their toxic and addictive effects. Although d-AMPH has a higher affinity for DAT than METH (Howell and Kimmel, 2008), the latter is a more potent and also more perilous stimulant than d-AMPH. This could be as a result of their differing effects on cellular targets such as MAOs, mitochondrial electron transport chain complexes and their interactions with different signal transduction pathways. METH is more lipophilic than d-AMPH. Therefore, it readily enters the cell via diffusion in addition to DAT-dependent uptake. Furthermore, METH has been shown to release more DA and intracellular Ca2+ than d-AMPH at physiologic membrane potentials. These effects can be blocked by DAT inhibitors (Goodwin et al., 2009). This increased DA release perhaps provides an explanation for the enhanced abuse potential and the strong euphoric effects of acute METH exposure in humans. Chronic METH abuse leads to the degeneration of monoaminergic terminals (Davidson et al., 2001; Krasnova and Cadet, 2009) and reduced DAT and DA levels in the striatum of mice, rats and monkeys (Anderson and Itzhak, 2006; Graham et al., 2008; Melega et al., 2008). Similar effects have been reported in people subjected to positron emission tomography (PET) (Volkow et al., 2001). In contrast to MDMA, the metabolism of d-AMPH/METH does not appear to be significant in the manifestation of drug neurotoxicity. However, increases in DA metabolism following d-AMPH/METH-induced DA release have been implicated in the expression of amphetamine neurotoxicity, primarily through the production of oxidative stress (Krasnova and Cadet, 2009).
  6. ^ Matsumoto RR, Nguyen L, Kaushal N, Robson MJ (2014). "Sigma (σ) receptors as potential therapeutic targets to mitigate psychostimulant effects". Adv. Pharmacol. 69: 323–386. doi:10.1016/B978-0-12-420118-7.00009-3. PMID 24484982.
  7. ^ Kaushal N, Matsumoto RR (March 2011). "Role of sigma receptors in methamphetamine-induced neurotoxicity". Curr Neuropharmacol. 9 (1): 54–57. doi:10.2174/157015911795016930. PMC 3137201. PMID 21886562.
  8. ^ Rodvelt KR, Miller DK (September 2010). "Could sigma receptor ligands be a treatment for methamphetamine addiction?". Curr Drug Abuse Rev. 3 (3): 156–162. doi:10.2174/1874473711003030156. PMID 21054260.
  9. ^ Friend DM, Fricks-Gleason AN, Keefe KA (2014). "Is there a role for nitric oxide in methamphetamine-induced dopamine terminal degeneration?". Neurotox Res. 25 (2): 153–60. doi:10.1007/s12640-013-9415-2. PMC 3880644. PMID 23918001.
  10. ^ Cadet JL, Bisagno V (January 2016). "Neuropsychological Consequences of Chronic Drug Use: Relevance to Treatment Approaches". Front. Psychiatry. 6: 189. doi:10.3389/fpsyt.2015.00189. PMC 4713863. PMID 26834649.{{cite journal}}: CS1 maint: unflagged free DOI (link)

The external link to "Drug Trafficking Aryan Brotherhood Methamphetamine Operation Dismantled, FBI" is dead (https://www.fbi.gov/news/stories/2015/december/drug-trafficking/). I did a search on the site and found a new link, but I can not edit a protected page. So here it is if anyone wants to correct it:

https://www.fbi.gov/news/stories/aryan-brotherhood-methamphetamine-operation-dismantled

104.51.149.199 (talk) 11:36, 8 November 2016 (UTC)

Thanks. I have updated the link accordingly. (In the future, you can use {{Edit semi-protected}} to call attention to requests such as this to get ensure a quicker response.) -- Ed (Edgar181) 12:38, 8 November 2016 (UTC)

Semi-protected edit request on 16 September 2017

I would like to suggest some information on the recovery of crystal-meth and its advanced brain functionality. Diffuse approx 5 bottles of Sacred Frankincense (15ml each) in a diffuser in a small room and breathe in. It will repair all damage done it is never too late or too much damage. It will take about a month to use 5 bottles, 1 every 5 days. This will give you a healthier brain that someone who has eaten a gluten free diet, multi-vitamin, and probiotic their entire life. A crystal-meth addict who does not do this recovery should not quit crystal-meth as it will leave you VERY unhappy. A normal brain has 3 new and unknown parts to it. Normally the signal enters the first brain and bounces in a specific manner a few errors and bounces back out and repeats, it is supposed to do another way, with crystal meth the signal bounces around in a more advanced way then the signal continues to the second brain and passes through no function no errors before the signal gets to the 3rd and largest brain section and a piece of dna is cloned from a piece of crystal-meth the signal enters the brain bounces off the specific spot and ricochets off the dna crystal and goes out of service and it starts over from the beginning. The advanced brain functionality is responsible for your brains health. Crystal meth is being used in the research for a cure for this brain malfunction and eternal brain health. Pebaudhi (talk) 12:06, 16 September 2017 (UTC)

