Talk:Dextroamphetamine

Subject Effects

The 'Subject Effects' section of the article reads like an advertisement. —Preceding unsigned comment added by 71.249.105.66 (talk) 13:53, 28 September 2007 (UTC)

Literature

"Dexedrine" is also mentioned in Fleming's "Goldfinger". It was distributed on the train before the raid on Fort Knox.

Greetings,

I'm trying my best to throw in some contributions about this (and other) fascinating things here on Wikipedia but haven't seen any obvious ways to upload/link to further graphics which I have w/o replacing the one at the head of the article, which I'd rather not do.

If you search for

Dexedrine Spansule

In the images section, you'll see the image I'm referring to; I uploaded it before, but it was deleted due to my not having stated more explicitly that I was the creator (and therefore sole owner of copyright, and able to transfer same). I've re-uploaded it, and hopefully made it clearer as to its origin.

Further images may be found at http://www.dextroamphetamine.net/ - I suppose, worst case, I can simply link to the graphics on my site from here. I'm not averse to that, though am not trying to contravert anything on Wikipedia in any way if they're averse to externally linked graphics....

Anyone, please advise. I'll upload more as time permits.

~RTF~ Rtf 17:44, 28 April 2006 (UTC)

Not to rehash something long since settled, however, this is worth noting [entire post edited for brevity; for context, vide infra]:

[...] And I don't think d-amphetamine is commonly used to make meth anyway: methamphetamine doesn't mention it, and making Schedule II drugs from Schedule II drugs strikes me as kind of silly. [...]

Ok: Theoretically, yes, one can (and, I suppose, in some far-off-crazy-land, people do) make one from the other. Please note that to do so

A) Takes more than a little understanding of chemistry (not something your local HS student is going to whip up in a garage); B) Takes some seriously professional-grade facilities (an inert-atmosphere, positive-pressure workspace is only the beginning...); C) While one could, per street wisdom (feh), increase potency/jazz up "mere" D-amphetamine --> Methamphetamine, the potency gain versus conversion ratio (~0.70% or less, IIRC, and that's not counting mechanical loss, and presuming otherwise perfect conditions) would -- to the extent of *MY* knowledge, which is admittedly limited -- definitely NOT be even remotely close to cost-effective in any way, shape, or form.

In practice, can it be done? Yes. Has it been done? It appears so, from what I've gathered (and no, I cite no refs there, so take it or leave it). Does/is there at least one method publicly available which is accurate? I know of at least one which was floating around the net and which, per my comparison of it with offline resources and doing quick sanity checks, for all intents and purposes, what was delineated was an accurate (if commercially non-viable) means of doing so.

Again, I'm not arguing that A) conversion of D-amphetamine to Meth is rampant in practice (it's more likely virtually unknown in the 'wild'); nor am I arguing that the reference should be reinstated, necessarily (at least not the latter half); just putting this forward for your consideration.

I'm aware this is tardy beyond any sort of reasonable time-frame, and if it is discounted as such, no offense taken...Though please accept my apologies for the slooooow turnaround on my end. Work, life....Why must these things CONSTANTLY interfere with my REAL life, online? ;D

[...] Also, is 28 in "10-28 hours" maybe a little on the high side? I'm sure it can go that high or higher in poor metabolizers (defective CYP2D6 is uncommon, but not rare), but it can go lower too in ultra-rapid metabolizers... either way, surely not typical. Am I missing something or several somethings? SVI 16:40, 25 May 2006 (UTC)

It's been a week or so, so I'm assuming there are no objections to removing the meth paragraph. Just took it out now. I'll leave half-life to someone more knowledgeable about the relevant pharmacokinetics, though. SVI 06:52, 3 June 2006 (UTC) [...]

I believe that the reason the half-life has such a wide range is that it can vary widely even within the same person. In addition to being metabolized, d-amph can also be excreted unchanged in urine. But that route is strongly dependent on urinary pH, which is in turn strongly dependent on what the person ate and drank in the preceding several hours. The 28 hour figure sounds about right for the case of alkaline urine where 95%+ of the elimination is due to metabolism rather than excretion. 69.21.93.150 23:19, 11 July 2006 (UTC) Konrad

I have a reasonable familiarity with pharmacokinetics, and while there are a number of variables which can drastically influence half-life, elimination/excretion times, bioconversion, peak plasma concentration and the like when it comes to D-amphetamine, many of the same may be said to be true, as well, of *most* (if not all) of similar phenethylamines -- at least the H2O soluble ones (which L-amp is not, and D-amp is).

While it's too late, and I'm too cognitively beat from a long work day to detail much more, suffice to say that many of the rules which apply to (say) many of Shulgin's P's apply here, as well: urinary & blood acidifiers will reduce peak times, hasten elimination, and contrariwise, urinary & blood alkalinizers will act in the reverse way.

The bioavailability of most phenethylamines is generally low (note the percentages of everything chemically similar to amphetamines intact excretion, e.g., MDMA, MDA, Mescaline, the list goes on); naturally, this has a lot to do with the manner of intake (assumption being Sulfate or Chloride salt, not freely basic forms, and oral only); in the case of an overly acidic system, the general rule is as cited above; for the overly alkaline system, the reverse (with a far better bioconversion ratio, and less unchanged salt excretion, IIRC - references provided later, I'm just being lazy for now, sorry).

The higher water-solubility factor which one obtains with the Dextro-handed version of amphetamine, and which extends to derivations, including those with the methyl group added, also inclines one to think that the "average" person (barring bizarre dietary/contraindicated meds/genetic quirks) would have no unchanged or metabolized amounts of this in their system within 24-48 hours (dose dependent). A quick reference to the Merck Index (and the PDR - feh) says the same. Curiously enough, now I have to wonder just how long the Levo-amphetamine version remains? Anyone have any data on that, or am I forced to open a book again (j/k).

~RTF~

Hi - Sorry I didn't respond to you sooner, but current events & work have kept me occupied for the present....In any case, I included the above information for no other reason than to *be* encyclopedic: yes, you are correct, it *is* obvious that d-methamphetamine is d-amphetamine + a methyl group....Just as it is obvious to you or I what the prefixes of d- and l- stand for. As I know for a fact there are people in existence so dim I wouldn't let them operate a VCR much less a computer, it stands to reason that there are probably those operating computers and accessing the Internet who are not, to put it kindly, Chemical Wizards or remotely close to understanding their native language, much less anything nearing Jargon specific to a given scientific field; hence the extended explanation.

That said, I have no problems with your removal of it; hell, *I* am far to lazy to edit myself, so I can only thank you (honestly) for taking the time to do it for me. My point there was actually that (contrary to popular belief) there really isn't much in the way of proof that 'Meth' is any stronger than Dexedrine; on the contrary, there are studies indicating otherwise, with the subjects unable to tell the difference, even. That I cannot cite the precise time/date/place/name/research groups involved with some studies I read about some time ago *does* render these facts (I suppose) inadmissible, in a technical sense, so I don't have much room to argue the point; in short, no disagreements from I. RTF

Clinical Usage: Indications

The language in the Clinical Usage section is mixing medical issues with legal ones. In the case of the US, the FDA decides approval, while the medical community decides indications. The phrases "accepted indications" or "non-approved inidications" are mixing up the two. *Any* drug can be prescribed for *any* indication as long as it's approved for some use.

69.21.93.150 23:19, 11 July 2006 (UTC) Konrad

very true... clonazepam is an "anticonvusant" gabapentin is an "anticonvusant" viagra is for "ED" but clonazepam is perscribed for anxiety, depression, ocd, adhd, insomnia, schitzo type disorders, personality disorders. gabapentin is commonly perscribed for depression and insomnia. and viagra has been used to regulate blood pressure. medications get aprroved by the FDA arnt set in stone for one disorder. off-label use is allowed... just not covered by insurance companys if someone gets in trouble.

Agenda

Here are some changes I'm planning to make to the article. Comments and suggestions are welcome. (Finished items are crossed out. KonradG 18:40, 11 September 2006 (UTC))

• Split history & overview into seperate sections. Perhaps put back some of the regulatory stuff I deleted.
• Add info about DA mediating reward effect and NE mediating anorectic effect. (Find ref on the Tyrosine depletion experiments that show this)
• Add some discussion on acute tolerance. Subjective effects vs plasma concentrations. Ideally find some direct data comparing AMP to other stimulants in this regard.
• Mention subjective effects begin more slowly because of BBB
• LD50 in rats, lowest known fatal doses in humans
• Explain amphetamine psychosis
• Add other CYP450 enzyme responsible for conversion to hydroxyamphetamine
• (New item Sept 12) Saw several mentions of half-life in children being as low as 6 hours! Find refs and update half-life info.

KonradG 12:52, 8 September 2006 (UTC)

Anyone know to properly cite a quote from a book? I temporarily put a link to a website referring to "The Pharmacological Basis of Therapeutics", but I'd like to make the cite specific to page 553 of the 7th edition. KonradG 18:36, 11 September 2006 (UTC)

Note about anti sea-sickness use

Experiment Description for: Inflight Salivary Pharmacokinetics of Scopolamine and Dextroamphetamine (DSO 457)

http://lsda.jsc.nasa.gov/scripts/experiment/exp_descrp_pop_up.cfm?exp_id=DSO%20457&string=&current_string=

Scopolamine/dextroamphetamine, a drug combination used to prevent motion sickness, was studied because of its frequent use by crewmembers during flight and its reportedly variable pharmacokinetics and poor bioavailability on the ground.

--Charles Gaudette 19:40, 8 September 2006 (UTC)

Dexatrim

A new Wikipedian, Uncwfu2, recently tried to add Dexatrim to the article. I mildly agree with the revert. I want to throw some notes into the talk page about Dexatrim just to get them journaled; especially as at this time there is no article about Dexatrim on Wikipedia (that I could find). KonradG stated in his revert that: "Dexatrim is phenylpropanolamine, not d-amphetamine". That was true, but Dexatrim has switched (by the account I could find) to ephedrine. It seems to me that the name "Dexatrim" was deliberately devised because the marketers: (1) wanted to link themselves to, or (2) wish they could actually use, dextroamphetamine. If that conjecture can be factually made with a credible reference, then Dexatrim may very well have a place in the popular culture section. --Charles Gaudette 21:18, 4 October 2006 (UTC)

According to their site, Dexatrim used to contain ephedrine but doesn't any more. I reverted the addition because I thought it was the result of someone confusing the two chemicals. If the intent was to clarify that Dexatrim is *not* d-amphetamine, I see no problem with putting it back. KonradG 01:10, 5 October 2006 (UTC)

My first edit as a Wikipedian was intended to point out the similarity in nomenclature between Dexatrim and Dexadrine. I now realize that this was a poor attempt at making the connection. Thanks for the dialog and feedback.

Somebody put this in the article:

"[quote] There is a widespread myth that, while Dexedrine acts as stimulant in people without ADHD, it causes the opposite reaction in those with the condition. [/quote]

I would really like to address this claim. I have been diagnosed with Adult ADD, secondary to organic minimal brain dysfunction. My doctor has prescribed Adderall for me, and I am currently taking 20 mg. per day. Dexedrine is essentially the primary ingredient in Adderall, which is a mixture of amphetamine salts. For me, these amphetamines do indeed have exactly the opposite effect of a stimulant. If it some kind of secondary effect of an increase in concentration, then it is doing the most remarkable job of imitating an anti-anxiety/relaxant drug that I could possibly imagine. My blood pressure and pulse both go down on this drug, and I am extremely calm and relaxed-- I actually sometimes have a hard time staying awake. Saying that this is *not* the opposite of a stimulant effect is really just meaningless. That's what the effect *is*-- giving it a different name is just playing word games. Whoever wrote this certainly did not source their "proof," and they clearly did not actually talk to anyone who has ADD and takes this drug.

Catherine Danielson"

Miserlou 19:23, 3 January 2007 (UTC)

The dextro isomer is not the primary ingredient. The levo isomer has arguably more biological activity, and is responsible for the euphoric qualities of Adderall. The claim that it "calms someone down" is completely subjective, whereas the fact that it increases levels of catecholamines can be said with considerable objectivity. The drug is a still classified a stimulant, regardless of how it influences someone's feelings or behavior. Fuzzform 23:58, 28 May 2007 (UTC)

The calming effect is interesting, but it doesn't contradict what was written above. The point of that section (which I wrote), is not that a paradoxical calming effect is not possible, but that it does not indicate the subject has ADD. Perhaps the langugage should be clarified, but I'm putting it back in without a cite, since it's very hard to come up with references for something that doesn't happen. The point is two-fold: the drug is not a sedative but a stimulant, and that's still true whether you have ADD or not. Low doses of many stimulants can have a sedating effect, nicotine for example. KonradG 20:50, 4 January 2007 (UTC)

I've changed the wording a bit to hopefully make it a bit more clear. KonradG 17:42, 8 January 2007 (UTC)

Regarding the notice of Benzedrine as being a formulation containing D-amphetamine....

...Well, that should be amended. Just a thought.

