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long-term effects of adderall?


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#1 dprice218

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Posted 04 May 2007 - 01:07 AM


Heya folks,


Before beginning, I'll briefly introduce myself. I'm a 22 year old male college senior studying philosophy and cognitive science. I stumbled across this site a few weeks ago and have spent a lot of time looking at some of the discussions involving modafinil as well as other nootropics. Anyway, thanks for all the input, it's really nice to be able to get this information in one place.

I was "diagnosed" with ADHD when I was 14. Originally I was prescribed ritalin but then went on to adderall and eventually to adderall XR. Overall, I would consider myself in very good health. I have about 8% body fat and yield consistently great cholesterol levels. Blood pressure is usually a bit high, but I tend to drink a lot of coffee, in addition to the adderall. I've been fairly consistent about working out at least 2-3 times per week. This mostly includes weight training and some light cardio. At one point I was benching almost twice my weight. Anyway, enough about my general health.

I've been on adderall xr since 10th grade I think, so that would be 5-6 years of adderall use. Dosages ranged from 20-40mg per day. I want to make clear that I don't use the drug recreationally, but I do use it (by and large) every day. I've never snorted it, but I have used it to stay up all night to write papers and so forth (though never more than the total dose I was alloted in a given 24 hour period) I'm very competitive when it comes to grades and academic performance, and unfortunately I think the adderall compliments that disposition. Being a philosophy major requires a sort of thinking that I think adderall satisfies very well. I set very high standards for myself in my papers and presentations, all of which are very critical in nature (I'm thinking to think that learning philosophy amounts to learning how to be the best sort of argumentative). It's come to the point where it's very difficult to be able to do school work without it.

Anyway, there have been several occassions over the past few years where I've completely stopped use for 2-3 weeks. I notice during these times that the first 2-3 days after stopping I'm extremely tired. I'm fairly certain that my prolonged adderall use, despite the fact that I've used it "as prescribed", has caused significant if not unalterable changes to my sleep cycle.

Anyway, I just got done reading the post about "meth and the brain". Obviously, the brains of those individuals who abuse meth are probably leagues more "damaged" than mine is. But I began to think: seeing as how adderall (being composed of two amphetamine salts) is rather chemically similar to meth, then what exactly is the difference in terms of their respective neurotoxicity effects? Wouldn't prolonged use of adderall, even if it were mostly consistend with prescribed dosages, cause a similar (albeit relatively lessened) version of the sort of neurological damage present in meth users? I can't really find much in the way of long term studies of people who use adderall as directed.

Also, assuming there is damage to the dopamine (DA) systems of the brain with prolonged adderall use, is this damage irreversible in the same sense that meth (ab)use is irreversible (or at least looking like its irreversible, depending on the system of the brain you're talking about)?


I recently started modafinil and like it. I'm thinking of just switching to modafinil eventually because honestly prolonged adderall use really scares me. I have not been able to really stop for long periods of time because (as I mentioned) of my sense of obligation to perform as well as I can in school (maintaining a 3.85 gpa in my philosophy major, 3.6 overall, doing research in visual attention, and writing a senior thesis on intentionality....it's already 50 pages).

What can you people tell me about the questions I asked? I realize there's a difference between prolonged adderall (prescribed) use and prolonged methamphetamine abuse, but the differences (in my mind) may be more in the realm of "matters of degree" and not necessarily of a different type or quality. That kind of scares me, unless someone can point me in another direction.
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#2 Futurist1000

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Posted 04 May 2007 - 01:50 AM

I would not worry about the neurotoxicity too much. Amphetamine has been prescribed for over 50 years with little indication of causing many long term neurological problems. A lot of studies on animals are not valid in humans. For one thing humans have higher levels of antioxidant defenses in their neurons than shorter lived species. Amphetamine does probably lead to higher levels of hydrogen peroxide which could generate the dangerous hydroxyl free radical. It might be prudent to take an antioxidant. I've seen some good things about selenium reducing methamphetamine neurotoxicity. I think one of the main things that amphetamine would do is downregulate your dopamine/norepinephrine receptors and possibly transporters. This however is homeostasis not neurotoxicity. Your brain tries to adjust to too much activity by downregulation. So when you aren't taking the drug you would have less activity at those receptors and this could lead to fatigue, depression, anhedonia etc. Eventually however after abstaining from the drug your brain should re-upregulate those receptors but it could take a long time. I myself take adderall and also supplement with selenium just in case. I would definitely recommend against over-heating (i.e. too much exercise) because it might reduce the ability of your antioxidant defense system to work.
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#3 oregon

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Posted 04 May 2007 - 03:50 AM

Take a look at this:
http://groups.google...cde898fd3ba8b30
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#4 dprice218

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Posted 04 May 2007 - 05:40 AM

Awesome man thanks for the information.

