155 replies to this topic

[aLurker]

tl;dr

I'm sure lots of people appreciate your review of these combinations so thanks for that.
That said, your reasoning is based on the questionable premise that you can accurately somehow "feel" neuroprotective/excitotoxic effects of quite low doses of these substances. I'm far from convinced that's the case in this context. Good to see that you've found things you feel are helpful though.

[Delta Gamma]

Excitotoxicity becomes particularly acute after 24hrs without sleep, especially if you've forgotten to eat. At this point I believe that I can actually feel some aspects of the excitoxicity taking placing, and it is at times like these when I can feel the effects (or lack thereof) of a particular neuroprotectant: the acute sensations of the excitotoxic storm dissipate, as does the associated "brain fog." Previously, I'd felt the strongest neuroprotective responses from:

BioPQQ
GreenSelect Green Tea Phytosome
Meriva Turmeric Phytosome
Astaxanthin
NADH (sublingual)
Sam-e
P5P + Methyl B12 (sublingual)
Fish Oil + Acetyl L-Carnitine (low dose of ALCAR seems to synergize with the Adderall, while anything >300mg seems to compete with it.
Magnesium Orotate

N-Acetyl Cystine + mineral ascorbate (for glutathione production) is also extremely effective for neuroprotection, but at the price of effectively knocking out the effects of the Adderall and causing its own short-lived variety of brainfog.

Excellent post J.Galt! I like how you mentioned all the draw backs, past experiances, combinations, and consulted a MD for this. I must say that this was worth the wait haha

I'm not sure if you read the pubmed link on lithium's actions on VMAT2, but its very interesting to think that there may be a way to deal with one of the biggest problems with amphetamine's pharmacology. There may be some other actions which do play a role in this response, but just looking at the risk:benefit ratio you report with these dosages is incredible. It also shows some potential for directly preventing neurotoxicity by blocking several pro-apoptosis functions in mitochondria, but I'm not sure of the doses required.

That said, your reasoning is based on the questionable premise that you can accurately somehow "feel" neuroprotective/excitotoxic effects of quite low doses of these substances. I'm far from convinced that's the case in this context. Good to see that you've found things you feel are helpful though.

While it may be dubious as to whether someone can feel brain damage in anything but a stroke type scenario, if it improves cognition and side effects its still worth considering.

Lithium seems to have markedly different actions at therapeutic dosages depending on the duration and dosage of the treatment, resulting in really freaking hard to interpret studies. But, it does exhibit glutamate transporter inhibition and then massive upregulation on time scales that could be less than a week. However, this study found it to inhibit glutamate release acutely in rats.

It is possible that at very low doses it affects the NMDAR/NO pathway, which has a MASSIVE number of things affected by it (including blood pressure), and may still activate/inhibit some of the host of other proteins it interacts with at therapeutic dosages. A good review of the topic can be found here:

The NMDA receptor/nitric oxide pathway: a target for the therapeutic and toxic effects of lithium
Mehdi Ghasemi1, 2, E-mail The Corresponding Author and Ahmad Reza Dehpour2, E-mail The Corresponding Author
1 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

Unfortunately lithium is one of the biggest mysteries of pharmacology so I can't really go that far into detail on it, but suffice to say very low dose lithium has been show to have beneficial effects even in large populations (as evidenced by the studies of Li+ in water vs suicides) among other things.

I'd like to get some more data-points on this stuff if anyone's interested. As long as the dosage is low its a very safe compound with known benefits.

I'll stop this post now before it becomes a more disjointed dumping ground for pharmacological studies, and get back to studying for my final tomorrow haha.

[Delta Gamma]

http://www.cnsforum...._2/default.aspx
http://www.cnsforum....up/default.aspx
http://www.cnsforum....gh/default.aspx
http://www.cnsforum....ow/default.aspx
http://www.cnsforum....ib/default.aspx

Some illustrations of simplified relevant mechanisms for those who wish to learn how amphetamine, MAOI's, and the DAT play into amphetamine.

[Mindweaver]

Will Vitamin C be sufficient enough to protect the neurotoxic effects of using Adderall (20MG XR) to study?

If so, what is the best way to pre-load? Night before? Hour before? During ingestion?

Edited by Mindweaver, 24 April 2011 - 07:36 PM.

[Delta Gamma]

Will Vitamin C be sufficient enough to protect the neurotoxic effects of using Adderall (20MG XR) to study?

If so, what is the best way to pre-load? Night before? Hour before? During ingestion?

Well it would help more than nothing, but vitamin c has a low maximal effect as only so much can be absorbed and it has a very short half life in the body. Also, large doses may become pro-oxidants and acidify the body resulting in increased amphetamine excretion.

If you take a multivitamin and drink half a airborne (those effervescent cold prevention tablets) a hour after and again 6-8ish hours later you've got a solid basic level of protection.
CoQ10 however should be taken about 4 hours before with a small meal, as with curcumin.

[Mindweaver]

This morning I took roughly 15mg Adderall XR, with 500 mg ALA/ALCAR blend and about a half of a bottle of Apple Juice (100% daily value vitamin C)

The effects seem much cleaner, I may be a little less "upped" than I would be from this dose, but it's generally better than being jittery and dealing with sweating/teeth grinding (neither of these effects being present). I'm wondering if this has to do with the neuro-protective properities of ALCAR/ALCA/VC, or am I wishful thinking?

Edited by Mindweaver, 25 April 2011 - 03:17 PM.

[Delta Gamma]

This morning I took roughly 15mg Adderall XR, with 500 mg ALA/ALCAR blend and about a half of a bottle of Apple Juice (100% daily value vitamin C)

The effects seem much cleaner, I may be a little less "upped" than I would be from this dose, but it's generally better than being jittery and dealing with sweating/teeth grinding (neither of these effects being present). I'm wondering if this has to do with the neuro-protective properities of ALCAR/ALCA/VC, or am I wishful thinking?

The ALCAR/ALA probably is doing the most of it, though the apple juice may play some role. Vitamin C is required for a lot of biological functions including catecholamine synthesis, so that may have something to do with it. I have a friend who has a very strict regime for when he takes vitamin C and amphetamine, so its definitely got some effect on the subjective experience.

Vitamin C on its own doesn't have much of a antioxidant effect in the human body, but when consumed with a source of polyphenols or flavonoids it "gains" the ability to recycle itself and therefore other antioxidants. I haven't covered the ALCAR/ALA stuff yet, partly because ALA's effects on a CR diet in rats freaks me out, but ALCAR was shown to prevent MDMA neurotoxicity in a few rat studies.

[Mindweaver]

Are there any physical effects that are noticeable from neurotoxicity? Would feeling a pressure/headache in different regions of your brain indicate cell death, or is it probably just a come-down/dopamine crash/stress?

