2626 replies to this topic

[Droplet33]

Just a anecdote, but i noticed that the stack felt a lot stronger when combined with coconut oil, especially with a bit of fasting. It seem to make sense, good fuel help the engine .

[Jeoshua]

Anecdotal, but it's at least n=3 now. I had the same experience when using coconut cream in my coffee. I was trying to make basically a bulletproof coffee, and only had the creme. It ended up very delicious of course, but interestingly enough, for the next few days while drinking this concoction (which can be found previously in this thread) I did experence EXTREME potentiation of the CILTEP stack. To the point where I had to swear off my coffee blend because I was too energetic, too focused, and started looking into something that could deal with the increased effects, which I settled on with 250-500mg Agmatine.

Plus, Dave Asprey himself uses his Upgraded MCT Oil in his Bulletproof Coffee, which he takes spaced through the day along with a CILTEP blend. MCT is basically like high octane synthetic gasoline to Coconut Oil's crude. And he swears by the stuff.

Edited by Jeoshua, 10 March 2014 - 04:48 PM.

[MizTen]

Yes, coconut oil really does amplify certain things for me. I discovered that first with Adderall a few years ago, then with a CILTEP type stack, then with uridine added, now with 1-3 mg of iodine (Iosol).
It also seems to ameliorate the afternoon come-down that can occur with such a stack. Gotta be careful with coffee, though.

[swen]

Currently I'm combining the stack with Huperzine-A en Alpha-GPC. All short-temory or working memory problems are gone. I follow a diet high in acetylcholine but still supplementing extra.

Makes sense, when on CILTEP I functioned like i had a acetylcholine deficit (using the Braverman test). Awesome tip Abelard, using this test to debug the problem

[Charles J. Daniels]

According to the following page, luteolin is most soluble in an alkali, and only sparingly soluble in water: http://www.appliedhe...7072&Itemid=202

[stephen_b]

What I can take away from this is that there's plenty of room for improvement in the PDE4 Inhibition/cAMP effect... just not this way.

Abelard, while you are trying out some new things, you might want to give the dendrobium extract I mentioned here and here a try.

[abelard lindsay]

Hey all, I've been trying to mix CILTEP with Racetam's lately and I can't for the life of me keep my paired associates scores from dropping when I add Piracetam. I'm up to about 2.5 grams of ALCAR and I'm still not able to keep paired associates above a six where I'm normally at a 7 on average or 8 on a good day or 9 occasionally when I take galantamine.

I guess coluracetam is the 800lb gorilla of choline modulating supplements as it actually tweaks the cholinergic system directly but I'm a bit scared of that stuff after I got excessive ach headaches for two weeks after taking that and had to take benadryl. Maybe I'll try alpha gpc and some of the other cholinergics to see if I can get my levels up enough to get at least back to a 7. Huperzine and Galantamine work great but are a bit unpredictable and I wouldn't take them more than once a week. With about 800mg of ALCAR I can keep paired associates at a 7 with just CILTEP alone, this is the basis of the first page recommendation and the natural stacks formulation but Piracetam seems to overwhelm the ALCAR.

BTW, CILTEP is for long-term memory as I pointed out over here : http://forum.natural...rt-term-memory/ and not for short term memory.

Edited by abelard lindsay, 11 March 2014 - 07:12 PM.

[Charles J. Daniels]

Could this be related to working memory somehow? I've been following the recommendation to take agmatine with ciltep to keep cAMP from increasing in some unwanted regions that affect working memory. I see that this issue happens upon additional of piracetam, but perhaps it is not as much the piracetam as it is the state it has to work with. If piracetam revs up a degraded system, perhaps it turns out worse.