~RTF~

Jadet46 I was very surprised when I first took dexroamphetamine. I took 2 5mg. tab. and my first reaction was calm. I felt sleepy but within 10 min. or so that seems to go away. I do not have more physical energy but I do seem to go on a talking spree. My anxiety goes away, I stop thinking about 20 things I need to do and am able to focus on the most important. I am a better driver, being someone who had many car accidents when I was younger. I am relaxed. I wish the feeling lasted longer. When I was first diagnosed I was told it was believed those with ADD/ADHD had lower levels of norepinephrine and that amphetamines helped the brain make more therefore our brains would be able to function more normal, not hyper because instead of too little norepenephine we now would have a more normal level enabling us to concentrate better and focus better because our brain would be better able to sort through all the stimuli we take in, instead of being overwhelmed by it. I was told that was a function of norepenephrine. I was told that was why someone who has normal levels of norepenephrine would be hyper because they did not need more. Higher levels would cause this hyper effect. I have never once had (enjoyed this effect). Every single time it is the same. I feel sleepy, wake up, then feel calm, relaxed, anxiety free, and my brain feels able to process information without confusion as to where to begin. I actually can choose a project to begin where without it I need to use a huge amount of concentration to tell myself which project to start and continue to convince myself to stick with it, and that it is relevant. Otherwise I have a thousand ideas, do not know which to choose, and either end up doing 3 or 4 projects at a time or doing nothing because I cannot seem to decide which to start or even if I should do it at all. I am not sure if ADD is neurological or not. But this sounds neurological to me. I know any disorder involving the brain is very hard to understand with how little we really know the brain. Especially since for so many years studies have separated the brain from the body, now realizing they interconnect, duh....who knows what causes anything. There are so many chemicals in our air, water and food. I know earlier, but especially in the 40's and 50's science discovered so many 'good' chemicals to preserve our foods and clean our water, make our plastics, and whatever, now to find out they were not the miracles they thought, but deadly. Who knows if our parents injesting these things caused us brain damage. There are other factors, we have more stress than in any other time in history. We sleep less than our grandparents. Who really knows what causes these things or exactly what they are. When they finally figure ADD out we may be very surprised at what its causes are. I do know it is real. Whatever it is. I do believe there is a true disorder of ADD and also actalikes that are caused by stress, sugar/foods, lack of sleep. At any rate I was very interested to find out someone else felt so calm and relaxed. It isn't the first time I have heard this but that was from my brother. I don't talk or tell too many people about my ADD. I am not interested in the usual response that it is not real. So, I learned years ago not to speak about it. —Preceding unsigned comment added by Jadet46 (talk • contribs) 19:51, 30 September 2007 (UTC)

chronic use section

I believe this section to categorically wrong in it's assumptions. Tolerance is not a "given" with therapeutic levels of stimulants. The citations refer to rat studies and nearly all rat studies involve the injection of stimulants and usually dosage levels that are not equivalent to human dosages. "Reverse tolerance" is also assumed from these studies. The growth retardation and drug holiday sentence is also not supported by the literature. --scuro 04:21, 25 March 2007 (UTC)

I've seen a source that supports possible growth retardation in children from long term use, I think it was the Australian Drug Guide. cyclosarin 06:37, 29 March 2007 (UTC)

The growth retarding effects this drug has on children is very simply explained: the drug is an anoretic. An organism cannot grow without food. Fuzzform 00:01, 29 May 2007 (UTC)

I put a lot of thought into the discussion of tolerance, and I would hope it is the best-referenced and most accurate part of the article (as far as a general overview can be). This part in particular is signifcant: "[R]egular users commonly experience a quick decrease of unwanted side effects, without an equivalent loss of its stimulant properties. Notably, the sensitization is induced more quickly, and persists far longer than withdrawal-related effects, suggesting a phenomenon more complex than a simple tolerance-induced withdrawal syndrome."

Jadet46 In my experience I have had both. Decrease of unwanted side effects. And a decrease of the effects I want. Neither completely go away, but there is a definite decrease. I have tried to take a pill or two more to see if that was the problem. But there was no considerable change to merit more chemicals in my body. So I cherish the time I am focused and anxiety free and hope to someday go the natural route, to see if that works. Because even though I am grateful for the medication I do realize there are side effects and risks. I also believe there is a way naturally to help ADD and probably for the longer term and better but it is also the harder route. I believe you have to be committed and focused and determined to form many new habits. That is not always so easy in our busy society. But it is on my list of to do's. Of which I have many! —Preceding unsigned comment added by Jadet46 (talk • contribs) 20:04, 30 September 2007 (UTC)

That seems that agree with what you're saying in that tolerance is not a given with therapeutic use. Tolerance to the *desired* effects is not a given, even though tolerance seems to develop just as expected for the secondary physical effects, like increased blood pressure. So it's hard to make any general statements about tolerance without finding a counter-example, even though tolerance is such an important topic for this class of drugs.

I hope you don think I was trying to put a particular spin on this data. The only reason I happened to choose rat data for some cites was that it was the most direct example of the "reverse tolerance" phenonmenon. There as several good reviews on the topic, and I think the one used most was Chronic Amphetamine Use and Abuse from this list by the American College of Neuropsychopharmacology. KonradG 06:06, 31 March 2007 (UTC)

Sorry, but much more editing is needed. First off, what is meant by chronic use? The laymen will be confused by this point. Are we talking about chronic drug use or are we talking about the therapeutic use of stimulants? If we are talking therapeutic use, a title such as,"effects of long term use of therapeutic Dextroamphetamine", would be better. Chronic, as it is defined in the dictionary, has a negative connotation to it and while there can be negative side effects with the drug, generally therapeutic stimulants used for ADHD and other disorders are probably the most effective class of drugs for any mental disorder. It generally has very positive outcomes.

Secondly tolerance isn't even really an issue with the therapeutic use of Dextroamphetamine. At least not in the way that the layman would understand the word...and finally how did "withdrawal" get into that sentence?

The rat study can't be used as a citation for the therapeutic use of stimulants. It simply does not relate and should be deleted.

Whatever point you are trying to make, make it more clearly. I'm not worried about spin, I'm more worried what the average reader will take away from that passage. --scuro 10:22, 31 March 2007 (UTC)

Who said anything about therapeutic use? Commercial applications of the drug represent just one aspect of a much larger body of knowledge. Even if this article were restricted to that use, which it isn't, I don't know where you got the idea that tolerance is not an issue. I'd like to see your references before you go deleting stuff. KonradG 08:33, 3 April 2007 (UTC)

It is not I who have to provide citations. I have questioned material in the article and this needs to be supported. If not, it should be deleted. This is not a debate but simply my request that the section follow Wiki policy. The major problem of that section is that it needs a rewrite starting with the title. Is this section about the therapeutic use of the drug or drug abuse? Is it meant to be about both uses of the drugs? What specifically happens which each application? Why does this happen? If the terms withdrawal and tolerance are used with reference to the therapeutic use of the drug, make sure you have citations.--scuro 10:53, 3 April 2007 (UTC)

First off, it's up to you to provide cites, since you're the one making unsupported claims about therapeutic use in humans. The article already cites two sources for a simple statement about amphetamine tolerance. Secondly, you're way out of your depth on this one. You're telling me something doesn't exist, when just counting what's lying on my floor, there's one review and two studies discussing why it happens! KonradG 03:34, 5 April 2007 (UTC)

No use getting flustered over this one, Konrad; stick to a discussion of the article, not the person. Amphetamines are pretty much universally (or at, terrestrially) regarded as addictive drugs, whether they are taken legally or otherwise. I understand that some people may not want to admit to themselves (or others) that they are taking potentially addictive drugs... however, it is a well established fact that this class of drugs is (psychologically) addictive. Fuzzform 00:11, 29 May 2007 (UTC)

Chronic use would mean that they are using dextroamphetamines 24/7, a lot of people do not take it while they are sleeping. They do not constantly chornically use dextroamphetamine, they periodically use dextroamphetamine, I might go as far to say as the periodically use acute doses.Edward Bower 05:39, 5 April 2007 (UTC)

That isn't the definition of "chronic use". Chronic use generally implies daily administration for an extended period of time. The number of times per day is irrelevant. Hence, daily use as prescribed by a doctor is considered "chronic use". Fuzzform 00:11, 29 May 2007 (UTC)

Konrad, personal attacks against other Wiki members goes against Wiki policy. You have no right to do this nor do you have anything more then the most limited knowledge about my capabilities or background. Continue with such abuse and I will report you.

I'll also ask you to kindly reconsider the edit request so that I won't change your intended meaning if I do the edit. This subsection will cause confusion in the reader's mind. Contrary to your previous objections, there is a major difference between the action of therapeutic use of a drug like Adderall and the action of other stimulants and their delivery method, mentioned in your citations. I'll ask again, does this section relate to the therapeutic use of stimulants? If so, state this clearly. Such information is of high importance to Wikipedia. You can't simply sit on the fence on this one. - i.e. (Who said anything about therapeutic use? Commercial applications of the drug represent just one aspect of a much larger body of knowledge. Even if this article were restricted to that use, which it isn't..). If we are talking about the therapeutic use of stimulants, these studies do not meet the Wiki criteria of requiring excellent citations for extraordinary claims. As you most likely have discovered no reliable source such as a government institution backs your claims.--scuro 06:16, 6 April 2007 (UTC)

Since Konrad hasn't responded to any concerns stated on the last post in discussion and no one else has objected, the section will be deleted again. I want to further point out that the citations given are useless to support any points made in this subsection particularly in relationship to the drug Dextroamphetamine. These citations are rat studies which don't use Dextroamphetamine, the drug is injected the directly into the rat, and the studies use doses that exceed theraputic levels. --scuro 02:18, 9 April 2007 (UTC)

(Un-indent) Have you actually read the studies, or are you just assuming they don't use dextroamphetamine because it doesn't explicitly says so in the abstract? If you have, maybe you can tell me what the doses were for the chronic administration study? And if you think it's a personal attack for me to tell you that you're out of your depth, why don't you show me how you calculated the human equivalent dose for that study, since you claim its exceeds therapeutic doses.

And from your other questions, I'm guessing you haven't read the review I linked above. The extent to which the deleted paragraph applies to therapeutic use is a complicated issue. I gave a brief overview of well-known phenomenon, and that's all I feel like doing. You're in no position to demand that I explain how it applies for any particular case you happen to care about. I'm not your personal tutor. KonradG 18:58, 9 April 2007 (UTC)

I did read one study, I didn't bother with the second study because it was pointless to do so because the mice were injected with Amphetamine. Both studies never used Dextroamphetamine.

Funny that I am answering your questions but you deem that it is unworthy your time to answer a number of serious questions about the validity of the information you posted. I contend that this information is misleading the public about medication they may be using. If you have contempt for me, do you also have contempt for the Wikipedian audience also?--scuro 20:09, 9 April 2007 (UTC)

If the type is not specified, amphetamine is generally assumed to refer to the d isomer, and the terms are used interchangably. See reference 13 for an example. It says amphetamine in the title, but dextro-amphetamine in the abstract.

The problem is not the questions, but your eagerness to delete carefully-researched material unless I answer the questions to your satisfaction. We disagree on the relevance of the cites, but this is not unsourced material, so you can't simply to delete it without consensus. That's now how Wikipedia's attribution policy works. KonradG 21:56, 9 April 2007 (UTC)

Third opinion

Wikipedia:Third opinion: "The third-opinion process requires good faith on both sides of the dispute." In addition, Wikipedia:Civility is not merely a suggestion but policy. — Athænara ✉ 19:36, 9 April 2007 (UTC)

there is good will here to improve the article

If it is simply a question of following protocol...I can live with that. Although there is no consensus to be gotten because no one else has added to this particular discussion. Currently the chronic use subsection is not in the article. That is a solution or as suggested earlier, the subsection can be edited to make it acceptable. One of the primary things that would need to be changed would be to clearly state what the information in this subsection refers to. Is this section is about the therapeutic use of Dex?.. or the chronic abuse of the drug? This should be stated clearly in the title and also in the body. If you believe there is no difference between the two uses, state that also. Once that is done, then the ideas and information collaborating the ideas can be sorted out.

Finally Konrad, when posting in discussion, you don't post inside of someone else's previous post. I've moved your segment that was inserted into my post to your latest post. --scuro 00:42, 10 April 2007 (UTC)

It's common practice, and allows a point-by-point response. I'm not aware of etiquette rules prohibiting it.

Now, your suggestion for resolving this is to leave it deleted unless I re-edit it to be acceptable to you, and it meets the list of demands you gave above. "Once that is done" you say, "the ideas and information collaborating the ideas can be sorted out."

That's exactly what you asked for to begin with, so obviously I disagree. Do you still believe that this is a simple issue of deleting unsourced claims, and not a regular content dispute? If so we should try an RfC to see how well that idea holds up to scrutiny. Otherwise, I suggest you read WP:CONS and we can proceed from there. KonradG 04:40, 10 April 2007 (UTC)

Konrad, the chronic section was simply too ambiguous to leave as is. Was this section about: 1) the abuse of dextroamphetamine, 2) therapeutic use of dextroamphetamine, 3) both uses, 4) the use of any stimulant, 5) or the abuse of any stimulant? It's simply remarkable that this simple question can't be answered. The most intelligent people that I have known take the time explain complex things in a way that anyone can understand, and will answer questions from all. Remember also that the goal of any Wiki page is always to improve the quality of the article.

Finally, I can't tell you if this is a content dispute or a citation dispute because I simply don't know what specifically that subsection of the article is about.--scuro 11:35, 10 April 2007 (UTC)

The only thing that's remarkable is that you're so determined to remove certain material, when you know so little about it. You were willing to force a unilateral deletion on the grounds that the cited sources don't apply, when you hadn't read the sources and weren't able to even recognize the *NAME* of the drug in question! And you still haven't restored it after that mistake was pointed out to you. That is, in fact remarkable, since it seems very much at odds with WP:NPOV.

Moving on, you say that "the chronic section was simply too ambiguous to leave as is." Well, that's not your decision to make. Since you choose to ignore Wikipedia policy on consensus, this discussion is over. I've wasted enough time having you unilaterally deleting the material and then make ransom demands for its return. I'm restoring the disputed text. KonradG 04:14, 12 April 2007 (UTC)

Keep a lid on the drama, will you Konrad? All of your most recent false accusations are aggressive and personal in nature. This is disappointing especially since I have already warned you about personal attacks. Following Wiki policy I have posted a message on your talk page and want to also bring this to your attention. http://en.wikipedia.org/wiki/Wikipedia:No_personal_attacks#Consequences_of_personal_attacks

It now looks like you are unwilling to answer the most basic of questions that go to the core question of the validity of the information posted. Without your cooperation and good faith, even Wiki third party is not an option. For the time being I have posted a NPOV tag on the section. Finally, just to reiterate, the question that needs an answer is simply,what specific drug(s) and use(therapeutic or abuse?) does the term chronic make reference too? --scuro 11:00, 12 April 2007 (UTC)

I've responded on my talk page. And by the way, it is considered bad form to tag content deletion as a minor edit. That's usually reserved for correcting typos or broken links. As for your question, I'm willing to answer it now that you're disputing the content rather than deleting it without consensus.

