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Chemically induced LTP?

ciltep pde4 forskolin ltp

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#181 abelard lindsay

  • Location:Mare Serenitatis Circumlunar Corporate Republic

Posted 26 May 2012 - 03:57 AM

Yeah, I was just responding to trip96's question about it. Plus, it gets included in some pro-energy supplements, so it's good to know what it does.



Eur J Pharmacol. 1992 Apr 29;215(1):17-22.
Effect of different subtypes of cognition enhancers on long-term potentiation in the rat dentate gyrus in vivo.
,,,
The higher doses of the two latter drugs, administered 5 min before tetanic stimulation, induced a significant potentiation of LTP, whereas a significant inhibition of LTP was obtained when the drugs were administered 30 min before tetanic stimulation. Based on the results obtained from guinea pig hippocampal slices, an LTP-potentiating effect of all compounds tested could have been anticipated, but this was not supported by our data. The apparent contradiction between the in vivo and in vitro results is discussed. PMID:1516646


So the effect lasts less than 30 minutes and causes inhibition of LTP afterwards. Doesn't sound like it's particularly better than what we've already got in the stack.

Quote

Nihon Yakurigaku Zasshi. 1993 Sep;102(3):225-34.
[Pharmacology of long-term potentiation].
...
The production of LTP in the hippocampus is facilitated by many factors such as epidermal growth factor, fibroblast growth factors, somatostatin, M1 receptor agonists and many drugs like anirasetam, bifemelane, idebenone, indeloxazine and vinpocetine, but inhibited by M2-receptor agonists, scopolamine and midazolam. In addition to electrophysiological methods, LTP-like phenomena in 2-deoxyglucose uptake and leucine incorporation can be detected. These LTP phenomena in several animal models will be useful as indices for evaluating facilitatory actions of various compounds on learning/memory functions. PMID:8104851


This is a really old article (1993). Pretty sure this was before CREB/PKA/LTP was discovered.

Here's a later article that's more interesting that says that Vinpocetine increases CREB phosphyloridation in alcohol damaged animals. It's also a full-text.
http://www.ncbi.nlm....pubmed/19680548

PLoS One. 2009 Aug 14;4(8):e6643.
Phosphodiesterase inhibition increases CREB phosphorylation and restores orientation selectivity in a model of fetal alcohol spectrum disorders.
Krahe TE, Wang W, Medina AE.
Source

Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Abstract
BACKGROUND:

Fetal alcohol spectrum disorders (FASD) are the leading cause of mental retardation in the western world and children with FASD present altered somatosensory, auditory and visual processing. There is growing evidence that some of these sensory processing problems may be related to altered cortical maps caused by impaired developmental neuronal plasticity.
METHODOLOGY/PRINCIPAL FINDINGS:
Here we show that the primary visual cortex of ferrets exposed to alcohol during the third trimester equivalent of human gestation have decreased CREB phosphorylation and poor orientation selectivity revealed by western blotting, optical imaging of intrinsic signals and single-unit extracellular recording techniques. Treating animals several days after the period of alcohol exposure with a phosphodiesterase type 1 inhibitor (Vinpocetine) increased CREB phosphorylation and restored orientation selectivity columns and neuronal orientation tuning.
CONCLUSIONS/SIGNIFICANCE:
These findings suggest that CREB function is important for the maturation of orientation selectivity and that plasticity enhancement by vinpocetine may play a role in the treatment of sensory problems in FASD.
PMID: 19680548


This is a good paper that references back to all the research on CREB and neuronal plasticity. I skimmed it and it doesn't really go into the biochemical mechanism of action of Vinpocetine except to say it's a PDE1 inhibitor.

#182 zrbarnes Re: Chemically induced LTP?

  • Location:USA

Posted 26 May 2012 - 04:57 AM

Good to know.

One thing I've been wondering about is LTD. Does this stack compromise it?

Also, adequate mineral intake is obviously important for health, but is there anything that should be increased with this stack?

Magnesium was always essential while talking amps.

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#183 zrbarnes Re: Chemically induced LTP?

  • Location:USA

Posted 26 May 2012 - 09:46 AM

I've been taking ~1mg of lithium orate every night for a while now, as one of those "I can't imagine this would help much, but it can't really hurt..." kinds of supplements.

I really have no idea what doses would effect LTP, so maybe someone else could give some input on how it would tie together.

Neuropharmacology. 2012 Apr 5. [Epub ahead of print]
Lithium: A switch from LTD- to LTP-like plasticity in human cortex.

Voytovych H, Kriváneková L, Ziemann U.

Source

Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16, D-60528 Frankfurt am Main, Germany.