[Jeoshua]

That's actually slightly counter to what I found through research on Agmatine. It doesn't keep cAMP from increasing, but rather mitigates some of the effects of that increased cAMP in the PFC, and is not efficiently absorbed into most other parts of the brain. That, and Agmatine works quite strongly on extrasynaptic HCN and not as strongly on synaptic areas of the nervous system, so with coadministration with Forskolin the overall effect profile is shifted more strongly to the synaptic region and away from the extrasynaptic areas. In the PFC this leads to much more precise "cascades", which are crucial for working memory and almost negligeble for long term memory, the later being more dependant upon actual brain structure "hard-coding" the memories in question, and the former having more to do with actual precisely cascading memories.

To look at it through the lens of the computer metaphor is helpful here. Working memory is in RAM, coursing through the computer but not stored anywhere in particular, Short Term memory is on a swap file on the hard drive, having been stored for some time, whereas Long Term memory is closer to a hardwired chip.

Close, tho. The Forskolin seems to prefer the Hippocampus more than Agmatine, and the Agmatine seems to have a preference for the PFC. It doesn't shield one from increased cAMP, but it does mitigate the effects when it comes to working memory.

Edited by Jeoshua, 11 March 2014 - 07:42 PM.

[abelard lindsay]

That's actually slightly counter to what I found through research on Agmatine. It doesn't keep cAMP from increasing, but rather mitigates some of the effects of that increased cAMP in the PFC, and is not efficiently absorbed into most other parts of the brain. That, and Agmatine works quite strongly on extrasynaptic HCN and not as strongly on synaptic areas of the nervous system, so with coadministration with Forskolin the overall effect profile is shifted more strongly to the synaptic region and away from the extrasynaptic areas. In the PFC this leads to much more precise "cascades", which are crucial for working memory and almost negligeble for long term memory, the later being more dependant upon actual brain structure "hard-coding" the memories in question, and the former having more to do with actual precisely cascading memories.

...

Close, tho. The Forskolin seems to prefer the Hippocampus more than Agmatine, and the Agmatine seems to have a preference for the PFC. It doesn't shield one from increased cAMP, but it does mitigate the effects when it comes to working memory.

Do you have a citation for how it lowers cAMP in the PFC or how it mediates the effects of increased cAMP in the PFC or works on extrasynaptic HCN?

Seems like agmatine increases cAMP throughout the body.

http://www.ncbi.nlm....pubmed/24523404

AGM was added to drinking water for 4 or 8 weeks. We used 13C or 15N tracers to assess metabolic reactions and fluxes, and real-time quantitative PCR to determine gene(s) expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP.

Also agmatine looks to be a net negative for learning and memory. This is suggested to be mediated through its NMDA antagonism.

http://www.ncbi.nlm....pubmed/12175451

These studies indicate that systemically administered agmatine selectively impairs behavioral inferences of specific types of learning and memory.]

http://www.ncbi.nlm....pubmed/10821214

Acquisition deficit and time-dependent retrograde amnesia for contextual fear conditioning in agmatine-treated rats.

Edited by abelard lindsay, 13 March 2014 - 03:55 AM.

[Jeoshua]

The information on the studies I found for Agmatine can be found back on page 78:
http://www.longecity.../page__st__2310

[abelard lindsay]

The information on the studies I found for Agmatine can be found back on page 78:
http://www.longecity.../page__st__2310

I looked at that and I couldn't really find the part about the HCN channels and lowering cAMP in the PFC.

I did a search for Jeoshua and agmatine and found two studies.

http://www.ncbi.nlm....pubmed/20451544

In this study, the effects of agmatine on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of the rat dentate gyrus (DG) on saline or morphine-treated rats were investigated. Population spikes (PS), evoked by stimulation of the LPP, was recorded from DG region.
Acute agmatine (2.5-10mg/kg, s.c.) treatment facilitated hippocampal LTP. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and agmatine (10mg/kg, s.c.) restored the amplitude of PS that was attenuated by morphine. Chronic morphine treatment resulted in the enhancement of hippocampal LTP, agmatine co-administered with morphine significantly attenuated the enhancement of morphine on hippocampal LTP. Imidazoline receptor antagonist idazoxan (5mg/kg, i.p.) reversed the effect of agmatine. These results suggest that agmatine attenuated the effect of morphine on hippocampal LTP, possibly through activation of imidazoline receptor.