  Not done. Nonsense. -- Ed (Edgar181) 12:09, 16 September 2017 (UTC)
It doesn't seem like a good idea to mix meth and LSD like that. Seppi333 (Insert ) 18:11, 16 September 2017 (UTC)

Therapeutic use of methamphetamine in Canada

There are examples of meth use where the person reports positive changes that outlast the effects of the drug. I suspect that oral use may lead to more of these changes than snorting or smoking it.

Is there room on this site for reports of therapeutic effects? Maybe a new heading on the main methamphetamine page?

People should be informed if there are longlasting effects — Preceding unsigned comment added by Bhellos (talkcontribs) 19:45, 11 November 2016 (UTC)

Lacking sources that meet WP:MEDRS, this is merely promoting a FRINGE viewpoint. Either produce reliable sources, or this will be removed shortly. John from Idegon (talk) 19:58, 11 November 2016 (UTC)
I think the editor is attempting to be constructive. Let's not bite the newbies. There is a large learning curve. Anyway, what John from Idegon is trying to get at is that biomedical information requires more stringent sourcing standards (since people's health is at stake). If you can find a scholarly review article or meta-analysis supporting what you're saying we can include this. Sizeofint (talk) 23:15, 11 November 2016 (UTC)

Lead

The article says " 'Meth' and 'crystal meth' redirect here." But no synonyms are given. Some slang names would we useful. 31.49.105.253 (talk) 01:22, 15 February 2017 (UTC)

They are in the note in the first sentence. Sizeofint (talk) 04:57, 16 February 2017 (UTC)
That isn't the first sentence... that is an article hatnote which is fairly commonly skipped (much in the same way readers unconsciously skip-over ads [see, Ad blindness] on a website [see also Inattentional blindness]) unless something tips the user to think they are looking at the wrong article. A hatnote saying a term redirects to this article does not necessarily mean the terms in the hatnote are synonyms for the article topic (for several article, such terms in a hotnote turn out to be explicitly not synonyms), it only means those terms redirect here. IP user above does have a point that common synonyms should be mentioned in case people end up here wondering what a term refers to. — al-Shimoni (talk) 12:23, 21 February 2017 (UTC)
He was talking about this note. Seppi333 (Insert ) 05:17, 22 February 2017 (UTC)

Civilian use of Pervitin in WWII Germany

Suggested addition to Section 8 -History, society, and culture. (I'd add it myself but have not mastered footnoting.)

[1]

[Excerpt from a book review entitled] The Very Drugged Nazis by Antony Beevor

Blitzed: Drugs in the Third Reich by Norman Ohler, translated from the German by Shaun Whiteside Houghton Mifflin Harcourt, 292 pp., $28.00

"By 1938, large parts of the population were using Pervitin on an almost regular basis, including students preparing for exams, nurses on night duty, businessmen under pressure, and mothers dealing with the pressures of Kinder, Küche, Kirche (children, kitchen, church—to which the Nazis thought women should be relegated)... Its consumption came to be seen as entirely normal."

Cliffewiki (talk) 15:42, 20 March 2017 (UTC)

References

  1. ^ New York Review of Books, March 9, 2017 Issue

Semi-protected edit request on 25 April 2017

Change: Methods of ingestion are Oral, Intravenous, Anal-(rectal), Vaginal and Intra-muscular; to; "Methods of ingestion are Oral, Nasal, Intravenous, Anal-(rectal), Vaginal and Intra-muscular". Purple Chrissy (talk) 02:06, 25 April 2017 (UTC)

What method is left out of this list? Why don't we just say "it is often injected or ingested but can be administrated by any method" instead of being so oddly and verbosely specific.--45.72.141.216 (talk) 05:34, 8 May 2017 (UTC)
The ocular route seems to be excluded ;). Sizeofint (talk) 02:40, 9 May 2017 (UTC)
As is smoking, which I understand is doable. All the more reason to ditch the exhaustive list idea.--45.72.141.216 (talk) 21:20, 10 May 2017 (UTC)
Purple Chrissy, are you talking about the list in the infobox? I believe "insufflation" already covers the nasal/sinus route. Sizeofint (talk) 07:48, 11 May 2017 (UTC)
  No action As Sizeofint points out, nasal administration already included. There is no text starting with "methods of ingestion..." so there is nothing else indicated as needing changes. Eggishorn (talk) (contrib) 18:53, 30 May 2017 (UTC)

