Talk:Methamphetamine

message: Reason for edit: Small grammatical error. 
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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)
replies: text: - FlightTime (open channel) 03:00, 18 July 2023 (UTC)
thread_title:  Semi-protected edit request on 18 July 2023 

message: "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)
replies: text: See History_and_culture_of_substituted_amphetamines#Illegal_synthesis. --WikiLinuz (talk) 01:54, 14 November 2023 (UTC)
thread_title:  This article needs mentions and definitions of  "super meth" and "P2P meth"  

message: 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)
replies: text:  Methamphetamine have established addiction liability. Methamphetamine#Addictive. That linked paper doesn't say methamphetamine has 10-15% addiction liability. --WikiLinuz (talk) 00:05, 8 March 2024 (UTC)
thread_title:  Semi-protected edit request on 7 March 2024 

message: 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,
#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. 
#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 
#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?  
#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. 
#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? 
#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?.   
#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).:  
#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)
thread_title:  Methamphetamine "direct" neurotoxicity validity