2626 replies to this topic

[unbeatableking]

The problem as I see it is number one: studies have proven that the stack has no effect on working memory whatsoever.

And number two, from an anecdotal perspective, a lot of people are reporting negatives with regards to working memory.

Book reading is heavily reliant on working memory. Without that capacity, the consolidation of memories will not occur - you can't consolidate something you have not processed and absorbed after all.

I am speaking from an encoding + rote memory perspective by the way.

[unbeatableking]

Biologically, short-term memory is a temporary potentiation of neural connections that can become long-term memory through the process of rehearsal and meaningful association. Not much is known about the underlying biological mechanisms of long-term memory, but the process of long-term potentiation, which involves a physical change in the structure of neurons, has been proposed as the mechanism by which short-term memories move into long-term storage. The time scale involved at each level of memory processing remains under investigation.

Ergo, anything that doesn't enter your short-term memory/working memory cannot enter your long-term memory.

[IA87]

I took 3.85 mg forskolin + 250 mg of quercetin, waited an hour or so, and then did some dual-n-back. My scores started out where I expected them, and then I had one round that went a bit better than I was used to; however, performance declined after that. I am doing significantly worse than average for several rounds in a row. I took another 250 mg of quercetin and did not notice any difference in score for around 20 minutes. After that, however, my score began to decrease even more. I could chalk this up to placebo effect, but I don't think this is the case; I feel more confident and feel like I can focus better, so I would think that any placebo effect would be positive.

Does anyone know which (forskolin or quercetin) is absorbed faster by the body? I wonder if the initial 250 mg of quercetin resulted in a working memory boost (or did nothing) and then the addition of forskolin decreased working memory due to too much cAMP. The second 250 mg dose of quercetin would have then aggravated the issue.

Thoughts?

[unbeatableking]

From thee experiences in this thread, it seems like Quercetin by itself either does nothing or increases memory, albeit slightly.

Forskolin is a different matter entirely.

I have taken Quercetin by itself many times in the past, note that I was taking two grams a day. I felt no issues at all.

Upon adding Forskolin things started going downhill. You will also notice many posts in this topic saying the same thing.

The problem is that a lot of people who talk about the CILTEP stack are doing so from a behavioral perspective. Again, I am talking from the perspective of memory. I will not discount the concentration boost from this stack. What worries me is the working memory impairment brought upon by the stack in question.

Edited by unbeatableking, 19 August 2012 - 09:17 PM.

[IA87]

And what did you experience when you were taking quercetin by itself?

[unbeatableking]

Memory increase. Potentiation of stimulants. I was satisfied.

Minor headache, but I chalk that up to the 2 gram daily dosage. At 500 mg, I am unaffected.

Upon adding Forskolin to the stack? Couldn't encode information anymore. Even stuff I had read previously.

[IA87]

"At 500 mg, I am unaffected." - is your memory increase is maintained?

I forgot to mention that I took 36 mg of concerta (legal Rx).

[unbeatableking]

When I mean unaffected, I mean 'no side-effects'.

I have tried 500 mg of Quercetin without Forskolin - with roughly the same positive effects.

Upon doing so WITH Forskolin, brain fog ensued.

[unbeatableking]

I have gone through studies showing LTP benefits without the use of Forskolin or any other cAMP raising substance.

http://www.ncbi.nlm....les/PMC3309535/

So the contention that the stack is useless without Forskolin is moot. Again, speaking from the memory perspective.

Here is another study involving Rolipram without the use of Forskolin:

http://www.ncbi.nlm....ubmed/18558503/

There are a lot of studies like this. I really think we should reflect on the addition of Forskolin.

Edited by unbeatableking, 19 August 2012 - 09:43 PM.

[unbeatableking]

6 studies and counting guys.

This is interesting, one study that finally shows a benefit with regards to working memory.

Again, this is with the PDE4 inhibitor alone:

Rolipram, a selective inhibitor of type 4 cyclic AMP phosphodiesterase (PDE4), completely reversed the amnesic effects of MK-801 on working and reference memory(F[4,64] = 11.10; p < .0001 and F[4,64] = 2.53; p < .05, respectively) at doses of 0.01–0.1 mg/kg in the radial-arm maze task. Similar antagonism by rolipram of the effects of MK-801 was observed on inhibitory avoidance behavior (F[3,35] = 190.8; p < .0001).In vitro evidence suggests that an increase in cAMP concentrations may mediate the observed behavioral effects of rolipram. In the absence of PDE4 inhibition, NMDA did not increase cAMP concentrations in primary cultures of rat cerebral cortical neurons. However, when PDE4 was inhibited with rolipram, NMDA markedly elevated cAMP. These observations suggest that PDE4 is an integral component of the NMDA receptor-mediated signal transduction pathway involved in memory processes. Inhibitors of PDE4 may act on this pathway to produce their effects on memory and may represent a new class of cognitive enhancers.

Edited by unbeatableking, 19 August 2012 - 10:03 PM.

