106 replies to this topic

[zrbarnes]

abelard lindsay, on 15 May 2012 - 11:01 PM, said:

It seems that the people who are having good results are taking dopamine activating supplements or drugs.  This would make sense as the cAMP/CREB cascade is triggered by dopamine receptor activation(http://www.ncbi.nlm....pubmed/21057772).

Me: L-Phenylalanine (Amino acid building block of Dopamine)
ZRBarnes: Adderall
Health Nutty: Looking at your stack (http://www.longecity...-on-perfection/) Ginko is the only dopamine increasing element (http://www.ncbi.nlm....pubmed/20411379) I see besides Caffeine.  Methylene Blue does all kinds of funky stuff but it's supposedly not dopamine increasing.

Anyway, I  know we're getting kind of complicated here but I am going to revise the CILTEP stack a bit.
One Herbal PDE4 inhibitor

• Artichoke Extract or
  
• Activated Quercetin

One cAMP increaser

• Forskolin

Optionally, a dopamine increasing supplement:

• L-Pheynylalanine (Don't confuse it with DL-Phenylalanine)
  
• Caffeine (helps but may not be enough by itself)
  
• Ginko

I very much agree with this. I have a feeling that any of the classical stimulants (including ephedrine, psuedoephedrine, DMAA, yohimbine, etc) would work here, and I wonder if some of the other dopamine increasers would work (Mucuna pruriens, l-tyrosine, etc).

However, I wonder about how much norepinepherine plays into this.

That reminds me, I have a couple D-amphetamines left from a long time ago. They didn't work as well for motivation as Adderall did, which I attributed to the l-amp salt in Adderall preferring NE. If I replace the Adderall with a small dose of the d-amp, which mostly only effects dopamine, it should give me an idea of how much the motivating effects of the CILTEP stack rely on dopamine, and how much on the norepinepherine. I'll report back tomorrow.

Today's experimental stack caused a bit of overstimulation and lightheadedness for about an hour after I first took it, but I took it on an empty stomach first thing in the morning.

I woke up, took 1 artichoke, 1 quercetin, 1 celery seed, 1 rosemary, 10mg of forskolin, 5mg of Adderall, and 50mg of caffeine.

I ate a couple hours later, and I felt a lot better. After lunch, I took some echinacea, goldenseal root, and berberine, and drank a cup of the Runa Guayusa tea.

I feel pretty awesome right now. Very focused, motivated, great mood, clear headed, and not irritable when I'm around people. I don't feel superhuman, but I do feel like I'm "at my best". In the end, that is all I am trying to achieve.

Edited by zrbarnes, 15 May 2012 - 11:47 PM.

[kevinseven11]

I would add Uridine as a dopamine increasing supplement.
Why does marijuana decrease cAMP levels? St Johns Wort has been shown to activate CREB, perhaps add to the list?

[abelard lindsay]

I would add Catuaba as a dopamine increasing supplement (http://www.ncbi.nlm....pubmed/15991001)

.  

It's pretty strong, a bit like Rhodiola.  I've been taking that one off and on for years.

Edited by abelard lindsay, 16 May 2012 - 12:36 AM.

[khemix]

abelard lindsay, on 10 May 2012 - 05:15 AM, said:

Gamerzneed, on 10 May 2012 - 05:01 AM, said:

It's not that caffeine makes me feel bad, it's just that it gives me brainfog, it makes me feel more stressed but not in a bad way, it feels like a pressure to get things done unfortunately it brain fogs me though. Do you think magnesium would have any synergism with the combo?

Magnesium, especially Magnesium threonate (MgT), works on a different pathway.  It is a NMDA anatoginst.  NMDA receptors are associated with short term memory.  When they are blocked by an antagonist, the brain produces more to compensate.  More NMDA receptors = better short term memory.  Also, NMDA anatagonism is kind of pleasant but doesn't make one feel smarter while it's on-going.  It's the neurogenisis caused by the body's reaction to the NMDA anatagonism that makes for the nootropic effect.