The statement refers to d-amphetamine, although it's also true for other stimulants. If you're asking specifically about reverse tolerance, I've seen similar studies with methamphetamine and cocaine. I don't know how what you mean by therapeutic use vs abuse. Are you talking about the dose, route of administration, or both? Regular, rather than reverse tolerance can be seen with essentially any use at any dose. The only question is the degree of tolerance and its duration. And the answer to that is complicated enough that there are probably three different mechanisms for how it happens. KonradG 22:37, 12 April 2007 (UTC)

Thanks for the reply Konrad, it is appreciated. Can you expand further on the posible three different mechanisms involved? That would be of interest to me. --scuro 03:28, 13 April 2007 (UTC)

There are quite a few that have been investigated, but it's hard to tell which ones are the most important because no single cause is clearly dominant. It's likely that at least three of them have significant effects. Look for the section called "Mechanisms Underlying Sensitization and Tolerance" in here [1]. KonradG 17:19, 13 April 2007 (UTC)

(Un-indent) Here's a little detail that bothers me... Anybody here know of any adult male patient prescribed half a gram of d-amphetamine a day? Well folks, this is what Chaudhry, citation 12, uses to induce reverse tolerance, i.e., 6mg/kg/day. In those humans who'd survive (and those escaping madness), I suppose reverse tolerance might be an issue.

Clearly this is not a clinical dose, hence not a valid clinical issue. The highest recommended dose levels of d-amphetamine in ADD at 1.0mg/kg (Joseph Biederman) while many physicians won't exceed 0.5mg/kg. These are TOTAL daily amounts given in divided doses (typically tid or in sustained released form) gradually increased from smaller doses. (I'll give citations if desired)

Extrapolating from rats--and different rat species--can also be an issue. Further these lab researchers are frequently trying to produce "undesirable" effects to study. This is clearly antithetical to physicians who want to minimize adverse effects.

Respectfully Konrad, I disagree with you. This "reverse tolerance" isn't appropriate under "Side effects of therapeutic use." Such sloppiness is typical of moralists invested in the fearmongering of antipsychiatry.

For clarification of theraputic use vs abuse or non-theraputic use see: Biederman J, Spencer TJ, Wilens TE, Prince JB, Faraone SV. Treatment of ADHD with stimulant medications: response to Nissen perspective in The New England Journal of Medicine. J Am Acad Child Adolesc Psychiatry. 2006;45:817-823. http://www.massgeneral.org/pediatricpsych/docs/NEJMltr.pdf Romith 08:32, 13 April 2007 (UTC)

What do you guys have against rats? Rodents have feeling too, you know! But seriously, it was Scuro who changed the title to "Side effects of therapeutic use." I was just describing an interesting effect, since amphetamine use is one of the rare cases where it's been documented. Whether the same effect is seen in therapeutic use shouldn't be an issue for justifying the inclusion of such content in an encyclopedia.

However, that's not to say it doesn't happen. The very first link I gave in this discussion states, "Even without considering the rodent to man correction, 0.25–1.0 mg/kg/day is clearly within the dose range quoted in most paradigms of locomotion sensitization in experimental animals." And simple Google search returns [2] and [3].

Anyway, I'm still not sure whether this dispute is specifically about reverse tolerance or tolerance itself. I believe Scuro objected to the use of the words "tolerance" and "withdrawal". All I know is that he's very unhappy about my interpretation of some esoteric medical issue, for reasons that have more to do with public perception than with medicine. The link you posted is a good example of the kind of political BS actively try to avoid. There's a reason I choose to edit this article instead of, for example, methylphenidate. If you want to talk about what amphetaine does, that's great. But if you're interested in advocating which uses are proper, and which are "abuse", then leave me out of it, cause I don't give a damn. KonradG 18:18, 13 April 2007 (UTC)

Chornic vs Abuse

I dont know if they are necessarily the same thing, I think that maybe chornic use should not be under abuse, I changed every instance of the word "use" in the chronic section to read "chornic use" because better in my opinion, but I dont know if it should be in a section called "abuse", abuse is so subjectively defined, why not just call it chronic use and make sure that everytime it says "use" in the paragraph it says "chronic use" instead, to be explicitly clear. What do you guys think?Edward Bower 02:13, 14 April 2007 (UTC)

The summary of both studies start with the phrase, chronically administration amphetamine. I took another look at the study and Romith is correct, in the Chaudhry citation 6 mg/kg/day were used to demonstrate reverse tolerance. In the Leith study the rats were injected with stimulants. Clearly we are not talking about the therapeutic use of stimulants but rather the results of abusing drugs. Another big clue that these studies are investigating drug abuse is the fact that is that National Institute on Drug Abuse provided funding. Therefore the subsection has been edited to reflect this information. It has also been moved and the NPOV has been removed. Hopefully this is the solution.

Finally Wikipedia should consider changing it's policy and not allow studies to be used as citations. Most Wikipedians can't access the full body of a study and instead must rely on the summary. One study or even two studies do not create a body of evidence and the interpretation of the studies by readers can be faulty as this debate clearly illustrates. --scuro 02:15, 14 April 2007 (UTC)

This is how I see the definition of chronic(and I am not going to say I understand it better than anyone else so I welcome all others to share their thoughts on this so we can all understand better): Let me try to give an example, if I were using some benedryl, someone could say I am using it or abusing it, from whatever prospective they want to look at it as, they could say I'm abusing it because I take it for sleep and thats not what the FDA indicates it for, they could say I am using it becuase maybe it helps me sleep(maybe it actually inhibits my sleep but thats besides the point). Now then I think theres another adjective to help me think about this all: "periodic"; If i am taking benedryl once every week, someone might say I am periodically abusing benedryl, another person might say I am periodically using benedryl. And then theres another adjective: "chronic", and this gets kind of where I dont understand the word that much, I guess chronic is a type of "periodic" where the periods in between administration are so small that the effects have a large overlap and there is(maybe there has to be?) a constant exposure. So maybe I am given a fentynl patch and told to always wear my patch because I have some bad pains in my foot, I think this would definately be chronic, if I replace the patch every two days becuase its is still entering my system so much, so someone might say I am chronically using fentnyl applying another transdermal patch periodically, then again another person might say that I faked a foot injury and that I am "chronically abusing fentnyl". I hope that was clear enough for people to understand what Im trying to understand myself THANKS!Edward Bower 02:34, 14 April 2007 (UTC)

http://www.usdoj.gov/ndic/pubs7/7343/index.htm#chronic%20drug%20abuse

Chronic drug abuse is the habitual abuse of licit or illicit drugs to the extent that the abuse substantially injures a person's health or substantially interferes with his or her social or economic functioning. Furthermore, any person who has lost the power of self-control over the use of drugs is considered a chronic drug abuser.

Chronic refers to a condition that persists or progresses over time. The word also has a negative connotation so you don't here phrases like, "chronic love". The citations clearly show abuse. The stimulants injected and given at high doses in the studies is drug abuse. When stimulants are abused withdrawl and tolerance can occur.--scuro 03:08, 14 April 2007 (UTC)

The mice(whatever rodents they were) were prescribed the drugs by doctors and were under the supervision by doctors and I'm sure if mice could talk the doctors would have told them "use as much as you want", how is that abuse?Edward Bower 03:15, 14 April 2007 (UTC)

Humans abuse alcohol all the time...and come on now, these rats were not prescribed anything. They were injected and given a dose that would cause the drug abuse effect the scientists wanted to see.--scuro 10:42, 14 April 2007 (UTC)

Konrad's cited studies are about both the abuse and chronic use of stimulants. Let me illustrate why. These rats got a dose of 6mg/kg. It was a single dose. My daughter takes a dose of .275mg/kg. The dose that she takes is in extended release form that works for most of her day. I'd roughly extrapolate that any given moment in her day no more then then .035 mg/kg are active within her. By merely increasing her dose by .025 mg/kg she may get a headache and the dose may not be as effective. Here is the rub, many drugs are therapeutic at lower levels but dangerous at higher levels. That would also be true of alcohol. I'd worry that a dose that was 18-20 times higher then her regular dose would do serious harm to my daughter. This dose would be a single dose and not extended release. Rats are not humans and the conversion scale may not be straight 1:1. Perhaps Konrad could explain further, I believe he has researched this topic.

Back to the term abuse and the definition I provided;...abuse substantially injures a person's health or substantially interferes with his or her social or economic functioning. Clearly the rats were given stimulants at abusive levels, that is what the researchers were studying. It's a no brainer and the NPOV tag should come off. Actually if we are speaking of drug abuse the section should be beefed up and include more information about tolerance and withdrawal. --scuro 00:40, 15 April 2007 (UTC)

If you wish to add information about how and why dextroamphetamine is "abused" or illicitly used, I think that should mostly go in the "illicit use" subsection of the "uses of dextroamphetamine" section. I will certainly do so as I come accross information about dextroamphetamine being abused (although I don't find reading such information exciting so I'm not goint so seek out liturature about such things, but as I come accross that information I'll try to bring it to this wikiarticle).

So your daughter takes 0.275mg/kg of dexedrine spansules, if that's what you're saying then you probably realizethat's not 0.275mg/kg entering into her blood stream all at ounce, that's over the entire day, you might also realize that this .275mg/kg is of dextroamphetamine sulfate so that would be about 0.2mg/kg/day of dextroamphetamine (I take about 0.5mg/kg/day). I'm glad that dextroamphetamine helps your daughter and I. Dextroamphetamine is a psychoactive substance, regardless of the intent anyone has about decisions to adminsture it. Just because it is 18-20 times the dose your daughter takes does not mean that is abuse, and it does not change the pharmacology of it. Someone could be abusing dextroamphetamine at the doses that your daughter is taking, dose says nothing about abuse. BUUUUUUT if you think it's important that dose be mentioned when talking about the studies in question then maybe it would be important to include the dose. My point is that I believe that the word abuse should not even appear in the sections about the tolerence and withdrawal mechanims, these sections are part of the neurochemistry of dextroamphetamine, that's where they belong and if there are ZERO studies contradicting it a statement about chemistry then how is it controversial?

I want the information about the dextroamphetamines withdrawal and tolerence mechanisms inside the pharmacology section because this information does not change reguardless if a doctor prescribed me 10000000mg/day of dextroamphetamine or if I was in a club injecting 10000000mg/day of dextroamphetamine. Whether or not I am 'abusing' dextroamphetamine is irrelivant to that section.

Maybe we could have a statement(and it'd be really good if we could find some liturature to support it) inside the toelrence and withdrawal section about tolerence in really low doses of dextroamphetamine (in addition to the high chronic doses), maybe the statement would say something like "in a clinical setting, at doses below under 2mg/day there seems to be tolerence for the first few days of adminstration and then the response levels off and is generally consistant" or whatever the case may be. I just think it's important to talk about the neurochemical mechanims of dextroamphetamine in the pharmacology section, and although I have yet to read the two studies in question(and I am now very interested in reading something about dextroamphetamine that caused such a commotion!!), I would venture to guess that they talk about neurochemistry and not social implications. Again, I think we can talk about abuse of dextroamphetamine in the illicit use section which is under the uses of dextroamphetamine section, and when it pertains to history it can be talked about in the history section. Thanks for reading my unorganised reply :)Edward Bower 02:05, 15 April 2007 (UTC)

That last post was hard to get my head around. Could you paraphrase it, give better order?

Generally the point that I am trying to make is that at some dosage of a drug, the drug will no longer have any therapeutic effects and taking the drug at that dosage is drug abuse. At such high levels the drug will only be detrimental to the individual. What is that dosage? You are right, it depends on the individual but certainly 6mg/kg is an abusive dose for any individual on this planet. Perhaps it is the term abuse that you don't like. Can you think of a better term that describes levels of a drug that far exceed therapeutic levels? Also be very careful when using the term tolerance. I don't agree that theraputic levels of stimulants cause drug tolerance. --scuro 15:28, 15 April 2007 (UTC)

I don't know of just one word, maybe just the entire phrase "doseage levels that far exceed therapeutic levels", and I just want to also say that dextroamphetamine can be "abused" at .1mg/day and you probably aren't doing much harm to your body unless you are using this doese inplace of sleep.Edward Bower 15:46, 15 April 2007 (UTC)

Would it not be like a spectrum in that:

-at low doses there are some theraputic effects,

-at optimum dosage there are full theraputic effects,

-at a higher dose lesser theraputic effects and some detrimental effects,

-at a much higher dose no theraputic effects and greater detrimental effects,

-finally to a dosage that would be deadly.

I've seen charts that illustrate the above. I'm guessing that abuse would be at that point in the spectrum where there are no longer theraputic effects. Is it possible that .1 mg would bring someone to that stage? Highly unlikely but possible...say a young small child. --scuro 02:16, 16 April 2007 (UTC)

Scuro, I gave three sources regarding reverse tolerance in humans at therapeutic doses in my reply to Romith. And if you don't think therapeutic doses cause (regular) tolerance, you should ready the second paragraph of "Time course and elimination" in this article. I wrote it a while ago and it's got four references on just that topic. The tolerance isn't complete but that doesn't mean there's none at all. KonradG 17:51, 16 April 2007 (UTC)

...the rodent to man correction, 0.25–1.0 mg/kg/day - If I read that right .25 mg in a rat is like 1 mg per person. So using my previous example and subtracting the sulphate from her meds am I right to draw the rough conclusion that the rats in Konrad's citation recieved over 100 times my daughter's dose?!??? Furthermore, the rats would have had the bulk of this dose working in their brain within the hour while my daughters dose is time released to work throughout the whole day?!!! Konrad, if you know so much about this field why are using such citations and equating the conclusions with theraputic drug use?

Looking at the next batch of citations the first thing that strikes me is the title of citation #1 which is "Chronic Amphetamine Use and Abuse". Dohhh!!! Those pesky titles just ruin everything. How about some mainstream citations Konrad? If institution x states reverse tolerance is an issue for theraputic use I would accept the conclusions that you have drawn. Trouble is you won't find any. As it now stands all I see are citations that speak to drug abuse issues only.--scuro 08:49, 17 April 2007 (UTC)

No, that's not what it says. 0.25–1.0 mg/kg/day is a range of doses, not a conversion factor. And it doesn't mean the daily dose was given all at once. Those are amounts which are "clearly within the dose range" for reverse tolerance in animals, "even without considering the rodent to man correction". I don't know how much more plainly it can be stated.

