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Piracetam - How to get all the benefits from it

piracetam nootropics non-responders oxiracetam aniracetam noopept memory cognition learning choline

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#331 Isochroma

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Posted 28 November 2012 - 02:00 AM

The images fail to capture the difference between the colors of the street lights.

In addition to the increase in color saturation and sharpness, the individual lights show very different colors which are not visible in these photos.

Finally, there is a third visual effect which I call the Electric Shine. It is the difference between 'flat' color and 'metallic' or 'shiny' color or reflectance. It shows up on two kinds of sights: intense lights (incandescent, HPS, metal halide, mercury vapor, sun but not dimmer lights like fluorescent tubes) and chromed/shiny surfaces.

It's an electricality to the images. Chromed surfaces like faucets, hubcaps, etc. look super-shiny and especially when coated in drops of water, there is a super-shinyness.

For light sources it shows as a metallic-shinyness to the light. The opposite of flatness. It might actually be a secondary chromatic saturation effect but I have classed it as a third effect (the first two being color saturation and image sharpness (especially edge sharpness).

The images below can only show color saturation and edge sharpness differences. They show none of the metallicity-shiny-chromed effect.


Posted Image

No Racetam


Posted Image

Piracetam


Posted Image

Piracetam + MSG


Posted Image

Aniracetam


Posted Image

Oxiracetam


Edited by Isochroma-Reborn, 28 November 2012 - 02:09 AM.


#332 Isochroma

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Posted 28 November 2012 - 02:44 AM

Racetam Visual FX Animated!

Be sure to enable GIF animation in your browser - below is an animated GIF of the five images in the previous post, for easier interimage comparison.

Unfortunately this board won't show anything but the first frame of the animated GIF - at least in Firefox 3.6.28.

You might have to save it to your desktop and view it with an image viewer/editor to see the animation. It animates OK for me in Windows Picture and Fax Viewer and IrfanView.


Posted Image


Edited by Isochroma-Reborn, 28 November 2012 - 02:52 AM.

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#333 norepinephrine

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Posted 28 November 2012 - 06:31 AM

That's cool and all, but I think most of us take racetams for the cognitive enhancing effects and regard enhanced visual acuity as an added, though minor, side effect.

#334 Isochroma

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Posted 28 November 2012 - 06:51 AM

You misinterpreted me. I like the colors too, but like you and others I also take racetams for the nootropic effect.

If you re-read my post, I mentioned that the mental anti-fatigue effect is correlated with the color/brightness increase.

So the colors serve as a kind of signpost - a measure of the other effects.

Also, unlike using language to try to describe the other effects, using images I can directly show the differences.

Pictures are worth many millions of words.

Also, the level of color enhancement correlates with the mitochondrial energy experiments that show the racetams' powers in descending order of power: Oxiracetam > Aniracetam > Piracetam.

I will be posting those studies shortly so the correlation data can be inspected by all.
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#335 SuperjackDid_

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Posted 28 November 2012 - 07:21 AM

How to lower this side effect ,stop more than a month ,very amazing effect not go anywhere ,or my brain already altered by this side effect ?

This is side-effect not over-stimulation symptom?,so we can get along with Piracetam while having this effect ,but jut to keep it minimal ?

I fully agreed on color sharpness increase ,mental fatigue will increase .

Edited by Nootropix, 28 November 2012 - 07:25 AM.


#336 Isochroma

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Posted 28 November 2012 - 09:56 PM

You are correct. For me, the color enhancement of Oxiracetam can last for up to a month after stopping intake.

That goes for the mental anti-fatigue effect too.

Which is why I can't say for sure that the MSG is going to have the effects I need it to in combination with Piracetam - it's only day 15 today of the combo so there's still a significant chance that what I'm feeling is leftovers from the Oxiracetam and Pramiracetam.

#337 Introspecta

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Posted 28 November 2012 - 10:50 PM

Your not even the least bit concerned that you are way over dosing your MSG? Why not just get some Glutamic acid and dose 100 mgs once a day instead of poisoning yourself with MSG. Have you ever researched the dangers of MSG?
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#338 Isochroma

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Posted 28 November 2012 - 11:26 PM

Of course I did the research.