(Ignore things like dehydration, sleep deprivation and malnutrition as factors, as I did my best to avoid these potential factors)

Edited by Mindweaver, 26 April 2011 - 05:49 AM.

[Delta Gamma]

Are there any physical effects that are noticeable from neurotoxicity? Would feeling a pressure/headache in different regions of your brain indicate cell death, or is it probably just a come-down/dopamine crash/stress?

(Ignore things like dehydration, sleep deprivation and malnutrition as factors, as I did my best to avoid these potential factors)

Probably just crashes or some sort of vascular issue, I wouldn't lose too much sleep over it.
Neurotoxicity is very hard to gauge in all but the most severe cases, so unless you start going psychotic you're not going to see anything from 15mg amphetamine. This thread is more designed to help prevent the slow accumulation of damage which could present itself as, say Parkinsons, later in life.

If you're worried about the potential damage, probably the best thing you can do is avoid dehydration, sleep deprivation, and malnutrition as you said; there are plenty of tips and potential stacks in this thread if you're interested in increasing your protection.
Also, if you can, get some sun. Vitamin D is some wonderful stuff.

[Mindweaver]

Is there a possibility that using Adderall infrequently (maybe 2-3 times in one week, once every few months; like during finals week) can cause Alzheimer's later on? I have a very basic understanding of it's effects on the dopaminergic system and Alzheimer's relationship to dopamine depletion/dysfunction.. but not like you might have Delta Gamma. I use Adderall very infrequently, as I said, but when I do use it it's normally in multiple times in close proximity with eachother; am I at risk?

Edited by Mindweaver, 27 April 2011 - 02:41 AM.

[Delta Gamma]

Is there a possibility that using Adderall infrequently (maybe 2-3 times in one week, once every few months; like during finals week) can cause Alzheimer's later on? I have a very basic understanding of it's effects on the dopaminergic system and Alzheimer's relationship to dopamine depletion/dysfunction.. but not like you might have Delta Gamma. I use Adderall very infrequently, as I said, but when I do use it it's normally in multiple times in close proximity with eachother; am I at risk?

I don't think any studies have looked at that, but given how old a drug amphetamine is I think we would have seen something come up by now if it had a strong correlation. I may be studying pharmacology, but I don't know all there is to know about this stuff, so I could be wrong on this.

Don't lose too much sleep over this just take some of the basic precautions, eat healthy, and exercise and I'm sure you'll be fine.

[J. Galt]

Are there any physical effects that are noticeable from neurotoxicity? Would feeling a pressure/headache in different regions of your brain indicate cell death, or is it probably just a come-down/dopamine crash/stress?

(Ignore things like dehydration, sleep deprivation and malnutrition as factors, as I did my best to avoid these potential factors)

Many will disagree with me on this point, but I believe that yes, there are several. In my own experience, it was not until practicing meditation for several months that I became aware enough of my brain to observe and isolate the specific sensations which I intuitively feel associate with neurotoxicity. I have no scientific evidence to back this up, but speaking experientially I am quite confident in my ability to detect acute neurotoxicity beyond a certain threshold. I have used this feedback to refine my supplement regimen and nutrition, and feel that by learning to feel and listen to my body I have greatly reduced and reversed the harm done by years of Adderall use, chronic stress, all-niters, etc.

I would describe the different observable physical effects not so much as pressure, but more like a "burning" sensation of sorts. That's not a precise term, as this is all rather abstract and difficult to articulate. I hesitate to even try given the decidedly unscientific nature of this personal methodology. I will however attempt to do so upon request, though I'm not sure how much good it would be to anyone else. Let me know if anyone is interested and I'll try to describe the different sensations more precisely.

Acute pressure changes like you mention are most likely indicative of variations in blood and vascular pressure, usually in response to excess or severely depleted NE. IME, if you can feel your pulse in your head, then your BP is way too high, and I would recommend procuring a BP cuff to monitor it yourself. If you are regularly experiencing physical sensations of pressure in your brain while on Adderall, your body is probably telling you something here, and you should mention this to your doctor ASAP.

Before I reversed many of my amphetamine-related physical problems I did feel increased pressure in my head, usually as a throbbing headache after 36hrs of Adderall-fueld sleep deprivation or during the subsequent crash. My BP during these periods was dangerously high (as in stroke risk territory, which is particularly concerning seeing as I'm a young male. I found that Niacin and a homeopathic preparation called "Adrenal Support" from NatraBio were the most helpful remedies to alleviate symptoms in the short term (note: counterintuitively, low-dose aspirin seemed to make it worse), but it took months of an intensive cardiovascular health and atherosclerosis regimen to eliminate these problems and return to proper help.

My best advice is to learn meditation and practice deep breathing exercises as a means to become more attuned to your body and interpret its feedback more precisely. Again this is NOT scientific, just my personal conviction.

Has anyone else had similar experience?

Edited by J. Galt, 27 April 2011 - 09:59 AM.

[J. Galt]

Is there a possibility that using Adderall infrequently (maybe 2-3 times in one week, once every few months; like during finals week) can cause Alzheimer's later on? I have a very basic understanding of it's effects on the dopaminergic system and Alzheimer's relationship to dopamine depletion/dysfunction.. but not like you might have Delta Gamma. I use Adderall very infrequently, as I said, but when I do use it it's normally in multiple times in close proximity with eachother; am I at risk?

I don't think any studies have looked at that, but given how old a drug amphetamine is I think we would have seen something come up by now if it had a strong correlation. I may be studying pharmacology, but I don't know all there is to know about this stuff, so I could be wrong on this.

Don't lose too much sleep over this just take some of the basic precautions, eat healthy, and exercise and I'm sure you'll be fine.

I can't speak to the excitotoxicity here, but I can definitely tell you that the more frequently you take it the faster your tolerance will increase and the worse the side effects will be. Vacations and drug holidays are crucial for safe amphetamine use. Vasoconstriction, elevated cortisol, insomnia, weight gain/loss, depression, irritability, and hypertension will all tend to increase the longer you take it without breaks. If you're talking 2-3 days at a time a few times a month as you describe, then you're probably fine in the short run, and I can't see this significantly elevating your risk of disease later in life. But there are a few problems with using in this range that I would caution you against.

1) Your tolerance will probably start to increase. This process is gradual, but can quickly escalate if not kept under tight control. This requires a high level of self-discipline.

2) Psychological dependence is almost certain to develop after a semester or two of this usage pattern, and eventually you may find that you NEED it for exams and demanding assignments, or at least feel that you do, in order to maintain your performance.

3) The combination of points 1 and 2 is a cocktail for dependency or addiction. This can really sneak up on people if they aren't careful. Watch yourself closely for creeping incrementalism in dosage and frequency. Better yet, ask a close friend to keep an eye out for any signs of dependence, changes in mood, personality, or behavior that could indicate a problem, just to be safe. Make sure it's someone you can trust to be objective, level-headed, and completely honest; drinking buddies are poor candidates.