I just gave you three references, and you read only the title of one and ignored the others. Not only that, but it's at least the third time that I'm citing that review, and you still won't look at it. Incidentally, it was also the first thing I gave you right at the start of this long and fruitless discussion. As far as I can tell, you've simply ignored every cite I gave you, even though you specifically asked for them. Whatever your reasons, you are determined to present a certain view, and can't or won't be convinced otherwise. I can no longer reasonably assume that you're willing to present a neutral point of view, though your own views may be held in good faith. KonradG 22:26, 18 April 2007 (UTC)

"Ohhh the drama!"

I don't know how much more plainly it can be stated...I just gave you....and you read only....at least the third time that I'm....you still won't....the thing I gave you...you've simply ignored every cite I gave you, even though you....whatever your reasons, your are determined.... I can no longer reasonably assume that you're...though your own.... Konrad, all these personal (I, you, I'm, you've, your, you're) words in such a short burst of writing. Get a grip buddy.

Tell ya what, go and find me that reverse tolerance citation from say the NIMH or a similar national institution which I've been asking from the start. Find me that one and I'll change the article myself!!! If I haven't spent much time on the other citations it's because the first 2 were clearly bogus with regards to therapeutic stimulant use...so why bother? Must I read every scientific study posted if the journey is fruitless? --scuro 03:31, 19 April 2007 (UTC)

I've already told you specifically that the cites I gave Romith were all regarding sensitization in humans. Meaning they're not the rat studies. Of course, I also said that in the original post, which you apparently overlooked. Which is why I mentioned you by name the second time ("Scuro, I gave three sources..."). KonradG 04:25, 19 April 2007 (UTC)

The article is titled Dextroampetamine which is most commonly used as a therapeutic stimulant. Your citations in the article refer to reverse tolerance. As I have stated before it should have been clearly stated in the subsection if reverse tolerance occurs with the therapeutic use of stimulants. Now before we shift gears into sensitization, we need to get some business out of the way. Lets be clear, do you fully agree that reverse tolerance has nothing to do with the therapeutic use of stimulants?--scuro 10:11, 19 April 2007 (UTC)

Unbelievable. Reverse tolerance is sensitization! They're two common names refering to the same phenomenon, and they're both given right in the first sentence of the disputed paragraph. You didn't know the name of the drug which this article was about, and now it turns out you're not even sure what it is that you're disputing? I don't know what you're trying to do here, but it's been extremely disruptive and it's time something was done about it. KonradG 17:06, 19 April 2007 (UTC)

When you get all dramatic like that Konrad, you forget to communicate about the topic at hand. I'll post my question again for you,do you fully agree that reverse tolerance has nothing to do with the therapeutic use of stimulants? --scuro 23:13, 19 April 2007 (UTC)

Failing to answer a basic question about a post leaves the door open for future editing. Without a response to the question, do you fully agree that reverse tolerance has nothing to do with the therapeutic use of stimulants?, I'll be editing the post to reflect the majority viewpoint of experts in the field and of wiki members. --scuro 20:41, 20 April 2007 (UTC)

You don't get your way just because you keep asking questions until people get tired of answering them. Ignorance in one thing, but claiming your views "reflect the majority viewpoint of experts in the field and of wiki members" is just plain dishonest. KonradG 03:09, 3 May 2007 (UTC)

Still after all that time off, not answering the simplist of questions...the drama continues....yawn.....--scuro 03:23, 3 May 2007 (UTC)

I smell a rat or uncle Bob

Subsections Compared to methylphenidates and Compared to dextromethamphetamine uses the subjective anaylsis of Dr. Bob and single rat studies to support conclusions. Have we not gotten beyond the point where we are going to make conclusions based on a study? Are there reliable citations that support the same information? Some of the observations sound good yet other observations sound off. The first subsection is totally without citation. Can someone give us more information on these subsections? --scuro 11:36, 16 April 2007 (UTC)

Check the history, there were citations for those but they were removed, I think it's all in the Arnold review of many studies, so i think it may be in the history from when i originally wrote those here.Edward Bower 12:53, 16 April 2007 (UTC)

can you go back and put the citations back in? --scuro 01:43, 17 April 2007 (UTC)

A more experienced editor removed them, and I am going to side with him, nevertheless if you'd like to see the citation you can go to page history and go back to early saturday morning I believe(orsometime around then.Edward Bower 15:50, 17 April 2007 (UTC)

If the citations are good, someone should have just reason for removing them. Why strip citations from information?--scuro 10:14, 19 April 2007 (UTC)

"Even without considering the rodent to man correction"

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11205415&dopt=Abstract This range of doses was also found to be comparable to the lowest behaviorally effective doses of d-AMP (SC or PO) in normal human adults, which suggests that the sensitivity to the behavioral effects of amphetamine in these two species is fairly comparable. This study would suggest there is no correction needed.

If the dosages are comparable, using Bower's posted information also found on wiki, roughly 3/4 of any med dosage is of the amphetamine and the rest is of sulphate. Thus one can roughly extrapolate that the rat dosage of 6mg/kg is approximately more like a dosage of 8mg/kg given in a single dose as compared to the maximum clinical human extended release dose is 1mg/kg. My daughter of 15 receives a dose of .275mg/kg of extended release. Clearly the rat 6mg/kg dosage is not a therapeutic dose.

This information has been posted to help clarify the type of drug use refered to in the chronic use subsection which uses rat study citations.

Any flaws in this reasoning?--scuro 02:11, 22 April 2007 (UTC)

The main flaw is that you're ignoring the doses used in the other studies I provided. Not to mention the conclusions of the review article and all the studies it cites. KonradG 03:16, 3 May 2007 (UTC)

Nice to see you back Konrad, did you go on vacation? I didn't ignore the dose nor did I ignore the review article. That is unless you want to make reference to the injected mice but that opens up a whole different can of worms. Nice try, I did my homework.--scuro 03:20, 3 May 2007 (UTC)

Like I said, I don't think you're acting in good faith, so this discussion is just frustrating. For example, if you did your homework, how is it you keep ignoring those studies called "Behavioral sensitization in humans" and "Modeling Sensitization to Stimulants in Humans"? They're cited in the disputed section and I've specifically pointed them out to you several times so you couldn't possible miss them. I event pointed out how I had previously pointed them out several times. Remember this?

I've already told you specifically that the cites I gave Romith were all regarding sensitization in humans. Meaning they're not the rat studies. Of course, I also said that in the original post, which you apparently overlooked. Which is why I mentioned you by name the second time ("Scuro, I gave three sources..."). KonradG 04:25, 19 April 2007 (UTC)

What more can I possibly do? KonradG 04:23, 3 May 2007 (UTC)

Konrad, sorry that I haven't kept up but you seem to have your knickers in a knot once more and can't seem to leave me alone. Now you are seeking my attention in other parts of Wikipedia. Hopefully my comments will ease your concerns. I have to wonder, is this ongoing pestering not a desire to seek conflict?

Originally your reverse tolerance section was supported by two citations. You made a point of stating that reverse tolerance should be considered a possible issue with the therapeutic use of stimulants. eg.. "you're the one making unsupported claims about therapeutic use in humans".

The citations did not support in any way any conclusion about the therapeutic use of stimulants and RT.

Citation #1- injected rats(therapeutic use excludes injection as a delivery method)

Citation #2- dose of 6 mg/kg rats(we have spent a lot of time to demonstrate that this dose would be considered dangerous or even life threatening in humans, regardless...clearly that dose far exceeds the equivalent highest recommended therapeutic dose and must be considered abusive)

Then we got...

Citation #3 - this is an excellent overview provided by the respected institution called the, American College of Neuropsychopharmacology. But as this information was found not to mainly focus on therapeutic use we got a new request to look at...

Citation#4and#5 - Interesting looking studies but...

Which tree do you want me to bark up? I feel like I am on a wild goose chase and that when the next source is lacking you simply will bring up more studies and then insult my intelligence once more. So who is not acting in good faith? Can we end this? My preference is that we use citation #3 because it is the better wikipedia style reference. In science, as you probably know, one single study or even two studies does not allow definitive conclusions to be drawn.

Your right, I haven't looked at citation #4 or #5 and can do so at your request but this is not an easy process for me and is bothersome. So what will it be Konrad? Where should we focus our attention? Finally Konrad, once I have given my full attention to your source(s) and we have established something, can you leave me alone?--scuro 23:00, 9 May 2007 (UTC)

a definition of sensitization/reverse tolerance

Your right Konrad, I never did give your citations a thorough read. My focus of interest was related to therapeutic drug use and as soon as I saw the drug abuse delivery method in the one study and the dosage level in the second citation provided I knew that reverse tolerance was about drug addiction. I had hoped that you would see this too, evidently not. So to move forward to better the article and before edits are made to clarify the difference therapeutic use and drug abuse in the chronic subsection, I thought a working definition in layman's terms would help. Here goes.

Drug hypersensitivity or (Sensitization/reverse tolerance) is the increasing effect that a drug of abuse will have in response to intermittent and/or smaller amounts of the drug at a later period of time. These increasing effects usually are undesirable ones. This effect is contingent on several factors including the environment and the necessity of measured behaviours for existence. Sensitization is often used in reference to drug abuse behaviours such as craving and why cravings persist even after long periods of abstinence. It is important to remember that this is a theory and that observed effects have generally only been reproduced with lab rats.

With regards to theraputic use/drug abuse/tolerance/and reverse tolerance - a summary of a summary, the citation follows:

The initial low-dose effects of central stimulants induces at least two concomitant effects. One effect is to induce arousal-attentive mechanisms, a general energizing effect noted in rodents as exploratory locomotion. In humans, this effect is primarily expressed as an activation of attentive mechanisms and energizing/focusing of ongoing activities, coupled with secondary, generalized feeling of well-being. The focusing effect accounts for the therapeutic use of stimulants in ADHD, while in adults even therapeutic doses can induce various mild degrees of euphoria....Animals administered low stimulant doses often engage in the specific exploratory behaviors; when the exact same series of behaviors are repeated over multiple administrations, the phenomena takes on the characteristics of accidental conditioning, i.e., the initial ongoing arousal behavior become accidentally conditioned to the reinforcing effects of low-dose stimulants. As the dose is increased, behavior becomes more and more constricted, and reduced, often to a fragment of the original behavior. However, unless the original behavior is compatible with one of the dopamine-activated, species-specific behaviors, the conditioned behavior fades away and is replaced by a species-specific stereotypy, e.g., repetitious sniffing, licking, or gnawing in the rodents....If the experimental animal is required to activate a manipulandi to obtain the stimulant, the behavior around the manipulandi, as drug accumulates, increasingly takes on some form of a species-specific stereotyped pattern....Thus, the species-specific behavior, which is an acquisition behavior in the animal's natural behavioral repertoire, now becomes drug acquisition operant behavior with a compulsive nature. Whether contingently or non-contingently related, the repetitious, compulsive behaviors in humans are described as being very pleasurable; stimulant abusers often state that they will take the stimulants in order to engage in these activities. For example, methamphetamine addicts take the drug to activate their drawing or painting compulsions which indeed sometimes results in works of art, or they engage in taking machines apart, repairing them, and sometimes actually putting them back together....Gradually, over time and increasing doses, especially with high-dose utilization, there is a transition to the high-dose platform of drug abuse. With these higher doses, massive tolerance develops to the energizing and reinforcing effects of the drugs as well as to the neurotoxic (but not to the psychogenic) adverse effects....During the withdrawal period, drug craving appears most intense during the first two weeks, yet reappears periodically for weeks afterwards. Drug craving has been described as activated by various stimulant cues, e.g., white powder, etc. resulting in automatic acquisition behaviors coming into play—often with little consciousness of the process....Sensitization to intermittent stimulant dosing is generally recognized as inducing stereotyped behaviors that are reactivated by lower doses than were required to activate them initially. Quite reasonably, it has been proposed as a mechanism underlying stimulant-induced psychosis. Yet, continuous dosing induces perhaps even more bizarre hyper-reactive behaviors in animal models that can be reactivated by test doses even months later...Despite the numerous adverse effects of high-dose amphetamine abuse, amphetamines have a definite place in the FDA-recognized treatment of attention deficit disorder and narcolepsy....The lack of evidence for increasing sensitivity to drug abuse or psychosis in a carefully managed medical population would indicate that lower dose sensitization animal models may not be readily applicable to sensitization models of abuse reinforcement and psychosis. http://www.acnp.org/G4/GN401000166/CH162.html

Any flaws in the definiton or support material--scuro 13:56, 22 April 2007 (UTC)?

What's your point? All it says is that low-dose sensitization doesn't explain drug abuse or psychosis. That same paper also says that such sensitization from therapeutic use is CLEARLY expected to happen. It's so clear that the authors of this review specifically state that it was "quite reasonable" for others to investigate its connections to abuse and psychosis, even though it turned out to be a dead end.

Look, obviously you're seeing only what you want to see. You're completely, hopelessly wrong on a topic that you don't know the first thing about. Just drop it and stop wasting my time. KonradG 03:46, 3 May 2007 (UTC)

Konrad...the rudeness is unbecoming an unnecessary. Simply give quotations from the text to support your ideas and make your point. I should point out to you that any quote will be negated by the fact that the overview starts out by stating that it won't explore the use of therapeutic stimulants.

In the US, there are only two Food and Drug Administration (FDA) approved indications for dextroamphetamine and methylphenidate: 1) narcolepsy and 2) attention deficit hyperactivity disorder (ADHD). In Europe, some countries have prohibited any use of stimulants. However, most experts agree that in ADHD and narcolepsy, stimulants have an definitive and uncontroversial therapeutic role when used judiciously. Because of this agreement on specific therapeutic applications for these drugs, their use will not be reviewed here. Rather, we will discuss the use of stimulants for other problems, those for which stimulant administration may be somewhat more controversial.