Wheat gluten (protein) is 24% glutamate by weight.

It's the most common by far of the 22 amino acids.

There's no problem. No sides yet either.

My jar of Accent recommends 1/2 teaspoon per dose.

Oh yeah! I got the pricing on the BIG BOY, a 50LB bag of pure MSG!

It only costs $59.95 at my local buyer's club. So I'll be buying one of those and biking it home if the testing works good :)

As for danger, let's look at all those posters on this forum and others who are taking Adderall (Amphetamine).

It's already been proven to cause brain mass loss and damage, orally using the same low doses that are used to treat ADHD. That's proven. I have the study on my hard drive and can post it here for your examination. Oral use of MSG has never caused any such damages even at extremely high doses. I have studies that use oral MSG doses double mine in volunteer humans.

If you look at the damage-finding studies on MSG, every single one uses massive injected doses (IV, intraperitonal, intracerebral, etc.) that totally overwhelm the brain's natural efflux pumps. It has been commented in at least one study that such conditions are highly abnormal and completely unattainable using oral dosing.

Edited by Isochroma-Reborn, 28 November 2012 - 11:37 PM.


#339 Isochroma

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Posted 29 November 2012 - 12:28 AM

MSG = Miracle Super Generator
God = Generator Operator Destroyer

I was lazy this morning and forgot to mention five effects I'm getting from the MSG + Piracetam combo that never appeared in all the years of dosing PIR and other racetams:

1. Since starting 15g/day MSG, I notice mildly looser stools. Not frank diarrhea like that caused by Oxiracetam, just smoother creamier throne-nougats.

2. An enormous increase in my thinking capability and complexity - completely unlike PIR alone.

3. A distinct yet mild stimulant-like effect which is especially noticeable when I normally get sleepy/tired at night shortly before bed. It's totally noticeable and occurs every day now. Very distinct.

4. A huge increase in sleep quality - even better than PIR or any other racetam alone. I sleep really SOLIDLY now, and for about 1 extra hour too. This has also meant that I am clearer and more awake during the day.

5. A distinct increase in the length and quality of REM dreaming. My dreaming is now so packed full that I can't even count the number of dreams per night nor the vast collection of communications, encounters and other happenings in them.

In total I am liking this MSG a lot! It's adding up to a complexity that never existed before. The sum of its effects in combination with PIR has been highly positive for me.

And a single negative observation: MSG helps not a bit with the anger / bitchiness that comes from PIR. I assume choline would do that but I never bother with it. I prefer to run in anger/bitch mode. I should probably add choline. My current B-Complex supplement has a paltry 300mg Choline Bitartrate and I take only one pill per day. It's enough for survival.

Oh, one more thing. If my experiences (improving daily) for the last three days can be counted on as true MSG-related effects: the stimulatory (anti-mental-fatigue/sleepiness) effects of the PIR-MSG combo are at level or slightly more powerful than even the most powerful 'higher' racetams that I have tried: Oxiracetam and Nefiracetam. I get less fatigue with this combo than with either of those at any dose - without their side effects, dangers (Nefiracetam) or financial costs. Without MSG Piracetam is so weak as to be almost useless to me.

Edited by Isochroma-Reborn, 29 November 2012 - 12:49 AM.

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#340 Isochroma

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Posted 01 December 2012 - 11:46 PM

Today I found some more research data on humans fed MSG.

The PDF linked below is the full research paper. For brevity I quote only the abstract below it:

Plasma glutamate concentrations in adult subjects ingesting monosodium L-glutamate in consomme

Abstract:

"The effect of MSG ingestion in consomme on the plasma glutamate concentration response was studied in normal adult subjects. In the first study nine subjects ingested three different consomme servings (providing 0, 25 and 50 mg/kg body weight MSG) in a Latin square design. Plasma glutamate concentrations were not significantly increased over baseline (3.69 +/- 1.08 mumol/dl) when no added MSG was present. However, mean peak plasma glutamate levels increased proportional to dose when MSG was added (10.2 +/- 2.00 and 17.0 +/- 8.06 mumol/dl at 25 and 50 mg/kg body weight respectively). Since six of the nine subjects in this study reported an idiosyncratic symptom response when tested with MSG at 150 mg/kg body weight, nine additional subjects were also studied. They ingested consomme providing MSG at 0 and 50 mg/kg body weight. No significant differences in plasma amino acid responses were noted between the two groups of subjects."