So the dentate gyrus which is in the hippocampus and not the PFC. Still cool that this is mediated by the imidazoline receptor.

SO.... What does the imidazoline receptor have to do with cAMP?

http://www.ncbi.nlm....pubmed/10825384

. On the other hand, benazoline and other I(1) receptor-selective imidazolines decreased forskolin-stimulated cAMP level in the cells expressing I(1)R, in a rauwolscine- and pertussis toxin-insensitive manner.

Ooooh interesting. So we're decreasing camp in I(1)R receptor expressing cells.

http://www.plosone.o...al.pone.0054563

Mostly expressed in the Cerebral cortex and less so in the hippocampus if you look at figure 2... Lovely

------------------

On to your next study....

http://www.ncbi.nlm..../pubmed/7715734

Thus, we have confirmed that agmatine recognizes alpha 2-adrenoceptor binding sites and, therefore, is a CDS [clonidine displacing substance].

So it's a bit of an A2A antagonist like caffeine or at least it displaces clonidine. Not super important.

Anyway... The I(1)R agonism and the localization of this receptor is a good enough reason for me to try it.

[Jeoshua]

Basically it doesn't "add" anything to the stack, it rather takes something away... but that something is anxiety and mild confusion. It just sort of takes the edge off, to put it in non-scientific terms.

I have been using Agmatine to treat ADHD, recently, with some amount of success, coupled with ZMA and B-Complex. Magnesium and B6 supplementation on their own have been shown to have a pretty statistically signifigant effect on improvement in ADHD symptoms, and Magnesium is often defficient in American diets, so their addition to my daily stack was a no brainer. The Agmatine doesn't have too many actual studies beyond it's effects on iNOS (which it seems to reduce), and it's "body building" potential is greatly overstated and, I feel, a bit of a lie.

At any rate, the science behind it is interesting, if a bit sketchy, but I found that overall Agmatine mitigated the working memory deficit with CILTEP very effectively at 200-250mg, although it did cause a bit of mental dulling around 500mg. I weigh around 150lbs... so the dosage I used was around 3 mg/kg for those beneficial effects.

Oh, and the PFC cAMP angle is actually... well. Let's just say that I found Agmatine while looking for something that decreased PFC cAMP. Magnesium was a candidate, as was Agmatine, as was Lithium. Turns out that none of them really do the trick besides Magnesium, but that's whole-body and not locallized. Agmatine is localized in an interesting manner, but has only minor effects on cAMP, and Lithium has too many side effect to be used in high doses.

Edited by Jeoshua, 13 March 2014 - 02:11 PM.

[hephaestus]

I tried taking a 125mg lithium orotate after reading about people using it in their daily stacks, and it knocked me out. I passed out at like 8pm and didn't wake up until the next day. I occasionally use it as a sleep aid at 1-2mg of elemental lithium (25-50mg LiO) sublingually. I believe it works by suppressing norepinephrine release.

[Potent]

According to the structure in wikipedia, mesembrine in Zembrin seems to be fat soluble. Are you guys taking Zembrin with fat, or have you noticed a better effect on an empty stomach?

[abelard lindsay]

According to the structure in wikipedia, mesembrine in Zembrin seems to be fat soluble. Are you guys taking Zembrin with fat, or have you noticed a better effect on an empty stomach?

FYI, Mesembrine is the main SSRI in zembrin. Mesembrenone is the main PDE4 inhibitor.

[Potent]

According to the structure in wikipedia, mesembrine in Zembrin seems to be fat soluble. Are you guys taking Zembrin with fat, or have you noticed a better effect on an empty stomach?

FYI, Mesembrine is the main SSRI in zembrin. Mesembrenone is the main PDE4 inhibitor.

