15 replies to this topic

[nezxon]

My stack is designed to provide neuroprotection, anti-aging properties (e.g. cell plasticity), and cognitive performance improvement by enhancing memory, concentration, synaptic transmission speed, and reaction time. This is not a plan for a stack, it is the stack I am taking on a daily basis (I began this iteration of my stack about 2 weeks ago)

To achieve these goals I'm attempting to improve the efficiency of the cholinergic system:

• Facilitate the production of acetylcholine with a high intake of acetylcholine precursors. (Lecithin, ALCAR)
• Inhibit the destruction of acetylcholine through effective doses of Huperzine A.
• Efficiently use acetylcholine with supplements to provide stimulation, energy, and focus (Racetams, Adrafinil, DMAA, Noopept, Caffeine)
• Provide a support system of nutrients that are precursors or enhancers to the many metabolic processes involved (multi-vitamin, fish oil, ubiquinol, ursolic acid)

I've organized my stack into three categories:

Nootropics: Supplements that, in my estimation, qualify under C.E. Giurgea's definition of a nootropic:
2 x 1,200 mg Lecithin (triple strength) three times daily (Total Daily Dose: 7,200 mg [2,280 mg choline])
1 x 750 mg ALCAR three times daily (Total Daily Dose: 2,250 mg)
1 x 500 mg Pramiracetam three times daily (Total Daily Dose: 1,500 mg)
1 x 800 mg Oxiracetam three times daily (Total Daily Dose: 2,400 mg)
2 x 200 mcg Huperzine A three times daily (Total Daily Dose: 1,200 mcg)

Health Supplements: Supplements to enhance overall health
1 x 100 mg Ubiquinol once daily (Total Daily Dose: 100 mg)
2 x Multi-Vitamin (Ray and Terry's Total Daily Care Formula) three times daily (Total Daily Dose: 6 tablets)
1 x 1,000 mg Fish Oil (EPA/DHA Mega 420/280) three times daily (Total Daily Dose: 3,000 mg [1,260 EPA/840 DHA])
6 x 600 mg Ursobolic three times daily (Total Daily Dose: 10,800 mg [2,700 mg Ursolic Acid])

Congitive Performance Enhancers: Supplements that may offer cognitive improvements, but which I have disqualified as nootropics either due to their side effect profiles or a lack of available information.
1 x 600 mg Adrafinil twice daily (Total Daily Dose: 1,200 mg)
1 x 30 mg Noopept twice daily (Total Daily Dose: 60 mg)
2 x 20 mg DMAA once daily (Total Daily Dose: 40 mg)
1 x 200 mg Caffeine twice daily (Total Daily Dose: 400 mg)

Notable Changes

Phased out Piracetam and Aniracetam - This really has nothing to do with efficacy, it's mostly cost. I was previously taking all 4 racetams; reducing to Oxiracetam and Pramiracetam seem to offer the same benefits. Even if cost weren't a factor, I'm actually so impressed with the "high-octane" or "cleaner" feel (that's the best way I can seem to describe it), that I don't feel Aniracetam and Piracetam are strictly necessary for me. I still believe racetams in general are necessary, core nootropics, but I've decided that the newer racetams are suitable as a complete replacement for me.

Phased out Picamilon, Pyritinol, and Sulbutiamine - Cut due to cost. If cost weren't a factor, I think these would be permanent staples.

Phased out Centrophenoxine - Cut due to cost. I think it's a valuable supplement for cognitive improvement and anti-aging, but it seems fairly expensive to take effective doses of it.

Lecithin instead of CDP-Choline of Alpha GPC - Lecithin is comparatively cheaper and has natural time-release properties. I think I've noticed a distinct boost in performance with the additional choline. I haven't experienced any headaches. I'm not sure if this is due to Lecithin's properties, high choline tolerance, or maybe something in my stack is balancing it out.

Increased Fish Oil - Only a slight increase, my bodily health has steadily improved since I began Fish Oil supplementation about 7 years ago. I've always had good health results (improved [lower] blood pressure, stellar cholesterol levels), and with this change I think I'm getting a better ratio of EPA/DHA.

Increased Huperzine A - After reading some reports of the minimum therapeutic dose being 400 mcg, and the effective duration being 6 hours, I decided to try a more aggressive approach with it, and I think the results are promising so far. My memory seems at least a little sharper than with the lower doses I was taking, but obviously this could be due to a number of refinements in my stack.

Ursolic Acid - After reading some articles, I thought it seemed to offer some significant promise in terms of improving cellular efficiency. At this point I am not making recommendation for or against this, it's just a personal experiment.