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Plasma pyroglutamic acid levels after oral administration of monosodium glutamate to human volunteers

Abstract:

"Plasma levels of pyroglutamic (PY) and glutamic (GA) acids have been measured after oral administration of monosodium glutamate (MSG) to 6 human volunteers. MSG (43 mg/kg) was administered either after an overnight fast or immediately after a normal meal. In fasting subjects plasma GA peak levels were about 2.3 times the basal levels whereas the increase in plasma PY levels were only 1.5-fold. When MSG was administered with a meal plasma GA levels were raised, to a lesser extent, while no increase could be observed in plasma PY."


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Importantly, the second study shows a change in the ratio of Glutamic Acid:Pyroglutamic Acid when MSG is ingested. Specifically, Glutamic Acid increases 53% more than Pyroglutamic Acid when MSG is ingested alone. Ingestion of MSG with a meal decreases the effect because other amino acids compete for absorption and metabolism. This changes the ratio of the two chemicals and that is the key to altering the brain's autosense regulatory loop toward decreased export of Glutamic Acid and/or increased production of Glutamic Acid within the brain.

Edited by Isochroma-Reborn, 02 December 2012 - 12:06 AM.

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#341 alecnevsky

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Posted 02 December 2012 - 12:08 AM

"As for danger, let's look at all those posters on this forum and others who are taking Adderall (Amphetamine). It's already been proven to cause brain mass loss and damage, orally using the same low doses that are used to treat ADHD. That's proven. I have the study on my hard drive and can post it here for your examination." Can you either pm me this study or post / link it? I am interested whether this is due to excess dopamine or something else...

Edited by alecnevsky, 02 December 2012 - 12:09 AM.


#342 Isochroma

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Posted 02 December 2012 - 12:28 AM

Unlike most other studies, this one used oral, low doses of amphetamine - the same doses that children receive for ADHD - to make a more realistic assessment of whether such dosing could cause brain damage. Other studies use higher doses injected into the body or brain which is not only unnatural and not the current practice for low-dose ADHD treatment but also overwhelms any potential limiters that prevent damage such as absorption rate, transport carrier saturation or metabolism. It was found that such dosing does indeed produce brain damage:

Amphetamine Treatment Similar to That Used in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder Damages Dopaminergic Nerve Endings in the Striatum of Adult Nonhuman Primates

Full PDF

Abstract:

Pharmacotherapy with amphetamine is effective in the management of attention-deficit/hyperactivity disorder (ADHD), now recognized in adults as well as in children and adolescents. Here we demonstrate that amphetamine treatment, similar to that used clinically for adult ADHD, damages dopaminergic nerve endings in the striatum of adult nonhuman primates. Furthermore, plasma concentrations of amphetamine associated with dopaminergic neurotoxicity in nonhuman primates are on the order of those reported in young patients receiving amphetamine for the management of ADHD. These findings may have implications for the pathophysiology and treatment of ADHD. Further preclinical and clinical studies are needed to evaluate the dopaminergic neurotoxic potential of therapeutic doses of amphetamine in children as well as adults.


Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neuropsychiatric illness, afflicting 3 to 9% of school-age children and 1 to 5% of adults worldwide (Leung and Lemay, 2003; Biederman and Faraone, 2004; Wilens et al., 2004). For years, psychomotor stimulant drugs have been the mainstay of ADHD treatment (Greenhill et al., 2002; Fone and Nutt, 2005), and in the last decade, their use has increased substantially (Olfson et al., 2003; Robison et al., 2004). Of the various stimulant drugs used in the treatment of ADHD, amphetamine is among the most often prescribed (Greenhill et al., 2002; Fone and Nutt, 2005), both in children and adults (Wilens et al., 2004; Dodson, 2005).