Also, was just talking to my friend who is a chemistry major. He said that the chemical distinction between methamphetamine and just regular adderall is more significant than one would think: adding a methyl group can have emergent effects, even though it sounds very insignificant.
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#5 dprice218

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Posted 04 May 2007 - 05:47 AM

Take a look at this:
http://groups.google...cde898fd3ba8b30


Hmm, that's not a very pleasant story. However, I might add that I have not had symptoms anywhere to anywhere near the extent of this person. It seems like he was particularly sensitive to the effects of the drug, and as a few responders pointed out, several aspects of his story seem fishy.

I'm thinking that at some point though I should get a PET scan or a functional MRI to make sure I'm deficit-free.
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#6 dprice218

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Posted 04 May 2007 - 05:53 AM

I myself take adderall and also supplement with selenium just in case.  I would definitely recommend against over-heating (i.e. too much exercise) because it might reduce the ability of your antioxidant defense system to work.


Yeah, I'm definitely aware of the downregulation of the DA and NE receptors. And for those cases in which I did stop for a couple of weeks, I noticed that even after a week of abstinence I regained some functionality, at the least I wasn't feeling sleepy all the time. As far as selenium, I'll have to get on that. I noticed that when I was taking a "homeopathetic" treatment for ADHD (called Attend)--which contained a number of nootropics discussed frequently in these forums--adderall seemed to have less side effects (like the come-down effect. At the least I fairly regularly take Fish Oil and a multi-vitamin. I also take creatine off and on. I really notice a difference when I do these things vs. when I don't.
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#7 mike250

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Posted 04 May 2007 - 06:07 AM

do you have any studies on the creatine dprice218
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#8 dprice218

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Posted 04 May 2007 - 06:13 AM

do you have any studies on the creatine dprice218


Well, I've certainly read some literature on it. This website has a nice summary of research related to creatine, but its mostly with respect to its anaerobic performance-boosting properties.

Creatine Supplementation


I do remember reading somewhere about creatine's potential neuroprotective properties. I'm sure that sort of claim is not nearly as well-founded, though.
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#9 oregon

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Posted 04 May 2007 - 08:26 AM

Take a look at this:
http://groups.google...cde898fd3ba8b30

several aspects of his story seem fishy.

Adderall has been linked to severe heart problems, psychosis, and stroke:
http://www.rxlist.co...c/amphet_ad.htm

Adderall is banned in Canada after 20 sudden deaths:
http://www.druginjur...lth-Canada.html

Edited by oregon, 04 May 2007 - 09:06 AM.

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#10 dprice218

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Posted 04 May 2007 - 03:05 PM

Take a look at this:
http://groups.google...cde898fd3ba8b30

several aspects of his story seem fishy.

Adderall has been linked to severe heart problems, psychosis, and stroke:
http://www.rxlist.co...c/amphet_ad.htm

Adderall is banned in Canada after 20 sudden deaths:
http://www.druginjur...lth-Canada.html


Yeah, I'm familiar with those reports. It should be noted that those cases are described in somewhat underdetermined ways: i.e. it is not acknowledged the extent of the relationship between cardiac abnormalities and those users of adderall who experienced the heart failures. Also, canada recently re-established the medical use of adderall and adderall xr. I've read several studies which showed that adderall use of up to two years was safe so long as certain medical precautions were put into practice, in particular measuring blood pressure regularly and other tests to determine whether or not cardiac abnormalities are present.