Let me know if the use of color lends clarity. An experiment in formatting (obviously inspired by posters in another thread). I was hoping to emphasize key details better. The link to the multivitamin is just for informational purposes, in case people are curious about the exact contents, I'm not affiliated with them.

[conradshark]

Nice one! Well written and explained.

How do you feel with it? Isn't it a bit too much?

I'm thinking about using to improve cholinergic system aswell (mainly long-term memory), but sometimes you need some motivation too, coming mainly from dopaminergic activity. Adrafinil maybe does the job for you but I have none..
Can someone recommend something? Sulbuthiamine maybe..

Also Huperzine A, 400mcg isn't it a lot? I've read on a study that the dose was like yours 400 mcg, for having better memory.. gonna try 200 mcg then if needed up it.

And you mixture Caffeine (stimulant) with Adrafinil too? Aren't you too stimulated?

[health_nutty]

I'm surprised that you aren't taking Aniracetam considering it is the only racetam that is an ampakines.

I'm worried about using acetylcholinesterase inhibitors because of this:
Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation

http://www.pnas.org/content/101/7/2140

Although HupA has a relatively short half life of five hours, the effect on ACh lasts up to 48 hours!
1: Chem Biol Interact. 2008 May 3. [Epub ahead of print] <script language="JavaScript1.2">Links
Protection of red blood cell acetylcholinesterase by oral huperzine A against ex vivo soman exposure: Next generation prophylaxis and sequestering of acetylcholinesterase over butyrylcholinesterase.
Haigh JR, Johnston SR, Peppernay A, Mattern PJ, Garcia GE, Doctor BP, Gordon RK, Aisen PS. Walter Reed Army Institute of Research, Division of Biochemistry, 503 Robert Grant Road, Silver Spring, MD 20910-7500, USA.

As part of a phase Ib clinical trial to determine the tolerability and safety of the highly specific acetylcholinesterase (AChE) inhibitor huperzine A, twelve (12) healthy elderly individuals received an escalating dose regimen of huperzine A (100, 200, 300, and 400mug doses, twice daily for a week at each dose), with three (3) individuals as controls receiving a placebo. Using the WRAIR whole blood cholinesterase assay, red blood cell AChE and plasma butyrylcholinesterase (BChE) were measured in unprocessed whole blood samples from the volunteers following each dose, and then for up to 48h following the final and highest (400mug) dose to monitor the profile of inhibition and recovery of AChE. Significant inhibition of AChE was observed, ranging from 30-40% after 100mug to >50% at 400mug, and peaking 1.5h after the last dose. Gradual recovery of AChE activity then occurs, but even 48h after the last dose red blood cell AChE was about 10% below control (pre-dose) values. Huperzine A levels in plasma peaked 1.5h after the final 400mug dose (5.47+/-2.15ng/mL). Plasma BChE was unaffected by huperzine A treatment (as expected). Aliquots of huperzine A-containing (from three individuals) and placebo blood samples were exposed ex vivo to the irreversible nerve agent soman (GD) for 10min, followed by removal of unbound huperzine and soman from the blood by passing through a small C(18) reverse phase spin column. Eluted blood was diluted in buffer, and aliquots taken at various time intervals for AChE and BChE activity measurement to determine the time taken to achieve full return in activity of the free enzyme (dissociation from the active site of AChE by huperzine A), and thus the proportion of AChE that can be protected from soman exposure. Huperzine A-inhibited red blood cell (RBC) AChE activity was restored almost to the level that was initially inhibited by the drug. The increased doses of huperzine A used were well tolerated by these patients and in this ex vivo study sequestered more red blood cell AChE than has been previously demonstrated for pyridostigmine bromide (PB), indicating the potential improved prophylaxis against organophosphate (OP) poisoning.

PMID: 18572153 [PubMed - as supplied by publisher].

[conradshark]

That is a really good point, however it's goes either way:

The lack of a physostigmine treatment-induced impairment on the mirror-tracing task was consistent with other reports that have suggested that procedural memory consolidation may depend primarily on REM sleep
However, inconsistencies in reports indicating whether SWS or REM sleep may be more critical for memory consolidation of declarative and/or procedural tasks make such a dissociation premature. Alternatively, it has been suggested that the degree to which memory consolidation depends on REM sleep may be related to the complexity of the newly acquired memory rather than the type of memory (17)

http://www.pnas.org/...101/7/1795.long

REM is also associated with memory consolidation. REM and waking (awake?) is associated with high levels of acetylcholine:

Activation of the cholinergic system has been demonstrated to enhance attention, learning, and memory consolidation and to facilitate plasticity after physiological manipulations and during development (6–8). Acetylcholine levels are high during waking and rapid eye movement (REM; also known as paradoxical) sleep (9). These observations seem consistent with the possibility that REM sleep may play an important role in facilitating synaptic plasticity of recently acquired memory traces.

