2626 replies to this topic

[hephaestus]

I didn't say anything about the study, and I certainly didn't call it flawed, as you seem to be implying. I haven't even read it, and never claimed to.

[unbeatableking]

^



:( :( :(

Edited by unbeatableking, 22 August 2012 - 12:38 AM.

[hephaestus]

I'm the one being an idiot, yet you're the one posting retarded image macros to a nootropics forum? At least you've got the superiority complex sorted out early. You'll make a fine doctor, douchebag.

[unbeatableking]

Why would you say that to someone asking for an apology? It really blows my mind.

Edited by unbeatableking, 22 August 2012 - 12:39 AM.

[abelard lindsay]

Has anyone had STM problems with Artichoke? I find with Quercetin and especially Hesperidin I get working memory deficits and become quite irritable after a few days. Based on my research over on the fluid intelligence thread, this may have something to do with MAO-A inhibition. Quercetin is a know MAO-A inhibitor and working memory deficits and aggression are linked to weak MAO-A activity (see fluid intelligence thread). There could be some other method of action at work here.

cAMP is present all over the body. Where it builds up is a function of the activity of the PDE subtype present in that part of the body and there are a lot of them, including many subtypes of the major groups such as PDE4 such as pde4a1 or pde4a2. Some PDE4 variants when inhibited cause vomiting, which is why Rolipram never got to market. Thus, cAMP buildup in the Pre-frontal cortex that leads to working memory deficits may be mediated by a different PDE variant than is activated by CILTEP. I'm posting from my phone so I can't properly research right now but I'll look at this in a bit.

Edited by abelard lindsay, 22 August 2012 - 12:59 AM.

[hephaestus]

I never experienced the swimmy feeling that others have reported until I switched from amphetamine to mph, with artichoke, hesperidin, or quercetin. Do you notice those together, or are they distinct symptoms?

Edited by hephaestus, 22 August 2012 - 12:40 AM.

[unbeatableking]

[hephaestus]

Can we report posts or something? Dude is obviously just trolling.

[unbeatableking]

We got the CILTEP 'inventor' to chime in and finally report that the stack does indeed cause working memory issues. He's been on it the longest. Wouldn't have happened had we not pressed it this far.

And I'm trolling?

[unbeatableking]

The MAOI hypothesis can't account for the working memory boost brought upon by guanfacine, which counters the cAMP/HCN pathway.

It doesn't explain why Rolipram also seems to inhibit working memory. So I am inclined to discount the MAOI hypothesis.

http://www.ncbi.nlm....les/PMC1783631/

[IA87]

Well, I can say I did significantly better today in terms of working memory. I took DHA/EPA, multivit., creatine, concerta, and vitamin D. On the previous night I slept for roughly five hours; however, I still noticed an improvement in WM despite the lack of sleep.

On a somewhat unrelated note, I believe that 54 mg concerta is a bit too strong for me. I get a little overfocused (and not always on the right thing), and as a result my reading speed is reduced significantly. I will try the same regimen tomorrow with the concerta 36 (I have one pill left) mg substituted for the concerta 54 mg.

[abelard lindsay]

The MAOI hypothesis can't account for the working memory boost brought upon by guanfacine, which counters the cAMP/HCN pathway.

It doesn't explain why Rolipram also seems to inhibit working memory. So I am inclined to discount the MAOI hypothesis.

http://www.ncbi.nlm....les/PMC1783631/

I read your study.

Rolipram had no effect on performance on its own (70.42 ± 2.25% after rolipram vs. 67.63 ± 0.76% after saline: F(1,7) = 3.23, P = 0.17), but reversed the enhancing effects of guan- facine (81.67 ± 1.65% correct after guanfacine treatment vs. 69.88 ± 1.11% after guanfacine + rolipram: F(1,7) = 51.3, P = 0.0002; no significant difference between saline treatment and guanfacine + rolipram: F(1,7) = 3.57, P = 0.101). An analysis of guanfacine’s effects on performance at each delay length confirmed the previous statistical analyses. There was a significant main effect of guanfacine treatment (F(1,7) = 25.46, P = 0.002) and a significant main effect of delay (F(4,28) = 6.48, P = 0.001).