I'm sure many will feel I'm being overly cautious here, but I've seen this happen to varying degrees since starting college, and now as a senior find myself bombarded before exams with desperate texts from no less than a dozen friends looking for Adderall.

Again, you're probably fine. I'm not claiming that the sky is falling or anything, but merely urge caution and honest self-appraisal to keep usage down to a minimum and catch any early warning signs before a real problem can develop.

Hope this helps.

Edited by J. Galt, 27 April 2011 - 11:52 AM.

[J. Galt]

Is there a possibility that using Adderall infrequently (maybe 2-3 times in one week, once every few months; like during finals week) can cause Alzheimer's later on? I have a very basic understanding of it's effects on the dopaminergic system and Alzheimer's relationship to dopamine depletion/dysfunction.. but not like you might have Delta Gamma. I use Adderall very infrequently, as I said, but when I do use it it's normally in multiple times in close proximity with eachother; am I at risk?

I think you might be thinking of Parkinson's here as it directly related to dopamine dysfunction. Chronic usage can definitely elevate risks for Parkinson's later in life, but probably not at the frequency you describe as long as the dose is within normal therapeutic range.

[Mindweaver]

Are there any physical effects that are noticeable from neurotoxicity? Would feeling a pressure/headache in different regions of your brain indicate cell death, or is it probably just a come-down/dopamine crash/stress?

(Ignore things like dehydration, sleep deprivation and malnutrition as factors, as I did my best to avoid these potential factors)

Many will disagree with me on this point, but I believe that yes, there are several. In my own experience, it was not until practicing meditation for several months that I became aware enough of my brain to observe and isolate the specific sensations which I intuitively feel associate with neurotoxicity. I have no scientific evidence to back this up, but speaking experientially I am quite confident in my ability to detect acute neurotoxicity beyond a certain threshold. I have used this feedback to refine my supplement regimen and nutrition, and feel that by learning to feel and listen to my body I have greatly reduced and reversed the harm done by years of Adderall use, chronic stress, all-niters, etc.

I would describe the different observable physical effects not so much as pressure, but more like a "burning" sensation of sorts. That's not a precise term, as this is all rather abstract and difficult to articulate. I hesitate to even try given the decidedly unscientific nature of this personal methodology. I will however attempt to do so upon request, though I'm not sure how much good it would be to anyone else. Let me know if anyone is interested and I'll try to describe the different sensations more precisely.

Acute pressure changes like you mention are most likely indicative of variations in blood and vascular pressure, usually in response to excess or severely depleted NE. IME, if you can feel your pulse in your head, then your BP is way too high, and I would recommend procuring a BP cuff to monitor it yourself. If you are regularly experiencing physical sensations of pressure in your brain while on Adderall, your body is probably telling you something here, and you should mention this to your doctor ASAP.

Before I reversed many of my amphetamine-related physical problems I did feel increased pressure in my head, usually as a throbbing headache after 36hrs of Adderall-fueld sleep deprivation or during the subsequent crash. My BP during these periods was dangerously high (as in stroke risk territory, which is particularly concerning seeing as I'm a young male. I found that Niacin and a homeopathic preparation called "Adrenal Support" from NatraBio were the most helpful remedies to alleviate symptoms in the short term (note: counterintuitively, low-dose aspirin seemed to make it worse), but it took months of an intensive cardiovascular health and atherosclerosis regimen to eliminate these problems and return to proper help.

My best advice is to learn meditation and practice deep breathing exercises as a means to become more attuned to your body and interpret its feedback more precisely. Again this is NOT scientific, just my personal conviction.

Has anyone else had similar experience?

Well.. I never take it to pull all nighters. I take it maybe 2-4 times in 2 weeks every 2-3 months, so there's your vacation. I'm productive on it (12 hour study sessions) and I don't use it for recreation. My resting BP is optimal, in fact my pulse rate is like 5-10 clicks lower than average. I'm active and exercise relatively often. My breath rate is extremely controlled.. I sometimes wonder if it's unhealthy that I don't take anywhere near deep breaths. They're soft, silent, and I seem to get enough oxygen because it's almost a hassle to take a deep breath lol. So I'm guessing that if you went through what you went through and I'm not anywhere near the level of use you were, I'll be fine.

[Delta Gamma]

I'd like to have a little help gathering information from other forums about amphetamine neurotoxicity, so if you guys could help me out by grabbing 1 or 2 unmentioned threads from other sites such as Mind and Muscle and posting them here I think that would be a great way to expand out knowledge of the topic.

Also I just drank 4 Monster Energies so I'm back to cramming for my final tomorrow. Peace!

-DG

[Delta Gamma]

To those posters who do not have a firm grounding in science I strongly suggest against migrating to M&M as the discussion is of a very different tone than here.

Here is the wealth of M&M's amphetamine related knowledge:
http://www.mindandmu...d-amphetamines/
http://www.mindandmu...amine-toxicity/
http://www.mindandmu...of-amphetamine/ <-gold
http://www.mindandmu...sion-continues/
http://www.mindandmu...nd-amphetamine/
http://www.mindandmu...ine withdrawal\
http://www.mindandmu...-of-parkinsons/
http://www.mindandmu...amineephedrine/
http://www.mindandmu...n-testosterone/
http://www.mindandmu...ding-d1-and-d2/
http://www.mindandmu...hetamine-abuse/
http://www.mindandmu...hetamines-plus/
http://www.mindandmu...-neurotoxicity/
http://www.mindandmu...hdrawal-thread/

I've had a good run on this site, but I don't believe I'll be coming back. This site has devolved from a place where cutting edge research was discussed by a group of intelligent and motivated posters to a place where people are simply looking to be spoon feed them information about basic questions perhaps only tangentially related to the general topic. I know this may seem harsh, but given the environment I work, study, and live in it gets grating to have to deal with such basic questions time and time again.

Now for personal goodbyes:

Chrono: you're doing a great job despite what you must be dealing with in your personal life. I'm just sad to see how this site has made the change from a hard science based discussion to a very basic psychopharmacology board. While I know you don't control all the things on Immist you're doing very well with the section you have. Also, I understand that we have different ideas as to what we want this site to become and I respect that you are more supportive of the emotional/holistic approach to cognitive enhancement while I prefer a more direct approach to altering various systems. I'll also, albeit sheepishly, acknowledge that your approach is likely superior to mine for the majority of the people on this board.

J. Galt: you've been a great guy to have on this board. You seamlessly blend personal experience with scientific backing in a manner which is both riveting and informative, I'd be more than glad to see you make the same migration I will in a few days. Look for a new poster on M&M with some sort of Greek letter based name.