At least that's my conclusion.

And from your article in full-text (I have access to almost all magazines):

Although our results
provide confirmatory evidence for this integrative model of
sleep-related memory function, it is conceptual in nature and
needs further testing in various aspects.
Whereas postlearning administration of cholinergic agonists has
not been studied in humans, some studies in animals report
enhancing effects on long-term memory when cholinergic receptor
agonists are administered immediately after learning

Only when large
amounts of SWS are missing can impaired memory consolidation be seen..

But it's a good point. Is there any AChE Inhibitor that doesn't last that long? If we use HupA we have to use it like twice a week or something to have some proper low levels and consolidation occur in sleep aswell.
In 24h it's still an advantage to take AChE Inhibitors..

[health_nutty]

But it's a good point. Is there any AChE Inhibitor that doesn't last that long? If we use HupA we have to use it like twice a week or something to have some proper low levels and consolidation occur in sleep aswell.
In 24h it's still an advantage to take AChE Inhibitors..

Why not just take ACh precursors in the morning / afternoon and leave AChE alone? If precursors sufficiently boost ACh, what advantage is there to inhibiting AChE?

[conradshark]

Yes, maybe you are right.

From another article:
Behav Brain Res. 2011 Aug 10;221(2):499-504. Epub 2011 Jan 14.
The cholinergic system, EEG and sleep.

Interestingly, slowing of the EEG and circadian changes can be reversed by cholinesterase inhibitors; for example, donepezil reliably increased the percentage of REM sleep and total sleep time in a number of studies (reviewed in [4]). What remains to be confirmed however is whether improved sleep patterns may directly counteract memory deterioration, i.e. whether cholinergically controlled sleep disruptions contribute to the progressive cognitive decline or are merely an additional disease biomarker. Nevertheless, evidence available from respective studies strongly suggests a close link between sleep, EEG and the cholinergic system in health and disease.

[nezxon]

How do you feel with it? Isn't it a bit too much?

I feel alert and focused, but not over-stimulated. I don't think any part of it seems like too much, except the price tag (about $270/mo).

but sometimes you need some motivation too, coming mainly from dopaminergic activity. Adrafinil maybe does the job for you but I have none..
Can someone recommend something? Sulbuthiamine maybe..

The two main supplements I think help motivation are Pramiracetam and Oxiracetam. As you already mentioned, I think it's possible Adrafinil and Sulbutiamine improve motivation too.

Also Huperzine A, 400mcg isn't it a lot? I've read on a study that the dose was like yours 400 mcg, for having better memory.. gonna try 200 mcg then if needed up it.

400 mcg of Huperzine A three times per day is probably more than most, but I don't think it seems dangerously high. I took 100 mcg Huperzine A once daily for about 3 months. I didn't see any notable improvement in performance in any area compared to before I started taking it, so I decided to try a much higher dose before ruling it out.

[health_nutty]

Any thoughts on Aniracetam? It's mechanism of action is unique as it is the only racetam that is an ampakine. Also, what do you think AChE inhibitors affecting memory consolidation? Especially that 400ucg...

[nezxon]

Any thoughts on Aniracetam? It's mechanism of action is unique as it is the only racetam that is an ampakine. Also, what do you think AChE inhibitors affecting memory consolidation? Especially that 400ucg...

I think Aniracetam seems to be a potent nootropic, I just think the other racetams seem a little better. I took Aniracetam as part of my stack for about a year and it was the first of the racetams I tried. It's my understanding all of the racetams have shown some ampakine activity, though Aniracetam seems to be the most prominently mentioned by many sources. Aniracetam's half-life is reportedly much shorter, so both Oxiracetam and Pramiracetam seem like better all-day cognitive performance enhancers. Aniracetam didn't lose out by a huge margin, I barely cut it from my stack. Unfortunately it was one thing too many. If cost weren't a factor, I'd be happy to include it again.

I think it's possible that AChE inhibitors affect memory consolidation, hopefully in a good way. Things that improve cognitive performance while conscious should similarly improve some of the functions the brain performs during unconscious time. Admittedly, that kind of logic is probably the basis of many specious factoids. Still, I think the mind is still similar to the body in many ways. Just like exercising improves the body's functioning, all the way down to a cellular level, 24hrs/day not just during exercise; improving cholinergic function should improve the brain's function during sleep too, not just during mental exercise.