So Rolipram counteracts guanfacine but does not have any significant effect on working memory by itself and even a slightly positive effect vs saline, but not rising to a statistically significant threshold. So the above study would suggest to me that lowered cAMP improves working memory but raised cAMP does not have a deleterious effects on working memory.

I think the MAO-A theory still has some life in it. So.... Hands up, who's had a bad working memory experience with Artichoke? I sure haven't.

Edited by abelard lindsay, 22 August 2012 - 01:25 AM.

[canz]

So far it seems that 10mg/500mg is the right dose for me. I will continue to take theanine with the stack as I feel that it balances my neurotransmitters enough to prevent over stimulation or sedation that the stack may cause. Tomorrow I will re-attempt tests on the cambridge website as well as dual-n-back and see if my results have improved while on this stack. I have not experienced any tiredness on this stack at all.

Good to hear it.

L-theanine would be a good adjunct to this stack for anyone with issues of irritability, anxiety or nervousness (which I attribute to the forskolin causing increased glutamate release).

We' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916990/']We have shown that the activation of adenylyl cyclase with forskolin enhanced the amplitude of EPSCs and abolished LTD. This finding is consistent with numerous studies showing that activation of adenylyl cyclase increases the probability of glutamate release (Chavez-Noriega & Stevens, 1994; Tzounopoulos et al. 1998).

→ source (external link)

L-theanine has been a godsend for me so far, but I'm not so sure about the CILTEP. Today I took 10mg/450mg (the NOW brand is 450mg not 500mg/typo on my part) along with 400mg theanine. I didn't experience the lift in mood that I had the first day, and in fact felt a little anxious, even with the theanine in my system. That subsided and I attempted some tests on cambridge. Last week I took at least one test from each area without taking anything, then took each test again with 200mg theanine/50mg caffeine and increased my scores significantly. Today I took each test again and on the odd one out I actually got 50% less of what I got last week (can't remember right now what the score was, but remember it was half of my higher score) on theanine/caffeine. It got to the point during the tests that I could not concentrate at all and my mind felt extremely tired. I spaced out and couldn't focus. A few hours after this I started to feel the pressure headache coming on that I had yesterday. It wasn't as bad as yesterday, but it's there. I also experienced some irritability. I had taken two more 200mg doses of theanine today as well. Something about this stack is not agreeing with me, and I actually think it may be reversing my cognition. I am not as well versed as the rest of you on PDE inhibitors, CREB and other workings of the brain so I can only go off of what I've read in this thread and pub med studies which I have limited understanding of based on my knowledge or lack thereof.

Any suggestions? I may just stick to theanine and caffeine.

[unbeatableking]

So the above study would suggest to me that lowered cAMP improves working memory but raised cAMP does not have a deleterious effects on working memory.

How does this explain the HCN/cAMP issue mentioned repeatedly in this thread then? It shows that the unimpeded agonism of cAMP on HCN, leading to the extended 'open' status of this channel, causes deficits in working memory.

Edited by unbeatableking, 22 August 2012 - 01:34 AM.

[abelard lindsay]

Any suggestions? I may just stick to theanine and caffeine.

Are you taking the L-Phenylalanine with it?

[unbeatableking]

Recent research suggests that cAMP affects the function of higher-order thinking in the prefrontal cortex through its regulation of ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN). When cAMP stimulates the HCN, the channels open, closing the brain cell to communication and thus interfering with the function of the prefrontal cortex. This research, especially the cognitive deficits in age-related illnesses and ADHD, is of interest to researchers studying the brain.^[5]

[abelard lindsay]

So the above study would suggest to me that lowered cAMP improves working memory but raised cAMP does not have a deleterious effects on working memory.

