43 replies to this topic

[chrono]

Thanks for that paper, Animal. They used 1.5mg/kg, which is well within the range of therapeutic dosing in human equivalence ( (about .24mg/kg FWIW). Your comparison to the MDMA literature may be an apt one, though in this case, it seems like there's essentially no quantitative human data demonstrating problems at 'therapauetic' levels, though I don't think there have been many intensive studies, either.

Amphetamine is something that is hard for many people to talk about objectively, for various reasons, but hopefully we can still do so without personal insults. I for one am very eager to examine the evidence either way, because like for many others, adderall is the most beneficial agent I've ever tried. Even if there is damage or drawbacks, it may still be an acceptable tradeoff, for some, or it may make sense for non-chronic usage. I think what's needed is more elucidation of mechanisms and levels, so the choice can be a more informed one.

Edited by chrono, 13 October 2010 - 11:39 PM.

[NR2(x)]

Amp does do extensive damage to dopamine neurons, down regulation is the dominant cause.


NR2(x), on 13 October 2010 - 04:15 PM, said:

The body achieves down regulation in many ways, loss of a significant fraction of said neurons is obviously damage to those said neurons

Sorry my language was very poor. I should have said that negative feed back processes to AMP are responisble for the loss of Dopaminerginic neurons. Thanks Crono

. I'd like to see some evidence that the brain "downregulates" by killing off significant parts of its own neurological systems, because it would have implications for literally everything we discuss here.

This is the precise role of extrasynatpic NMDAR's amoung other signal transduction pathways. Extrasynaptic NMDArs decrease metabolic output, increase apopotsis, decrease survival gene expression, decrease neurotransmission etc, furthermore it is the dominant cause of all neurodegeneration. The body has evolved these receptors to actually achieve this end. Theres alot more, not in the mood to thread together lots of dissperate parts.

Animal, I would question your asserstion that amphetamine is general bad for the brain. We know that there are strong positive acute effects, does this translate into long term gains. I understand that medicating ADHD leads to higher IQ's. Oh well have to go look for some science..
I underrstand that you take Burpionin and Modafinil, these drugs have almost an identical MOA

Edited by chrono, 14 October 2010 - 07:06 AM.

[Ark]

Amp does do extensive damage to dopamine neurons, down regulation is the dominant cause.


NR2(x), on 13 October 2010 - 04:15 PM, said:

The body achieves down regulation in many ways, loss of a significant fraction of said neurons is obviously damage to those said neurons

Sorry my language was very poor. I should have said that negative feed back processes to AMP are responisble for the loss of Dopaminerginic neurons. Thanks Crono

. I'd like to see some evidence that the brain "downregulates" by killing off significant parts of its own neurological systems, because it would have implications for literally everything we discuss here.

This is the precise role of extrasynatpic NMDAR's amoung other signal transduction pathways. Extrasynaptic NMDArs decrease metabolic output, increase apopotsis, decrease survival gene expression, decrease neurotransmission etc, furthermore it is the dominant cause of all neurodegeneration. The body has evolved these receptors to actually achieve this end. Theres alot more, not in the mood to thread together lots of dissperate parts.

Animal, I would question your asserstion that amphetamine is general bad for the brain. We know that there are strong positive acute effects, does this translate into long term gains. I understand that medicating ADHD leads to higher IQ's. Oh well have to go look for some science..
I underrstand that you take Burpionin and Modafinil, these drugs have almost an identical MOA

Your assuming that there is a direct correlation to overall learned IQ and brain health, I think you can become very smart, even with a half rotted brain.
You can learn and your brain will continue to rewire just re-circuiting other non essential higher functions. You can become the smartest man in the world but if lose the ability to enjoy it, its not worth much.

Edited by Ark, 14 October 2010 - 05:00 AM.

[bobman]

There is so much evidence for the detrimental effects of amphetamine administration over an extended time period I don't know why anyone is trying to argue the opposite; unless of course it's just to reassure themselves about their amphetamine habits.