The thing I'm really wondering about is use of MORE than 2 years. There is literally nothing on that. And again, I'd like to gain some insight with respect to the relationship between the neurotoxicity of prescribed adderall use and methamphetamine abuse. I can't find anything on that either.
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#11 rfarris

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Posted 04 May 2007 - 04:21 PM

I took dexedrine for a couple of years and eventually ended up having a cerebral hemorrhage. I wouldn't recommend it.
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#12 ora101

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Posted 08 May 2007 - 02:29 AM

From what I can understand, Meth is signifantly more dangerous on account of its effect on 5HT neurons, whereas Adderall is purely DA and NE stimulating.

Edit: also, I've found taking ALA concurrently is helpful in reducing the pronounced side effects, as well as the weird brain-cloudiness I sometimes experience. It makes the Adderall feel "cleaner" if that makes any sense.
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#13 dprice218

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Posted 08 May 2007 - 10:07 PM

From what I can understand, Meth is signifantly more dangerous on account of its effect on 5HT neurons, whereas Adderall is purely DA and NE stimulating.

Edit: also, I've found taking ALA concurrently is helpful in reducing the pronounced side effects, as well as the weird brain-cloudiness I sometimes experience.  It makes the Adderall feel "cleaner" if that makes any sense.


What's ALA?


Thanks for the info!
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#14 oregon

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Posted 09 May 2007 - 04:08 AM

What's ALA?

Alpha Lipoic Acid
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#15 fast turtle

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Posted 10 May 2007 - 11:50 PM

"Amphetamine treatment similar to that used in the treatment of adult attention-deficit/hyperactivity disorder damages dopaminergic nerve endings in the striatum of adult nonhuman primates."
http://www.ncbi.nlm....4752&query_hl=1

Though, methamphetamine is about 5 times as neurotoxic as amphetamine is. But anyway..

You can probably cut down on neurotoxicity with doses of ALA, inosine, or idebenone, since the damage is mostly oxidative in nature.. It's still a pretty crude and old medication, though, you're better off with methylphenidate, or nothing.

I'm sorry to hear that you've been on these medications for such a long time. It is strongly my belief that those with still actively developing brains not be exposed to any strongly active drugs. I wouldn't be surprised if we end up with some fucked up adults in 10-20 years.
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#16 graatch

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Posted 14 May 2007 - 08:49 PM

Complex issue. Many conflicting viewpoints. Turtle, Frangible in particular on the M&M boards takes issue with that abstract, and I often challenge him on it as I have greater worries than he.

However:
1) Humans differ from primates at primary amine receptors, which is what amphetamines target.
2) With 50+ years of widespread, longterm prescription of amphetamine, you'd think the in-vivo evidence would be compelling.

(Frangible does claim extensive research in this area to be done, above and beyond two years of clinical use I think? SPECT-scans, performance testing, cadaver examination, etc. I'd check the abstracts yourself, I'm too fucking ADD)

3) I am not convinced the measure used in the study (disappearance of dopamine transporters) is an accurate sign of neurotoxicity. This could (and likely does IMO) reflect neuroplastic changes following amphetamine administration, and interestingly enough, ADD-type brains could probably benefit from a loss of DAT, as DAT in ADD-manifesting individuals has been shown to be elevated up to average 70% from non-ADD controls; and the DAT is what is blocked by drugs such as cocaine and methylphenidate -- it removes dopamine from process.
4) As my friend pointed out to me, the abstract is already suspect coming out of one doktor Ricaurte's lab.

... anyone remember, Ricaurte of the famous MDMA neurotoxicity study? Irresponsible DEA shill? ;)

There is considerable evidence of permanent methamphetamine neurotoxicity at very high doses of the drug over extended periods in long-term abusers. These seem to be ridiculous amounts compared to typical use, maybe some thousands of mg of methamphetamine daily over an extended period of time. Then again, tolerance builds rapidly to methamphetamine use and the high-dose meth abuser may be getting the same effect from these doses as she once got from much milder doses.

methylphenidate: Interestingly, most of the abstracts that show methamphetamine neurotoxicity which also test cocaine or methylphenidate fail to produce lasting neurotoxic changes using either cocaine or methylphenidate. This is supported in long-term studies of cocaine abusers as compared to amphetamine abusers, in which cocaine users seem to recover much more quickly on cognitive measures than amphetamine users do -- parts of the brain in heavy methamphetamine users have not been shown to recover, after 2+ years. Therefore, neurotoxicity may be a property of amphetamine's mode of action -- the release of neurotransmitters, rather than a blocking of reuptake transporters which raises circulating levels.