How does this explain the HCN/cAMP issue mentioned repeatedly in this thread then? It shows that the unimpeded agonism of cAMP on HCN, leading to the extended 'open' status of this channel, causes deficits in working memory.

I don't know

Well that's only your theory. Theorizing is great, but just because you repeat it in a couple of posts doesn't mean it corresponds with experimental evidence. A hypothesis must be proven by an experiment. This is not string theory. Show me a study where Rolipram or another PDE4 inhibitor by itself, or with Forskolin inhibits working memory. We already have experimental evidence in the study I quoted above that it does not.

[unbeatableking]

It has to be noted that the evidence I have presented grants a much clearer path towards the hypothesis I have elucidated in this thread.

I did not posit this hypothesis, in truth, I am repeating the conclusion one of the studies in this thread brought upon.

To be frank, this hypothesis is much more parsimonious than the one you keep pressing. Let's not go beyond the literature.

[unbeatableking]

To be frank, I myself have noticed this rise in complaints amongst non-artichoke users. Found it odd.

Posted it a few pages back but edited it out. Didn't make any sense at that time.

Lindsay, may I suggest re-starting with artichoke? Come back here perhaps and see if something changes? Along with those of you with some artichoke left.

Not going to start with this again.

Edited by unbeatableking, 22 August 2012 - 01:51 AM.

[abelard lindsay]

Recent research suggests that cAMP affects the function of higher-order thinking in the prefrontal cortex through its regulation of ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN). When cAMP stimulates the HCN, the channels open, closing the brain cell to communication and thus interfering with the function of the prefrontal cortex. This research, especially the cognitive deficits in age-related illnesses and ADHD, is of interest to researchers studying the brain.^[5]

I did some research for you... With Forskolin, at lower concentrations, there is spatial memory impairment.
http://www.ncbi.nlm....pubmed/19433899

To explore the role of protein kinase A (PKA) in regulating tau phosphorylation and spatial memory, we injectedforskolin, an activator of PKA, at different concentrations into the rat brains. We found that forskolin at concentrations up to 80 microM enhanced tau phosphorylation and was associated with prominent spatial memory impairment. Higher concentrations of forskolin, up to 200 microM, were associated with reduced phosphorylation levels of tau and no memory deficits. Forskolin elevated cAMP and activated PKA in a dose-dependent manner. When infused at 200 microM, forskolin also resulted in the activation and overexpression of protein phosphatase-2A (PP-2A) and attenuated the okadaic acid-induced PP-2A inhibition. These data suggest that the upregulation of PKA by forskolinto a certain level may activate PP-2A but that the latter can ameliorate the PKA-induced tau phosphorylation andmemory impairment in the rats.

...but not at higher concentrations... Perhaps some sort of U curve effect going on here with forskolin?

Here's a nice chart from that study I quoted earlier (http://www.ncbi.nlm....les/PMC1783631/):




Notice Rolipram somewhat improves working memory compared to Saline (though not rising to the level of statistical significance) and reverses Guafanicine's working memory benefit.

Edited by abelard lindsay, 22 August 2012 - 01:55 AM.

[IA87]

It's too bad I can't combine concerta with guafanicine; I did a quick webmd check and found some possible interactions that are quite disturbing. http://www.drugs.com...1219-13992.html

Edited by IA87, 22 August 2012 - 02:19 AM.

[hephaestus]

Sorry I got all worked up earlier, but you can be quite abrasive.

[unbeatableking]

No problem. I take no offense and an apology is not necessary. What is important is that we deal with the problems mentioned in this thread, which I shall compile:

1. We have yet to come up with a way to correct the STM deficit brought upon by this stack. And studies do show that this is more than just a myth.

2. We have yet to come up with an effective, frill-free PDE4-inhibitor.

3. Forskolin. Yes. It kills the GI system and doesn't seem viable in the long-term.

[gizmobrain]

1. I encourage you to keep investigating a novel solution for this problem. The studies show that excessive cAMP signalling can cause a degradation of spatial working memory. The readily available solution (as suggested numerous times in this thread) would be to find the dosage which increases your cAMP levels to the optimum amount, instead of overshooting it into the "excessive" area.