Abstract

Lithium, a simple cation, is the mainstay treatment of bipolar disorder. Deficient synaptic plasticity is considered one important mechanism of this disease. Lithium inhibits glycogen synthase kinase-3beta (GSK-3β), which is involved in the regulation of synaptic plasticity. In animal preparations, inhibition of GSK-3β by lithium up-regulated long-term potentiation (LTP) of excitatory synapses but down-regulated long-term depression (LTD). The effects of lithium on plasticity in the human brain are unexplored. We tested the effects of a single oral dose of 900 mg of lithium on LTP-/LTD-like plasticity in human motor cortex induced by established paired associative transcranial magnetic stimulation (PAS(LTP), PAS(LTD)) protocols. We studied 10 healthy adults in a placebo-controlled double-blind randomized crossover design. PAS-induced plasticity was indexed by change in motor evoked potential amplitude recorded in a hand muscle. In the placebo session, subjects were stratified, according to the known variability of the PAS(LTP) response, into PAS(LTP) 'LTP responders' and PAS(LTP) 'LTD responders' (n = 5 each). Lithium did not affect the PAS(LTP)-induced LTP-like plasticity in the 'LTP responders', but switched the PAS(LTP)-induced LTD-like plasticity in the 'LTD responders' to LTP-like plasticity. In contrast, lithium had no effect on the PAS(LTD)-induced LTD-like plasticity in the 'LTD responders'. We provide first-time evidence that lithium significantly modulates brain stimulation induced plasticity in human cortex. The switch from LTD- to LTP-like plasticity is best explained by the inhibitory action of lithium on GSK-3β. This conclusion is necessarily circumstantial because GSK-3β activity was not directly measured. We discuss that other important plasticity-related modes actions of lithium cannot explain our findings.
Copyright © 2012 Elsevier Ltd. All rights reserved. PMID:22507665


Lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus.

Son H, Yu IT, Hwang SJ, Kim JS, Lee SH, Lee YS, Kaang BK.

Source

Department of Biochemistry, Hanyang University College of Medicine, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, South Korea. hyeonson@hanyang.ac.kr
Erratum in

  • J Neurochem. 2003 Jun;85(6):1624. Sang-Hum, L [corrected to Sang-Hun, L].

Abstract

We measured the temporal and spatial profiles of neural precursor cells, hippocampal long-term potentiation (LTP), and signaling molecules in neurogenesis-induced adult rats. Chronic lithium treatment produced a significant 54% and 40% increase in the numbers of bromodeoxyuridine [BrdU(+)] cells after 12 h and 28 days, respectively, after treatment completion in the dentate gyrus (DG). Both LTP obtained from slices perfused with artificial cerebrospinal fluid (ACSF-LTP) and LTP recorded in the presence of bicuculline (bicuculline-LTP) were significantly greater in the lithium group than in the saline controls. Although the number of BrdU(+) cells, approximately 90% of which were double-labeled with a neural marker neuronal nuclear protein, were markedly increased in the granule cell layer (GCL) 28 days after the completion of the 28-day lithium treatment, the magnitude of LTP observed at this time was similar to that observed 12 h after completing the 28-day lithium treatment. However, protein levels of calcium and calmodulin-dependent protein kinase II, p-Elk and TrkB were highly elevated until 28 days after the 28-day lithium treatment. Acute lithium treatment for 2 days also enhanced LTP, which was accompanied by the elevated expression of p-CREB, but not by neurogenesis. Our results suggest that the enhancement of LTP is independent of the increased number of neurons per se and it is more closely associated with key molecules, which are probably involved in neurogenesis. PMID:12716419



#184 summertimex Re: Chemically induced LTP?

  • Location:usa

Posted 26 May 2012 - 09:54 AM

Good to know.

One thing I've been wondering about is LTD. Does this stack compromise it?

Also, adequate mineral intake is obviously important for health, but is there anything that should be increased with this stack?

Magnesium was always essential while talking amps.



Well in increasing neurogenesis you're going to want a slightly higher intake of things that are components or precursors to components of a cell. A lot of things count that could sound mundane, but in fact play a big role. Calcium is a component that "structures" skeletons its not only used in bone or for cell transmission, lecithin could increase mylein sheath and vitamin C repairs, protects and builds extracellular matrix protein.

If you really need to get your brain cooking, for example "traumatic brain injury", from your brain being asleep for several months. I just did this yesterday. Take a bunch of neuron nutrients, some protein, and an LTP increaser. I took the racetam stack earlier in the day, then I took more more alpha-gpc, antioxidants, omega 3 and aniracetam about 25 minutes before going on a 3 hour walk. I then came home and ate food, protein bar a couple more nutrients. Then I sprayed some deer velvet antler under my tongue when my brain was already cooking. This elongated the excercise LTP with the LTP increaser, so my brain kept on cooking and I took some more alpha-gpc and oxiracetam. I then went somewhere, and then went to sleep. So going in to sleep elongated the LTP further. I then woke up and my brain was still swirming around, and kind of like a heated feeling. I dont feel smarter currently, actually less articulate because of the acetylcholine push, but my consciousness at base level is more awake.

Edited by gen6k, 26 May 2012 - 10:37 AM.


#185 zrbarnes Re: Chemically induced LTP?

  • Location:USA

Posted 26 May 2012 - 11:02 PM

I've been wondering about Calcium for a while now. I know it was not recommended while taking amps, because it could further cause problems with magnesium. Yet it is usually recommended for use with Piracetam.

I have a vague understanding of the calcium channels and what not, but I'd love to hear some info about it in relation to this stack.

Also, I picked up a Monster Rehab energy drink today. Amongst the ingredients list, I noticed Quercetin. How long until Forskolin starts being added? :)

Edited by zrbarnes, 26 May 2012 - 11:04 PM.