One conjecture (of Frangible's) is that MA/A neurotoxicity is a result of hyperthermia, which does not occur at typical amphetamine doses (but does, I think, occur with the typical recreational dose of MDMA) and does occur at much higher amphetamine dosages.

However, hyperthermia also could occur in theory from extremely high dosages of cocaine and methylphenidate, which again have not been shown to create the lasting structural damage that high-dose methamphetamine do. In fact, these drugs often indicate a protective effect. So, not sure on that one.
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#17 graatch

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Posted 14 May 2007 - 08:51 PM

From what I've seen, the quality of output of rock musicians and artists tends to decline dramatically after they begin a long affair with amphetamine. ;)

Then again, David Bowie had Low.

---

Look, posters like "dopamine" who posts here and on M&M once in a while know more about this than me, try asking them straight-up. I'm still waiting for his response on the current thread.
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#18 xanadu

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Posted 14 May 2007 - 11:47 PM

Why use amphetamines at all? They have a dubious safety record at best and are neurotoxic. I would recommend piracetam as a mental stimulant along with choline. Other safe stimulants are rhodiola rosea, st john's wort and perhaps ginseng. Piracetam is great for focus and creativity. It is also very safe for long term use.
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#19 doug123

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Posted 15 May 2007 - 01:04 AM

Heya folks,


Before beginning, I'll briefly introduce myself.  I'm a 22 year old male college senior studying philosophy and cognitive science.  I stumbled across this site a few weeks ago and have spent a lot of time looking at some of the discussions involving modafinil as well as other nootropics.  Anyway, thanks for all the input, it's really nice to be able to get this information in one place.

I was "diagnosed" with ADHD when I was 14.  Originally I was prescribed ritalin but then went on to adderall and eventually to adderall XR.  Overall, I would consider myself in very good health.  I have about 8% body fat and yield consistently great cholesterol levels.  Blood pressure is usually a bit high, but I tend to drink a lot of coffee, in addition to the adderall.  I've been fairly consistent about working out at least 2-3 times per week.  This mostly includes weight training and some light cardio.  At one point I was benching almost twice my weight.  Anyway, enough about my general health. 

I've been on adderall xr since 10th grade I think, so that would be 5-6 years of adderall use.  Dosages ranged from 20-40mg per day. I want to make clear that I don't use the drug recreationally, but I do use it (by and large) every day. I've never snorted it, but I have used it to stay up all night to write papers and so forth (though never more than the total dose I was alloted in a given 24 hour period) I'm very competitive when it comes to grades and academic performance, and unfortunately I think the adderall compliments that disposition.  Being a philosophy major requires a sort of thinking that I think adderall satisfies very well.  I set very high standards for myself in my papers and presentations, all of which are very critical in nature (I'm thinking to think that learning philosophy amounts to learning how to be the best sort of argumentative).  It's come to the point where it's very difficult to be able to do school work without it. 

Anyway, there have been several occassions over the past few years where I've completely stopped use for 2-3 weeks.  I notice during these times that the first 2-3 days after stopping I'm extremely tired.  I'm fairly certain that my prolonged adderall use, despite the fact that I've used it "as prescribed", has caused significant if not unalterable changes to my sleep cycle. 

Anyway, I just got done reading the post about "meth and the brain".  Obviously, the brains of those individuals who abuse meth are probably leagues more "damaged" than mine is.  But I began to think: seeing as how adderall (being composed of two amphetamine salts) is rather chemically similar to meth, then what exactly is the difference in terms of their respective neurotoxicity effects?  Wouldn't prolonged use of adderall, even if it were mostly consistend with prescribed dosages, cause a similar (albeit relatively lessened) version of the sort of neurological damage present in meth users?  I can't really find much in the way of long term studies of people who use adderall as directed. 

Also, assuming there is damage to the dopamine (DA) systems of the brain with prolonged adderall use, is this damage irreversible in the same sense that meth (ab)use is irreversible (or at least looking like its irreversible, depending on the system of the brain you're talking about)?