Anyways, I wish you all the best

-Delta Gamma

[Delta Gamma]

I can't speak to the excitotoxicity here, but I can definitely tell you that the more frequently you take it the faster your tolerance will increase and the worse the side effects will be. Vacations and drug holidays are crucial for safe amphetamine use. Vasoconstriction, elevated cortisol, insomnia, weight gain/loss, depression, irritability, and hypertension will all tend to increase the longer you take it without breaks. If you're talking 2-3 days at a time a few times a month as you describe, then you're probably fine in the short run, and I can't see this significantly elevating your risk of disease later in life. But there are a few problems with using in this range that I would caution you against.

1) Your tolerance will probably start to increase. This process is gradual, but can quickly escalate if not kept under tight control. This requires a high level of self-discipline.

2) Psychological dependence is almost certain to develop after a semester or two of this usage pattern, and eventually you may find that you NEED it for exams and demanding assignments, or at least feel that you do, in order to maintain your performance.

3) The combination of points 1 and 2 is a cocktail for dependency or addiction. This can really sneak up on people if they aren't careful. Watch yourself closely for creeping incrementalism in dosage and frequency. Better yet, ask a close friend to keep an eye out for any signs of dependence, changes in mood, personality, or behavior that could indicate a problem, just to be safe. Make sure it's someone you can trust to be objective, level-headed, and completely honest; drinking buddies are poor candidates.

I'm sure many will feel I'm being overly cautious here, but I've seen this happen to varying degrees since starting college, and now as a senior find myself bombarded before exams with desperate texts from no less than a dozen friends looking for Adderall.

Again, you're probably fine. I'm not claiming that the sky is falling or anything, but merely urge caution and honest self-appraisal to keep usage down to a minimum and catch any early warning signs before a real problem can develop.

Hope this helps.

Hey, I just continued this thread over at bluelight and was hoping you could share your current stack and how its working you for you for us. Also, I linked this thread to http://www.bluelight...ad.php?t=577851 as I believe that bluelight.ru may benefit from having a detailed discussion on the topic.

Thanks man
-DG or Epsilon Alpha

[Valor5]

Hey Delta Gamma:

I think you have done a great job so far. I have read through your thread and I probably need to go through it about ten more times. I am sure that is true for all of us. Thanks for the in-depth research.

You made a recommendation of Elemental Mg, does this mean just any good supp. with Mg in it? I guess that would be the case, because no one can ingest pure magnesium as it is reactive with the atmosphere, lol.

You also made a recommendation of hydrating with blueberry juice. The concentrate from NSI has 26g of sugar and 110 calories per serving. That is for one cup. If you took one of those per hour you would get in 8 hours 208g of sugar and 880 calories. Now for a brain on amphetamine all this sugar might be a good thing, right or wrong? Also, if wrong, should the person instead take a blueberry extract?

Something I read that fascinated me while thinking on the sugar question was this article at pubmed. It said that glucose competes with amphetamines and reduces activity and sterotypy. I found that fascinating because that explains why people on amphetamines say that they do not feel hungry because essentially amphetamines do what glucose does in a single pill.
Glucose and the brain and amphetamines effects on rats

So now I am asking is the reduction in activity a good thing or a bad thing? I think it depends again because I think if you have high serotonin along with dopamine it makes rats go in circles and do what scientists would consider not good behavior etc.

I am also asking the relevance of glucose in the brain if you are taking amphetamines, only because a high glucose consumption competes with dopamine and amp. and I read that it does something to albumin in the kidneys and maybe prooxidant in that part of the body if excessive. Which begs the question of amphetamines and the kidneys also which would be less than glucose I imagine of course. My ADD just wants to take me in all directions but I can't help it there is just so much to look at.

Longecity should be more organized in terms of bodysystems etc.

There are different types of studies invivo, invitro, animal, human, organ, system, etc. It seems to me that one substance will have differing effects on each of these systems and to gain a comprehensive view we have to understand each. At this time I do not think the science industry is organized that way but who knows it may work out nonetheless yet it would seem to me to be better if we did it systematically but then again the body is so complex it may be impossible I suppose because humans are essentially flawed as is nature and we would need a lot of perfect models in order to carry out perfect experiments with perfect controls but we do not have perfect specimens, I don't think, I guess that is why we have a large sample in order to have more confidence in the results . So, our task is even harder because we do not have perfect models.

[jlspartz]

I've found that a low dose of Adderall plus potentiators and NMDA receptor antagonists work. I don't know who originally said take Vitamin C on here to have a smoother effect, but citric acid negates amphetamine's effects - you have to take them more than 2 hours apart (and even then it wipes out any benefit for myself). I take omeprazole - an antacid which potentiates amphetamines. I also take magnesium glycinate for a NMDA receptor antagonist to block a large influx of calcium that would trigger glutamate and apoptosis. I include B-complex because they're essential for proper functioning of the dopamineric system. And then I take zinc off and on - an uncompetitive voltage-dependent NMDA receptor antagonist like magnesium, but binds within the channel and on the outside (shown to work when magnesium tolerant NMDA receptors are an issue). Also, zinc decreases the optimum dosage of amphetamine by 37% on average. I take it off and on because when I take it it increases the effects of amps, until about 3 or 4 days into taking it, and then it just blocks it, and so I stop taking it and the effects come back strong again. I read that amphetamine's effects are somewhat reliant on the glutamate transmission, so blocking it entirely wouldn't be beneficial. Here's one abstract on that:

Here we show that amphetamine may also excite dopamine neurons through modulation of glutamate neurotransmission. Amphetamine potently inhibits metabotropic glutamate receptor (mGluR)-mediated IPSPs in dopamine neurons, but has no effect on ionotropic glutamate receptor-mediated EPSCs. Amphetamine desensitizes the mGluR-mediated hyperpolarization through release of dopamine, activation of postsynaptic α1 adrenergic receptors, and suppression of InsP3-induced calcium release from internal stores. By selectively suppressing the inhibitory component of glutamate-mediated transmission, amphetamine may promote burst firing of dopamine neurons. Through this mechanism, amphetamine may enhance phasic release of dopamine, which is important in the neural processing of reward.

Also, there was a study on dosage timing so as not to build up tolerance and the conclusion was that IR doses 6 hours apart had no tolerance build-up, a constant release or anything under 4 hours apart had a large tolerance build-up, and XR doses that spread the release out by 4-6 hours had a very minute amount of tolerance build-up. Different dosage amounts throughout the day didn't make a difference. I don't have the time to look up the sources right now, but if anyone wants I could find them later.

Edited by jlspartz, 17 June 2011 - 08:41 PM.