[gizmobrain]

It sounds like to me you are wanting to target working memory. There was some discussion on this midway through this thread, but nothing solid ever came of it. The main point of the stack was to chemically induce LTP. It was only as a side effect that I noticed increased motivation and energy (and probably related to my particular brain chemistry).

For creating an adjunct stack to target working memory, start with some creatine as it is cheap and easy to come by. If you eat a steady dose of red meat, you probably won't see too much of improvement. If your diet is lacking, you will probably see substantial gains.

Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p < 0.0001) on both working memory (backward digit span) and intelligence (Raven's Advanced Progressive Matrices), both tasks that require speed of processing. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance.

→ source (external link)

Edited by zrbarnes, 19 August 2012 - 10:25 PM.

[unbeatableking]

I am not overtly concerned with increasing working memory.

What people in this topic are concerned with, is the impairment brought upon working memory as a result of this stack.

I'm fine with no working memory boost whatsoever - but a baseline drop, decreasing my overall performance consequently, is something I do not desire.

If LTP is improved, and short-term memory is clearly impaired by the stack in question, then I don't see any reason why people should take the stack any other time than right before bed, as the consolidation of memories occurs at bed time.

[gizmobrain]

LTP isn't the same thing as memory consolidation during sleep. LTP happens throughout the day, as well.

Also, with all the enhanced NMDA firing going on, you can wave goodbye to sleeping if you take this before bed.

For those who are experiencing decreased working memory, my guess is that the forskolin is throwing off another neurotransmitter, causing a type of brainfog which interferes with the ability to process the information. For me, my working memory does not change while taking the stack, and Abelard has said many times that he is able to process substantial amounts of text while "under the influence".

For those with working memory issues while on CILTEP, I'm curious to know if adding TMG, sarcosine, d-serine, or glycine works at resolving this (or if it makes the problem worse). Also, uridine, galantamine, or n-acetyl-cysteine.

Edited by zrbarnes, 19 August 2012 - 11:00 PM.

[unbeatableking]

I meant LTP happens concurrently with deep-sleep induced memory consolidation during sleep.

Given that you can't encode/learn anything on the stack, you might as well take it prior to sleeping.

The Forskolin/neurotransmitter hypothesis is debatable. The bulk of the evidence hedges on an excess of cAMP - not directly related to any specific neurotransmitter.

Also, a study done on excess-cAMP induced working memory deficits implicated ion-channel issues as opposed to any concrete neurotransmitter dysfunction.

Abelard went through videos of mathematical concepts. Sifted through his posts. Nothing there about textbook/rote reading.

And no, I do not think the issue has anything to do with hypo-active NMDA functioning. That is pure speculation.

[IA87]

LTP isn't the same thing as memory consolidation during sleep. LTP happens throughout the day, as well.

Also, with all the enhanced NMDA firing going on, you can wave goodbye to sleeping if you take this before bed.

For those who are experiencing decreased working memory, my guess is that the forskolin is throwing off another neurotransmitter, causing a type of brainfog which interferes with the ability to process the information. For me, my working memory does not change while taking the stack, and Abelard has said many times that he is able to process substantial amounts of text while "under the influence".

For those with working memory issues while on CILTEP, I'm curious to know if adding TMG, sarcosine, d-serine, or glycine works at resolving this (or if it makes the problem worse). Also, uridine, galantamine, or n-acetyl-cysteine.

I take NAC and uridine.

[unbeatableking]

Lately, I've been learning about NMDA, and I've got a wild theory that needs to be tested. For those of us lacking motivation and are not anxious, I'm wondering if the issue at hand is hypo-NMDA activity.

I have to repeat: our issues have nothing to do with behavior or mood.

[unbeatableking]

@zrbarnes

I recall you mentioning that you once took DS Craze with the CILTEP stack?

Well, you have the answer to your question then: DS Craze has a glycinergic.

In the form of TMG as I remember?

Either way, I don't find that explanation congruent with the issues mentioned in this thread.

[gizmobrain]

Actually, I've always felt like my case is one of hypoactive NMDA state normally vs. regular NMDA state on CILTEP.

Sometimes I do take Craze, and yes it has TMG in it, as well as Creatine. That doesn't so much answer my question... since I'm not having any problems with working memory while on CILTEP. I am asking about people who do.

If you normally border the line between regular and hyperactive NMDA state, I feel like CILTEP may push you over the edge. This actually could lead to working memory deficits and other issues. That's why I said "or if it makes the problem worse".

Edited by zrbarnes, 19 August 2012 - 11:24 PM.

[unbeatableking]

Given that one of the studies presented here had presented a viable explanation as to why the stack might inhibit working memory, I see no reason to believe in the NMDA argument.

And if this argument were true, then those of us here who suffer from working memory deficits because of the stack, should also experience working memory issues whilst off of the CILTEP stack.

As the anecdotes here prove, the NMDA-hypoactivity hypothesis isn't true. Which is why people here say their memories get worse on CILTEP.