Chronic amphetamine treatment reduces NGF and BDNF in the rat brain

Francesco Angelucciab, Susanne H.M. Grubera, Aram El Khourya, Pietro Attilio Tonalib, Aleksander A. MathéaCorresponding Author Informationemail address

Received 3 January 2007; received in revised form 19 February 2007; accepted 6 March 2007.
Abstract

Amphetamines (methamphetamine and d-amphetamine) are dopaminergic and noradrenergic agonists and are highly addictive drugs with neurotoxic effect on the brain. In human subjects, it has also been observed that amphetamine causes psychosis resembling positive symptoms of schizophrenia. Neurotrophins are molecules involved in neuronal survival and plasticity and protect neurons against (BDNF) are the most abundant neurotrophins in the central nervous system (CNS) and are important survival factors for cholinergic and dopaminergic neurons. Interestingly, it has been proposed that deficits in the production or utilization of neurotrophins participate in the pathogenesis of schizophrenia. In this study in order to investigate the mechanism of amphetamine-induced neurotoxicity and further elucidate the role of neurotrophins in the pathogenesis of schizophrenia we administered intraperitoneally d-amphetamine for 8 days to rats and measured the levels of neurotrophins NGF and BDNF in selected brain regions by ELISA. Amphetamine reduced NGF levels in the hippocampus, occipital cortex and hypothalamus and of BDNF in the occipital cortex and hypothalamus. Thus the present data indicate that chronic amphetamine can reduce the levels of NGF and BDNF in selected brain regions. This reduction may account for some of the effects of amphetamine in the CNS neurons and provides evidences for the role of neurotrophins in schizophrenia.

I wouldn't even need to see studies to confirm it's negative effects, it's observed all the time anecdotally in chronic users as their cognition deteriorates. It's the same as the MDMA studies which seem to indicate minimal damage. When only specific neurological structures are focused on, it can be difficult to ascertain the actual extent of the detrimental effects on the individual as a whole. But when you speak to the majority of long term chronic users of amphetamines or MDMA they will confirm the gradual decline in cognition/personality/mood that they have experienced. I mean we get enough individuals on this site looking for a solution to their drug induced deficits, whether there is clinical evidence to support it or not.

Medievil, you can't even claim to maintain only therapeutic doses of amphetamines either, probably like the majority of ADD addicts. It's a substance that is often abused by individuals who are prescribed it, simply because of the dopaminergic nature of its effects. So lets not keep using the 'therapeutic doses' excuse to try and pretend that it's a perfectly healthy drug to be hooked on for life.


Also the person who said:

I don't see how amphetamine use in your 50's is "completely" different than its use in your teens

Is obviously a bit ignorant if they can't see the difference between a 60 year old man who becomes an addict and dies 20 years later, suffering from mental decline which can arguably be attributed to his age; and a 12 year old child addict who uses amphetamines daily for 40 years and suffers the cognitive consequences of this in his 50's. Of course the fact that the child's brain is still developing is a major factor also.

That was me, thanks for the rude comment. Yes a developing brain could experience a greater negative impact, but that's not something as apparent as you'd think, take a look at tbi, and nothing says the kid has to use the amphetamines for 40 years at abusive doses. In any case you'd first need to show that amphetamines cause cognitive decline at therapeutic doses.

[medievil]

I wouldn't even need to see studies to confirm it's negative effects, it's observed all the time anecdotally in chronic users as their cognition deteriorates. It's the same as the MDMA studies which seem to indicate minimal damage. When only specific neurological structures are focused on, it can be difficult to ascertain the actual extent of the detrimental effects on the individual as a whole. But when you speak to the majority of long term chronic users of amphetamines or MDMA they will confirm the gradual decline in cognition/personality/mood that they have experienced. I mean we get enough individuals on this site looking for a solution to their drug induced deficits, whether there is clinical evidence to support it or not.