#186 owtsgmi Re: Chemically induced LTP?

  • Location:Los Angeles, CA

Posted 27 May 2012 - 03:35 PM

Here is another interesting angle from another forum, concerning High COMT enzyme activity = low dopamine = social anxiety/depression/etc. The OP discovered that he had a certain gene that caused the high levels of the COMT enzyme. He suffers from negative symptoms:

lack of motivation, ADD and even the social phobia. Patients with high COMT activity are reported to be less motivated and more prone to ADD symptoms.


He found the following supplements to be helpful to combat the symptoms:


I'm not implying that this is the only cause of social phobia but it's definitely one that can be diagnosed and even treated. There are certain compounds that inhibit the COMT enzyme and improve some of these issues. The most effective ones seem to be:

  • Rhodiola Rosea
  • EGCG
  • Oleuropein
  • Quercetin
  • Vitamin C


Part of the reason I find this interesting is I have some of these symptoms and CILTEP is helping. I particularly notice how it obliterates social phobia. I also regularly rotate Rhodiola and EGCG into my stack as high value supps. I also take 1.5g or so C each day.

The key takeaway is combating the High COMT enzyme activity.

Read more at the link below, but there is a DNA test he took that discovered his condition:


I got the information after doing my gene test with 23andme. I ran the raw data through another software called promethease and that was among the results. I've seen this discussed a few times but it hasn't gotten a lot of attention.

I have a MET158VAL polymorphism in the COMT gene with the genotype VAL/VAL. That means the enzyme catechol-o-methyl transferase is highly active in my body and brain. This enzyme methylates many compounds, rendering them inactive.



To me, this add some weight behind the CILTEP stack. The forskolin addition, may be the discovery that kicks it into high gear.

http://www.socialanx...-enzyme-182919/

Edited by owtsgmi, 27 May 2012 - 03:38 PM.

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#187 Junk Master Re: Chemically induced LTP?

  • Location:United States

Posted 28 May 2012 - 03:42 AM

Very good post above. I suffer anxiety/depression and just started the forskolin, querectin, in addition to Uridine, Piracetam, Wellburtin, and Ropinirpole. So far, so good.

#188 owtsgmi Re: Chemically induced LTP?

  • Location:Los Angeles, CA

Posted 28 May 2012 - 04:55 AM

Thanks, Junk Master! Best of luck with your updated regimen. Keep us posted.

Edited by owtsgmi, 28 May 2012 - 04:56 AM.


#189 abelard lindsay Re: Chemically induced LTP?

  • Location:Mare Serenitatis Circumlunar Corporate Republic

Posted 28 May 2012 - 06:54 AM

I got a PM asking me to answer a couple of questions.... So here's a little FAQ. Remember, this was all invented on this thread by me piecing the scientific research together so please report back with any information you may have on this stack or studies you think may shed light on it. All the information presented here is based on my personal experiences, the journal articles I have referenced in this thread and contributions from forum members.

What is the effective dosage?

I have experimented around with a lot of different dosages and the most predictable and reliable for me is

*Herbal PDE4 Inhibitor
one to two pills Now Foods Artichoke Extract *or* Source Naturals Activated Quercetin (1 or 2 pills max),
*cAMP increase
One Solaray Forskolin pill and
*Dopamine Source
2 or 3 Now Phenylalanine pills.

I take this in the morning and do not re-dose for the rest of the day. If I want to pick things up a little, I add some caffeine later in the day as necessary.

Your results may vary. IMHO, dosages are better too low than too high.

I feel weird sometimes is this because of the Forskolin?

I would suggest lowering dosages. Yes, this stack is powerful.

Or could it be because of the Quercetin?

1g a day is waaaaay too much Quercetin in my experience. 3 Artichoke Pills is also too many for me. 2 is a high dosage that I use when studying hard crap like the MITX course. 1 is good for general social interaction.

Or is it the L-Phenylalanine?

Luckily, with L-Phenylalanine the body is in charge of how much gets metabolized, it's an essential amino acid after all, so the Phenylalanine is not where I would expect to run into dosage problems.

What about Coffee?

Coffee tends to wear off really fast but seems to positively stack. I use it to give little boosts to the stack throughout the day.

What about Tolerance?

I can only speak from personal experience. However, I've been taking this stack since last December. I was really worried that it was too good and there were going to be some sort of side effects, which is why I only vaguely hinted at how this stack works until recently. So far so good and I haven't built up any tolerance, neither has ZRBarnes or anyone else taking it so far that I'm aware of. In fact, ZRBarnes' says his Adderal tolerance has significantly decreased on this stack.

What about DOPAC build up and PDE1-5 Inhibition?

Based on the evidence I've seen, I don't think this stack increases dopamine metabolism significantly enough to cause excessive DOPAC build up. It's my theory that the main effects come from the increased downstream effects of dopamine on memory per unit of dopamine.

PDE1-5 inhibition except 4 are a bit of an unknown. I haven't researched these deeply. Just to be safe, I wouldn't take Vinpocetine(PDE1) or Horny Goat Weed(PDE5) with this stack, as it may increase their effects unpredictably, for better or worse. Resveratrol works on PDE1, 3 and 4... So I wouldn't recommend it as the main PDE inhibitor either.