The POV tag will be added on again. --scuro 18:23, 4 May 2007 (UTC)

so the question is

Why do we have a subsection of the dex article about an effect of drug abuse clinically observable only in rats? This behaviour is not clearly understood, is theoretical, and extrapolations about this behaviour can not be made to humans. Should this not be a separate article so as not to confuse the reader with theoretical associations to a drug widely used for ADHD and Narcolepsy?--scuro 22:03, 22 April 2007 (UTC)

I think it's fine having it in here, but rats cant abuse drugs, so we should lets look for a better way to incoperate these sources into the article, it must tell us SOMETHING about some part of how dextroamphetamine works at some dose, and I think it's valuable information knowing about all doses of dextroamphetamine becuase one day there might be some kind of model that can explain why it does what it does at low doses and it does what it does at higher doses.Edward Bower 02:48, 23 April 2007 (UTC)

Rats can't abuse drugs? Sure they can and do if they have control of a source of drugs.

Reverse tolerance is a meaty issue. It's not like one can make any definitive statements about any aspect of this observed behaviour. It also does seem to be related to other drug abuse behaviours such as tolerance and withdrawal. It apparently happens differently even amoungst a similar class of drugs such as stimulants. To do it justice would take a lot more then the 3 sentences Konrad wrote. The article cited below has good information about a theoretical model of stimulant abuse and talks briefly about the theraputic use of stimulants. It also has this to say,"most experts agree that in ADHD and narcolepsy, stimulants have an definitive and uncontroversial therapeutic role when used judiciously. Because of this agreement on specific therapeutic applications for these drugs, their use will not be reviewed here". The American college of Neuropsychopharmacology clearly does not see similar things happening between the abuse of stimulants and the theraputic use of stimulants.

Changes were honestly and sincerely made in the article to reflect information posted in discussion. http://www.acnp.org/G4/GN401000166/CH162.htm --scuro 04:24, 23 April 2007 (UTC)

If an individual with ADHD is administering a drug at the exact same times over the same periodic intervals using the same method using the same dose, the fact that it is being therapeutically used or abused DOES NOT MATTER. Any difference in subject effects would be based on the placebo effect. Having said this, I'll also add that abuse of stimulants usually does not happen like therapeutic use, but theoretically it could. What do you think about that Scuro?Edward Bower 20:51, 23 April 2007 (UTC)

DOES NOT MATTER?..look at that sentence again...it does not compute....difference based on the placebo effect???? I'm not following.--scuro 08:28, 5 May 2007 (UTC)

What does this statement: "Because of this agreement on specific therapeutic applications for these drugs, their use will not be reviewed here" mean? cyclosarin 07:24, 5 May 2007 (UTC)

What the statement means is that the scientific overview which looked at all studies to date, did not explore the use of theraputic drugs. Why? ...because stimulants like dex that are used in a theraputic way have a, "definitive and uncontroversial therapeutic role". There is a wide and overwhelming body of scientific evidence that supports this view. ADHD is the most studied childhood disorder out there and researchers have done many studies on the action of theraputic stimulants. Generally speaking none question the theraputic action nor do they see controversial side effects. Thus we have the quote, "Because of this agreement on specific therapeutic applications for these drugs, their use will not be reviewed here". Reverse tolerance with regards to the theraputic use of stimulants is a none issue to them...and that's why immediatly after those quotes they state,"Rather, we will discuss the use of stimulants for other problems, those for which stimulant administration may be somewhat more controversial". --scuro 08:28, 5 May 2007 (UTC)

It doesn't say therapeutic use won't be reviewed, only those two "specific therapeutic applications", i.e. ADHD and narcolepsy. Not that it matters, since you're quoting it out of context. That sentence is about the topics covered in the section entitled Clinical Uses. The review then goes on to discuss abuse a different section, and sensitization in yet another. And that last one has a part called Do Chronic Therapeutic Doses of Amphetamine Induce Sensitization to Adverse Effects?, which specifically addresses ADHD and narcolepsy. In fact, the word ADHD appears 13 times in four paragraphs! So the question is, Scuro, how is it that managed to overlook that? KonradG 07:16, 6 May 2007 (UTC)

Here is the 13 mentions ADHD passage for anyone, highly doubt there is anyone left in the building, who is still interested. Judge for yourself.

Do Chronic Therapeutic Doses of Amphetamine Induce Sensitization to Adverse Effects?

The issue of ‘sensitization' to adverse effects following repeated low to moderate doses of stimulants is a critical issue in the treatment of attention deficit hyperactivity disorders (ADHD) in children as well as adolescents and adults. Is there sensitization to drug reinforcement or potential for psychosis? The suggested dose range for methylphenidate and dextroamphetamine dosing in most children is 0.3– 2.0 mg/kg daily and slightly lower doses for adolescents and adults. The dose for dextroamphetamine is cited as being approximately half that for methylphenidate (226). Even without considering the rodent to man correction, 0.25–1.0 mg/kg/day is clearly within the dose range quoted in most paradigms of locomotion sensitization in experimental animals. Studies in adolescents generally indicate that the stimulants are efficacious and safe in the treatment of ADHD (226). There are no reported differences in the incidence of substance abuse in medicated vs. unmedicated adolescents (90); this is based on a review of eight outcome studies comprising 580 adolescents previously treated with stimulants for six months to five years. Looney (135) suggested that adequate treatment of ADHD children and adolescents with stimulants may indeed have a protective effect against the development of substance abuse. There have been no systematic studies on the risk for development of substance abuse in ADHD adults treated with stimulants, and such a study would have difficulties based on the high comorbidity of adult ADHD and stimulant abuse.

With regard to the development of psychosis in children, an extensive review on stimulant treatment of ADHD (100 studies which included 4,200 patients) reported only six cases of psychosis (14). There are, however, 20 case reports in the literature of stimulant-induced psychosis in children treated with stimulants for ADHD (226). Considering that psychosis is thought to be a dose-related phenomena primarily occurring at higher doses, along with the potential difficulty in mg/kg/day dosing in children, these incidences are really quite low given the magnitude of the incidence of ADHD and its stimulant treatment. Rounsaville et al. (181) has reported that upwards of 40% of stimulant abusers have a comorbid diagnosis of ADHD. There has been some reflection that stimulant abuse is an effort by the patient to self-medicate. Recently, Biederman et al. (19) reported that adults with ADHD also have high rates of comorbid antisocial, depressive and anxiety disorders providing a different perspective from the drug abuse clinic patient. Moreover, recent evidence (201) indicates that adult attention deficit disorder requires stimulant treatment (methylphenidate) in doses similar to those in childhood ADHD (i.e., 1.0 mg/kg/day). This raises the question whether some of the abuse potential in ADHD adults may be inappropriate self-medication in the search for a higher effective dose even with illegal stimulants.

Another clinical problem treated with amphetamine and other stimulants is narcolepsy, a condition treated over many years at amphetamine doses ²40 mg/day or methylphenidate ²60 mg/day (although higher doses than this have been used by many clinicians). Concerns regarding tolerance, undesirable side effects and drug dependency are reasons most frequently cited for limiting the use of stimulants for treating narcolepsy symptoms. However, a systematic review of the literature on the use of these agents revealed that there was no evidence from prospective randomized studies for these dependence phenomena in patients treated for sleep disorders (150). Mitler (150) further stated that " . . . we know of no published data showing that patients with narcolepsy or other primary sleep disorders either abuse or become physically dependent on stimulants." They comment that the case reports of adverse effects primarily come from studies of drug abuse populations or from retrospective studies. For a 70 kg person, 40 mg would certainly be within the dose that, in rats, induces sensitization. The lack of evidence for increasing sensitivity to drug abuse or psychosis in a carefully managed medical population would indicate that lower dose sensitization animal models may not be readily applicable to sensitization models of abuse reinforcement and psychosis.

I was done with this debate but Konrad sought me out by deleting my edits on another page. You can read the gory details here. ->http://en.wikipedia.org/wiki/User_talk:Scuro#3RR_Violation The really funny thing here is that technically he broke the three edit rule first. Seems he wanted my attention to say we are no longer an item. The ol', "He didn't dump me, I dumped him", story.--scuro 04:09, 10 May 2007 (UTC)

For the record, the "other page" is Amphetamine, where the sensitization section from this article was copied word-for-word. Secondly, I've already addressed the bolded section of the quote above, so I won't repeat it here, but it's in my post (which Scuro ignored) dated May 3rd. And Scuro, 3RR means you can't exceed three reverts, so I couldn't have violated it even if you count my first edit as a revert. KonradG 18:05, 14 May 2007 (UTC)

"We've had over a month of discussion over 3 disputed sentences, and it hasn't solved anything". Your words Konrad, not mine. Why bother unless you are looking for conflict?--scuro 01:33, 15 May 2007 (UTC)

How often is Dexedrine prescribed compared to Adderall?

Here I read: http://en.wikipedia.org/wiki/Adderall#Government_warnings that Adderall is prescribed 37 million times in 4 years. How often is Dexedrine prescribed? --134.155.99.41 17:23, 2 May 2007 (UTC)

dexedrine is not commonly perscribed anymore because of its high potential for abuse. they usually only perscribe it now for SEVERE ADHD, narcolepsy, military still uses it some times, and if you have adhd and depression they might perscribe it because of its euphoric effectsJonM.D. (talk) 10:02, 25 December 2007 (UTC)

Use vs. abuse

So far as I can tell, legally "abuse" is defined as "unauthorized" use. So the issue is one of authority, not physiology or science. Example: if I injure myself and take a friends' pain pill, that's legally drug abuse. If I'm a doctor and prescribe for myself, it's still drug abuse! If I go to a second doctor and get a prescription, however, it's merely use. Same injury, same pill, same action-- but abuse has been turned into simple use by the proper signature. Likewise (more interestingly), if I'm a civilian pilot and take amphetamine to sharpen my reactions and lengthen my endurance for a flight, that's legally abuse. Even if could convince my friend the doctor to prescribe amphetamine for this purpose, I think the medical board might even decide it was "abuse" when it reviewed the doctor's prescription for such a thing, if I happened to have an air accident and my blood tox screen was reviewed by the FAA and DEA. But if I'm a military pilot, and my military doctor gives me a "go-pill" for an air combat mission, as is usually done for most military combat missions, that's not abuse, but "use." Even though the FDA (which still rules military medical matters) would certainly define it as completely off-label use, and one that would be "abuse" for a civilian, for this reason. But the DEA would prosecute neither doctor nor patient, in the military setting; nor would the relevant medical board take action.

Anyway, in this context, I'm curious about the contention above that rats can "abuse" drugs, in an experimental setting. How in the world does that happen? First, rats don't know about laws or authority, so they can't really "abuse" any drug, any more than infants can. And even if they could, in an experiment, if there was such a thing as a rat presciption, the rat would certainly have it (the rat's lab, for an authorized experiment, would have a lab DEA number, and so forth). In any case, talking about rat drug "abuse" strikes me as like talking about rat-committed "murder" ("murder" = unauthorized killing). It's very odd! SBHarris 04:03, 11 May 2007 (UTC)

That's a view that I agree with, and Steve Harris did a great job of articulating it. Now, what should we change about this article if ?(presupposing we all can agree on this)Edward Bower 04:49, 11 May 2007 (UTC)

---

---

I'm thinking it is 'legally' abusing a drug when you take more than prescribed of your own legal drug prescription. It seems it would be 'illegal' drug abuse if you took someone else's legal prescription since that action is illegal and an abuse since that drug was not prescribed for you. Unless of course you mean 'illegal drug' abuse of which it is illegal all-around and more than likely abuse. Jadet46 —Preceding unsigned comment added by Jadet46 (talk • contribs) 21:22, 30 September 2007 (UTC)

"drug abuse is simply excessive use of a drug or use of a drug for purposes for which it was not medically intended". http://www.nlm.nih.gov/medlineplus/ency/article/001522.htm --- "Drug abuse is the use of illicit drugs, or the abuse of prescription or over-the-counter drugs. The abuse of legitimate drugs (prescription or over-the-counter) can happen when people use the drugs in a manner or in quantities other than directed, or for purposes that are not legitimate". http://www.nlm.nih.gov/medlineplus/ency/article/001945.htm --- "The Health Officers Council of British Columbia — in their 2005 policy discussion paper, A Public Health Approach to Drug Control in Canada — has adopted a public health model of psychoactive substance use that challenges the simplistic black-and-white construction of the binary (or complementary) antonyms "use" vs. "abuse". This model explicitly recognizes a spectrum of use, ranging from beneficial use to chronic dependence (see diagram to the right). http://en.wikipedia.org/wiki/Drug_abuse#Public_health_definitions

2.1. Definition of non-medical use, abuse, and dependence

It might be useful at the outset to discuss the terms ‘non-medical use,’ ‘abuse,’ and ‘dependence’ since these terms form the crux of this position paper. ‘Non-medical use’ of a prescription drug is defined in the National Household Survey on Drug Abuse (NHSDA) as using a psychotherapeutic drug ‘even once, that was not prescribed for you, or that you took only for the experience or feeling it caused’ (SAMHSA, 2002a).