[health_nutty]

Any thoughts on Aniracetam? It's mechanism of action is unique as it is the only racetam that is an ampakine. Also, what do you think AChE inhibitors affecting memory consolidation? Especially that 400ucg...

I think Aniracetam seems to be a potent nootropic, I just think the other racetams seem a little better. I took Aniracetam as part of my stack for about a year and it was the first of the racetams I tried. It's my understanding all of the racetams have shown some ampakine activity, though Aniracetam seems to be the most prominently mentioned by many sources. Aniracetam's half-life is reportedly much shorter, so both Oxiracetam and Pramiracetam seem like better all-day cognitive performance enhancers. Aniracetam didn't lose out by a huge margin, I barely cut it from my stack. Unfortunately it was one thing too many. If cost weren't a factor, I'd be happy to include it again.

I think it's possible that AChE inhibitors affect memory consolidation, hopefully in a good way. Things that improve cognitive performance while conscious should similarly improve some of the functions the brain performs during unconscious time. Admittedly, that kind of logic is probably the basis of many specious factoids. Still, I think the mind is still similar to the body in many ways. Just like exercising improves the body's functioning, all the way down to a cellular level, 24hrs/day not just during exercise; improving cholinergic function should improve the brain's function during sleep too, not just during mental exercise.

The noticable effects you can feel of Pram (or even Oxi) are better than Ani. However, what about the AMPA upregulation? I did quite a bit of research and I couldn't find any solid evidence (in actual studies) that any of other racetams upregulated AMPA. In fact, the more I looked into it the more evidence I saw that Ani is unique in this aspect. I saw a wikipedia article and other websites that claim that Pram is an ampakine, but no study to back up the claim.

Because of this I've decided to combine the best of both worlds: Take Pram and Ani. Pram for the motiviation and focus and Ani for the ampakine effect. The results have been fantastic.

[nezxon]

http://www.ncbi.nlm....pubmed/20163115

"We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to GluA2 and GluA3 in a very similar manner..."

"Piracetam is a very weak modulator of AMPA receptors, increasing responses (presumably due to a block of desensitization) with a relatively low affinity"

A number of sources, many studies which can be found on pubmed, seem to indicate that Piracetam, Aniracetam, Oxiracetam, Pramiracetam, and Noopept are all positive allosteric modulators of the AMPA receptor. Some studies seem to indicate both Aniracetam and Noopept exhibit markedly stronger AMPA activity than Piracetam and Oxiracetam, though exactly where Pramiracetam falls on the spectrum isn't quite clear to me due to an almost complete lack of studies.

It does seem that Aniracetam offers uniquely potent AMPA modulation compared to other racetams, but I find it hard to judge the best combination when mixing multiple racetams together. If you're after ampakine activity, Ani/Pram seems like the right direction to go. If you make an addition to your stack, noopept is said to share their preference for AMPA receptors. http://www.ncbi.nlm....pubmed/21476267 Although the evidence could be considered weak given this is an in vitro rat study, it's at least a positive indication supporting the idea that noopept has strong AMPA affinity.

One of the benefits of the racetams seems to be that they have multiple modes of action. Racetamic modulation of glutamate receptors, although promising, is just one mode of action; I think their function as cholinergics is probably just as important. I would describe all the racetams as fairly weak, broad-spectrum nootropics. Aniracetam may be the most potent of the first-generation ampakines, but I think we're probably talking about very narrow margins of ampakine activity.

I'm glad you've had good results because I think that's what counts. Whether it's Pram/Ani, Pram/Oxi, or just plain Piracetam, I'd rather get decent results with a possibly sub-optimal stack than take nothing at all. On a daily basis I don't really experience any noticeable effect from any of the racetams. I felt a slight boost at first, and there seem to be subtle changes in feeling when I refine my stack every few months, but most of the perceptible feelings seem almost entirely normalized.

[nezxon]

I'm just writing to wrap things up here and say goodbye, after I post this I'm going to log out of Longecity and I won't post again. Over the last year I've developed a seemingly effective nootropic stack for myself as a result of information I found mentioned or linked to from this forum. I doubt it's optimal, or even very good in a theoretical sense, due to a severe lack of information I need to answer specific questions in order to make more significant progress in refinement. For future reference, I don't suggest anyone adopt my stack. Take it with a grain of salt, you don't know much about me other than what I post here, so look at my stack for what it is: a collection of supplements that some guy says might have helped him some. As they say, YMMV.