I recently started modafinil and like it.  I'm thinking of just switching to modafinil eventually because honestly prolonged adderall use really scares me.  I have not been able to really stop for long periods of time because (as I mentioned) of my sense of obligation to perform as well as I can in school (maintaining a 3.85 gpa in my philosophy major, 3.6 overall, doing research in visual attention, and writing a senior thesis on intentionality....it's already 50 pages). 

What can you people tell me about the questions I asked?  I realize there's a difference between prolonged adderall (prescribed) use and prolonged methamphetamine abuse, but the differences (in my mind) may be more in the realm of "matters of degree" and not necessarily of a different type or quality.  That kind of scares me, unless someone can point me in another direction.


I might suggest examining the evidence first yourself.

Look here.

Take care.
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#20 graatch

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Posted 15 May 2007 - 01:10 AM

>and are neurotoxic

Again, whether or not neurotoxicity is relevant at clinical dosages is an unresolved question.

Did I mention I no longer take stimulants, for numerous reasons? But the discussion of neurotoxicity is another thing entirely ...
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#21 fast turtle

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Posted 16 May 2007 - 11:21 PM

http://www.ncbi.nlm....l=pubmed_docsum

Progression of cellular adaptations in medial prefrontal and orbitofrontal cortex in response to repeated amphetamine.
Homayoun H, Moghaddam B.

Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

Recent theories on addiction implicate adaptive changes in prefrontal cortex (PFC) neurons in reinforcing and psychotomimetic properties of psychostimulants, yet little is known about how neuronal responses to these drugs change over time. Here we describe electrophysiological evidence for a progressive and sustained change in the response of PFC neurons to amphetamine during repeated exposure. In spontaneously behaving rats and in rats engaged in an instrumental responding task, we followed the activity of medial PFC (mPFC) and orbitofrontal cortex (OFC) neurons during daily exposure to amphetamine and after a post-withdrawal challenge. Repeated amphetamine increased the number of responsive neurons and the magnitude of responses and modified spontaneous burst patterns. These changes were apparent after a few exposures to amphetamine, were amplified after withdrawal, and were region specific in that repeated amphetamine increasingly produced inhibitory responses in mPFC and excitatory responses in OFC. In behaviorally engaged animals, the gradual enhancement in mPFC inhibition and OFC overactivation correlated with a progressive impairment of instrumental responding. Furthermore, these changes were evident predominately in neurons that displayed phasic responses during task-related events. These rapid-onset and sustained cellular adaptations suggest that even limited exposure to psychostimulants may reduce the influence of mPFC neurons on behavior while at the same time exaggerating information encoded by OFC neurons.


Poor Ricaurte, over 100+ peer reviewed papers and one fluke and no one believes you anymore...

Whether or not so called neurotoxicity is detrimental or not is arguable, but I don't think the fact that amphetamines cause permanent or at least long lasting changes to the brain is. It seems something specific to the amphetamine structure itself more than anything else, as there are tons of substituted amphetamines causing demonstrable neurotoxicity in rodents. However, it's interesting to note that alpha-ethyltryptamine has been shown to cause reductions similar to those of MDMA after usage; perhaps it has more to do with the basicity of the molecule affecting membrane potential in the cytoplasm and storage vesicles, and the subsequent intracellular and extracellular release of monoamines that occurs in response. Additionally METH and AMP can't really be compared because of the SER-related properties of METH being so different from AMP.

Wellbutrin is a substituted amphetamine, and I've always wondered whether it too held any potential in terms of neurotoxicity.. the meta-chloro substitution is well known for causing very bad neurotoxicity in substituted amphetamine studies. The drug companies never seemed too interested in investigating this!

Hyperthermia is very relevent to amphetamine-type neurotoxicity because the superoxides which tend to cause things to go kaboom in neurons don't seem to form unless the temperature is beyond a certain threshold (probably one of the reasons METH is so much worse, serotonin release = elevated central and peripheral temperature!). What if someone goes on a light jog while taking amphetamines, though? Temperature modulation is a normal part of everyday living.
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#22 jolly

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Posted 18 May 2007 - 04:23 PM

From what I can understand, Meth is signifantly more dangerous on account of its effect on 5HT neurons, whereas Adderall is purely DA and NE stimulating.