The perfect nootropics is a stack that stimulates all facets of intelligence so MgT can be used to take care of the short term side and CILTEP to take care of the long term side which the short term side feeds into.  There might be something odd with your brain though.  It sounds like you've got some other underlying problems that you should focus on getting fixed. Have you been to an endocrinologist to get your levels checked?

sorry, but can you provide a source that confirms antagonizing NMDA leads to improved short term memory? from a conceptual point of view this doesn't make any sense... your brain would only upregulate to return to unimpeded levels. and once you went off the antagonist your gains would be lost to down regulation. using something like memantine in an alzheimers patient makes sense because you want to reduce the excess glutamate activity which is frying brain cells. in a normal patient however, i can only see a loss in learning potential and memory.

by this logic, one should use antipsychotics to upregulate dopamine receptors and improve brain function.

Edited by khemix, 16 May 2012 - 02:08 AM.

[abelard lindsay]

khemix, on 16 May 2012 - 02:05 AM, said:

sorry, but can you provide a source that confirms antagonizing NMDA leads to improved short term memory? from a conceptual point of view this doesn't make any sense... your brain would only upregulate to return to unimpeded levels. and once you went off the antagonist your gains would be lost to down regulation. using something like memantine in an alzheimers patient makes sense because you want to reduce the excess glutamate activity which is frying brain cells. in a normal patient however, i can only see a loss in learning potential and memory.

by this logic, one should use antipsychotics to upregulate dopamine receptors and improve brain function.

This is not some kooky theory I came up with.  It's what the authors of the original MgT study theorize is the mechanism of action.

http://www.longecity...353#entry411353

Quote

The question of whether all this would be beneficial in humans is a good one. The authors propose (and confirm by several analyses) that increased synaptic plasticity and activity is due to upregulation of NMDA receptors (via homeostatic response to Mg NMDAR channel blockage, and leading to higher NMDA current during burst activity). Higher brain Mg increased the ratio of phosphorylated CamKII and CREB (but not their total expression), as well as the ratio of NR2B to NR2A/NR1 subunits (these have a positive effect on short- and long-term potentiation, and plasticity). Downstream of this, BDNF was increased by 36% (BDNF is regulated by level of CREB activation). Tests also found increased levels of synaptophysin and synaptobrevin, indicating increased density of presynaptic boutons, and an increase in the number of functional presynaptic release sites. (As Lufega said, this paper is a great read...they really followed the question through pretty deeply)

You can argue on that thread that the authors of the study have the wrong hypothesis if you'd like.  Let's not turn this thread into another MgT thread.  There are already plenty.

Edited by abelard lindsay, 16 May 2012 - 04:44 AM.

[zrbarnes]

Magnesium L-Threonate is interesting. When I take a full dose, it hits me about 30 minutes later. It's a relaxing sensation, except for that initial panic of "what the heck just happened... oh yeah, I took some stuff a little while ago". I usually take it in the evening after I'm done stimulating my brain, along with some P5P.

I wish it wasn't so expensive. I rarely take it because it costs about a $1 a day. Add that on top of some of the other stuff I'm trialing, and it gets pretty pricey just to have a functioning brain.

Edited by zrbarnes, 16 May 2012 - 04:55 AM.

[owtsgmi]

kevinseven11, on 15 May 2012 - 11:26 PM, said:

I would add Uridine as a dopamine increasing supplement.
Why does marijuana decrease cAMP levels? St Johns Wort has been shown to activate CREB, perhaps add to the list?

I was thinking the same thing about a potential synergy with uridine.  Uridine is not an overt dopamine enhancer - more of a modulater/balancer.  Seems it could plug in well to the CILTEP stack.  Any personal experiences?

Edited by owtsgmi, 16 May 2012 - 03:21 PM.

[abelard lindsay]

owtsgmi, on 16 May 2012 - 03:19 PM, said:

kevinseven11, on 15 May 2012 - 11:26 PM, said:

I would add Uridine as a dopamine increasing supplement.
Why does marijuana decrease cAMP levels? St Johns Wort has been shown to activate CREB, perhaps add to the list?

I was thinking the same thing about a potential synergy with uridine.  Uridine is not an overt dopamine enhancer - more of a modulater/balancer.  Seems it could plug in well to the CILTEP stack.  Any personal experiences?

I added uridine to my stack at the end of last week.  It was too strong for my taste.  It felt like a serotonin effect, IMHO.  Perhaps it was synergistic with CILTEP?  I'm not going to continue taking it.

Edited by abelard lindsay, Yesterday, 03:33 AM.