[Delta Gamma]

Hey Delta Gamma:

I think you have done a great job so far. I have read through your thread and I probably need to go through it about ten more times. I am sure that is true for all of us. Thanks for the in-depth research.

You made a recommendation of Elemental Mg, does this mean just any good supp. with Mg in it? I guess that would be the case, because no one can ingest pure magnesium as it is reactive with the atmosphere, lol.

You also made a recommendation of hydrating with blueberry juice. The concentrate from NSI has 26g of sugar and 110 calories per serving. That is for one cup. If you took one of those per hour you would get in 8 hours 208g of sugar and 880 calories. Now for a brain on amphetamine all this sugar might be a good thing, right or wrong? Also, if wrong, should the person instead take a blueberry extract?

Something I read that fascinated me while thinking on the sugar question was this article at pubmed. It said that glucose competes with amphetamines and reduces activity and sterotypy. I found that fascinating because that explains why people on amphetamines say that they do not feel hungry because essentially amphetamines do what glucose does in a single pill.
Glucose and the brain and amphetamines effects on rats

So now I am asking is the reduction in activity a good thing or a bad thing? I think it depends again because I think if you have high serotonin along with dopamine it makes rats go in circles and do what scientists would consider not good behavior etc.

I am also asking the relevance of glucose in the brain if you are taking amphetamines, only because a high glucose consumption competes with dopamine and amp. and I read that it does something to albumin in the kidneys and maybe prooxidant in that part of the body if excessive. Which begs the question of amphetamines and the kidneys also which would be less than glucose I imagine of course. My ADD just wants to take me in all directions but I can't help it there is just so much to look at.

Thanks
As far as magnesium goes, you're right it should just be any form that has decent bioavailbility. As far as glucose goes, as long as you keep your consumption of fruits to natural or unsweetened juices I think you should be fine. If you find that all that glucose negatively effects you then a extract should suffice in a much less delicious manner haha. I think if you just moderated your consumption you would avoid that issue, though keep in mind that study was done on rats with a destroyed DA/NE system due to 6HODA.
I'm unaware of the glucose/albumin/oxidation link so I can't comment on that, but feel free to post on it if you feel it merits concern.

I've found that a low dose of Adderall plus potentiators and NMDA receptor antagonists work. I don't know who originally said take Vitamin C on here to have a smoother effect, but citric acid negates amphetamine's effects - you have to take them more than 2 hours apart (and even then it wipes out any benefit for myself). I take omeprazole - an antacid which potentiates amphetamines. I also take magnesium glycinate for a NMDA receptor antagonist to block a large influx of calcium that would trigger glutamate and apoptosis. I include B-complex because they're essential for proper functioning of the dopamineric system. And then I take zinc off and on - an uncompetitive voltage-dependent NMDA receptor antagonist like magnesium, but binds within the channel and on the outside (shown to work when magnesium tolerant NMDA receptors are an issue). Also, zinc decreases the optimum dosage of amphetamine by 37% on average. I take it off and on because when I take it it increases the effects of amps, until about 3 or 4 days into taking it, and then it just blocks it, and so I stop taking it and the effects come back strong again. I read that amphetamine's effects are somewhat reliant on the glutamate transmission, so blocking it entirely wouldn't be beneficial. Here's one abstract on that:

Here we show that amphetamine may also excite dopamine neurons through modulation of glutamate neurotransmission. Amphetamine potently inhibits metabotropic glutamate receptor (mGluR)-mediated IPSPs in dopamine neurons, but has no effect on ionotropic glutamate receptor-mediated EPSCs. Amphetamine desensitizes the mGluR-mediated hyperpolarization through release of dopamine, activation of postsynaptic α1 adrenergic receptors, and suppression of InsP3-induced calcium release from internal stores. By selectively suppressing the inhibitory component of glutamate-mediated transmission, amphetamine may promote burst firing of dopamine neurons. Through this mechanism, amphetamine may enhance phasic release of dopamine, which is important in the neural processing of reward.

Also, there was a study on dosage timing so as not to build up tolerance and the conclusion was that IR doses 6 hours apart had no tolerance build-up, a constant release or anything under 4 hours apart had a large tolerance build-up, and XR doses that spread the release out by 4-6 hours had a very minute amount of tolerance build-up. Different dosage amounts throughout the day didn't make a difference. I don't have the time to look up the sources right now, but if anyone wants I could find them later.

Zn supplementation may be a good idea as far as tolerance goes, but its much harder to recommend a general dosage for than magnesium. Also, if you could dig up those studies you just quoted that would be pretty win .

I was under the impression that amphetamine tolerance was due to the fast and hard depletion of DA/NE and receptor desenstization on the short term so if you could dig up that study it could provide some insight into mechanisms that we haven't discussed yet. mGluR is a interesting topic as far as potential leads go.

[jlspartz]

Zn supplementation may be a good idea as far as tolerance goes, but its much harder to recommend a general dosage for than magnesium. Also, if you could dig up those studies you just quoted that would be pretty win .

I was under the impression that amphetamine tolerance was due to the fast and hard depletion of DA/NE and receptor desenstization on the short term so if you could dig up that study it could provide some insight into mechanisms that we haven't discussed yet. mGluR is a interesting topic as far as potential leads go.

Here is the study on zinc potentiation. http://www.ncbi.nlm....pubmed/21309695
Here is a study on the glutamate blocking mechanics of zinc. http://www.ncbi.nlm....pubmed/21504727
I can't find the study on administration frequency of amphetamine affecting tolerance. But all the latest findings on amphetamine sensitization were pointing to genes and the hippocampus. This one specifically indicating BDNF. http://www.ncbi.nlm....pubmed/21570990

Repeated amphetamine treatment also increased VTA BDNF, while both acute and repeated amphetamine treatment increased Fos and Fos-BDNF co-labeling, an effect enhanced in sensitized rats. These findings point to a role of cortico-tegmental BDNF in long-term amphetamine sensitization.

Maybe someone more educated than I can tell us how this can possibly be avoided.

[jlspartz]

Also very interesting:

http://www.ncbi.nlm....pubmed/20649843

Stimulation of retinoic acid receptors (RARs) protects midbrain dopaminergic neurons, presumably via up-regulation of brain-derived neurotrophic factor (BDNF) expression. The present study was focused on unexplored signaling mechanisms linking RAR stimulation to BDNF expression. Rat midbrain slice cultures treated with an RAR agonist Am80 showed increased tissue levels of BDNF mRNA and protein as compared to cultures without treatment. Am80-induced increase in BDNF expression was observed in dopaminergic neurons, which was blocked by inhibition of extracellular signal-regulated kinase (ERK) activation. We also found that Am80 increased neuronal nitric oxide synthase expression in dopaminergic neurons even during ERK inhibition, and this increase was accompanied by 8-nitro-cyclic GMP formation. Notably, the effect of Am80 on BDNF expression was attenuated by inhibitors of nitric oxide synthase, soluble guanylyl cyclase and cyclic GMP-dependent protein kinase (PKG). Am80-induced ERK phosphorylation in dopaminergic neurons was also attenuated by inhibition of soluble guanylyl cyclase and PKG. Moreover, 8-Br-cyclic GMP induced ERK phosphorylation and BDNF expression in dopaminergic neurons. These results suggest that, by recruiting cyclic GMP and PKG, neuronal nitric oxide synthase-derived nitric oxide plays a novel and essential role in RAR signaling leading to ERK-dependent BDNF up-regulation in midbrain dopaminergic neurons.