Medievil, you can't even claim to maintain only therapeutic doses of amphetamines either, probably like the majority of ADD addicts. It's a substance that is often abused by individuals who are prescribed it, simply because of the dopaminergic nature of its effects. So lets not keep using the 'therapeutic doses' excuse to try and pretend that it's a perfectly healthy drug to be hooked on for life.

Well, i know several ppl on amp and havent seen their cognition detoriating...

I mean we get enough individuals on this site looking for a solution to their drug induced deficits, whether there is clinical evidence to support it or not.

Sure but lets look at how many people take MDMA, that there are soo many harmedn on this site can indicate something or can mean shit, therefor the study's are better to look that.

Me claiming i stay with therapeutic doses? No my friend when ive had amp the bast couple occusions my addictive personality takes over wich is no solution for anything, hence i started AMT and a bunch of other stuff to fix me up, and keep me away from abusing the stuff, but you cant compare every person that takes amp therapeutically with men, most just take it as prescribed

[medievil]

Even if there is damage or drawbacks, it may still be an acceptable tradeoff, for some

Exactly, there's no way i can fix up my anxiety without AMP or AMT, its either that or living a non happe life.

[medievil]

Chronic amphetamine treatment reduces NGF and BDNF in the rat brain

Francesco Angelucciab, Susanne H.M. Grubera, Aram El Khourya, Pietro Attilio Tonalib, Aleksander A. MathéaCorresponding Author Informationemail address

Received 3 January 2007; received in revised form 19 February 2007; accepted 6 March 2007.
Abstract

Amphetamines (methamphetamine and d-amphetamine) are dopaminergic and noradrenergic agonists and are highly addictive drugs with neurotoxic effect on the brain. In human subjects, it has also been observed that amphetamine causes psychosis resembling positive symptoms of schizophrenia. Neurotrophins are molecules involved in neuronal survival and plasticity and protect neurons against (BDNF) are the most abundant neurotrophins in the central nervous system (CNS) and are important survival factors for cholinergic and dopaminergic neurons. Interestingly, it has been proposed that deficits in the production or utilization of neurotrophins participate in the pathogenesis of schizophrenia. In this study in order to investigate the mechanism of amphetamine-induced neurotoxicity and further elucidate the role of neurotrophins in the pathogenesis of schizophrenia we administered intraperitoneally d-amphetamine for 8 days to rats and measured the levels of neurotrophins NGF and BDNF in selected brain regions by ELISA. Amphetamine reduced NGF levels in the hippocampus, occipital cortex and hypothalamus and of BDNF in the occipital cortex and hypothalamus. Thus the present data indicate that chronic amphetamine can reduce the levels of NGF and BDNF in selected brain regions. This reduction may account for some of the effects of amphetamine in the CNS neurons and provides evidences for the role of neurotrophins in schizophrenia.

Shit! it reduces BDNF.

Neurosci Lett. 2005 Nov 11;388(2):112-5.
High concentrations of plasma brain-derived neurotrophic factor in methamphetamine users.
Kim DJ, Roh S, Kim Y, Yoon SJ, Lee HK, Han CS, Kim YK.

Department of Psychiatry, College of Medicine, Korea University Ansan Hospital, Kyunggi Province, Seoul, Korea.
Abstract
Methamphetamine is a highly addictive drug that has a neurotoxic effect on the brain. A growing body of evidence suggests that brain-derived neurotrophic factor (BDNF) is associated with addictive behavior. The present study investigated the changes in plasma BDNF concentration that were induced by chronic methamphetamine use. Using an enzyme-linked immunosorbent assay (ELISA), we measured peripheral BDNF levels in methamphetamine users and in a control group. The plasma BDNF concentrations of methamphetamine users were significantly higher compared with those of controls (2536.3 pg/ml versus 1352.6 pg/ml). This finding suggests that BDNF plays some role in the neurotoxicity of methamphetamine.

Wait, all on meth, it increases BDNF, problem solved!