Word. Mesembrenone, the enantiomer with an extra double bond, if my ochem ain't fuzzy. On the 'Brenone as we speak.
iHerb has a cheaper version of the Zembrin extract through Source Naturals - half the price of the other one. Feels similar, although I can't say 100% without a direct comparison.
http://www.iherb.com...=4&sr=null&ic=2

I'm on both Zembrin and Artichoke, and I feel a bit brain foggy, which I haven't felt in the past on both.
You mentioned Tinnitus and feeling a bit out of it on both Zembrin + Artichoke... maybe the "feeling out of it" is my brain fog?
I'll try just Zembrin, since it completely inhibits PDE-4.

However what do you do on Forskolin + Zembrin when the Zembrin wears off and you still need to study? I'm thinking about dosing Zembrin 3X / day with Forskolin, since Zembrin seems to last 4 hours or so with me.

Edited by Potent, 14 March 2014 - 12:53 AM.

[abelard lindsay]

So I took 250mg Agmatine with the ol' Natural Stacks CILTEP and Piracetam. Woah... this thing is a powerful anxiolitic. Cambridge scores were good too. Got an 8 on Paired Associates even! The anxiolitic effects were the most noticeable though. I think I'm going to give this a try with Zembrin tomorrow.


** Update **

I had a lot of trouble sleeping last night and had to take Benadryl, Magnesium and GABA. This turned my normally boring CILTEP/Piracetam stack into something else. The experience was fun during the day but it really paid for itself in not being able to fall asleep and general uneasiness and jitters at night. Not something I will try again.

BTW I took 2.4g piracetam with 250mg agmatine and CILTEP. I took 1.2g piracetam + 250mg agmatine and CILTEP on the previous day and that was fine. The effect could have built up over multiple days for all I know.

Edited by abelard lindsay, 14 March 2014 - 11:50 PM.

[chung_pao]

*Note on taking isolated LUTEOLIN, rather than artichoke:
The effect is much less sedative, and I feel more focused.
The PDE-inhibition is still very strong, and lasts 12+ hours from 50 mg.
Preliminarily it seems that taking luteolin is an improvement from taking artichoke extract.
The resulting effect seems to become more of an isolated PDE-inhibitor, with much fewer mechanisms involved.

Although, I can't promise that I'm completely accurate until this is tested, I can at least say that it makes a very interesting comparison.

[abelard lindsay]

I think I've had enough time to get a perspective on the Agmantine + CILTEP.

At 1.2g Piracetam + 250mg Agmantine + 3 CILTEP (Natural Stacks) I had a really good experience. The anxiolytic effect was pronounced. I felt kind of like I was on vacation in a brand new city walking around areas that were familiar to me. I had a great programming session and I felt very quick and sociable. I was able to sleep at night without any trouble.

At 2.4g Piracetam + 250mg Agmantine + 3 CILTEP I was a bit hypomanic and careless. The anxiolytic effect was a bit too much and I was lacking motivation to work because I was just too relaxed about everything. That night I got a bit of a choline overload and couldn't get my brain to turn off even at 2am. I took a benadryl and fell immediately asleep and then woke up anxious and disturbed a few hours later and had to take magnesium and gaba to calm down. I slept badly for the rest of the night.

The next day I didn't take anything except a multivitamin and was really productive even though I had slept badly. Things seemed a bit crisper and easier and the next night I slept well. Maybe this is just a dosage problem or a cycling problem. I think next week I'll try this with lower dosages. That was the thing with forskolin, it was all about getting the dosage right, even if that meant getting it down to 4mg, which by the standards of the supplements on the market was ridiculously low.

[Jeoshua]

One thing that I am totally unclear on, as of yet, is the half-life of Agmatine. Systemically, it looks like it only has a 10 minute or so half-life, but in the brain seems to be as much as 10 hours. That's a pretty big gap, and a 10 hour half-life is absolutely nothing to sneeze at. Also it's entirely possible that, once crossing the BBB, it undergoes some other change that might push that half-life out even further, as far as the effects go. I haven't really seen any in-depth studies on the exact pharmacokinetics of it, as far as metabolites and other changes I am completely in the dark.