[InquilineKea]

Probably just crashes or some sort of vascular issue, I wouldn't lose too much sleep over it.
Neurotoxicity is very hard to gauge in all but the most severe cases, so unless you start going psychotic you're not going to see anything from 15mg amphetamine. This thread is more designed to help prevent the slow accumulation of damage which could present itself as, say Parkinsons, later in life.

It could possibly be interpreted as a process that could decrease working memory: http://www.scienceda...91021172655.htm

The declines in short-term or "working" memory are most pronounced when the rats are exposed during adolescence, rather than as adults, the researchers found.
"Animals that were given the amphetamine during the adolescent time period were worse at tasks requiring working memory than adult animals that were given the same amount of amphetamine as adults," said psychology professor Joshua Gulley, who led the study with graduate student Jessica Stanis. "This tells us that their working memory capacity has been significantly altered by that pre-exposure to amphetamine."

BUT, it shows that adolescents are most vulnerable, and I believe that this process is independent of neurotoxicity, as neurons (that still grow terminals/synapses) will "adapt" to the artificially high dopamine concentrations, and may not "decide" to grow as long or as dense.

In any case, I would still call it inconclusive. Although I would still be somewhat concerned about working memory decline, it is merely a future area where I'd like to see research (and maybe a future area that others can investigate)


Here are some articles I just looked at.

http://www.sciencedi...163104783913110 first. BUT, the article here has everything to do with arousal and nothing to do with working memory, so we have to toss it out (I'm still bringing it up since it's still important to show which studies we need to tag as irrelevant)

Retention deficits in discrete trial delayed alternation and delayed matching to sample tasks following administration of d-amphetamine have been interpreted to support the view that arousal facilitates the decay of information from short-term memory (STM) (Kesner, 1973). But since amphetamine causes numerous changes in performance, alternative explanations of the deficit are also plausible. In an attempt to separate drug effects on memory from those on performance, the effects of d-amphetamine on spatial memory in the radial maze were studied in rats. The unusually long span of accurate working memory in this setting permits drug administration within the retention interval as well as prior to the to-be-remembered event (TBRE). In rats tested at a 5-hr retention interval d-amphetamine (2 mg/kg) disrupted retention when given 0.5 hr before or 4.5 hr after the TBRE, but the same treatment 0 or 2 hr after the TBRE or 3 hr before the TBRE was without effect. At a 5-hr retention interval 3 mg/kg d-amphetamine impaired performance if given 2 hr after the TBRE, but not when given 0 hr after the TBRE or 3 hr before the TBRE. However, when the retention interval was lengthened to 7 hr, administering 3 mg/kg d-amphetamine 2 hr after the TBRE did not disrupt performance. The effects of d-amphetamine on spatial memory are best explained in terms of the well established effects of the drug on motor activity and appetite. Similar changes in performance may account for the “memory” impairments observed after amphetamine treatment in other tasks.

http://www.sciencedi...166432802000402 might be negative

Repeated exposure to psychomotor stimulants produces long-lasting molecular, cellular and locomotor behavioral changes. Such changes are likely to contribute to the development of drug addiction and psychosis. It is not clear whether these durable changes are accompanied by lasting changes in cognition. We examined the long-term effects of repeated treatment with phencyclidine (PCP) or amphetamine on working memory, using a discrete, paired-trials, delayed-alternation task sensitive to the acute effects of PCP and amphetamine, and to the integrity of the prefrontal cortex. Twice daily treatment with PCP (5.0 mg/kg) or amphetamine (2.5 mg/kg) for 5 days did not produce lasting, significant impairments in alternation performance in comparison to either pre-treatment baseline performance or to the vehicle-treated group. Subsequent challenge doses of PCP (1, 3 and 5 mg/kg) produced alternation deficits in vehicle, PCP, and amphetamine pre-treated groups that were dependent on dose, but not on pre-treatment regimen. However, rats pre-treated with PCP showed a trend towards sensitization in response to PCP challenge. The present data suggest that psychostimulant treatment regimens that are reported to produce long-lasting changes in neural morphology and locomotor behavior may not produce equally durable changes in working memory.

http://www.sciencedi...163104784910203 is also arousal related, so toss it.

[InquilineKea]

Probably just crashes or some sort of vascular issue, I wouldn't lose too much sleep over it.
Neurotoxicity is very hard to gauge in all but the most severe cases, so unless you start going psychotic you're not going to see anything from 15mg amphetamine. This thread is more designed to help prevent the slow accumulation of damage which could present itself as, say Parkinsons, later in life.

It could possibly be interpreted as a process that could decrease working memory: http://www.scienceda...91021172655.htm

The declines in short-term or "working" memory are most pronounced when the rats are exposed during adolescence, rather than as adults, the researchers found.
"Animals that were given the amphetamine during the adolescent time period were worse at tasks requiring working memory than adult animals that were given the same amount of amphetamine as adults," said psychology professor Joshua Gulley, who led the study with graduate student Jessica Stanis. "This tells us that their working memory capacity has been significantly altered by that pre-exposure to amphetamine."

BUT, it shows that adolescents are most vulnerable, and I believe that this process is independent of neurotoxicity, as neurons (that still grow terminals/synapses) will "adapt" to the artificially high dopamine concentrations, and may not "decide" to grow as long or as dense.