As the use of amphetamine in the treatment of ADHD has increased, a large body of preclinical data has accrued indicating that amphetamine has the potential to damage brain dopamine-containing neurons in experimental animals. In particular, animals treated with amphetamine develop lasting reductions in striatal dopamine, its major metabolite dihydroxyphenylacetic acid (DOPAC), its rate-limiting enzyme tyrosine hydroxylase, its membrane transporter (DAT), and its vesicular transporter (VMAT2) (Gibb et al., 1994; McCann and Ricaurte, 2004). Anatomic studies indicate that lasting dopaminergic deficits after amphetamine are due to damage of dopaminergic nerve endings in the striatum, with sparing of dopaminergic nerve cell bodies in the substantia nigra.


Despite these preclinical data and growing awareness of potential long-term adverse effects of stimulant ADHD medications (Volkow and Insel, 2003; Fone and Nutt, 2005), there has been little expressed concern over possible dopaminergic neurotoxicity in humans receiving amphetamine for the treatment of ADHD. In large measure, this appears to be due to the fact that, as noted by various authors (Vitiello, 2001a,b; Greenhill et al., 2002; Fone and Nutt, 2005), doses, routes, and regimens of administration used in amphetamine neurotoxicity studies in animals differ significantly from those used in the treatment of ADHD.


The purpose of the present study was to determine whether amphetamine treatment, similar to that used clinically in the therapy of adult ADHD, produces long-term effects on brain dopaminergic neurons in adult nonhuman primates. Initial studies used baboons as experimental subjects because their size (20–30 kg) allows for administration of amphetamine at an absolute dose similar to that used in ADHD. To further simulate the clinical use of amphetamine, we trained baboons to self-administer amphetamine by mouth. We tested a 3:1 mixture of dextro- and levo-amphetamine, because one of the more common formulations used in the treatment of ADHD consists of a combination of 75% dextro-amphetamine and 25% levo-amphetamine. In a final set of studies, we used squirrel monkeys to test the species generality of our findings.


Edited by Isochroma-Reborn, 02 December 2012 - 12:35 AM.


#343 Dissolvedissolve

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Posted 02 December 2012 - 01:13 AM


Although the present preclinical observations may have clinical implications, it would be premature to extrapolate them to humans receiving amphetamine treatment for ADHD for several reasons. First, the dopaminergic neurotoxicity may only occur in the context of doses of amphetamine that result in plasma concentrations comparable with those found in these experiments; lower dosage regimens that engender lower plasma amphetamine concentrations may not
be associated with toxic effects on central dopaminergic neurons.


→ source (external link)


(The authors also mention a bunch of caveats about applying animal results to humans.)

I just wanted to point out this quote. The study does establish that amphetamine may be neurotoxic at the high therapeutic range, but it does not establish that a low dose along with tolerance prevention strategies, as suggested by some members here, is neurotoxic. It is definitely an interesting read regardless, and it is more support for the idea that daily amphetamine treatment with increasing doses is probably unwise.

And just one other thing. I see nothing terribly wrong with supplementing glutamic acid, although I'd be wary of its excitatory effects. I would be very wary of supplementing MSG - not because of the glutamate component, but simply because ingesting 15000 mg of sodium daily is absurd.

Edited by Dissolvedissolve, 02 December 2012 - 01:14 AM.


#344 #1stunna

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Posted 02 December 2012 - 01:20 AM

Adderall vyvanse and ritalin feel like putting jet fuel in your brain. I don't like the side effectslike racing herart and anxiety.

2.2g piracetam + b vitamins + fish oil + choline and I am on point, I've been taking this combo before work with great results. Feel more positive and well spoken, improve concentration and memory. Adding ginko soon.

#345 Isochroma

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Posted 02 December 2012 - 01:24 AM

B-Vitamins and Fish Oil are excellent supplements to really get the most from Piracetam.

When I increased my fish oil dose from 4g/day to 14g/day the Piracetam effects increased about 30% with more vivid dreaming too.