2.1.1. Clinical definitions of drug abuse

Abuse of a prescription drug can be defined in several different ways. In the context of the treatment of a diagnosable disorder, there are two classification systems, one by the American Psychiatric Association (APA) and one by the WHO. The APA uses a precise set of psychiatric criteria from the Diagnostic and Statistical Manual of Mental Disorders (fourth edition; DSM-IV, 1994) and the WHO uses a set of criteria from the International Classification of Diseases (ICD-10; WHO, 1992). In this position paper we will be using the DSM-IV definition of substance abuse disorder. That definition is a ‘maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by one or more of the following, occurring within a 12-month period: recurrent substance use, resulting in a failure to fulfill major obligations at work, school, or home; recurrent substance use in situations in which it is physically hazardous; recurrent substance-related legal problems; or continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance.’ ..... 2.1.2. Other definitions of drug abuse

There are several other definitions of substance (drug) abuse in the scientific, regulatory, and law enforcement communities, and four of them are listed below: Any harmful use, irrespective of whether the behavior constitutes a ‘disorder’ in the DSM-IV diagnostic nomenclature (Institute of Medicine [IOM], 1996). Non-medical use of a substance for psychic effect, dependence, or suicide attempt or gesture (SAMHSA, 2002b). Although the National Institute on Drug Abuse (NIDA) does not have an official definition of drug abuse, they have used ‘non-medical use of a substance’ as a definition in their educational materials (NIDA, Lucinda Miner, Chief of Science Policy, personal communication, May 21, 2002). Non-medical use of a drug (from the Federal Controlled Substances Act of 1970, Drug Enforcement Administration (DEA)). It is apparent that the term ‘drug abuse’ means different things to different people, even within the scientific community. Moreover, the existence of different definitions is not trivial, as the different definitions may be used to formulate drug policies by different organizations. Problems associated with drug use may be considered from a clinical perspective, focusing on the criteria for formal psychiatric diagnosis of drug abuse disorders (e.g. DSM-IV definition), or from a medicolegal perspective, focusing on instances of non-medical use or harmful use (the four definitions already given). It is beyond the scope of this position paper to select one definition that is ‘more correct’ than another. For the purposes of this position statement, indicators of problematic prescription opioid use will be grouped into non-medical use (use that has not been shown to meet DSM-IV criteria for substance abuse disorder) and abuse/dependence (use which meets DSM-IV criteria). Evidence shows that both non-medical use and abuse/dependence of prescription opioids are on the rise in the United States. http://64.233.179.104/scholar?hl=en&lr=&q=cache:11KiQmKSZ9EJ:www.psychology.ilstu.edu/cbs/readings/zacny2003.pdf+%22drug+abuse%22+and+definition+and+NIDA

"So the issue is one of authority"...not so fast Dr. Harris!! Because in reading the above citations the issue of maladaptive pattern of substance use and harmful use also seem to pop up several times with reference to drug abuse. As the above citations attest to, clearly there is no definitive definition. Even NIDA doesn't have definition. (hint) You can use that fact to drive a wedge between the issues that I brought and your original assumption!

So getting back to that rat with it's never ending supply of lab drugs....getting back to that burning issue that drives this whole examination. Certainly a rat can have a maladaptive pattern of substance use which is harmful to the rat. That rat doesn't need the script from his rat MD, nor does he need to be caught by the rat police to be abusing drugs.

--scuro . o 0 (wonders how many posts and insults to his intelligence he will have to endure on the topic of rat drug abuse) 11:12, 11 May 2007 (UTC)

rat drug abuse

Ah! You propose that the Darwinistic fitness of an action be taken as the measure of whether or not the action constitutes the "self-abuse" or "self-injury" of human or beast? And then what? I don't think that will make many people happy, since society (and most people in general) approve of all kinds of non-Darwinian actions, and don't approve of a lot of Darwinian ones. Moreover, few want humans to abide by the law of the jungle as do animals, even if we could find some animals that always behaved Darwinistically. Which we often seem to have a hard time doing, oddly enough. I think mainly since perfectly Darwinian behavor would require perfect prediction of the future in order to weigh outcomes of actions, therefore infinite intelligence. Say are we gunna do this propectively for decisions, or retrospectively? "You should've known better than to get addicted in the FIRST place, you rat, you!" SBHarris 02:03, 14 May 2007 (UTC)

Not only do rats have a maladaptive pattern of substance use that fails the Darwinian fitness test to be a rodent of high standing...they are no better then their distant cousins, the Lemmings.

In one study, rats were able to self-administer cocaine into dialysis tubes implanted in the nucleus accumbens by depressing a bar-lever. At first, rats will infrequently self-administer cocaine by pushing the bar-lever. As more and more time passes, the rat begins to push the bar-lever more and more frequently and will not stop from doing so even to eat or sleep. Eventually the rat dies of exhaustion.

http://sulcus.berkeley.edu/mcb/165_001/papers/manuscripts/_362.html

I hope we can bury this rat issue. Clearly those dirty rats keep can't keep their whistle clean any better then humans. --scuro 02:54, 14 May 2007 (UTC)

In my opinion, this whole thing with the rat studies is a red herring. To quote my first post in this discussion, way back on March 31, "The only reason I happened to choose rat data for some cites was that it was the most direct example of the 'reverse tolerance' phenonmenon." To satisfy Scuro's objection to the rat studies, I then added three cites which specifically addressed sensitization in humans. Since that time, this discussion has been going in circles because it appears that he is unwilling or unable to read them. For example, here's a direct quote from Scuro's post of April 19: "If I haven't spent much time on the other citations it's because the first 2 were clearly bogus with regards to therapeutic stimulant use...so why bother?" KonradG 17:50, 14 May 2007 (UTC)

Yeah...why bother? It's been a waste of my time so far with regards to the theraputic use of stimulants.--scuro 01:22, 15 May 2007 (UTC)

So if you're not going to bother discussing it, why won't you remove the NPOV tag? You can't have it both ways. And when this dispute doesn't turn out the way you want, you certainly can't expect to repeat the exact same claims in the Amphetamine article, and demand that any changes be discussed there seperately. KonradG 18:15, 15 May 2007 (UTC)

For some insight into Scuro's honesty, I invite others to take a look at this diff of Amphetamine, where he reverts my edit to the same disputed content discussed on this page, with the comment, "Undid revision 129437200 by KonradG -please post in discussion before making changes". After I restore it and refer back to this discussion, he removes the edit again, saying "different issue, different page...follow wiki guidelines". To me, that comment is intentionally misleading, if not outright dishonest. He couldn't get his way here, so he makes the same changes to an article on the same topic, to the content which was copied directly from this article, all the while claiming it's a "different issue". KonradG 18:15, 15 May 2007 (UTC)

Konrad...Konrad...Konrad...

You would do well to read these pages: WP:CON(This page documents an official policy on the English Wikipedia. It has wide acceptance among editors and is considered a standard that all users should follow. When editing this page, please ensure that your revision reflects consensus. When in doubt, discuss first on the talk page.) WP:NPA(This page in a nutshell: Comment on content, not on the contributor.) Sorry Konrad but this "dance" is over. I wish you well at Wikipedia and hope that you contribute further. I'm sorry if I have gotten personal in this debate. On reflection it was the wrong thing to do.--scuro 21:07, 15 May 2007 (UTC)

Mediation cabel conclusion- do not to remove POV tags of other editors without consensus

http://en.wikipedia.org/wiki/Wikipedia:Mediation_Cabal/Cases/2007-05-01_Electroconvulsive_therapy#unresolved_issues

"Basically, consensus should be attempted in good faith. Personal comments should be eliminated. No one owns a section and everyone can contribute at anytime. If several editors have attempted consensus and they don't want to get into a revert war it is acceptable to put a npov tag on a section especially if a case for bias has been made. No editor should take off a npov tag without consensus from the other editors".--03:26, 29 July 2007 (UTC)

The mediation cabal doesn't call the shots around here, and you have to seek consensus just like everyone else. You've refused to do that, as is plain in the discussion above. KonradG 17:22, 31 July 2007 (UTC)

Still angry...after all this time. I don't need consensus to put a POV tag on. You do need one to take it off. Please don't take it off again. I'm hoping with some time perhaps others will chime in, especially if the conversation is toned down. Perhaps a reasoned third party can seek the middle ground. That is the route I would like to take. Force the issue and I will call a mediation cabal about this issue, I have no worries here since what we have is a piece of original research WP:SYN.--scuro 18:38, 31 July 2007 (UTC)

But you see, there is a consensus. You were the only one disputing the content, and you have refused to take continue the discussion when other editors finally did show up. Since there are no active participants, I consider this a dead issue.

By the way, the mediation cabal won't help here, since I am no longer willing to assume good faith on your part. However, I encourage you to take whatever formal action you like. I'll be glad to defend the neutrality of the content and finally get this over with. KonradG 00:11, 1 August 2007 (UTC)

Thank you for not removing the POV tag. You are right, lets get this behind us. To start off with, I disagree with you about consensus. I remember several editors disagreed with your stance...but that is history as they say. The core disagreement is not a question of neutrality, it is a question of original research being posted on Wikipedia. I have no idea if you have a bias with regard to this article. I do know that the conclusions drawn go beyond what any of the researchers would state in public. The section also could be stated more coherently. I tried to correct that but even edits that simply tried to add clarity were deleted. All edits was deleted. I always assume good faith until I am painted into a corner. Perhaps the middle ground here would be for you to simply edit the passage yourself. Double check your assumptions about what the other authors of the studies stated. Do secondary sources such as the New York Times have an opinion on this? More importantly use simpler language so that the average reader can understand what is written. Perhaps this is simply a communication problem. Wikipedia wants passages that the layman can understand. Failing all this, simply post your arguments about why the section should not be altered on this page in very clear and precise manner. That would be the next step.--scuro 00:49, 1 August 2007 (UTC)

The tone of your message is extremely reasonable and cordial, but you are plainly mis-stating the facts in a way that I simply can't reconcile with a good-faith misunderstanding. I'm reverting your change, and this time it's your turn to jump through the hoops of the dispute resolution process. Take whatever formal action you feel is warranted.KonradG 03:59, 1 August 2007 (UTC)

That's because user Scuro (and whatever other usernames he may use for support) is engaging in a practice known as sophistry, a very severe form of abuse and inicivility on Wikipedia, in order to have his way. He's doing the same thing on the Electroconvulsive Therapy page. This is a copy of the warning I put on the electroconvulsive therapy talk page:

Warning to editors and readers at large regarding sophistry:

Please read the "modern usage" section of the page sophistry to understand the basis of my position here with regard to these character(s). Sophistry has many variations and levels of expertise, and in this case involves the intentional crafting of deceptive and illogical claims that put the opponent in a perpetual state of defense. The fallacious logic is often immediately recognized by the opponent, but often not by outsiders not deeply involved with the exchange. The sophist does not concede to the superiority of logic made by the opposing party in response, but rather continues to make further logically deceptive remarks in response along with demanding and unnecessary queries, which typically infuriates the opponent with the hope that the opponent will get himself into trouble due to his own outbursts. Sophistry in this particular case also involves intentional misrepresention and equivocation of the results of scientific studies, forcing the opponent to exhaustively correct and defend. On Wikipedia, sophistry can be used as an ultimate means to unjustly prevent what's loosely referred to around here as "consensus", and to also create what looks to be a genuine, good-natured hot debate on the surface where there really is none. In short, people with no proper justification for changes they want made to a page can use sophistry and abuse the mediation process into either forcing an exhausted opponent to concede or to force an unreasonable compromise, such that they ultimately are allowed to publish disinformation to the community. Danrz 04:28, 2 August 2007 (UTC)

Funny that you came to this page to make accusations, you must have a lot of time on your hands. Please Danrz if I am engaged in a "severe form of abuse", make the time to report me. Wikipedia takes abuse seriously.--scuro 11:06, 2 August 2007 (UTC)

What you're describing sounds *exactly* like my experiences with User:scuro on this page. It's the conversational equivalent of dealing witth Soviet bureaucracy. KonradG 16:40, 2 August 2007 (UTC)

You to have found each other, awesome!! You two have a lot in common. KonradG meet Danrz, Danrz meet KonradG 8)--scuro 18:58, 2 August 2007 (UTC)

Attempted dispute resolution

The main issue at the present moment is that I can not do my job as an editor. I can neither post on the chronic use subsection nor can I place a POV tag on this section. All edits and tags have been been deleted by KonradG. I guess there were a dozen or more attempts at editing this subsection. Discussion went no where and in fact got heated. I left the page but put on a POV so the layman would understand that certain editors did not agree with this passage. All the POV tags that I have posted have been deleted. I believe I have posted a dozen or two POV tags.

Following Wikipedia's resolving disputes policyWP:DR

Step one - I have talked to KonradG at length

Step two - I disengaged from the page for several weeks

Step three - Can not be done because Konrad G assumes bad faith ("since I am no longer willing to assume good faith on your part") and has stated so several times. Wikipedia :third opinion states: "Third opinion is a suggestion for the use of third-party mediators in a dispute. When editors cannot reach a compromise and need a third opinion, they may list a dispute here. The third-opinion process requires good faith on both sides of the dispute".

Step four - Is not relevant to this dispute: ("Asking at subject-specific Wikipedia:WikiProjects or policy pages relevant to the issue".)

Step five - would be a "Wikiquette alert, for problems with uncivil editors".

Balls in your court Konrad. Clearly I can not edit or warn the layman of what I perceive to be clearly faulty information about a medication that many readers have prescriptions for. Can we not solve this now?--scuro 04:55, 1 August 2007 (UTC)

Clearly, we can't. It's going to require intervention by a third party, so please proceed with the next step. KonradG 16:49, 2 August 2007 (UTC)

Third Op

Ground Rules and Other Notes

From a brief look it appears to me that the pov section template should remain. Obviously since the dispute as to whether it's pov or not is still underway - so why are we disputing whether a tag should be there.

That being said - each of you has either violated or come close to violated WP:3RR - I recommend you each follow the WP:1RR rule - which states that once you are reverted finish discussing on the page rather than get into a revert war.

I really don't think you guys need to go to Mediation for this - I think if you all calm down (which means no more typing while caps lock is on) and adhere to other Wikipedia policies, then you can settle it here. A few things I'm noticing with each of you-

1. Scuro - you not reading the sources is kind of ridiculous - you can't argue your point as to why the sources are wrong if you don't look at the sources
2. KonradG - assume good faith, just because your in a debate with someone doesn't mean you can disregard them as editors
3. Scuro - sarcasm like this: "You to have found each other, awesome!! You two have a lot in common." - aren't helpful. Did you think that was going to convince them?
4. KonradG - comments like this: "It's the conversational equivalent of dealing witth Soviet bureaucracy." - aren't helpful. Did you think that was going to convince them?

Again, I really think that if you guys are willing, you can resolve this through compromise - WP:NPOV issues are usually easy to handle - it's just a matter of compromise. I would strongly suggest starting the debate over from scratch - scuro why do you think the section is POV, KonradG what is your response. Go from there, I'll even try and help you guys out until then, but until it is solved, no revisions and the disputed tag stays up.--danielfolsom 19:37, 2 August 2007 (UTC)

I've just strayed into this from somewhere else (don't even try to guess where!). The most recent edit summary is: "yet another revert. someone please give an outside opinion." I gather the dispute is about one section: Chronic use. What I, as a complete ousider, see is:

1. the section itself is miniscule compared to the amount written about it on the talk page
2. If there is a POV, it is supported by five sources
3. If there is another POV (a) I would like to know what it is, and (b) it should be supported by at least one reputable source.