In any case, I would still call it inconclusive. Although I would still be somewhat concerned about working memory decline, it is merely a future area where I'd like to see research (and maybe a future area that others can investigate)


Here are some articles I just looked at.

http://www.sciencedi...163104783913110 first. BUT, the article here has everything to do with arousal and nothing to do with working memory, so we have to toss it out (I'm still bringing it up since it's still important to show which studies we need to tag as irrelevant)

Retention deficits in discrete trial delayed alternation and delayed matching to sample tasks following administration of d-amphetamine have been interpreted to support the view that arousal facilitates the decay of information from short-term memory (STM) (Kesner, 1973). But since amphetamine causes numerous changes in performance, alternative explanations of the deficit are also plausible. In an attempt to separate drug effects on memory from those on performance, the effects of d-amphetamine on spatial memory in the radial maze were studied in rats. The unusually long span of accurate working memory in this setting permits drug administration within the retention interval as well as prior to the to-be-remembered event (TBRE). In rats tested at a 5-hr retention interval d-amphetamine (2 mg/kg) disrupted retention when given 0.5 hr before or 4.5 hr after the TBRE, but the same treatment 0 or 2 hr after the TBRE or 3 hr before the TBRE was without effect. At a 5-hr retention interval 3 mg/kg d-amphetamine impaired performance if given 2 hr after the TBRE, but not when given 0 hr after the TBRE or 3 hr before the TBRE. However, when the retention interval was lengthened to 7 hr, administering 3 mg/kg d-amphetamine 2 hr after the TBRE did not disrupt performance. The effects of d-amphetamine on spatial memory are best explained in terms of the well established effects of the drug on motor activity and appetite. Similar changes in performance may account for the “memory” impairments observed after amphetamine treatment in other tasks.

http://www.sciencedi...166432802000402 might be negative

Repeated exposure to psychomotor stimulants produces long-lasting molecular, cellular and locomotor behavioral changes. Such changes are likely to contribute to the development of drug addiction and psychosis. It is not clear whether these durable changes are accompanied by lasting changes in cognition. We examined the long-term effects of repeated treatment with phencyclidine (PCP) or amphetamine on working memory, using a discrete, paired-trials, delayed-alternation task sensitive to the acute effects of PCP and amphetamine, and to the integrity of the prefrontal cortex. Twice daily treatment with PCP (5.0 mg/kg) or amphetamine (2.5 mg/kg) for 5 days did not produce lasting, significant impairments in alternation performance in comparison to either pre-treatment baseline performance or to the vehicle-treated group. Subsequent challenge doses of PCP (1, 3 and 5 mg/kg) produced alternation deficits in vehicle, PCP, and amphetamine pre-treated groups that were dependent on dose, but not on pre-treatment regimen. However, rats pre-treated with PCP showed a trend towards sensitization in response to PCP challenge. The present data suggest that psychostimulant treatment regimens that are reported to produce long-lasting changes in neural morphology and locomotor behavior may not produce equally durable changes in working memory.

http://www.sciencedi...163104784910203 is also arousal related, so toss it.

[Delta Gamma]

I can't find the study on administration frequency of amphetamine affecting tolerance. But all the latest findings on amphetamine sensitization were pointing to genes and the hippocampus. This one specifically indicating BDNF. http://www.ncbi.nlm....pubmed/21570990

Repeated amphetamine treatment also increased VTA BDNF, while both acute and repeated amphetamine treatment increased Fos and Fos-BDNF co-labeling, an effect enhanced in sensitized rats. These findings point to a role of cortico-tegmental BDNF in long-term amphetamine sensitization.

Maybe someone more educated than I can tell us how this can possibly be avoided.

Fos, and in particular Delta Fos-B is majorly involved in addiction through some paradoxical shift in glutamate receptors on the NAcc. It both increases the sensitivity to reward and decreases the NAcc's sensitivity to glutamate.

In rats sensitization occurs faster that tolerance, which (barring some exceptions) is the opposite of humans. A lot of these Fos proteins are activated by CREB which can be inhibited by curcumin and several other compounds which goes into gene expression like I discussed on bluelight.ru .
Its also worth noting that most Fos proteins are really freaking stable so they can hang along for months after the last exposure, which is why there can be extremely long term tolerance to some drug effects. Also, proteins in this family can induce apoptosis via signalling a death pathway.

http://en.wikipedia....FosB#Delta_FosB

[Delta Gamma]

Also very interesting:

http://www.ncbi.nlm....pubmed/20649843

Stimulation of retinoic acid receptors (RARs) protects midbrain dopaminergic neurons, presumably via up-regulation of brain-derived neurotrophic factor (BDNF) expression. The present study was focused on unexplored signaling mechanisms linking RAR stimulation to BDNF expression. Rat midbrain slice cultures treated with an RAR agonist Am80 showed increased tissue levels of BDNF mRNA and protein as compared to cultures without treatment. Am80-induced increase in BDNF expression was observed in dopaminergic neurons, which was blocked by inhibition of extracellular signal-regulated kinase (ERK) activation. We also found that Am80 increased neuronal nitric oxide synthase expression in dopaminergic neurons even during ERK inhibition, and this increase was accompanied by 8-nitro-cyclic GMP formation. Notably, the effect of Am80 on BDNF expression was attenuated by inhibitors of nitric oxide synthase, soluble guanylyl cyclase and cyclic GMP-dependent protein kinase (PKG). Am80-induced ERK phosphorylation in dopaminergic neurons was also attenuated by inhibition of soluble guanylyl cyclase and PKG. Moreover, 8-Br-cyclic GMP induced ERK phosphorylation and BDNF expression in dopaminergic neurons. These results suggest that, by recruiting cyclic GMP and PKG, neuronal nitric oxide synthase-derived nitric oxide plays a novel and essential role in RAR signaling leading to ERK-dependent BDNF up-regulation in midbrain dopaminergic neurons.

Hmmm, so this points us to a protective role for iNOS/nNos for once...
I guess this means inhibitors are off the table for protective measures, and vitamin A supplements and RNS scavengers seem like a more promising route now.

Damn genetics is complex, this is a CREB dependent pathway from what I gather and it may have some downstream effects on c-Fos. I'd need to have more data and time before I can say anything about what implications this will have.

http://en.wikipedia.org/wiki/CREM
http://en.wikipedia....APK/ERK_pathway
http://en.wikipedia....ription_factor)
and a good chunk of the Fos proteins seem to all be involved so I'm going to have my hands full as far as figuring out what's going on haha.

Any help researching this stuff in relation to amphetamine or methamphetamine would be great!

[Delta Gamma]

Probably just crashes or some sort of vascular issue, I wouldn't lose too much sleep over it.
Neurotoxicity is very hard to gauge in all but the most severe cases, so unless you start going psychotic you're not going to see anything from 15mg amphetamine. This thread is more designed to help prevent the slow accumulation of damage which could present itself as, say Parkinsons, later in life.

It could possibly be interpreted as a process that could decrease working memory: http://www.scienceda...91021172655.htm

The declines in short-term or "working" memory are most pronounced when the rats are exposed during adolescence, rather than as adults, the researchers found.
"Animals that were given the amphetamine during the adolescent time period were worse at tasks requiring working memory than adult animals that were given the same amount of amphetamine as adults," said psychology professor Joshua Gulley, who led the study with graduate student Jessica Stanis. "This tells us that their working memory capacity has been significantly altered by that pre-exposure to amphetamine."

BUT, it shows that adolescents are most vulnerable, and I believe that this process is independent of neurotoxicity, as neurons (that still grow terminals/synapses) will "adapt" to the artificially high dopamine concentrations, and may not "decide" to grow as long or as dense.