Remember when we were discussing NMDA activation? Replace "NMDA" with "cAMP" and you'll have my opinion on the subject. I was thinking strictly in terms of the glutamate release caused by forskolin as being hand in hand with cAMP, and confusing glutamate's irritability inducing effects with the spatial working memory issue with which you were speaking. Given your style of writing, I think I was justified in assuming you were under the influence of said irritability.

Another genuine question I've been wondering is: Have you researched the relation between the "short term memory" involved in reading texts in comparison to the method of action by which spatial working memory takes place? Are they, as you seem to assert, one and the same? My knowledge is limited on the issue at this point.

2. If you want to get into pharmaceutical options, its an entirely different game. As it stands right now, we have a few options that have been discussed, all with their own pros and cons. Readily available food sourced extracts and herbs rarely have the potency and narrow targets that pharmaceuticals have.

I'm not entirely sure what you mean by "frill-free". Which frills are you looking at here? That some people don't have good experiences with Quercetin (I do, though)? Artichoke has additional benefits beyond the goal of this stack, and is cheap and readily available. A higher quality source can make a difference too (I used Nature's Herbs and it knocked the socks off of "Vitamin World" brand.)

3. With 95% forskolin extract becoming easier to get, GI issues are much less of an issue. At small doses (~1-5mg), it also knocks out the majority of the long-term side effects as well.

Looking at alternatives, I'm not thinking Sesamin is going to make the cut either, since it has phytoestrogenic properties. In fact, I'm wondering if the cerebral antioxidant properties are directly because of this, given that estrogen is a powerful inhibitor of free radicals in cerebral blood vessels.

I know there are some other synthesized cAMP increasers, but I've not seen a readily available one yet. Have you found any?


At the end of the day, it seems like you are completely uninterested in further pursuing the mechanism by which this stack works, having condemned a rise in cAMP as leading you down a dark and deadly road of lowered intelligence, poor hygiene, and incestuous relationships. All of this can be found in the studies, of course.

Edited by zrbarnes, 22 August 2012 - 09:08 AM.

[canz]

Any suggestions? I may just stick to theanine and caffeine.

Are you taking the L-Phenylalanine with it?

I tried it with L-phenylalanine on day 2 and experienced severe irritability. I have taken l-phenylalanine by itself before and exprerience irritability so I just assume that translates to over saturation of dopamine?

[brainslugged]

All this talk about lower STM is counter to my experiences. I have, in fact, found that I have greater STM based on how I have felt. I feel like I can read and comprehend more easily, and my mind seems much clearer, but I have yet to notice any significant increases in LTP. I have only done one test that verifies the increased STM, but I will do more.

This stack seems to make stimulants much more powerful for me, and I suspect that is the cause of the increased STM. I am taking 500mg l-tyrosine with the stack.

[medievil]

Perhaps higher forskolin doses dont have a negative effect on working memory as it enhances the probability of glutamate release wich when significant enough enhances working memory overpowering this? not sure how glut release relates to it but it seems plausible.

Edited by medievil, 22 August 2012 - 02:36 PM.

[hephaestus]

I would definitely suggest supplementing theanine with this stack if it makes you irritable, should help a lot. Picamilon is another option with similar benefits. A recent study of various theanine products observed that suntheanine was the only one that was actually 100% l-theanine:

http://www.reddit.co...earch_from_the/

Edited by hephaestus, 22 August 2012 - 03:44 PM.

[hephaestus]

Any hypotheses as to why this stack would affect me so differently with amphetamines versus methylphenidate? A few days I took 10mg forskolin/500mg quercetin twice in a day without any negative effects when I was using it with amphetamines, but I got the swimmy feeling on Monday when combining it with mph with only 5mg forskolin/500mg quercetin.

[medievil]

Amp releases D serine and glutamate wich would make a big difference.