Wait what?

Or should we look further then just BDNF?

Hmm more BDNF?

Brain Res. 2002 Sep 13;949(1-2):218-27.
Brain-derived neurotrophic factor expression is increased in the rat amygdala, piriform cortex and hypothalamus following repeated amphetamine administration.
Meredith GE, Callen S, Scheuer DA.

Department of Basic Medical Science, University of Missouri-Kansas City, School of Medicine, 2411 Holmes Rd., Kansas City, MO 64108, USA. gloria.meredith@finchcms.edu
Abstract
The amygdala plays an important role in the regulation of motivational states, especially those associated with addiction. The amygdala also expresses high levels of brain-derived neurotrophic factor (BDNF), an activity-dependent neurotrophin that can influence the reinforcing and locomotor activating properties of psychostimulants. In the present study, we examined the effects of acute and repeated amphetamine administration on the expression and production of this factor in the forebrain of rats. Animals given a single, acute injection (5 mg/kg, i.p.) of D-amphetamine developed hyperactivity followed by stereotypical behavior but showed no change in the basal expression of BDNF mRNA or its immunocytochemical profile in any region except the piriform cortex. Repeated injections (5 days) of 5 mg/kg amphetamine were accompanied by an enhanced onset of stereotypical behavior and elevated BDNF mRNA in the basolateral amygdala, rostral piriform cortex and paraventricular nucleus of the hypothalamus. Repeated treatment also increased BDNF immunoreactivity in perikarya of these same regions. In addition, increased BDNF immunoreactivity was found in fibers of many projection targets of the basolateral amygdala--the central extended amygdala, olfactory tubercle, medial nucleus accumbens, and in small zones resembling striosomes in the dorsal medial striatum. These results suggest that the upregulation of BDNF expression and protein in the basolateral nucleus of the amygdala and its targets could be an important part of the neuroadaptive response to psychostimulants.

Copyright 2002 Elsevier Science B.V.

Edited by medievil, 21 October 2010 - 02:14 PM.

[Animal]

I underrstand that you take Burpionin and Modafinil, these drugs have almost an identical MOA

No they don't you spaz.

[jadamgo]

K, it wouldn't take much for me to believe that someone prescribed amphetamine who abuses it, even while complying with a doctor's orders, would have troubles after a few decades. I mean, really, you can't take psychoactive doses of amphetamine EVERY DAY for 50 years and not have some negative effects from it, at least if you have to withdraw. (Though I don't know whether or not the positive effects of having treated the ADHD for that many years outweigh the negatives.)

But... what about people whose consumption of amphetamine cannot POSSIBLY be called addiction?

Now, at this point, because it's turned into one of THOSE conversations, I'll need to point out that I do not use amphetamine. I've consumed amphetamine 4 times in my life and I didn't like any of them because I found it very dysphoric. But I understand that many people have the opposite reaction.

Back to the subject. What about people who take it because they need it to function, even though they don't like it that much? What about people who, despite suggestions from their physicians and from big pharma, take a medication holiday every weekend, and any other time they aren't at work (or school)? (That would include, for example, any vacation time when ADHD symptom control is not essential.) What are the risks of that usage pattern of amphetamine?

Edited by jadamgo, 21 October 2010 - 11:02 PM.

[Recovery]

Hello Guys,

I got my adhd diagnosed in July. After roughly three months of treatment, all I can say is that I would very much prefer to live only ten years under medication than forty years in an unmedicated state. Not that I'm in a hurry to die, but before I was given Concerta my life was basically misery. So for me, there is not argument whasoever about taking or not taking methylphenidate. The changes are dramatic. That med gives more than I can describe in a few lines. In addition, as it was mentionned earlier, when your adhd isn't treated you usually get addicted a way or another. I was carb addicted and got prediabete from it....It's pretty dangerous too, isn't it ? Anyway, as I said, for me life without these meds isn't life, so I'll take them gratefully of course.