The B-complex vitamins are also super-important for proper brain function - B1 (Thiamine) in particular.

#346 alecnevsky

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Posted 02 December 2012 - 02:11 AM

This is largely off-topic so anyone interested in piracetam alone should ignore this.

"Second, the mechanisms of amphetamine-induced dopaminergic neurotoxicity are not known, and theoretically, could be operant in nonhuman primates (and rodents) but not in humans."


I am going to go with: they [mechanisms] are likely similar! I think the JH researchers who wrote these "caveats" were just weary of people making wrong conclusions.

Indeed, given the fact that abnormalities in dopaminergic neural function are believed, in part, to underlie symptoms of ADHD (Fone and Nutt, 2005), any indication of abnormal dopaminergic function in amphetamine-treated patients might be attributed to underlying disease, rather than amphetamine neurotoxicity.


"Finally, the present findings may also have implications for the drug abuse field, because plasma amphetamine concentrations in some abusers substantially exceed those here shown to produce dopaminergic neurotoxicity in nonhuman primates."


Look at the numbers too:

"A closer examination of regional monoamine data revealed lasting dopaminergic deficits in the caudate nucleus and putamen of comparable magnitude (44–47% depletions), although smaller, but significant, deficits (approximately 30%) were also evident in the nucleus accumbens."


I mean, I've made my "preliminary conclusions" already...


Somehow I feel like prescribing Adderall, maybe not Ritalin, for ADHD is going to look like bloodletting in a decade or less.

Edited by alecnevsky, 02 December 2012 - 02:20 AM.


#347 Isochroma

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Posted 02 December 2012 - 04:47 AM

This may come as a shocker but at 7:30 PST today I have doubled my MSG dose to 5g, equal to my Piracetam dose. The rationale was not to increase the Piracetam synergy - which is achieved at half that dose or lower - but to decrease both brain and systemic ammonia.

It is now 8:36pm and I am experiencing two interesting things. 25 minutes post-ingestion I felt a strange pressure in my whole head that faded over about 7 minutes time. It's gone now.

Something else is gone too: the ammonia smell that has been worsening on my sweat for the last seven years - after exercise and even without exercise.

Three weeks ago I self-diagnosed with hyperammonemia, which is too much ammonia in the blood and brain. Ammonia is neurotoxic and produces a host of mental symptoms including brain fog and over the long-term, progressive brain damage and changes in the glutamatergic system.

I have just tonight downloaded three crucial studies which show MSG produces a large decrease in blood ammonia when taken orally in doses up to 150mg/kg and safely IV (intravenous) at 9g.

There are several chemicals which can help to decrease ammonia in the whole-body bloodstream but they don't help with brain ammonia load since they cannot penetrate the blood-brain barrier. Further, they are expensive, nearly unavailable and have side effects worse than any I've seen reported for MSG.

The problem with the brain and ammonia is that the brain can only eliminate ammonia in two ways: passive efflux and joining it with glutamate to form glutamine in astrocytes - those are the only ways. All the other organs in a human body convert ammonia to urea for safe, non-toxic urinary disposal. Glutamate cannot penetrate the blood-brain barrier but it is incorporated into glutamine by the enzyme Glutamine Synthetase combining it with ammonia in the astrocytes located at the inner side of the blood-brain barrier.

The MSG method has never been tried in humans for the purpose of reducing brain ammonia - or body ammonia for therapeutic purposes - so this is a pioneering experimental therapy.

Only one problem remains: the increased production of glutamine in the brain must be disposed of. Excess glutamine causes brain swelling - edema. I hope mine can deal with it.

Tomorrow I'm buying another 2 x 128g MSG. Next will be the 50lb bag.

As for the sodium overload concern: every gram of MSG contains only 160mg sodium. At (5g x 6) = 30g/day, total sodium = 4.8g. For only Piracetam enhancement at half that dose (2.5g x 6), total daily sodium consumption = 2.4g. Below is the label for pure MSG showing the sodium content:


Posted Image


Edited by Isochroma-Reborn, 02 December 2012 - 05:04 AM.