It is possible to take too much of this stack. When that happens I take GABA to slow things down (Natural Factors chewable brand is pretty good). The effect of the stack is really awesome IMHO, so it's easy to think that more will help but at least in my experience, my brain has its limit and any more than that brings negative effects.

I've found that it stacks well with:

Magnesium Threonate (at Night)
Piracetam
Caffeine

Does not stack well with:

Adderall (dosage needs to be greatly reduced) (Thanks ZRBarnes)
Aniracetam ( LTP induction causes Aniracetam to act as a GABA like signal inhibitor) (Thanks Health Nutty)
In my experience, stacking with pramiracetam is a bit weird. Makes me feel unmotivated and too relaxed. Probably similar to the aniracetam effect.

Edited by abelard lindsay, 28 May 2012 - 07:44 AM.


#190 trip96 Re: Chemically induced LTP?

  • Location:canada

Posted 28 May 2012 - 04:24 PM

Hey guys! So here is my latest idea for this. I have access to a ton of bulk powder and I cap all my own supps. I prevviously capped the forskolin with horny goat weed but now it's time to get it right. Here's what I am thinking for each capsule at this point with all the comments and research.

Capsule #1

Forskolin 10 mg ( I use the 20% extract from smart powders ) ( I know it his is more than 3.85 mg but I am taking 40 mg right now and it's not too much but obviously do not want to over stimulate )

L- Theanine 100 mg ( dopamine + and I also like the calming adaptogen effect )

Subulthiamine 100 mg ( one post about synergy, it's known for waking me up and I plan on taking this in the morning so if no one has anything bad to say ill through it in )

DL - phenylalanine 500 mg ( I know this has the synthetic D version and Lindsay says to not confuse but it's a lower dose and I need something to fill the rest of the capsules with, I figure this is appropriate )


Capsule 2

Quercetin 500 mg ( these I bought, yellowish stuff real good for allergies too, which I have a big problem with)


I would love some feedback before I cap these! I also have tons of extra ingredients so if something is missing or there is a better fit I may possibly have that to go in. One last thing, anyone have anything ideas that need testing?


#191 abelard lindsay Re: Chemically induced LTP?

  • Location:Mare Serenitatis Circumlunar Corporate Republic

Posted 28 May 2012 - 06:32 PM

Subulthiamine 100 mg ( one post about synergy, it's known for waking me up and I plan on taking this in the morning so if no one has anything bad to say ill through it in )

DL - phenylalanine 500 mg ( I know this has the synthetic D version and Lindsay says to not confuse but it's a lower dose and I need something to fill the rest of the capsules with, I figure this is appropriate )


DL-phenylalanine is something I would advise against taking with this stack. It's vastly different in its effect from L-Phenylalanine and tends to build tolerance and frankly leaves my a bit depressed for some time after taking it. I think it might even down-regulate dopamine receptors, totally defeating the point of this stack. L-Phenylalanine is ridiculously cheap so there's no reason to substitute. At purebulk.com you can get 250g of L-Phenylalanine, an 8 months supply, for $14.25. A two month supply from Amazon capped is $10.00.

If you search for DLPA or DL-phenylalanine on this board you'll find a lot of negative experiences. I don't think hardly anyone takes it as part of their daily stack. For example:
http://www.longecity...d-side-effects/
http://www.longecity...ffects-of-dlpa/
http://www.longecity...bad-depression/

Sulbutiamine is a bit overstimulating for me but I've generally not had a bad experience with taking it for long periods of time. If you want to experiment with adding Sulbutiamine I don't have an opinion either way. Report back if you do.

You might also just want to try the stack in the form I have taken it in for the last six months with good results. It's plenty strong, IMHO.

Edited by abelard lindsay, 28 May 2012 - 06:37 PM.

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#192 trip96 Re: Chemically induced LTP?

  • Location:canada

Posted 28 May 2012 - 07:23 PM

Thanks Lindsay! I will not cap them with the DL then. Any other supplements that synergizes with your stack? I will need to fill the capsules with something, tyrosine? I know you have had mixed results, I need about 500 mg of filler and don't have any actual filler like magnesium sterrate. I will order the l-phenylalanine but it will take 1.5 to 2 weeks to get here and I would love to get recording results immediately.

#193 medievil Re: Chemically induced LTP?

  • Location:Belguim

Posted 28 May 2012 - 07:38 PM

Only zaprinast (IC50 = 29-46 μM), sildenafil (IC50 = 2.6-11 μM), SCH 51866 (IC50 = 1.6-3.3 μM), and vardenafil (IC50 = 0.58-3.4 μM) have been identified as weak and nonselective inhibitors of PDE9 (Fischer et al., 1998; Guipponi et al., 1998; Soderling et al., 1998; Corbin and Francis, 2002; Rentero et al., 2003; Wang et al., 2003; Bischoff, 2004).

#194 abelard lindsay Re: Chemically induced LTP?