[health_nutty]

abelard lindsay, on 15 May 2012 - 11:01 PM, said:

Health Nutty: Looking at your stack (http://www.longecity...-on-perfection/) Ginko is the only dopamine increasing element (http://www.ncbi.nlm....pubmed/20411379) I see besides Caffeine.  Methylene Blue does all kinds of funky stuff but it's supposedly not dopamine increasing.

Anyway, I  know we're getting kind of complicated here but I am going to revise the CILTEP stack a bit.
One Herbal PDE4 inhibitor

• Artichoke Extract or
  
• Activated Quercetin

One cAMP increaser

• Forskolin

Optionally, a dopamine increasing supplement:

• L-Pheynylalanine (Don't confuse it with DL-Phenylalanine)
  
• Caffeine (helps but may not be enough by itself)
  
• Ginko

Interesting.  I'm getting decent but not stellar results with CILTEP.   Mabye I need a stronger dopamine increasing supplement?  I'm going to try adding L-Phenylalanine or L-Tyrosine and report back.

[magta39]

For those who find tyrosine or phenylalanine too stimulating, perhaps theanine?
Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats.

Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T.

Source

School of Food and Nutritional Sciences, The University of Shizuoka, Yada, Shizuoka, Japan. yokogosi@fns1.u-shizuoka-ken.ac.jp

Abstract

Theanine, r-glutamylethylamide, is one of the major components of amino acids in Japanese green tea. Effect of theanine on brain amino acids and monoamines, and the striatal release of dopamine (DA) was investigated. Determination of amino acids in the brain after the intragastric administration of theanine showed that theanine was incorporated into brain through blood-brain barrier via leucine-preferring transport system. The concentrations of norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the brain regions were unaffected by the theanine administration except in striatum. Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus. Direct administration of theanine into brain striatum by microinjection caused a significant increase of DA release in a dose-dependent manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the theanine-induced DA release. Pretreatment with the Ringer buffer containing an antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1 hr did not change the significant increase of DA release induced by theanine. However, in the case of pretreatment with AP-5, (+/-)-2-amino-5-phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine-induced DA release from striatum was significantly inhibited. These results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA.

[health_nutty]

Tyrosine and Quercetin purchased.  I'll give my feedback over the next couple of days.

[health_nutty]

Tyrosine never did anything when I tried it before.  I tried 500mg of tyrosine with this stack and I'm feeling energized and a bit manic.

[zrbarnes]

health_nutty, on 17 May 2012 - 11:15 PM, said:

Tyrosine never did anything when I tried it before.  I tried 500mg of tyrosine with this stack and I'm feeling energized and a bit manic.

This is essentially how I feel about most stimulants, caffeine included. Almost all of the effects were in the periphery, never mentally. Now, just about anything related to the dopamine system works, and works very well.

5mg of d-amphetamine + CILTEP worked very well today for focus and motivation, with great mood. When I take it without the CILTEP stack, it really only gives me extreme tunnel vision and irritability @ 20mg, and @ 5mg it does next to nothing.

L-tyrosine and L-phenylalanine used to nothing for me either, so I will definitely have to revisit those, since I am hoping to move away from prescription stimulants. In fact, I have a whole list of things that I'm going to have to re-evaluate!

I am really curious about the mechanism of action of why this works so well. I suppose until we convince someone to inject a bunch of rats and then cut their heads off, we will only be able to guess. It's just a little scary, because this stack makes me a functioning person, so I do plan to take it long term.

Once I get out of the guinea pig phase, I'll probably lower the doses as far as possible, just in case, unless we get some good lab studies that point to long term effects.

Edited by zrbarnes, Today, 02:02 AM.

[abelard lindsay]

zrbarnes, on 18 May 2012 - 01:56 AM, said:

I am really curious about the mechanism of action of why this works so well. I suppose until we convince someone to inject a bunch of rats and then cut their heads off, we will only be able to guess. It's just a little scary, because this stack makes me a functioning person, so I do plan to take it long term.