I am speaking as someone with experience of POV disputes, and I have never before seen one with so much talk on the talk page, and so little justification in the edits themselves. Scolaire 19:47, 2 August 2007 (UTC)

Yeah, I too have seen and been in quite a few POV disputes, but I have only seen this scenario maybe once. That being said - section size isn't really significant, a lot of times it's the smallest sections that get the most controversial. Either way, I suspect the outcome will be mentioning both sides of the debate in the article (with sources)--danielfolsom 19:51, 2 August 2007 (UTC)

As it should be! Scolaire 21:03, 2 August 2007 (UTC)

I'd like to clarify something here, especially in response to Danielfolsom's comments: I initially did assume good faith in this dispute. That can been seen from several months worth of discussion on this talk page. I did it over and over, despite the evidence that scuro was being deceptive. I am no longer willing to do that, because I believe scuro has no intention of understanding the material and seeking out a NPOV -- only of participating just enough to give the appearance of doing so.

I realize it's a huge amount of text, but please read over the earlier threads on this page. At least the first few, where scuro repeatedly confuses basic words relating to the topic and apparently doesn't even know what it is that he's trying to delete. He makes strong claims about references that it turns out he never read. I know you mean well, but it's kind of frustrating for you to you tell me to talk it out with him, when that's what I've been doing for months. It's not a POV dispute in that that we disagree about how to interpret the material; He makes no attempt at understanding it, and in fact deliberately avoids sources which would contradict him.

KonradG 17:05, 3 August 2007 (UTC)

I have read the close to all of it - and I see you both making mistakes, however based on that text I cannot make any assumption on bad faith - the point is now to put the mistakes behind each of you and start over. The way I see it no one has made more mistakes than the other - and if you aren't willing to take the high ground and start over than there is no opposition to scuro's suggestions. Scuro has laid out his points below, as he has started over, now the point is to come to a compromise and that involves you starting over by reading and responding to his arguments. Again what will probably end up happening is the report and a contradiction to the report will be stated, stating both sides is usually the resolve to any pov issue.--danielfolsom 17:26, 3 August 2007 (UTC)

I don't think that starting over is a helpful suggestion, in light of my complaints that I'm getting the run-around. I have read and responded to his arguments, but he just keeps repeating them. On the other hand, I am still willing to continue the previous discussion at the point where scuro abandoned it (see the exchange from May 15th). I would also appreciate any comments you have on specific issues of the dispute. Do you believe that there any points of contention that should clearly be conceded by either side?

As to at the point of bad faith, consider what happened with that last discussion: After two other editors (Edward Bower and SBHarris) weighed in, he refused to continue the discussion on this page, went to the Amphetamine page and re-started the same conflict with me there. Then he demanded that I re-start a new discussion on *that* page, so that I would have to defend the exact same passage yet again. At the same time, he would not remove the NPOV from this article, even though I specifically asked him to do so since he was unwilling to continue the discussion. After he made no response for a long time I removed the tag myself. And now he has re-appeared, replaced the tag, but still ignores the discussion, except to post about how I shouldn't remove the tag. Yet, he's perfectly willing to start over. Doesn't that sound a little bit like he's intentionally trying to drag things out? How many times should I have to cite the same references when someone keeps ignoring my responses?

KonradG 17:44, 6 August 2007 (UTC)

Sect. 1

I have attempted and continue to attempt mediation. From what I read of Wiki policy, third party is only to be used if both sides assume good faith so really what is the point of this? Konrad has clearly stated several times that he doesn't assume good faith. It's an impossible Wikipedian environment for me to work in. Every single edit and POV tag placement I have made has been reverted. Those edits have all been made in good faith to improve the article. Try to talk about it in talk and that door is shut too.

It's not that I haven't read the sources, it's when I read a source and I or others find that the conclusions that KonradG draws from the source having nothing or little to do with his passage, new sources are found. I stopped playing that game. We are up to a total of five sources with no commitment to a single source or a commitment to an end of sources. It's a game of musical chairs.

The primary beef is that I can't edit nor can I place a POV tag. Another editor has blocked my ability to communicate with regards to this passage. The secondary beef is that the Chronic use subsection is original research in that he draws conclusions from studies that the original researchers would have never made. Meanwhile unsuspecting readers who may take this drug will read this convoluted passage with mention of "induced sensitation that persists longer then withdrawal-related effects" and be very confused and probably worried. I can't even give these readers a heads up that at least one editor doesn't agree with this passage. I have also even tried to add other chronic effects of chronic use to round off this subsection...so that it is more in tune with the major issues of this topic. Chronic use is not all about reverse tolerance...but again, every single entry that I have made has been deleted.--scuro 00:11, 3 August 2007 (UTC)

Well I did add a pov tag - and scuro, in all fairness both sides have made mistakes as I outlined above - konrad didn't assume good faith - but neither did you (you wouldn't read the sources because you automatically assumed they were wrong). Now I'm saying let's start over - which you start to do in the second IP. Now one issue (or more so point of note) is if there is a consensus that the statement is fine - then the pov tag shouldn't be there - even if you think the statement is bad, however right now there's seemingly no consensus - so I have added an appropriate tag - wouldn't you agree?--danielfolsom 00:24, 3 August 2007 (UTC)

I wouldn't call that a POV tag and this is clearly also a POV dispute in that we have original research that is neither minority or majority opinion. I have no problems in admitting that I made mistakes and I have no problem in starting over.

For the record here is what a third editor wrote about the original citation that KonradG provided, clearly he found fault with the passage and the conclusions drawn from the citation;

Here's a little detail that bothers me... Anybody here know of any adult male patient prescribed half a gram of d-amphetamine a day? Well folks, this is what Chaudhry, citation 12, uses to induce reverse tolerance, i.e., 6mg/kg/day. In those humans who'd survive (and those escaping madness), I suppose reverse tolerance might be an issue. Clearly this is not a clinical dose, hence not a valid clinical issue. The highest recommended dose levels of d-amphetamine in ADD at 1.0mg/kg (Joseph Biederman) while many physicians won't exceed 0.5mg/kg. These are TOTAL daily amounts given in divided doses (typically tid or in sustained released form) gradually increased from smaller doses. (I'll give citations if desired) Extrapolating from rats--and different rat species--can also be an issue. Further these lab researchers are frequently trying to produce "undesirable" effects to study. This is clearly antithetical to physicians who want to minimize adverse effects. Respectfully Konrad, I disagree with you. This "reverse tolerance" isn't appropriate under "Side effects of therapeutic use." Such sloppiness is typical of moralists invested in the fearmongering of antipsychiatry. For clarification of theraputic use vs abuse or non-theraputic use see: Biederman J, Spencer TJ, Wilens TE, Prince JB, Faraone SV. Treatment of ADHD with stimulant medications: response to Nissen perspective in The New England Journal of Medicine. J Am Acad Child Adolesc Psychiatry. 2006;45:817-823. http://www.massgeneral.org/pediatricpsych/docs/NEJMltr.pdf Romith 08:32, 13 April 2007 (UTC)

--scuro 00:38, 3 August 2007 (UTC)

The passage is also hard to understand. It needs to be written in plain English as noted in the Wikipedian tutorials. What exactly does this mean: "While continuous dosing with amphetamine causes tolerance, intermittent use produces "reverse tolerance" or sensitization to its psychological effects. As a result, regular use commonly results in a quick decrease of unwanted side effects, but without an equivalent loss of its stimulant properties. Notably, the sensitization is induced more quickly, and persists far longer than withdrawal-related effects, suggesting a phenomenon more complex than a simple tolerance-induced withdrawal syndrome". The passage needs context badly for any sort of meaningful understanding. It has been plunked down in the chronic abuse section with no other cues to ground the information. Here are some questions that would point to areas where clarity is needed.

-starting with the title, what is chronic use? Is taking your medication chronic use? Does he mean chronic drug abuse?

-does continuous dosing mean at a therapeutic level or drug abuse? What is continuous dosing in this context...do we have a time frame?

-what sort of Amphetamine does this passage make reference too? All Amphetamines? They do not all have the same properties.

-does the intermittent use effect require prior drug use?...or is it seen totally independently? Again, at what drug level?

-which psychological effects does this passage make reference too?...good therapeutic effects, bad side effects...or both?

-Now after reading in the prior sentence about "sensitization to effects with intermittent use", how do we get to the next sentence which states that regular use quickly gets us to a decrease of unwanted side effects?

If the passage was clarified and flushed out perhaps this would end the dispute. It's pointless to see answers in talk unless KonradG is willing to let other editors edit the passage based on the information given. Best is if the answers are reflected in a new edit that is written in a more encyclopedic style:, clear and to the point. It would also be good to see the whole section flushed out depending on what Konrad defines chronic as being...with the most noteworthy information coming first. I am going to be away for a week on vacation. Hopefully some progress will be made. --scuro 12:12, 3 August 2007 (UTC)

As a certified layman here, perhaps it would help if I stated my interpretations? That is to say, the answers to the above questions that I as a layman infer from the passage in question:

• Chronic use: habitual, daily--use that results in a continuous, or nearly continuous exposure--some amount bio-available within the body.
• Continuous Dosing: Abuse vs therapuetic use is irrelevant. What is relevant is the continuous use. To a certaint extent, dosage does matter, but different dosages will have different results on different people. I think the question you are really looking at is dose vs overdose, not abuse vs therapeutic. I am considering an overdose any amount that begins to have interfering side effects.

I think that by 'abuse' you may intend to mean toxic exposure, but I don't think that is what is being heard.

Time frame is generally long term, but seeking a more rigid or specific timetable, such as week by week--I don't think that is practicable. Metabolisms and response vary so much--but then, I am a layman.

• Amphetamine Type: I'm guessing Dextroamphetamine as that is the title of the section. Not intended to be snide. If there are multiple formulations that go by the name Dextroamphetamine that have significantly different behaviors, I am unaware of it.

• Intermittent Use: I would assume that this does not require "prior drug use"--I am assuming you are referring to the use or abuse of other potentially illicit substances. My basic assumption is that this information is valid for an adult who made it through life without exposure to any medicines--as a full history of exposure to potentially psychoactive substances just isn't reasonable.

However, I agree that "intermittent use" is not very clearly defined. Does this work for weekly use? Monthly? Bi-annual?

Assuming the view of Chronic I have presented, is intermittent than any regimen where the substance is completely flushed from the body before the next dosing, over and interval of time?

My assumption is that dosage is irrelevant to the discussion and that the effects occur at whatever level the initial dosage caused. This is to say, if you had slightly improved focus, but a bad headache, intermittent use at the same dosage would yield about the same level of improvement but less headache.

• Pysychological Effects: The article clearly states that the negative side effects are diminished without a decrease in the good effects. To me, this means that the improved cognition and attention remain while the insomnia, headache, etc, are reduced.

• That sticky Trasition: A very valid point. My idea of Chronic is the same as regular. So if Chronic use causes tolerance, how can regular use result in the effects of reverse tolerance.

So, I would be looking for three terms to be more explicitly clarified: Chronic, Intermittent, Regular.Skinart 22:24, 10 August 2007 (UTC)

keep your eye on the ball

I could easily get dragged down and respond to any number of Konrad's complaints... let me simply say that I don't agree with all that is stated. But I'll stop there.

We need to keep this very simple. We have a 3 sentence passage entitled chronic effects. This is the only point of disagreement. Either the passage is encyclopedic or it is not. Either the passage is well written and can stand as is or it could use improvement. I suggest we do this in a two step process. The first step would be to see if the passage can be improved upon. Here is the passage as it stands in the text.

While continuous dosing with amphetamine causes tolerance, intermittent use produces "reverse tolerance" or sensitization to its psychological effects. As a result, regular use commonly results in a quick decrease of unwanted side effects, but without an equivalent loss of its stimulant properties. Notably, the sensitization is induced more quickly, and persists far longer than withdrawal-related effects, suggesting a phenomenon more complex than a simple tolerance-induced withdrawal syndrome.

Here is an attempt at a rewrite using Skinart's recent interpretation and a little of my own interpretation of what is said.

Daily use of dextroamphetamine causes tolerance. Irregular use without prior use causes "reverse tolerance". Specifically, daily use will cause a decrease in the drugs positive effects over time and may cause withdrawal symptoms, on the other hand irregular use allows for maximum benefit of the stimulants good properties while causing few if any negative side effects. This complex positive interaction of the body with Dextroamphetamine is called "drug sensitization" or "reverse tolerance".

I simply tried to get the main ideas down in more logical and coherent way as a starting point to end this dispute. I am asking that other editors to comment on this rewrite. Have I missed something in stating it in a more simpler way? Have I changed the meaning? Lets work in consensus as is wanted by Wikipedia and make it a better passage.--scuro 22:41, 11 August 2007 (UTC)

The additional details you added above are not in the source material which the section cites. Where does it say anything about producing "few if any negative side effects"? Why do characterize it is a "positive interaction"? What data supports your conclusions about daily use? And why are you so determined to re-write this paragraph if you're not willing to do the background research? KonradG 17:07, 13 August 2007 (UTC)

When left to interpret the passage this is what I came up with. It's a draft of an interpretation of what I think you were trying to get at. The goal was to clarity the passage....wiki is encyclopedic after all. These are not my ideas but merely what I assumed you were trying to get at stated in a simpler and more logical way. Again, that doesn't mean that I agree with these ideas but we need a starting point so I thought I would move the process along. The edit was done in good faith. Best would be if you could rewrite the passage yourself in a clear and understandable manner. Really, perhaps your intended meaning is straightforward and that would solve this dispute. Could you rewrite it for added clarity? I've made points previously that you can reference where the passage is confusing, perhaps it simply needs some flushing out of detail.--scuro 18:29, 13 August 2007 (UTC)

You're asking for a level of precision that is not available yet. We know sensitization gets more noticeable when dosing is done in intermittent bursts rather than gradual changes (like what you'd get with a slow-release formulation), but it's hard to say more than that without getting into speculation. KonradG 17:20, 14 August 2007 (UTC)

I'm not asking for anything at the moment but for clarification of the passage which simply hasn't been done after multiple requests. I believe it to be confusing to the average reader. Every single edit of mine has been deleted so it's not worth the effort. I can live with the tag that is currently on the passage. Best would be to get this water under the bridge but if you are in no hurry it doesn't matter. If necessary at some point in the future another editor will tackle this and it can be resolved at that time.--scuro 19:16, 14 August 2007 (UTC)

Let's see, you deleted the entire section here, here and here. Then you tried to downplay it by changing it to something different than what the cited sources actually stated [4][5]. Mis-representing the cited claims is not "clarification" but simple dishonesty, especially when it turns out that you never read them. KonradG 01:49, 15 August 2007 (UTC)

I believe we were asked to start over. You seem to want to drag the past in every chance you get.