Australian Schedule

The article states that methamphetamine is a Schedule 8 "prohibited substance" in Australia. This is confounded and incorrect. Schedule 8 are defined as "controlled drugs" and Schedule 9 as "prohibited substances". This point in the article needs to be verified and amended for accuracy. I'm guessing that Methamphetamine is most likely Schedule 9 as Schedule 8 drugs are regularly prescribed for medical treatment and there is no PBAC approval for methamphetamine.

Dr.khatmando (talk) 00:46, 19 June 2017 (UTC)

It is schedule 8 according to https://www.legislation.gov.au/Details/F2017L00057. I'll fix the wording. Sizeofint (talk) 04:40, 19 June 2017 (UTC)

Semi-protected edit request on 22 August 2017

Reference 138 link is dead. Use this one instead: https://www.fda.gov/regulatoryinformation/lawsenforcedbyfda/ucm148726.htm Trobc (talk) 18:47, 22 August 2017 (UTC)

  Done jd22292 (Jalen D. Folf) (talk) 19:18, 22 August 2017 (UTC)

Neutral point of view of this article

I'm not able to edit the article (because it is semi-protected), but I don't think it expresses a neutral point of view under the "recreational" sub-heading. Methamphetamine is abused broadly across different cultures and groups, but most of the recreational uses describe sexual uses and particularly gay male "San Francisco sub-culture".

I think this section should be flagged, then edited. — Preceding unsigned comment added by Thenamestom (talkcontribs) 14:22, 4 September 2017 (UTC)

The section was supposed to summarize party and play/chemsex, but instead focused on 1 US city in particular since that's what the source focused on. I've generalized the geographical focus in my recent edit; the existing coverage of that subculture is both encyclopedic and notable though, so IMO it should remain. If you have any suggestions on how to improve the section, feel free to comment further, or better yet, propose changes to the text. Seppi333 (Insert ) 16:42, 4 September 2017 (UTC)
I have to say that I agree that this is problematic. It almost reads like an advertisement for the recreational use of this drug, and it doesn't explain any of the historical factors that lead to it becoming one of the largest epidemics of drug use in the Western world, prominently in that section.--Senor Freebie (talk) 16:49, 20 August 2019 (UTC)

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Semi-protected edit request on 24 February 2018

Change "Is a strong central nervous system (CNS) Stimulant too "Is a (Potent central nervous system (CNS) stinmulant Jmspater (talk) 10:48, 24 February 2018 (UTC)

I changed the word 'strong' to the word 'potent' as the word potent better emphasises the powerfulness of this stimulant drug.--Literaturegeek | T@1k? 11:45, 24 February 2018 (UTC)

Hi @Tobby72:, Good work in finding this resource. I had a *quick* look at the references for this graph, and it would be good if you could take a closer look.

I think the caption should read “US Drug overdose related fatalities in 2016 were ### (you can add the case numbers on the y axis to get the total) including 7663 of those related to Methamphetamine overdose.”

This is because epidemiological data sets are collected from research studies and reporting systems, with outcomes accounted for by multiple factors. The explanatory notes for the drug related fatalities cases can be found at the CDC WONDER portal. Some of the data is taken from sources such as death certificates, and can list multiple causes.

For example blunt force head trauma due to high impact motor vehicle accident while under the influence of alcohol (my paraphrase). While we could say the motor vehicle accident killed the victim, we could also say the same for the alcohol. However the better statistical methods we often use to get the most out of this kind of data gives us a measurement of the best “risk factors” that account for a fatality.

However Herion overdose can certainly be clearer due to lower lethal dose (LD) I.e. in a naive (someone with little tolerance) patient is doesn’t take much to overdose. I emphasise that this is even more so the an opiates related to fentanyl which is many times more potent than herion.

However it takes considerable amounts of Methamphetamine to reach a lethal toxicity, and an underlying predisposition (or prodromal) to a disease may also partially account for fatality (e.g. preexisting heart condition). Furthermore the people who use illicit substances are usually poly drug users.

I don’t want to discourage you because I think you did a stellar job in locating this information and I have no doubt it is scholarly rigorous. The graph is also suitable for the a less technically savvy ready too. But I hoped that I could help you write a more accurate caption. I think I saw you used a similar graph on another article too, so if we can work together to write well now, it will hold us in good stead later on too!