[Sholrak]

Could be CILTEP (no matter you use luteoline, artichoke, zembrin/mesembronne, rolipram) be a nice and effective alternative to the amphetamine fenomena? I've come to a conclusion, once ciltep stablishes is like a constant amphetaminoid state with some passenger adrenaline speedy feeling that subside naturally. It's clearly a case of increased noradrenaline and adrenaline just by the dopamine increased and working more efficiently, just like amphetamine, in a more elegant a subtle (aka healthy) way. it's something perfect for the ADD symptoms, without the heart exhausting.

Could be the progesterone?


I

[Jeoshua]

Let me tell you that, as a person with ADHD, CILTEP did absolutely nothing like adderall, and overall my symptoms worsened. One of the hallmark traits of ADHD is actually hyperfocus that can't really be fully controlled, which is a side-effect of CILTEP that I have seem complained about in this thread. CILTEP is not an ADHD cure; it actually can cause at least one of its symptoms.

[abelard lindsay]

Let me tell you that, as a person with ADHD, CILTEP did absolutely nothing like adderall, and overall my symptoms worsened. One of the hallmark traits of ADHD is actually hyperfocus that can't really be fully controlled, which is a side-effect of CILTEP that I have seem complained about in this thread. CILTEP is not an ADHD cure; it actually can cause at least one of its symptoms.

Are you saying that it worsens your overfocused ADHD (Type 3)? There are six different types of ADHD and most include problems with short-attention span and distractibility.

http://www.healthcen...men-types-adhd/

According to his book and website, Dr. Amen classifies ADHD in one of the following subtypes. All of these subtypes include the primary symptoms of ADHD, persistent short attention span, distractibility, disorganization, procrastination and problems with forethought, judgment and impulse control plus those symptoms listed for the particular type. - See more at: http://www.healthcen...h.JhINs4wz.dpuf

...

Type 3: Overfocused ADD This type of ADHD includes the primary symptoms listed above plus cognitive inflexibility, trouble shifting attention, negative thought processes, worrying, oppositional. This type of ADHD is frequently seen in families where there are problems with addictions or obsesesive-compulsive disorder (OCD). - See more at: http://www.healthcen...h.JhINs4wz.dpuf

Maybe there's a clue in this because the other types among the six described in the article are Limbic and Temporal Lobe and the over-focused type is caused by an over-active cingulate gyrus system of the brain.


Some people think anti-depressants like St. John's Wart can help with this. :

http://www.novianneu...7E-C771CCE3A4FB

Overfocused ADD exhibits the same problems and symptoms of prefrontal cortex as with classic and inattentive ADD, but the difference is that the sufferer of over focused often cannot break away from a thought or behavior. This is because the cingulate system of the brain is overactive and often locks a person into self-destructive, negative, or repetitive behavior.Often a stimulant will cause temper problems if used alone. Therefore, it is usually helpful to have the person take an anti-depressant first and only later to add the stimulant. Another possible treatment is to use St. Johns Wort, a natural herbal anti-depressant, but it is important not to use both a traditional and an herbal anti-depressant at the same time.

Here's a slightly more authoritative citation. These all seem to reference back to the book Healing ADD, by Daniel G. Amen, M.D., 2001

http://books.google....gulate"&f=false

"Over focused" ADHD with SPECT showing hyperarousal in the anterior cingulate gyrus.

Edited by abelard lindsay, 16 March 2014 - 06:12 PM.