It's simple. Keep your eye on the ball. What is the problem? The problem is that the passage is confusing to the average reader. It doesn't really make sense when you look at it logically nor are the terms defined. Deal with these issues and we have something to talk about. Drag the past in and try to rekindle old conflicts with name calling and I'm outta here. I have really tried in total good faith. I can live with the stalemate.--scuro 03:31, 15 August 2007 (UTC)

User:Skinart, who calls himself a "certified layman", posted an accurate description above. He had no problems, except with the words chronic/intermittent/regular, which I agree are unclear. Let's say we replace all those with "intermittent use", and assume a time interval between doses that is roughly on the order of the half-life of the drug (or longer). Now can we get to the specific issue which concerns you, i.e. how that relates to therapeutic use? KonradG 17:26, 15 August 2007 (UTC)

I'm glad that the need for change to the text is finally realized. Please make the changes you suggested with regards to the text. There is more that could be done such as using plain english and flushing out details...but simply refining the information would be a significant start.--scuro 21:04, 15 August 2007 (UTC)

Let's just get to the point. You want that section state it only applies to drug abuse, correct? Do you acknowledge that I've provided several sources describing sensitization in humans? Two simple questions. KonradG 02:56, 16 August 2007 (UTC)

The main and only point right now is that the passage needs a revision. The ideas need to flow in a more logical way and they also need to be explained better with a lot more detail. People who read that passage are confused. Further communication is pointless until the passage gets a basic edit.--scuro 03:18, 16 August 2007 (UTC)

BE BOLD

WP:SOFIXIT Go ahead, tell me I am off my rocker, tell me that passage reads normal to you. Tell me it makes complete sense to you and Scuro, you have your knickers in a knot about this one. Don't be afraid...tell it as you see it.

As Wikipedia states: The Wikipedia community encourages users to be bold when updating articles. Wikis like ours develop faster when everybody helps to fix problems, correct grammar, add facts, make sure the wording is accurate, etc. We expect everyone to be bold. How many times have you read something and thought, "Why aren't these pages copy-edited?" Wikipedia not only allows you to add, revise, and edit the article — it wants you to do it. It does require some amount of politeness, but it works. You will see. Also, of course, others here will edit what you write. Do not take it personally. They, like all of us, just want to make Wikipedia as good as it can possibly be. Are we sheep? Change the passage if need be, tell me I am totally wrong...do whatever it takes to move this forward.--scuro 02:20, 14 August 2007 (UTC)

Let's try something different

I'm going to attempt to write the disputed paragraph in plain English. This is honestly the best interpretation I can come up with. If people point out where I'm wrong it may help us to re-phrase the paragraph so it is easily understood by everybody. It would also help if people can explain why it matters, because if it doesn't matter, it doesn't need to be here:

"If you take it all the time you'll get less benefit at the same dose, but if you take it some of the time you'll get greater benefit at the same dose. Therefore, if you take it regularly you get less of the side-effects but the same benefit. Interestingly, getting greater benefit at the same dose happens more quickly (and goes on for longer) than things to do with withdrawal, so maybe it's more complicated than just getting withdrawal symptoms because you've developed tolerance."

Scolaire 09:15, 16 August 2007 (UTC)

Yup, that's right. The reason it matters is that sensitization is a very unusual effect, and d-amphetamine is one of the drugs that's known to cause it. KonradG 11:56, 16 August 2007 (UTC)

Jadet46 01:48, 1 October 2007 (UTC)Jadet46 writes:(as I apologize for interupting) I AGREE! This is what happens to me. I actually have to go off my medication, sometimes for a week at a time in order for it to work its best. If I skip a day, the next dose works better than the last. If I take it regularly, the benefits lessen to almost nil. So, I have to rough it out and go off the medication in order for it to begin to work again. Yes this is important. It is important to get the most benefit at the lowest dose possible. If that means taking a day off or an afternoon in order not to have to put more chemicals in my body then it is worth it. Most of what I discover is by trial and error. It would be nice to have been able to read this information and try it right away instead of spending a couple of years of medicating to finally see a pattern. Also I am not a scientist, so I am always looking for a scientific explanation in order to completely understand what is going on. Jadet46 01:48, 1 October 2007 (UTC)Jade46

http://aolsearch.aol.com/aol/search?encquery=7c3e0fad5786d5d0c54da69e9e7146c4&invocationType=keyword_rollover&ie=UTF-8

You know we don't really need to personally explain why it matters. Do we need to go down the road of bias accusations? If reverse tolerance has either a positive or negative effect of significance you would think an institution like the NIMH or the Surgeon General would have already chimed in with their take on it. After all this would be a major concern for the millions of people who have a prescription to this drug. Previously I did take the time and looked thoroughly but couldn't find any solid secondary source which has discussed and clearly weighed in on this issue. Perhaps I missed something. If someone finds something we could simply cut and paste or paraphrase the appropriate passage. Otherwise we should consider the due weight policy. Are we taking note of an effect that may be real but is not understood properly and has little relevance to the article? Is this an effect only seen with drug addiction and should be explored in a stimulant drug addiction article?

Those are interesting questions but of more importance is any sort of forward progress on the subsection. As written it is hard to even discuss issues because it is not clear what the meaning is. Scolaire, your explanation also seems to contradict itself. How can you have the same benefit when "you take it some of the time" and "take it regularly"? Perhaps I have misunderstood that explanation. If so can you explain this further? Also I don't believe that any sort of drug tolerance behaviour has been established with dex at therapeutic levels. Therefore the explanation would have to be further qualified.--scuro 13:14, 16 August 2007 (UTC)

What I wrote was not an explanation, it was an attempt to translate the paragraph into plain English. If I got it right, and KonradG seems to think I did, then the paragraph makes no sense whatever. As Scuro says, it consistently contradicts itself, and it draws a conclusion about withdrawal based on statements about therapeutic effect. I was hoping that somebody would respond with an alternative version that actually said something meaningful, but if that isn't going to happen then this paragraph needs to be deleted, soonest. Scolaire 14:49, 16 August 2007 (UTC)

If you think it can be stated more simply, why not do so rather than deleting it? Note that the part about tolerance to side-effects was in there before I made any edits to the article, as seen here. Apart from that, everything in there comes straight from the cited sources. I wasn't drawing any conclusions about withdrawal, only summarizing what's in the ACNP review:

The mechanisms maintaining sensitization (to a subsequent stimulant challenge) over weeks and months after chronic intermittent administration are basically unknown. If one examines mechanisms prior to approximately 2–3 days after withdrawal, there is still a marked fluctuation of unstable, changing mechanisms. Since no mechanism associated with sensitization appears to be consistently maintained over the long course of sensitization, it is difficult to ascribe one specific mechanism to the expression of sensitization (223).

Tell me where you think I'm drawing my own conclusions, and I'll be happy to quote the relevant source. By the way, let me point out that the above quote is from a review article on this specific topic, from the Journal of The American College of Neuropsychopharmacology. Scuro just claimed that he "couldn't find any solid secondary source which has discussed and clearly weighed in on this issue", even though I've pointed that one out to him many times.

KonradG 17:24, 16 August 2007 (UTC)

If I thought it could be stated more simply, I would. But it doesn't actually make any sense. It is, literally, nonsense. Unless somebody can write something that does make sense, it must be deleted. What you have quoted above might mean something to a student of pharmacology. It means nothing to me. If it could be expressed in a way that is understandable to an average reader, fine. But what is there at the moment is both unreadable and nonsensical. I'm sorry, but that's the way it is. Scolaire 21:38, 16 August 2007 (UTC)

You know we can dance around in circles here in talk, endlessly...as has been done already. But lets actually get some forward progress with regards to the subsection. Lets change it for the better. It does contradict itself, it doesn't make sense. I don't think that is debatable. It needs a rewrite so that it can be understood by the lay reader. Great would be if Konrad did the rewrite. But while we are waiting lets take a baby step. Is the title "chronic use", a good title? Here is the word "chronic" as defined by webster's:"always present or encountered; especially : constantly vexing, weakening, or troubling". If this subsection has more to do with intermittent use why the title? Agree to change? Suggestions for a new title?

I did a check and there actually is a reverse tolerance wiki article. Much of this passage seems to be quoted directly from there. The corrections made here can be the basis of that article especially if reverse tolerance needs drug abuse to be present. If not we simply leave it in this article and decide the weight of the subsection at a later time. This way we are improving Wikipedia.--scuro 19:34, 16 August 2007 (UTC)

Jadet46 02:34, 1 October 2007 (UTC)Jadet46: Most of our knowledge of ADHD comes from studies over time. The scientific information on dextroamphetamines may be more solidly based, still some of the most important discoveries about a medication are by experimentation. We who take it are the 'lab rats.' If enough people write about their experience on the drug it will be better understood. I feel it is very important to know how to take a medication that may be in your life over a long period of time. Especially one that is addictive and could over time lose its effect and cause a person to need a higher dose to get the same benefit. If you can take less by not using it constantly but by taking it pretty regular with time off here and there and get the most benefit, and at the same time avoid a complete withdrawal, this is something very important to know. Many seem to be experiencing this same effect, building evidence that there is substance to this 'tolerance' idea. Therefore it is important to tell others what is known. In, of course, a much more scientific and intelligent way than I have explained so it looks good in Wikipedia. Jadet46

(If reverse tolerance has either a positive or negative effect of significance you would think an institution like the NIMH or the Surgeon General would have already chimed in with their take on it. After all this would be a major concern for the millions of people who have a prescription to this drug.)

Jadet46 01:48, 1 October 2007 (UTC)Jadet46: The above sentence was the one I was looking for. I believe this is a major concern maybe not to those whose pockets benefit from us taking every single pill. But it is a major concern for those of us who would like to take our meds and get the most benefit without taking more. I know there is information on this somewhere. I was in one of Dr. Biedermans studies. After the study, being told I had ADD, I looked into some of the medications. Dexadrine was the only one that didn't have a hair loss side-effect. Me having very long hair. I vaguely remember being told or reading somewhere, that I would develop a tolerance to this med and that I may need to go off of it a few days or week at a time. Not really paying attention then, but after a couple of years taking the med the information finally kicked in. If I had had a more complete explanation, from an encyclopedia explaining cause and effect I would have listened sooner and benefited sooner. I understand there needs to be sound evidence. Perhaps there has been a study on this that is evading everyone. You bookworms out there I have faith one of you will find this information.Jadet46 01:48, 1 October 2007 (UTC)Jadet46

some info

From http://www.nida.nih.gov/MeetSum/NS2000/Gatewayabs.html

Sensitization refers to the progressively enhanced behavioral and neural activation seen after repeated exposure to a single dose of a drug. The issue our participants will focus on is whether prior experience with one drug enhances the neural, behavioral, reinforcing or subjective characteristics of a second, different, drug (cross-sensitization).

Sensitization and cross-sensitization to neural, locomotor and other behavioral effects of stimulant drugs have been well documented in laboratory animals. However, evidence for sensitization to the effects of stimulants in humans is limited. Few controlled studies have examined the phenomenon in humans, in part because of practical and ethical concerns about administering drugs repeatedly to human volunteers. In addition, few studies have directly compared the effects of stimulants in experienced and inexperienced users. The limited evidence that is available suggests that some drug effects increase with repeated administration, while others decrease or remain unchanged. An important question is which, if any, of these effects is related to the etiology of drug abuse or dependence.

Now I am wondering if the passage as written is really about cross sensitization and simply cut and paste out of some article.--scuro 20:14, 16 August 2007 (UTC)

Worldwide View

Hi all, IMO, the History and Uses sections of this article are very US-specific. Perhaps the article needs that globalize/usa template on the top so other countries' editors feel inspired to contribute? Somno 07:51, 10 October 2007 (UTC)

article structure needs to follow Wiki policy

http://en.wikipedia.org/wiki/WP:MEDMOS#Drugs

   * History
   * Indications (available forms, if notable)
   * Contraindications
   * Adverse effects (including withdrawal)
   * Overdose (including toxicity)
   * Physical and chemical properties
   * Pharmacokinetics (absorption, distribution, metabolism and excretion)
   * Pharmacodynamics (mechanism of action)
   * Interactions
   * Legal status (including illicit use, off-label usage or unlicensed preparations if notable and sourced)
   * Veterinary use
   * References
   * External links (avoid if possible)

--scuro 12:37, 20 October 2007 (UTC)

Withdrawal

I decided to add a section on Withdrawal, open to further editing. I feel it is necessary due to various sources citing the dangers of abstaining from dextroamphetamine medications after long term use and the emphasis on dependancy. I added it as a heading but maybe it could be moved as a subheading under overdose or another appropriate heading. Any further information is welcome with citations. --TeChNoWC (talk) 13:52, 15 December 2007 (UTC)

I'll do a bit of digging here but from what I remember these issues are not as stark as they have been made out to be. Also this should be under the adverse effects as noted the article organization section above.--scuro (talk) 15:56, 15 December 2007 (UTC)

I've done some extra fiddling around but might need you to help me clarify appropriate sections and section names within the page, eg, how we would like to layout the available data so that it does match the proscribed layout. One pertaining question, for example, would be, does the Pharmacology section fit into 'physical and chemical properties?'. I would like a second opinion. re: my experience with the drug is that the given citations are correct, but its up to the research. --TeChNoWC (talk) 01:10, 16 December 2007 (UTC)

I'm on brain sleep mode so I'll get to your questions later in the week. One thing I will speak about now is confirming a viewpoint based on your own experiences. Wikipedia doesn't work that way. Basically it's all about what the trusted sources and experts say. We as editors have zero weight with regards to any issue. --scuro (talk) 03:18, 16 December 2007 (UTC)