So the last changes/refinements/notes I'll mention are:

• Based on further investigation into Aniracetam's chemical structure and activity (prompted by healthy_nutty's posts), I decided to add 1x750 mg Aniracetam three times per day and phase out Oxiracetam.
• Long-term, I plan to drop all of the supplements I categorized as "Cognitive Performance Enhancers" with the possible exception of Noopept, the jury is still out (yet again another case of severely lacking information).
• When I first looked into nootropics I think, similar to many other seekers, I fell into the trap of trying to pick supplements by how they made me feel. I think that's extremely deceptive, if not the most deceptive possible way to design a stack. We know drugs like opiods and benzodiazepines make us feel good, but they have a reportedly negative effect on memory. I think trying to pick what's good for you based on what feels good is building a sand castle. As I have refined my stack, I try to make decisions based on my understanding of the chemical structures, reported and studied neuropharmacological activity, and trying to synthesize an understanding of how the body reacts on a physiological and biochemical level. The perceptible feelings that may be caused by supplements only seems helpful as an elimination test (if it makes you feel bad, avoid it), but trying to judge efficacy on the basis of neutral and positive feedback seems fallacious. It's pretty much an established fact, things that are good for you don't always make you feel anything at all. There are millions of people taking multi-vitamins which I think are almost inarguably good for the vast majority of them. They don't walk around complaining about "you know, I took a multi-vitamin this morning and don't feel any different." I'm not sure why so many people, specifically at this forum, seem to think that the human body can only improve its function under the watchful gaze of the pleasure center of the brain. That just doesn't seem like a solid transhumanist philosophy to me.

That last point brings me to the main reason I've decided to just exit this forum. As much as I try to avoid it, it seems like too many threads become dominated with borderline drug-seeking behavior, people looking for Dr. Feelgood, obsessed with vivid colors, transcendent music, and seem to treat every conversation around here like all the talk about neurotransmitters, ion channels, and receptors are euphemisms for a secret way to get high "Hey man, I want the effects too! Tell me how to get the effects!". Getting into cognitive performance enhancers, nootropics, smart drugs, transhumanism, and brain health to find feelings of euphoria and ecstasy is like diving to the bottom of the ocean for a glass of water because you hear there's other people who are down there, then complaining about how salty it is, how unbearable the pressure is, and asking why everyone is down here to drink this shit. It's because the rest of us didn't dive down here for the water dumbass.

If anyone is thinking the Hyperspace/Scienceguy debacle has something to do with my deciding to leave, it really wasn't a huge factor. That whole thing was real short-lived, though I'm embarrassed that I bothered posting or participating in those threads and worried a little about my comments there reflecting poorly on me. I didn't care that much about their glutamate + calcium rant. Maybe glutamate or calcium is a missing component for some people, or maybe it's just another straw to grasp at in an effort to extract recreational value out of expensive drugs that don't seem to offer any instant gratification. Thank you for introducing me to the concept of nootropics.

[health_nutty]

I'm just writing to wrap things up here and say goodbye, after I post this I'm going to log out of Longecity and I won't post again.

I'm sorry to see another very rational scientific mind leave. Take a break, and if you feel like it post here again.

[Cephalon]

Damn! I read the whole thread and found nothing that can make me get super high. Shame - will look over at bluelight than ...

Edited by Cephalon, 14 May 2012 - 05:19 PM.

[panhedonic]

Nezxon, maybe you haven't logged out after all and you will see this.

I see your criticism a bit biased. Ultimately, it's all about human experience. We all seek effects (as in affecting reality or as in "feeling the effects). Be it long-term or short term, nobody here, I believe, is indifferent to feeling better/more intelligent/more capable. Any of these changes involve feeling the effects in our "quallia" (the intrinsic quality of our impressions) If this means feeling the effects, getting high in a recreational way, it's a matter of degrees, not a fundamental distinction.

If you don't want to feel better (either in sheer pleasure or by a perception of the value of your behavior) then you probably were born in a different planet. So judging "this forum" for the fact that some of us appreciate unusual or intense effects every now and then, is not only over-generalizing, but pretty short-sighted, and "high-horsed" I think. There goes my judging.

Especially taking into account that many people in these forums suffer from a mild-to-intense condition that directly affects how the feel everyday inside their consciousness cocoons.

Just my dos centavos.

[CIMN]

bumping thread as i found it very informative in regards to sleep.