Edit: also, I've found taking ALA concurrently is helpful in reducing the pronounced side effects, as well as the weird brain-cloudiness I sometimes experience.  It makes the Adderall feel "cleaner" if that makes any sense.


Try adding a choline donor to the mix - I've always found a choline boost to help clear up adderall / brain fog.
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#23 graatch

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Posted 20 May 2007 - 07:24 AM

> don't think the fact that amphetamines cause permanent or at least long lasting changes to the brain is.

Sure, don't give amphetamines to your pet monkey/hamster. Don't take 3+ gram doses ... Don't you think they'd have found something more significant in humans, at clinical dosages over extended periods? It's not like there's been lack of trying.

>Hyperthermia is very relevent to amphetamine-type neurotoxicity because the superoxides which tend to cause things to go kaboom in neurons don't seem to form unless the temperature is beyond a certain threshold

Well, what do you think about hyperthermia seen with cocaine (which also has a significant serotonin component), which doesn't seem (at any dose) to show the long-lasting neurotoxicity seen with high-dose meth? Or are you saying that hyperthermia + amphetamine mode of action produces something special as opposed to mere hyperthermia, hm?
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#24 fast turtle

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Posted 20 May 2007 - 06:15 PM

Well, what do you think about hyperthermia seen with cocaine (which also has a significant serotonin component), which doesn't seem (at any dose) to show the long-lasting neurotoxicity seen with high-dose meth? Or are you saying that hyperthermia + amphetamine mode of action produces something special as opposed to mere hyperthermia, hm?


I wouldn't be surprised if cocaine is at least a little neurotoxic (it is a mild releaser as well as reuptake inhibitor). But yes, the mechanisms by which AMP exerts neurotoxicity are unique and seems inherent mostly to simple phenethylamines.
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#25 lalaland45

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Posted 18 July 2007 - 11:47 PM

after taking adderall for almost a year (which is a very short amount of time compared to some people) I am very surprised it is legal. My doctor diagnosed me with ADD when I was 15, and I was happy because it seemed to be some sort of explanation. I took 15mg everyday and was ecstatic with the results. It turned me into some sort of genious that I am certaintly not with out the adderall. It almost felt like cheating on my tests. After a few months it began to mess up my sleep schedule - I would not get to bed until 3 or 4 in the morning because I was too stimulated with the different activities and what not.

Then in the morning I would wake up and take my dose. With out much sleep adderall is terrible. It makes you feel jumpy and too alert and your body feels dead.

It worsened my OCD symptons also. All I ever wanted to do was homework and I had to redo everything until it was perfect. One thing I loved about adderall is it made me very interested in school, I loved to learn!

I tried to work out everyday or so when I was on adderall but after awhile going home to do my homework became so much more appetizing!! During the day I would eat very little and binge when I got home. I lost a lot of weight and since I was underweight when I started on it this was very unhealthy.

The adderall stimulated my mind but my body stopped functioning properly. Walking became a great work out and when I would try to return to yoga or something my body would shake so much. My extremities began turning purple because adderall is a vascular constrictor. I took it monday - friday at school and gave myself a break on the weekends, although all I wanted to do was sleep then. By thursday morning every week I felt like getting up was almost impossible, but by monday I was fine again.

It made my heart race and hurt a little bit and I never wanted to drink water even though its a major dehydrant.

My mom was worried about me so we went to an alternative health doctor - a doctor that is not endorsed and funded by major drug companies (like all psychiatrists are). They doctor explained to me how dangerous adderall was. After taking blood, urine, and saliva tests the doctor showed me my results. My adrenal glands were about to give out. My levels of norepinephron and other natural stimulants were dangerously low. I was on the brim of adrenal fatigue.

Now that its summer I haven't been taking it and I feel great. I haven't gained any weight back but my muscles are fine and my body feels like its functioning fine. I'm on a supplement which supports your adrenal glands - something EVERYONE who takes adderall should take. I'm probably going to keep takaing adderall to the end of high school, just at a lower dose.
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#26 matter_of_time

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Posted 19 July 2007 - 05:26 PM

Which supplement did you take to support your addrenal glands?
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#27 graatch

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Posted 20 July 2007 - 03:54 AM

I wouldn't be surprised if cocaine is at least a little neurotoxic (it is a mild releaser as well as reuptake inhibitor)


Not long-term in studies, but then: apparently, reuptake inhibition in general seems to prevent amphetamine neurotoxicity. (cool, huh?)