  • Location:Mare Serenitatis Circumlunar Corporate Republic

Posted 28 May 2012 - 08:12 PM

Thanks Lindsay! I will not cap them with the DL then. Any other supplements that synergizes with your stack? I will need to fill the capsules with something, tyrosine? I know you have had mixed results, I need about 500 mg of filler and don't have any actual filler like magnesium sterrate. I will order the l-phenylalanine but it will take 1.5 to 2 weeks to get here and I would love to get recording results immediately.


Tyrosine would probably be fine. I haven't stacked with it but Health Nutty did and had good results. L-Phenylalanine is a very common basic supplement and will be available at practically any shop that carries vitamins.

#195 ansatz22 Re: Chemically induced LTP?

  • Location:US

Posted 28 May 2012 - 08:25 PM

Hi, can you help me troubleshoot?:

Taking:
PDE/cAMP: 500mg Artichoke, 200mg Foreskolin
anti-ox/supp: omega-3, vitD3, idebenone
AChE: creatine, DMAE, huperzineA, ALCAR, cdp-choline
DA: l-tyrosine, l-theanine

adderall 10mg 3 hours prior to taking this stack. Drinking cups of coffee throughout day.

I took this the first day; and it was excellent ! Able to read engineering/math papers and write code/debug quickly !!!

Second day, I took adderall with stack, not optimal effect.

Third day, tried to lag adderall and stack again, no real effect.

Today, eliminated adderall, no real effect.

Feel lack of motivation, decision-making. Going to switch out L-tyrosine with L-phenylalanine.

Does anyone have any advice? Really want to get back to the performance levels that I had the first day in a consistent way.

Before bed, I take melatonin and ZMA.
currently take as needed: oxi, ani, and pramiracetam, sulbatamine

Again, any suggestions on the next step ?

#196 abelard lindsay Re: Chemically induced LTP?

  • Location:Mare Serenitatis Circumlunar Corporate Republic

Posted 28 May 2012 - 09:27 PM

Hi, can you help me troubleshoot?:

Taking:
PDE/cAMP: 500mg Artichoke, 200mg Foreskolin
anti-ox/supp: omega-3, vitD3, idebenone
AChE: creatine, DMAE, huperzineA, ALCAR, cdp-choline
DA: l-tyrosine, l-theanine

Before bed, I take melatonin and ZMA.
currently take as needed: oxi, ani, and pramiracetam, sulbatamine

Again, any suggestions on the next step ?


The aniracetam can cause GABA like effects when LTP is induced that last for a while. This will give you the unmotivated too relaxed feeling that you're talking about. I've also found that Pramiracetam makes me a bit disinterested in getting work done too with this stack. Piracetam stacks well. Oxiracetam is a bit of an unknown as is noopept and sulbutamine.

Edited by abelard lindsay, 28 May 2012 - 09:29 PM.


#197 zrbarnes Re: Chemically induced LTP?

  • Location:USA

Posted 28 May 2012 - 09:35 PM

Hi, can you help me troubleshoot?:

Taking:
PDE/cAMP: 500mg Artichoke, 200mg Foreskolin
anti-ox/supp: omega-3, vitD3, idebenone
AChE: creatine, DMAE, huperzineA, ALCAR, cdp-choline
DA: l-tyrosine, l-theanine

adderall 10mg 3 hours prior to taking this stack. Drinking cups of coffee throughout day.

I took this the first day; and it was excellent ! Able to read engineering/math papers and write code/debug quickly !!!

Second day, I took adderall with stack, not optimal effect.

Third day, tried to lag adderall and stack again, no real effect.

Today, eliminated adderall, no real effect.

Feel lack of motivation, decision-making. Going to switch out L-tyrosine with L-phenylalanine.

Does anyone have any advice? Really want to get back to the performance levels that I had the first day in a consistent way.

Before bed, I take melatonin and ZMA.
currently take as needed: oxi, ani, and pramiracetam, sulbatamine

Again, any suggestions on the next step ?


To clarify: 200mg of Forskohlii (the herb)? Or was that a typo meaning 20mg Forskolin (the extract)?

I always took the CILTEP stack at the same time as the Adderall on an empty stomach to maximize the effects. I would eat about 45 minutes later because I would start to get a little light headed if I didn't.

#198 ansatz22 Re: Chemically induced LTP?

  • Location:US

Posted 28 May 2012 - 10:11 PM

In reply, yes it is 200mg forskohilii 20%.

Also, the first day with good effect I took the 3 racetams not recommended.
For the proceeding days, I have discontinued any racetam use, to no real result.
( Where/which brand piracetam (amazon/rhino) is recommended? )

How much adderall do you take zrbarnes ? Is it a U-shaped thing? Ill reintroduce it into the stack, and bump it up to 15mg.
I also take a Tums sometimes with the adderall. Do not really feel anything from tums, but read it helps with absorption, keeping dosage low.

Next, what is time between dosages? I tried this stack this morning, felt only slight cognitive effects. Do get slight upset stomach from this stuff. So right now, I feel borderline to try to reload. Is it advisable?

Finally, does anyone know how to unwind sublutamine? I took a high dose two nights ago and got a huge headache. Would melatonin or magnesium help at that point ?

Thanks

#199 zrbarnes Re: Chemically induced LTP?

  • Location:USA

Posted 29 May 2012 - 12:34 AM

In reply, yes it is 200mg forskohilii 20%.