In addition, methylphenidate might actually protect ADHDers from further degenerescence.

Edited by Recovery, 23 October 2010 - 09:46 AM.

[VoidPointer]

Hello Guys,

I got my adhd diagnosed in July. After roughly three months of treatment, all I can say is that I would very much prefer to live only ten years under medication than forty years in an unmedicated state. Not that I'm in a hurry to die, but before I was given Concerta my life was basically misery. So for me, there is not argument whasoever about taking or not taking methylphenidate. The changes are dramatic. That med gives more than I can describe in a few lines. In addition, as it was mentionned earlier, when your adhd isn't treated you usually get addicted a way or another. I was carb addicted and got prediabete from it....It's pretty dangerous too, isn't it ? Anyway, as I said, for me life without these meds isn't life, so I'll take them gratefully of course.

In addition, methylphenidate might actually protect ADHDers from further degenerescence.

The debate here is more about the long terms effects of the amphetamine ADD meds(Adderall, Dexedrine, etc). MPH works in a different way, and is viewed as less damaging to the brain.

One thing to keep in mind with Concerta (or really any stimulant) is that the body/brain over time does develop tolerance to the medication. The only way to avoid this tolerance is to take regular breaks from the meds when possible. Also exercise(on the days off) has helped me quite a bit.
I started off on Concerta, then later changed to Focalin (a newer single isomer version of methylphenidate). This med is even more effective for the inattentive symptoms of ADD. Not sure if it is available in France though.

[kikai93]

It never ceases to amaze me, these depths that some will plumb to feel secure in their addictions. More amazing is the evangelizing of addictions to others.

Adderall is more likely to have side effects than Dexedrine, the reason being the 4 amphetamine salts in Adderall having variable effects. The idea behind Adderall is to create a stim that doesn't carry the side effect baggage of euphoria, thus it includes levoamphetamine etc.
The problem with this is that the various salts all react differently in different biochemical environments and produce side effects by single administration as well as by concurrent administration. Adderall is more likely to produce cardiac events and strokes for instance. Dexedrine is more likely to produce (oh noes!) euphoria and co-morbid addictive syndromes. The facts are, all amphetamines are detrimental to cognitive processes, particularly those centered in the limbic system (emotional lability and paranoia for instance) over time. You can wait for the studies which aren't funded, or you can simply observe users. I think during the course of my life I've observed about 4000 AMP, DEX, and/or MPH users/abusers. Granted for some time I was in the field of clinical psychology, so perhaps I saw many of the worst affected. Nonetheless, I have never seen a long-term user of any of these agents who was 1) Unwilling to lie about effects to continue administration 2) Unaffected in the sense of vigilance (short term) or paranoia (long term) 3) Not negatively affected (when testable) in terms of raw cognition, problem solving, appropriate response, or general affect.

It is also interesting to note that only 3.5% of dextroamphetamine users and only 1% of methamphetamine users manage a full recovery. (meaning they stop using and stick to it)

If these drugs are the only thing that worked for you (you tried it all, and this is it) then far be it from me to rain on your parade.
If you haven't tried alternatives, and especially if you're young and can afford the time, quit, come down return to baseline.
Try meditation, concentration exercises, dual n back etc.
Try various non-toxic nootropic combinations (I posted my own version on another thread).
Try exercising daily in addition to or instead of all of the above.

Why? Because amphetamine and it's various analogues are demonstrably dangerous, and not necessarily therapeutic.
Besides, if you've ever chased the euphoria, you're a horrible candidate for lifetime therapeutic dosing.

[VoidPointer]

It never ceases to amaze me, these depths that some will plumb to feel secure in their addictions. More amazing is the evangelizing of addictions to others.