If you go back and read the research I posted, you'll see that dopamine has many effects in the brain and  cAMP/CREB triggered LTP is just one particularly interesting one that this stack is tweaking to be more sensitive.  The theory I have is that normally it would take a lot of dopamine to trigger the same effect, but any mechanism of stimulating that much dopamine would lead to all kinds of negative side effects, especially in the long run.  So now, when taking a relatively small amount of Phenylalanine or Tyrosine, I can stimulate this pathway without the excessive dopamine side effects it would normally take to trigger this pathway, especially over time as the body downregulates receptors to adjust to the increased dopamine influx.

One thing I really like to do when taking this stack is watch Khan Academy videos at double speed.  I watch them for literally hours.  I swear I get everything and it's thoroughly entertaining the whole way through.  I can remember them fairly well the next day, in fact if I go over them in my head a bit the following day, and the memories solidify.  It's also much easier to pay attention to what people are saying in social situations and bust out with extremely long complicated explanations of technical details without even a stutter.

Anecdotally, the effects from the Quercetin last for at least 24 hours and peak about 12 hours in.  It has a very long half life or it generates a lot of PDE inhibition and thus a lot of cAMP which may have a long half life.  Artichoke is much more mellow and seems to have a shorter half life.  There are definitely some negative effects when I take too much of this stack.  They pass after a few hours and I can usually avoid them by lowering the dosage.   I do not re-dose later in the day as the effects build for quite a long time, especially the Quercetin.

Edited by abelard lindsay, Today, 03:24 AM.

[health_nutty]

Albert, can you post your full stack?

Edited by health_nutty, Today, 03:43 AM.

[Gamerzneed]

abelard lindsay, on 18 May 2012 - 03:11 AM, said:

zrbarnes, on 18 May 2012 - 01:56 AM, said:

I am really curious about the mechanism of action of why this works so well. I suppose until we convince someone to inject a bunch of rats and then cut their heads off, we will only be able to guess. It's just a little scary, because this stack makes me a functioning person, so I do plan to take it long term.

If you go back and read the research I posted, you'll see that dopamine has many effects in the brain and  cAMP/CREB triggered LTP is just one particularly interesting one that this stack is tweaking to be more sensitive.  The theory I have is that normally it would take a lot of dopamine to trigger the same effect, but any mechanism of stimulating that much dopamine would lead to all kinds of negative side effects, especially in the long run.  So now, when taking a relatively small amount of Phenylalanine or Tyrosine, I can stimulate this pathway without the excessive dopamine side effects it would normally take to trigger this pathway, especially over time as the body downregulates receptors to adjust to the increased dopamine influx.

One thing I really like to do when taking this stack is watch Khan Academy videos at double speed.  I watch them for literally hours.  I swear I get everything and it's thoroughly entertaining the whole way through.  I can remember them fairly well the next day, in fact if I go over them in my head a bit the following day, and the memories solidify.  It's also much easier to pay attention to what people are saying in social situations and bust out with extremely long complicated explanations of technical details without even a stutter.

Anecdotally, the effects from the Quercetin last for at least 24 hours and peak about 12 hours in.  It has a very long half life or it generates a lot of PDE inhibition and thus a lot of cAMP which may have a long half life.  Artichoke is much more mellow and seems to have a shorter half life.  There are definitely some negative effects when I take too much of this stack.  They pass after a few hours and I can usually avoid them by lowering the dosage.   I do not re-dose later in the day as the effects build for quite a long time, especially the Quercetin.

do you think if I didn't get any results with artichoke + forskolin, Quercetin would make any kind of difference?
I wish I had that kind of reaction to this stack.

Edited by Gamerzneed, Today, 06:13 AM.

[abelard lindsay]

Gamerzneed, on 18 May 2012 - 06:10 AM, said:

do you think if I didn't get any results with artichoke + forskolin, Quercetin would make any kind of difference?
I wish I had that kind of reaction to this stack.

For starting out, artichoke is better, IMHO, as the effects last for a shorter length of time than quercetin.  If you don't like how you feel on the stack you'll have to wait a lot longer for the effects to clear with Quercetin.  

Have you tried adding L-Phenylalanine to your stack?  This might be the missing ingredient.  Health Nutty said that the stack was just decent until he added a dopamine pre-cursor (Tyrosine).  L-Phenylalanine is a much more conservative choice for starting out, as it's the basic amino acid from food that the brain uses to make dopamine so the body is well adapted as far as controlling and regulating the metabolism of it.  It's the dopamine source I use in my stack and it seems to work fine.  It's also fairly inexpensive.