Talk:Methamphetamine

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Good article Methamphetamine has been listed as one of the Natural sciences good articles under the good article criteria. If you can improve it further, please do so. If it no longer meets these criteria, you can reassess it.

Neurotoxicity update[edit]

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[edit]

Section reflist[edit]

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 4103010Freely accessible. 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 4377385Freely accessible. PMID 25861156. 
  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 4290678Freely accessible. PMID 25628526. 
  4. ^ Saha K, Sambo D, Richardson BD, Lin LM, Butler B, Villarroel L, et al. (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. 
  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 4497800Freely accessible. 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 3137201Freely accessible. 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 3880644Freely accessible. 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 4713863Freely accessible. PMID 26834649. 

Semi-Protected edit request: mechanism of action[edit]

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. 
  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 4052380Freely accessible. 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[edit]

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)

Yes check.svg 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[edit]

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" -- PubMed 18992021, PubMed 17134084, and PubMed 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.
     
  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 4159050Freely accessible. 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[edit]

Note to self: add a direct pathway for methamphetamine → phenylacetone (FMO3). Crystal Clear action edit add.png 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)

External links[edit]

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)

Therapeutic use of methamphetamine in Canada[edit]

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)