I hope this makes sense and is helpful, and please do go ahead and make those changes. I’m not here to stand on anyone’s toes.

If you think you need my help with this or something in the future, I’d be happy to help.

Good luck with this.

Cheers, Dr.khatmando (talk) 13:56, 17 August 2018 (UTC)

You sir, are correct. thanks for the clarification. Good day. — Preceding unsigned comment added by Hotshot714 (talkcontribs) 02:05, 9 November 2018 (UTC)

Error: Wrong Drug Under Medical Use

The drug used for medical reasons like narcolepsy and ADHD is amphetamine, not methamphetamine. Yes it sounds the same but the methamphetamine is the illegal version because it's way more potent and dangerous than the other one. They have different chemical structures. Hotshot714 (talk) 02:44, 29 October 2018 (UTC)

Hi@Hotshot714:, it depends on jurisdiction. In the US the Rx formulation of methamphetamine is produced under the name Desoxyn (see FDA prescriber’s information here ([[3]]). I believe it is rarely prescribed in the US, but that is what I have heard, not from clinical experience. As far as I know it is not approved for clinical in use in the UK, Australia, or EU countries, and is not listed as a WHO essential medication. I hope that clarifies things a bit. Cheers, Dr.khatmando (talk) 02:55, 29 October 2018 (UTC)

Stereochemistry

Current chembox is inconsistent as some items refer to racemate, others to dextromethamphetamine. Also note that INN names for methamphetamine refer to the single enantiomers, metamfetamine (+) and levmetamfetamine (−). —Mykhal (talk) 18:56, 11 November 2018 (UTC)

Thanks for pointing that out. I've removed it from the drugbox and article. The INNs are covered in Methamphetamine#cite_note-20. Seppi333 (Insert ) 16:02, 27 November 2018 (UTC)

Recreation

Section looks more like a promotional guide. :/ 96.31.177.52 (talk) 05:40, 8 May 2019 (UTC)

Do you have a specific suggestion to improve the section? TylerDurden8823 (talk) 03:42, 9 May 2019 (UTC)

Incorrect melting point

Melting point is 170 °C, not 3 °C. Reference source: National Center for Biotechnology Information. PubChem Database. Methamphetamine, CID=10836, https://pubchem.ncbi.nlm.nih.gov/compound/Methamphetamine (accessed on May 31, 2019) Marialeeg (talk) 06:22, 31 May 2019 (UTC)

Semi-protected edit request on 11 September 2019

Better source for footnote 19: http://www.nbcnews.com/id/6646180/ns/health-addictions/t/meths-aphrodisiac-effect-adds-drugs-allure/#.XXigWygzaUk 203.38.38.6 (talk) 07:26, 11 September 2019 (UTC)

  Done thanks.--Goldsztajn (talk) 13:53, 12 September 2019 (UTC)

Lattice structure

What is the lattice structure/crystal shape/crystal structure of methamphetamine hydrochloride (AKA crystal meth)? I don't think it is cubic, so is it hexagonal, monoclinic, or something else https://www.thoughtco.com/types-of-crystals-602156? This might explain it, but I'm not sure: https://onlinelibrary.wiley.com/doi/full/10.1002/pro.244 & https://journals.iucr.org/e/issues/2008/05/00/lh2608/lh2608.pdf --User123o987name (talk) 06:23, 28 November 2019 (UTC)

"Bingdu" listed at Redirects for discussion

 

An editor has asked for a discussion to address the redirect Bingdu. Please participate in the redirect discussion if you wish to do so. Hog Farm (talk) 19:59, 2 March 2020 (UTC)

Developed as "super drug" for intelligence

This chemical compound was actually discovered during WW2 while German chemists were searching for new drugs that radically boost intelligence in humans. At a certain level of government clearance you learn that in it's refined form, it is actually a "super drug" and it becomes legal a necessary part of staying alert and being able to process large amounts of stimuli simultaneously in the heat of the moment. Also widely used by many top level or "c-level" executives (CEO, CFO, etc...) as a way to stay at a performance level that is necessary to maximize profits and stay competitive and creative with the changing markets. Busterclark (talk) 17:19, 23 March 2020 (UTC)

Would you cite a reference for your story?   - Mark D Worthen PsyD (talk) (I'm a man—traditional male pronouns are fine.) 23:44, 13 May 2020 (UTC)

Semi-protected edit request on 13 May 2020

I want to add methamphetamine decompsotion temperature https://www.ncbi.nlm.nih.gov/pubmed/15538957ttps://www.ncbi.nlm.nih.gov/pubmed/15538957 It's starts at 315 C 185.211.158.179 (talk) 21:15, 13 May 2020 (UTC)