Adderall is more likely to have side effects than Dexedrine, the reason being the 4 amphetamine salts in Adderall having variable effects. The idea behind Adderall is to create a stim that doesn't carry the side effect baggage of euphoria, thus it includes levoamphetamine etc.
The problem with this is that the various salts all react differently in different biochemical environments and produce side effects by single administration as well as by concurrent administration. Adderall is more likely to produce cardiac events and strokes for instance. Dexedrine is more likely to produce (oh noes!) euphoria and co-morbid addictive syndromes. The facts are, all amphetamines are detrimental to cognitive processes, particularly those centered in the limbic system (emotional lability and paranoia for instance) over time. You can wait for the studies which aren't funded, or you can simply observe users. I think during the course of my life I've observed about 4000 AMP, DEX, and/or MPH users/abusers. Granted for some time I was in the field of clinical psychology, so perhaps I saw many of the worst affected. Nonetheless, I have never seen a long-term user of any of these agents who was 1) Unwilling to lie about effects to continue administration 2) Unaffected in the sense of vigilance (short term) or paranoia (long term) 3) Not negatively affected (when testable) in terms of raw cognition, problem solving, appropriate response, or general affect.

It is also interesting to note that only 3.5% of dextroamphetamine users and only 1% of methamphetamine users manage a full recovery. (meaning they stop using and stick to it)

If these drugs are the only thing that worked for you (you tried it all, and this is it) then far be it from me to rain on your parade.
If you haven't tried alternatives, and especially if you're young and can afford the time, quit, come down return to baseline.
Try meditation, concentration exercises, dual n back etc.
Try various non-toxic nootropic combinations (I posted my own version on another thread).
Try exercising daily in addition to or instead of all of the above.

Why? Because amphetamine and it's various analogues are demonstrably dangerous, and not necessarily therapeutic.
Besides, if you've ever chased the euphoria, you're a horrible candidate for lifetime therapeutic dosing.

Many big statements with no proof. To suggest that all who take stimulant medications are 'addicted' is inaccurate.They are prescribed by a MD after all. Over time most patients either stop taking the meds, or(if they are inclined towards addiction) move on to other drugs.
If an individual is merely after a 'high' they would not take stims, rather they would move on to Meth(which is about 6X stronger than moderate dose Adderall) or some other class of drug.

psychiatrist.knowledge > your.knowledge

Not negatively affected (when testable) in terms of raw cognition, problem solving, appropriate response, or general affect.

Really? back that up with human studies..
If you want to test your cognitive abilities against a long time user of MPH, I will rise to the challenge. With or without meds..

http://www.ncbi.nlm....pubmed/15965546

'Children receiving medications had significant increases in IQ scores, but no changes were found for those not taking medications'


I do agree that AMP is overprescribed and many may 'like' the euphoria, but these drugs do work in controlling ADD symptoms more effectively than any other known combination of 'safe' nootropics.

Statistically stims(when taken as prescribed) are less dangerous than driving in a car, taking aspirin, or drinking alcohol. And Dexedrine has been around longer than you have been alive, they still give it to US fighter pilots after all.


http://www.ncbi.nlm....pubmed/16035144

http://www.ncbi.nlm....pubmed/18381904

http://www.ncbi.nlm....pubmed/18685149

http://www.ncbi.nlm....pubmed/18204348

http://www.ncbi.nlm....pubmed/17572789

http://www.ncbi.nlm....pubmed/17343552

http://www.ncbi.nlm....pubmed/17169593

http://jpet.aspetjou...304/3/1181.full


Disclaimer: I do not take AMP, but if a MD decides that is what is needed to treat a patient, that is their business. I would rather see a ADD patient on Adderall, than have that same unmedicated individual driving around endangering others.
Like I have said before, these drugs can be dangerous, but for most legitimate patients the rewards outweigh the risks.

Ok, I am done 'evangelizing my addiction'.. Have a nice day..

Edited by VoidPointer, 01 November 2010 - 01:05 AM.

[medievil]

Really? back that up with human studies..

Youll need a ton of patience before those appear lol, atleast i even doubt they would ever apear, so no need for waiting, even better!

Edited by medievil, 01 November 2010 - 02:10 AM.