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

Also see prozac + MDMA studies.


===

lalaland: you could have tried lowering your dose/dose schedule/preparation
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#28 fast turtle

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Posted 20 July 2007 - 06:59 AM

Not long-term in studies, but then:  apparently, reuptake inhibition in general seems to prevent amphetamine neurotoxicity.  (cool, huh?)

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

Also see prozac + MDMA studies.


===

lalaland:  you could have tried lowering your dose/dose schedule/preparation


Probably because they keep the compounds from actually entering vesicular stores and working their magic (which is likely mostly via membrane depolarization). Unfortunately the listed study does not examine damage to serotonergic neurons, which is also caused by methamphetamine. Methamphetamine also seems to have an affinity for SERT, as does MDMA (hence why fluoxetine prevents MDMA-induced neurotoxicity). Unfortunately, administering MDMA with fluoxetine also seems to inhibit most of the psychoactive effect of MDMA.

Most of the rat studies with MDMA can be thrown out anyway because rats would never self-administer 5-20mg/kg MDMA to themselves recurrently, subcutaneously or intravenously -- rats will only habitually administer .25-1 mg/kg, IV, and that seems to be where the 'fun' zone is at for them.

http://www.ncbi.nlm....Pubmed_RVDocSum

If you equate the rat doses to human doses, even if you use the most minimal dose to produce toxicity (5mg/kg) you will see that for a 70kg person it's 350mg. The average IV dose in humans is in actuality about 50mg. Further, the acute plasma peak time of SC or IV cannot be compared to the more progressive plasma levels of oral dosage, nor can we figure out what the effects of various antioxidants in the diet are on the neurotoxicity of MDMA. Rats also produce much more MDA from MDMA than humans do via their metabolism, and MDA is more neurotoxic. However, we do know that simians seem to be more sensitive to neurotoxicity of phenethylamines than rats.

Really, it's a big "Who knows?" as far as MDMA neurotoxicity, since no one is bothering to do any research that might actually be comparable to what comprises most of the human consumption of MDMA. However, long-term studies of MDMA users show cognitive deficits across the board, which is probably a dead ringer that it's not good for your brain (however, almost all users of MDMA are also polydrug users).

I don't know so much about the studies of meth, except that the neurotoxic potential of methamphetamine seems tens times of that of MDMA (and the dose of methamphetamine is about 1/10th of that of MDMA -- fancy that?). I have used both methamphetamine and MDMA sparingly in the distant past and I would lean more towards them hurting my cognitive abilities than helping or not affecting them. I would not use them again. Once one of my friends IV'd 1.5 grams of methamphetamine and 500mg of MDMA in a suicide attempt, and now she has very, very bad cognitive troubles.
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#29 jubai

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Posted 20 July 2007 - 01:27 PM

Deprenyl can increase focus and motivation especially for ADHD sufferers

I would concur that Piracetam, modafinil, A-GPC etc are all healthier alternatives than the old, dark, cold amphetamines
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#30 subtletactics

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Posted 10 September 2007 - 08:21 PM

about the earlier post with dexedrine. Dexedrine is amphetamine-like, but acts more like a metamphetamine which has been shown to be related to CSF problems. Also brain hemorrhage can be due to stroke which is due to heart problems which would make sense with any uppers mixed with bad cardiovascular. Not sure the quality of evidence but i learned mdma and metamphetamines does show neurotoxity with seretogenic neurons. Although, the next slide shows that they grow back, but differently (less effective connections or something, i forget). Again, it's dealing with 5-HT. Only problems I've seen online with amphetamines are cardiovascular related, and the usual down-regulation. I mean stunted growth= it keeps you up (sleep:growth in kids). Psychotic episode= wrong dosage and a DA stimulant can produce a schiz like episode but not damaging. Etc. I'm just a biopsyc undergraduate, but in my opinion amphetamines, next to caffeine is one of my favorite drugs. I'd use it with caution and talk to a doctor when experiencing adverse effects.
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