200mg forskohlii * 20% = 40mg of Forskolin. When I take more than 20mg, I get vasodialation headaches. Forskohlii does not taste terrible, and you can put it in coffee or tea, so why don't you try cutting it in half for a few days to see if you get good results?

Also, the first day with good effect I took the 3 racetams not recommended.
For the proceeding days, I have discontinued any racetam use, to no real result.
( Where/which brand piracetam (amazon/rhino) is recommended? )


The problem is if you take too many supplements together without knowing what the baseline is, you can't figure out where the problem is. Try just taking the Forskohlii, artichoke and adderall, all at the same time, and see how it works for you.

How much adderall do you take zrbarnes ? Is it a U-shaped thing? Ill reintroduce it into the stack, and bump it up to 15mg.
I also take a Tums sometimes with the adderall. Do not really feel anything from tums, but read it helps with absorption, keeping dosage low.

Next, what is time between dosages?


I think it is important to take the Adderall either at the same time, or after you take the CILTEP stack. It did not work for me if I took it before CILTEP. I don't think I would try 15mg yet, especially if it is instant release (Adderall IR). More than 5mg caused me to have excessive jaw clinching which I had to treat with magnesium.

I would avoid the taking Tums (at least for now) because it might cause other issues such as the CILTEP stack not being absorbed right.

If you find that the effect still isn't strong enough, drink a couple cups of coffee/tea.

I am a 26 year old male that weighs 140lbs. I have symptoms similar to ADHD-PI, with my main symptoms being low energy, focus and motivation. This is what my regimen was for over a month, and I developed no discernible tolerance:

Morning (empty stomach):
  • 5mg Adderall IR
  • 2 Nature's Herbs Artichoke Extract capsules
  • 100mg of Forskohlii (20mg Forskolin)
Caffeinated coffee and tea throughout the day

Night (before bed):
  • 2 capsules of LEF brand Magnesium L-Threonate
  • 1/2 tablet Schiff's Sweet Slumber
I found that the effects lasted 8-10 hours with artichoke, longer with quercetin. Instead of using Adderall IR, I found that d-amphetamine extended release + quercetin worked even better, and lasted 12-14 hours. In comparison, 20mg of Adderall IR would only last about 4 hours for me by itself before I started taking CILTEP.

Edited by zrbarnes, 29 May 2012 - 12:42 AM.

  • like x 2

#200 Lufega Re: Chemically induced LTP?

  • Location:Miami, Fl.

Posted 29 May 2012 - 02:56 AM

I had a similar response when I trialed roflumilast (a potent PDE4 inhibitor) and combined it with forskolin. I couldn't last a whole month because of the GI side effects but the effect on LTP were very noticeable. I also got a similar response from using Carnosine. I tried to reproduce these effects and couldn't so I was probably using it along with something else that was synergistic. I didn't keep any notes at the time so I have no idea what it was. That said, Carnosine might be something that stack well with this. Increasing ghrelin through morning fasting is also another way to augment LTP. Might be worth taking this stack on an empty stomach for this same reason.

As I've said previously in this thread, I have some form of ADHD-PI, SCT, or something (the doctor's call it ADHD-PI, but I've never been hyperactive). I basically have no motivation, and a terrible working memory (the upside is that I never really get stressed, and I think outside the box more than my peers). I think I fit the bill of having "poor executive functioning".

Outside of amphetamines, other stimulants do nothing for mental focus or motivation (actually, nothing has ever worked except amphetamines, out of everything I've tried).


You just described yourself as a Warrior. Someone with a high COMT activity which reduces pre-frontal cortex dopamine. This type also tends to respond very well to amphetamines. Inhibiting COMT will also improve executive functions.

http://www.cnsspectr...x?articleid=642

#201 ansatz22 Re: Chemically induced LTP?

  • Location:US

Posted 29 May 2012 - 03:30 AM

Hi,

zrbarnes I think I am more like you(neurochemically) than abelard. However, adderall has never really worked for me. What has worked is Modafinil + ritalin. Never tried Modafinil + adderall. The first day on CILTP was better than the month supply I had of Modafinil + ritalin. Much smoother, not all the emotional ups/downs. Very interested to try Modafinil + CILTP.

Anyway, think I am responsive to the Modafinil because of MAOI properties, but never tried selegine or other MAOI. zbarnes do you still take selegine with this stack? I am amotivational, very creative and ambitious with projects, just cant finish or follow through. How was selegine + CILTP ?

I will try quercetine, pycnogenol, carnosine, l-phenylalanine, and modafinil. But ultimately just want to minimize as much as possible with no amphetamines.

#202 zrbarnes Re: Chemically induced LTP?

  • Location:USA

Posted 29 May 2012 - 04:21 AM

zrbarnes I think I am more like you(neurochemically) than abelard. However, adderall has never really worked for me. What has worked is Modafinil + ritalin. Never tried Modafinil + adderall. The first day on CILTP was better than the month supply I had of Modafinil + ritalin. Much smoother, not all the emotional ups/downs. Very interested to try Modafinil + CILTP.

Anyway, think I am responsive to the Modafinil because of MAOI properties, but never tried selegine or other MAOI. zbarnes do you still take selegine with this stack? I am amotivational, very creative and ambitious with projects, just cant finish or follow through. How was selegine + CILTP ?