In any case, I would still call it inconclusive. Although I would still be somewhat concerned about working memory decline, it is merely a future area where I'd like to see research (and maybe a future area that others can investigate)

I'll go through your post more when I have the time to, but it seems like a very interesting lead. Part of me thinks it might be due to the DA/ACh balance in the brain but I'm not sure.

But, great work man keep it up

[InquilineKea]

I'll go through your post more when I have the time to, but it seems like a very interesting lead. Part of me thinks it might be due to the DA/ACh balance in the brain but I'm not sure.

But, great work man keep it up

Thanks!

==

Hey Delta Gamma, are you still planning to leave this forum for bluelight? I saw the bluelight discussion, but the people there tend to make short non-comprehensive replies. This still seems like the best place to discuss stuff (there's also reddit's psychopharmacology, but the problem with reddit is that you can't top old threads like the one here, so ALL threads inevitably die). Which isn't the case here.

There might be some "stupid" questions here, but you can always choose to ignore them (just find some creative excuse). It's what ultimately happens in threads like these. Longecity is still the best place I've found for discussions like this.

[jlspartz]

Also very interesting:

http://www.ncbi.nlm....pubmed/20649843

Stimulation of retinoic acid receptors (RARs) protects midbrain dopaminergic neurons, presumably via up-regulation of brain-derived neurotrophic factor (BDNF) expression. The present study was focused on unexplored signaling mechanisms linking RAR stimulation to BDNF expression. Rat midbrain slice cultures treated with an RAR agonist Am80 showed increased tissue levels of BDNF mRNA and protein as compared to cultures without treatment. Am80-induced increase in BDNF expression was observed in dopaminergic neurons, which was blocked by inhibition of extracellular signal-regulated kinase (ERK) activation. We also found that Am80 increased neuronal nitric oxide synthase expression in dopaminergic neurons even during ERK inhibition, and this increase was accompanied by 8-nitro-cyclic GMP formation. Notably, the effect of Am80 on BDNF expression was attenuated by inhibitors of nitric oxide synthase, soluble guanylyl cyclase and cyclic GMP-dependent protein kinase (PKG). Am80-induced ERK phosphorylation in dopaminergic neurons was also attenuated by inhibition of soluble guanylyl cyclase and PKG. Moreover, 8-Br-cyclic GMP induced ERK phosphorylation and BDNF expression in dopaminergic neurons. These results suggest that, by recruiting cyclic GMP and PKG, neuronal nitric oxide synthase-derived nitric oxide plays a novel and essential role in RAR signaling leading to ERK-dependent BDNF up-regulation in midbrain dopaminergic neurons.

Hmmm, so this points us to a protective role for iNOS/nNos for once...
I guess this means inhibitors are off the table for protective measures, and vitamin A supplements and RNS scavengers seem like a more promising route now.

Damn genetics is complex, this is a CREB dependent pathway from what I gather and it may have some downstream effects on c-Fos. I'd need to have more data and time before I can say anything about what implications this will have.

http://en.wikipedia.org/wiki/CREM
http://en.wikipedia....APK/ERK_pathway
http://en.wikipedia....ription_factor)
and a good chunk of the Fos proteins seem to all be involved so I'm going to have my hands full as far as figuring out what's going on haha.

Any help researching this stuff in relation to amphetamine or methamphetamine would be great!

From everything that I've come across that has shown positive reduction in ADD/ADHD whether it be drug/supplement/lifestyle change/specific cognitive training - it all has one underlying similarity, BDNF (which protects the dopaminergic system and assists in neurogenesis. The pathway is ERK-CREB-BDNF. Here's another connection I just found. Out of the three pathways signaled, ERK is what modulated hyperactivity.

Recent investigations have shown that three major striatal-signaling pathways (protein kinase A/DARPP-32, Akt/glycogen synthase kinase 3, and ERK) are involved in the regulation of locomotor activity by the monoaminergic neurotransmitter dopamine. Here we used dopamine transporter knock-out mice to examine which particular changes in the regulation of these cell signaling mechanisms are associated with distinct behavioral responses to psychostimulants. In normal animals, amphetamine and methylphenidate increase extracellular levels of dopamine, leading to an enhancement of locomotor activity. However, in dopamine transporter knock-out mice that display a hyperactivity phenotype resulting from a persistent hyperdopaminergic state, these drugs antagonize hyperactivity. Under basal conditions, dopamine transporter knock-out mice show enhanced striatal DARPP-32 phosphorylation, activation of ERK, and inactivation of Akt as compared with wild-type littermates. However, administration of amphetamine or methylphenidate to these mice reveals that inhibition of ERK signaling is a common determinant for the ability of these drugs to antagonize hyperactivity. In contrast, psychostimulants activate ERK and induce hyperactivity in normal animals. In hyperactive mice psychostimulant-mediated behavioral inhibition and ERK regulation are also mimicked by the serotonergic drugs fluoxetine and 5-carboxamidotryptamine, thereby revealing the involvement of serotonin-dependent inhibition of striatal ERK signaling. Furthermore, direct inhibition of the ERK signaling cascade in vivo using the MEK inhibitor SL327 recapitulates the actions of psychostimulants in hyperactive mice and prevents the locomotor-enhancing effects of amphetamine in normal animals. These data suggest that the inhibitory action of psychostimulants on dopamine-dependent hyperactivity results from altered regulation of striatal ERK signaling. In addition, these results illustrate how altered homeostatic state of neurotransmission can influence in vivo signaling responses and biological actions of pharmacological agents used to manage psychiatric conditions such as Attention Deficit Hyperactivity Disorder (ADHD).

Other items that affect BDNF:
Omega 3s/DHA http://www.ncbi.nlm....pubmed/18620024
Exercise http://ep.physoc.org...0/1062.full.pdf
Meditation http://www.ncbi.nlm....pubmed/17905931
Short term sleep deprivation for the worse http://www.sciencedi...006899300027086
BDNF shows regenerative effect in Parkinson's http://www.ncbi.nlm....pubmed/21236244
Enriched Environment http://www.ncbi.nlm....pubmed/21236277
Green Tea http://www.ncbi.nlm....pubmed/19409206
Blueberries http://www.ncbi.nlm....pubmed/18457678
BDNF used for short term and long term memory and inhibitory learning which was found through inhibiting ERK http://www.ncbi.nlm....pubmed/12201640

Here's a study on amphetamine sensitization http://www.ncbi.nlm....pubmed/21570990
The effects of methylphenidate on BDNF and subsequently dopamine, and Arc are found to vary between juvenile and adult rats, which could explain memory loss being more pronouned when young. http://www.ncbi.nlm....pubmed/19222557