I mean, what? NMDA hypoactivity only occurs upon taking the stack? Even if you could posit a plausible mechanism of action for this occurrence, there are two or three studies which show that drug-induced NMDA antagonism is rectified by the addition of a PDE4 inhibitor.

Apart from the fact that it would be ludicrous to assume that this many people could have NMDA issues - your explanation is terribly unparsimonious.

Edited by unbeatableking, 19 August 2012 - 11:33 PM.

[unbeatableking]

@Zrbarnes

Anyways, if you ever need someone to brainstorm and discuss anything with, just send me a PM. I hope I can count on you, likewise.

[gizmobrain]

I still don't think you are reading me right.

Hyperactive NMDA = bad.

If you start out with a moderate to high amount of NMDA activity (but still in the healthy range), CILTEP may be pushing you into the Hyperactive NMDA area, leading to a working memory loss, brain fog, etc.

You literally are saying things that agree with me, but in a way that makes it sound like I'm saying the opposite.

Edited by zrbarnes, 19 August 2012 - 11:50 PM.

[unbeatableking]

The problem with that theory is that I don't see any evidence that supports it.

In theory, excess NMDA activity should lead to oxidative stress as brought upon by the unended influx of Ca2+ ions into the axonal membrane.

Which should induce exotoxicity, and concurrently, neuronal apoptosis.

But I don't see a plausible MOA that might induce that, from the perspective of the stack.

Ergo, the last thing I ought to be worrying about at that point is my academic performance. I am literally killing my brain cells at that point.

[gizmobrain]

Not necessarily, it depends on how those NMDA's are triggered on whether it is zapping your brain cells or not. I'm running out of time before work, so sorry for the lack of quality on the source (wikipedia):

Recently,[20] it has been noted that extrasynaptic NMDA receptor activation, triggered by both glutamate exposure or hypoxic/ischemic conditions, activate a CREB (cAMP response element binding) protein shut-off, which in turn caused loss of mitochondrial membrane potential and apoptosis. On the other hand, activation of synaptic NMDA receptors only activated the CREB pathway, which activates BDNF (brain-derived neurotrophic factor), not activating apoptosis

→ source (external link)

Do some checking into cAMP, forskolin, glutamate and NMDA on pubmed. Maybe you can find the connection I saw (or find evidence to prove me wrong ).

Edited by zrbarnes, 19 August 2012 - 11:57 PM.

[unbeatableking]

I was going to post that, but try re-reading that post, as it contradicts your theory.

The CILTEP stack does the exact opposite - it activates CREB:

Subchronic rolipram delivery activates hippocampal CREB and arc, enhances retention and slows down extinction of conditioned fear.

Number two? Both of these causes are rooted in two things:

1. The lack of oxygen

2. Excess glutamate

There is absolutely no connection between CILTEP and the NMDA-hyperactivity issue you've posited.

[unbeatableking]

Sifted through PubMed. Absolutely nothing there to prove or even add credence to this claim.

At this point, I honestly think you are picking straws.

Noticed something, the final sentence in your source also contradicts your claim:

On the other hand, activation of synaptic NMDA receptors only activated the CREB pathway, which activates BDNF (brain-derived neurotrophic factor), not activating apoptosis

On the other hand, this is indeed congruent with the source I posted above:

Subchronic rolipram delivery activates hippocampal CREB and arc, enhances retention and slows down extinction of conditioned fear.

Edited by unbeatableking, 20 August 2012 - 12:06 AM.

[gizmobrain]

Ok then, let's throw out the NMDA discussion.

Excessive cAMP signalling has been implicated in ADHD. ADHD has been linked to poor working memory. Rolipram has been shown to reduce working memory performance of aged monkeys.

At this point, you throw away CILTEP.

Unless you find that it works for you without hindering your working memory.

If you don't respond well to CILTEP, you'd be a good candidate guanfacine.

Edited by zrbarnes, 20 August 2012 - 12:22 AM.

[unbeatableking]

Finally, a plausible explanation that goes in line with research.

Given that you think that you yourself have ADHD though, why do you keep taking the stuff?

[gizmobrain]

I honestly think the current DSM standards for ADHD are bunk. I've never had hyperactivity issues. My symptoms fall more in the old DSMII ADD w/o hyperactivity standards, or the new "SCT" lingo.

Maybe my issue is hypoactive cAMP signaling.

Edited by zrbarnes, 20 August 2012 - 12:51 AM.

[unbeatableking]

I don't have ADHD. You said that you did however.

Isn't that a contradiction though? If that were the case, then CILTEP should make your ADHD worse, and in theory - you'd be a good candidate for guanfacine.

[unbeatableking]

Umm. You do know that the DSMIV: ADHD chapter has sub-types right...?

Hyperactivity isn't necessary for an ADHD diagnosis. Distractibility, memory and concentration issues are also plausible ADHD symptoms.

I literally have the big, gray DSMIV book in front of me (I use it as a paper-weight LOL).

Edited by unbeatableking, 20 August 2012 - 12:34 AM.