I will try quercetine, pycnogenol, carnosine, l-phenylalanine, and modafinil. But ultimately just want to minimize as much as possible with no amphetamines.


I have yet to try modafinil, but I know that Armodafinil does not work correctly for me. Its almost like taking a sugar pill. Nothing really happens. I'm not sure if the problem lies in my ability to metabolize it, or if its effects are blocked in my brain for some reason.

20mg of Ritalin makes me dizzy and vomit. 5mg makes me feel lightheaded and weird, but does help a bit with concentration. I've never really been able to evaluate the motivating effects of Ritalin because I'm always distracted by the slight nausea.

I haven't mentioned the Selegiline much because I didn't want to complicate things. I've trialed CILTEP without selegiline, and the success I've had with CILTEP has been there, regardless of whether or not I add selegiline. That being said, I have resumed taking it at ~1mg a day dose. I like the neuroprotectiveness of it, plus, with the MAOI-B activity, I figure that I probably need to use less stimulants in the long run.

The reason I can't trial a higher dose of Selegiline + CILTEP is because my insurance has ran out, and I only have 60 tablets of 5mg left. At 1mg a day, I will have enough to last me until next year when my insurance resumes.

I had a similar response when I trialed roflumilast (a potent PDE4 inhibitor) and combined it with forskolin. I couldn't last a whole month because of the GI side effects but the effect on LTP were very noticeable. I also got a similar response from using Carnosine. I tried to reproduce these effects and couldn't so I was probably using it along with something else that was synergistic. I didn't keep any notes at the time so I have no idea what it was. That said, Carnosine might be something that stack well with this. Increasing ghrelin through morning fasting is also another way to augment LTP. Might be worth taking this stack on an empty stomach for this same reason.

My old stack (adderall+artichoke+forskolin) mixed with Ghelin = crazy strong (but not in such a good way). I start getting lightheaded and "swimmy". One time, I made the mistake of taking high amounts of artichoke extract + a strong rosemary extract right after getting out of bed, and then not eating for a few hours. The whole world got very... weird. Once I ate, everything returned to normal again.

You just described yourself as a Warrior. Someone with a high COMT activity which reduces pre-frontal cortex dopamine. This type also tends to respond very well to amphetamines. Inhibiting COMT will also improve executive functions.

http://www.cnsspectr...x?articleid=642


I've been looking into COMT inhibition for a while. I tried targeting it, but couldn't find the right mix to knock it out (though I did find out that I respond positively to sublingual methylcobalamin). This stack has made me start to reevaluate all of my past research though, with COMT being one of the first I plan to hit.

I'm hoping to get a 23andme genetic test done, as soon as I get some bills paid off. It should give me clues about these types of things. Without knowing, its like throwing a dart in the dark trying to hit a bullseye.

I was just checking into Carnosine the other day. I'll have to look into it more.

#203 Lufega Re: Chemically induced LTP?

  • Location:Miami, Fl.

Posted 29 May 2012 - 12:54 PM

I happen to have forskolin and quercetin handy. I'm going to try 10 mg forskolin and 250 quercetin with 500 mg vitamin C. I also had two cups of cold-infused white tea which should provide some caffeine/EGCG both of which enhance LTP on their own and I'm doing this fasted until 1 pm. I know the forskolin dose is a bit high, but It's all I have right now. I'll be surprised if I feel anything since I've used these compounds on/off and even together in the past. I'm sure I would have noticed an effect before.

#204 ansatz22 Re: Chemically induced LTP?

  • Location:US

Posted 29 May 2012 - 03:19 PM

Hi, I have some notes I would like to share.
debugging:
took a simplified stack: 10mg adderall, 500mg artichoke, 100mgForskolin@20%, 1gram of l-tyrosine, small cup of coffee about twoone hour ago.
(I noticed today that I was taking below the bottle-recommended 1g dose of l-tyrosine.)

subjective:
My mind does feel quicker and not { hung up/negative limited mental options/distracting cognitive tasks/gallows humour/difficult social interaction-feeling(larrydavid_syndrome) } that I normally feel. But dont feel the motivation/executive function, ie the stay on track dont get distracted that I sorely lack. Affects are minimal; clear headed but not fully motivated; this write up/re-edit has distracted me now for 2 hours. This is better than baseline but not the CILTP that I felt; did I build tolerance in one day ?

objective:
On first/best dose of CILTP my dual-n-back increased to 4 for the first time. Today, I had no trouble maintaining n=3, and can move through it quickly, but not well enough to get back up to n=4. Motivation/energy right now is only at a level where I was able to play a few rounds for about 10 minutes at the n=3 level.

throwing darts:
I checked out 23andme, test is now at $300. Is there some motivation/MAOI/gene variants that can be tested for? Maybe I will get it done if there are some relevant genes I should be interested in. camKII gene ?

Modafinil, ritalin, and adderall all by themselves do not work for me. Only tried Modafinil + ritalin in combination and that got me going, in a certain way. My lack of response to adderall and ritalin, taken by themselves, has me believing COMT is fine. My lack of response to Modafinil by itself, also makes me believe MAOI is fundamentally ok. Selegiline seems good in that it combines MAOI/amphetamine, in trying to unlock the 'psycho-energic' effect.