[Jeoshua]

Type 3: Overfocused ADD This type of ADHD includes the primary symptoms listed above plus cognitive inflexibility, trouble shifting attention, negative thought processes, worrying, oppositional. This type of ADHD is frequently seen in families where there are problems with addictions or obsesesive-compulsive disorder (OCD). - See more at: http://www.healthcen...h.JhINs4wz.dpuf

This fits me to a "t", so yes I would absolutely be classifiable as Type 3. I've mostly overcome many of the basic symptoms through supplementing basic things like B Complex, Magnesium, and Fish Oil (which are part of my daily regimen almost no matter what nootropic I am looking into). More recently I came across Agmatine and, at low doses, it obliterates the inflexibility and inability to shift attention. CILTEP definitely made the later symptom much more noticeable, although I didn't come up with any way to test whether it was making it worse or making me more aware of it.

Edited by Jeoshua, 16 March 2014 - 10:12 PM.

[lexnaevtreymqupquxtewmubrr]

noob here. offtopic slightly but I'm looking to add these to my current regime::

quercetin
forloskin
MB
NMDA
agmatine




would there be any bad interactions with what I already take quite often/1-2 times a week?-
artichoke
insitol
uridine
Ubiquinol, Coq10, PQQ
tianeptine
hup a
astragalus
Sam-e
sunifiram
oxiracetam
mucuna pruriens

I have many other things I take daily but I don't think they'd create any hangups other than maybe the herbs/barks for respiratory health-- just checking

Edited by lexnaevtreymqupquxtewmubrr, 16 March 2014 - 10:32 PM.

[Jeoshua]

I would avoid taking any Acetylcholinesterase Inhibitors (Hup A) with Positive Acetylcholine Allosteric Modulators (Sunifiram). The effect can be overwhelmingly strong and is thought to be possibly damaging for long term dosages.

Also, quercetin is nice, and synergizes well with CILTEP, but can have a very long half-life.

[lexnaevtreymqupquxtewmubrr]

Sunifiram is potent alone ime so I'd never even contemplate adding huperzine (sounds scary actually) or even caffine
good to know

Edited by lexnaevtreymqupquxtewmubrr, 16 March 2014 - 10:28 PM.

[Charles J. Daniels]

I hear quercetin can have a long half-life in the ciltep stack, so taking that along with artichoke may be a bit much. Also, I always hear you shouldn't take CoQ10 (or any of its forms) with methylene blue (only in that they interefere, not that they cause a problem), and CoQ10 has a long half life as well.

[bzyb]

iHerb has a cheaper version of the Zembrin extract through Source Naturals - half the price of the other one. Feels similar, although I can't say 100% without a direct comparison.
http://www.iherb.com...=4&sr=null&ic=2

I'm on both Zembrin and Artichoke, and I feel a bit brain foggy, which I haven't felt in the past on both.
You mentioned Tinnitus and feeling a bit out of it on both Zembrin + Artichoke... maybe the "feeling out of it" is my brain fog?
I'll try just Zembrin, since it completely inhibits PDE-4.

However what do you do on Forskolin + Zembrin when the Zembrin wears off and you still need to study? I'm thinking about dosing Zembrin 3X / day with Forskolin, since Zembrin seems to last 4 hours or so with me.

Hey thanks for the cheaper zembrin recommendation, 40$/bottle was getting pricy. I was about ready to quit zembrin because its too expensive for a broke college student like me. I'm on the full Zembrin-Ciltep stack right now (took it 7 hours ago still going strong), always empty stomach since it works better when I fast. My general opinion about Zembrin is you're not really sure what you're going to get, except the short half-life! For it to work for me, I usually have to take 3-4 sublingual doses like today, so you can see why it can get expensive. After taking that many doses, I also began to get sleepy, so I took a gram of NALT (like it said on the first page) and I was back in business for few more hours of work.

I mostly use zembrin for the anxiolytic effects, but since everyone is mentioning agmantine I'll have to try that since I've tried about everything else to little to no avail. I'm also trying to cut out caffeine/coffee from my diet because of jitteryness. This stacked with Now MCT Oil capsules, green tea/theanine/l-glutamine and noise-proof headphones seems to work well for me for focus and calm.