  Not done for now: The abstract of the article (once the link is corrected) only discusses a specific reaction when MA is placed in a sealed tube with HCl, occuring at 315 C. Additionally, assuming you wanted this added in the infobox, there is no parameter specifically for this and I'm not sure which one would apply. An editor more knowledgeable in chemistry could verify this. RandomCanadian (talk | contribs) 21:48, 13 May 2020 (UTC)

Semi-protected edit request on 28 May 2020

Under "Epigenetic factors in methamphetamine addiction": "chronic methamphetamine use caused methylation of the lysine in position 4 of histone 3"

-that is H3K4me1, H3K4me3 (or possible H3K4me2). That should be linked.

  Not done: please provide reliable sources that support the change you want to be made. Naypta ☺ | ✉ talk page | 14:09, 28 May 2020 (UTC)
Here is for H3K4me3: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622560/
Here is for H3K4me2/H3K4me3: https://www.researchgate.net/publication/258251965_Methamphetamine-Associated_Memory_Is_Regulated_by_a_Writer_and_an_Eraser_of_Permissive_Histone_Methylation — Preceding unsigned comment added by 81.191.116.205 (talk) 15:00, 28 May 2020 (UTC)

Weird sentence in Fatality and other effects section

It should say like "5-60mg was a reported typical dose." The sentence that's there makes no sense at all. Quote from the currently cited source (source #41) "The dose used is about 5-60 mg of methamphetamine while the lethal dose reported is 200 mg." morsontologica (talk) 15:55, 24 October 2020 (UTC)

Hitler

So far there seems to be no material on Hitler's use of Pervitin, as documented in "The Hitler Book'. Since I have just finished reading this book, I would like to add some material on this subject (not that I'm asking permission.) Sardaka (talk) 08:42, 1 June 2021 (UTC)

Semi-protected edit request on 29 May 2021

The sentence below (last sentence, Neonatal Exposure section) requests a medical citation in support this claim. >>"She said drug exposure could interfere with the child's working memory and their ability to control impulses and think

  flexibly.[1][medical citation needed]"

I (dleitner97) did NOT write this line, nor do I support it, however there does exist peer-reviewed research into the subject. A 2009 article from the Journal of Developmental & Behavioral Pediatrics states: "In conclusion, we showed that differences in activation during verbal memory are evident despite similar levels of performance and IQ between methamphetamine-exposed and alcohol-exposed children." ( link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745202/ ).

Therefore, I am of the opinion that this statement is supported by contemporary research, and should be cited as such. This evidence should replace the ABC news source. Dleitner97 (talk) 01:50, 29 May 2021 (UTC)

  Partly done. I'm trimming down the use of the ABC source and adding in medical sources, but I didn't use yours because the sample size is too small. I do appreciate the effort.  Ganbaruby! (talk) 03:46, 29 May 2021 (UTC)

Manufacture

It seems there is currently no extensive information on the process of manufacturing or creation of Methamphetamine. I think some details additions about this subject could be added to the article. IdontLikeMormons223 (talk) 00:50, 1 August 2021 (UTC)

Bupropion and Naltrexone in Methamphetamine Use Disorder

Hi!

This January, a study was published that supports the use of a combination of buprenorphine and injectable naltrexone as a treatment for methamphetamine dependence.

Would someone like to add this info to the "addictive" section, 3.5?

DOI: 10.1056/NEJMoa2020214


Psychdoctah (talk) 13:56, 3 August 2021 (UTC)

Repeat paragraph about a study of 330 cbildren

Under neonatal affects the last paragraph has a sentence about 330 children repeated twice TheDrD1ng3r (talk) 17:13, 4 August 2021 (UTC)

  Already done. Alexcalamaro (talk) 19:46, 27 December 2021 (UTC)

Ortography of Polish name, surname

Doktor habilitowany nauk społecznych Łukasz Kamieński. https://nauka-polska.pl/#/profile/scientist?id=127662&_k=0i10fc

  Done Alexcalamaro (talk) 19:52, 27 December 2021 (UTC)

Semi-protected edit request on 4 November 2021

Change "Soldiers would only receive a couple tablets at a time" to "Soldiers would only receive a couple of tablets at a time" 87.74.188.194 (talk) 19:39, 4 November 2021 (UTC)

  Done twotwofourtysix(My talk page and contributions) 05:02, 5 November 2021 (UTC)
  1. ^ Cite error: The named reference ”2020-01-03_ABC” was invoked but never defined (see the help page).