However, I think I need to target executive functioning. I feel there is overlap between executive function and motivation. For improved executive function, modafinil has shown efficacy. I have read weight training provides benefit (vs aerobic training which improves mood and fluid intelligence). Bilingualism improves it as well. A good test for executive function is d-kefs. Top soccer players do very well on d-kefs.
https://en.wikipedia...utive_functions
http://www.plosone.o...al.pone.0034731


(***warning the following is speculation***)
I believe the weight training/executive functioning link may be based at the microtubule/camKII level:
http://www.sciguru.c...ry-Code-Cracked
So to target executive functioning maybe we need to go beyond LTP. The above link says memories are encoded in the microtubule lattice, as 6-bit protein-camKII-bytes. Modafinil's electrotonic coupling is determined to be CamKII-dependent. There are two types of camKII- specialized microtubule acting, and NT/receptor/LTP acting.
chemical-induced executive function:
1. l-carnosine, a-lino-acid, phosp-serine; stuff that helps build up neuronal microtubules
2. nerve growth factor. Maybe Ill try lions mane/ resveratrol / curcumin. Which is the best one for camKII ?
behavioral-induced executive function:
a) weight training. highRep-lowWeight

b) language training http://livemocha.com/

recap:
What is a good ngf for camKII ?

#205 abelard lindsay Re: Chemically induced LTP?

  • Location:Mare Serenitatis Circumlunar Corporate Republic

Posted 29 May 2012 - 03:59 PM

Hi, can you help me troubleshoot?:

Taking:
PDE/cAMP: 500mg Artichoke, 200mg Foreskolin
anti-ox/supp: omega-3, vitD3, idebenone
AChE: creatine, DMAE, huperzineA, ALCAR, cdp-choline
DA: l-tyrosine, l-theanine


Maybe the Tyrosine is causing tolerance issues or DA downregulation? I use Phenylalanine and/or Catuaba as my DA agonist. I also only take about 10mg Forskolin. You could also try Quercetin, about 600mg should do.

#206 owtsgmi Re: Chemically induced LTP?

  • Location:Los Angeles, CA

Posted 29 May 2012 - 05:32 PM


subjective:
My mind does feel quicker and not { hung up/negative limited mental options/distracting cognitive tasks/gallows humour/difficult social interaction-feeling(larrydavid_syndrome) } that I normally feel. But dont feel the motivation/executive function, ie the stay on track dont get distracted that I sorely lack. Affects are minimal; clear headed but not fully motivated; this write up/re-edit has distracted me now for 2 hours. This is better than baseline but not the CILTP that I felt; did I build tolerance in one day ?


I noticed a tolerance the second day on CILTEP (querciten/forskolin), so I took the original dose twice (spaced out) on day 3 and the benefits reappeared. You may have to play around with a little to find your optimal dose.

#207 medievil Re: Chemically induced LTP?

  • Location:Belguim

Posted 29 May 2012 - 05:45 PM

Im EXTREMELY curious how nefiracetam as a forskolin substitute would pan out; it does far more then increasing camp all actions that should synergetically enhance cognition.

On my blog i compiled a list of all abstracts on its MOA.

http://noveltreatmen...-potential.html

I would expect it to be really strong so one should start VERY low when combining quercetin; nefi and a stimulant.

nefi synergizes well with stimulants; unfortionally i ran out so i cant add it to my quercetin; ani; stimulant combo and ill be trying to add forskolin first.

#208 medievil Re: Chemically induced LTP?

  • Location:Belguim

Posted 29 May 2012 - 05:48 PM

Some here have reported that after a certain point people go beyond their brains capacity causing strange effects; this raises the question wheter its possible to raise the brains capacity as a next step? (as an example methylene blue accelerates the mitochondria with 40% effectively raising their capacity).

The mitochondria if im correct also play a role in LTP so im curious about the addition of MB.

#209 health_nutty Re: Chemically induced LTP?

  • Location:California

Posted 29 May 2012 - 06:30 PM

My optimal stack:
5 mg of forskolin 3 times a day (from 50mg of 10% powder)
50mg of 98% luteolin 3 times a day
500mg of L-Tyrosine 3 times a day (I will try phenylanine).
100-200mg of caffeine 3 times a day.
100mg of EGCG 3 times a day

Too much forskolin and I feel weird and spaced out. Same when I take even a small amount (100mg) of quercetin. Too much tyrosine also make me feel odd. I can't describe the feeling but it is not at all a good thing.

Combines will with Pramiracetam (for me).
Does not combine well with Aniracetam.
I tried Piracetam again and I still hate it (no improvement with this stack).
Combines well with MB (I'm taking 60mcg 3 times a day now).

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#210 medievil Re: Chemically induced LTP?

  • Location:Belguim

Posted 30 May 2012 - 02:22 PM

I licked some leftover nefiracetam out of the sup bottle i stored it in lol; dose may be way to small but ill see wheter it does anything; dont have any stim today but cafeine and zoloft (took 600mg to get some dri action feels like really weak ritalin) and quercetin. Also taking aniracetam tough.

Ill report back





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