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#348 SuperjackDid_

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Posted 02 December 2012 - 12:34 PM

5g of msg is too much ,few mg just working .


Fully agree on Piracetam without MSG is less effective or even useless .

Little MSG add ,much more different in effect .

Edited by Nootropix, 02 December 2012 - 12:41 PM.


#349 SuperjackDid_

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Posted 02 December 2012 - 03:52 PM

buzz again oh ,will my brain damage but glutamate /calicum is real enjoy finding your sweet spot .

my concentration really improve .

few mg of l-glutamic turn dull mood to buzz mood .


i also notice head much more warm like more blood flow to the brain ,really enjoy this effect .


let me try add more piracetam will report back .

Edited by Nootropix, 02 December 2012 - 04:46 PM.

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#350 SuperjackDid_

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Posted 02 December 2012 - 04:46 PM

ok ,next dose of piracetam really enjoy me ,it should normally give me more dull mood if i not incorporate l-glutamic .

problem solved for me .

l-glutamic is key for piracetam efficiency .
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#351 chung_pao

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Posted 02 December 2012 - 06:07 PM

Could you use L-glutamine to enhance Piracetam efficiency, not the same thing?

#352 Isochroma

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Posted 02 December 2012 - 08:20 PM

No, totally different molecule. Glutamine is the product of Glutamate + NH4 (Ammonia) = Glutamine.

It has different functions.

The high doses of MSG I'm taking are to detoxify NH4 (Ammonia).

I took 5g MSG at 11:45am this morning. It's now 12:20pm and I can feel the weird head pressure from it.

A lot of the MSG is turned into Aspartate shortly after absorption by the intestinal cells.

It's 12:45pm and the pressure in my head is subsiding but I've decided to cut back to 2.5g x 6 per day = 15g/day.

I suspect the pressure is due to glutamine accumulation causing edema.

Edited by Isochroma-Reborn, 02 December 2012 - 08:43 PM.

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#353 bugasman

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Posted 02 December 2012 - 09:10 PM

I can't believe Isochroma is back. Hey Iso, do you know why piracetam can induce depression in some individuals? Hyper-cholinergic drive?

Edited by bugasman, 02 December 2012 - 09:29 PM.


#354 Isochroma

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Posted 02 December 2012 - 10:25 PM

No idea. Did you try MSG yet?

If not, give it a try and report back. It can be bought cheap at most grocery stores.

It comes in these cute little devilish-red colored cardboard salt-shaker thingies.

#355 chung_pao

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Posted 02 December 2012 - 11:26 PM

MSG is unfortunately not available in Sweden, unless I go lurking for a Chinese supermarket in one of the alleys downtown.
Could I combine Piracetam + Glutamic acid (in the form of protein powder/milk) + Possibly Calcium?

I mean, I want the same effects as you're describing, but can't find MSG in pure form.

Isn't glutamic acid (food) processing into glutamate inside the body?

Edited by chung_pao, 02 December 2012 - 11:26 PM.


#356 Dissolvedissolve

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Posted 02 December 2012 - 11:42 PM

Glutamic acid is a safer alternative to MSG, since it doesn't contain the excess sodium. I know of no reason why MSG would be more bioavailable or effective.

#357 Michael Campbell

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Posted 02 December 2012 - 11:49 PM

In the US we can get Glutamine pretty easily; would this be a better (or at least as good as) alternative to actual MSG?

#358 Isochroma

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Posted 03 December 2012 - 12:37 AM

Dissolveddissolve: Incorrect. Sodium Glutamate and Hydrogen Glutamate are the same molecule. Only difference is one has a H+ cation, the other Na+ cation. The Na+ version contributes to sodium consumption. The two equilibriate in the human stomach (HCl). The acid form is hard to get and expensive - its only advantage is not contributing more sodium to the diet.

Michael Campbell: As has already been explained (read back in this thread) - glutamine is useless for Piracetam potentiation. It is not 'safer' either. The only kind of brain damage that can be obtained from oral use of MSG is accumulation of Glutamine causing astroglial swelling. Glutamate does not cause this but Glutamine does. Glutamate (MSG) can only be turned into the toxic Glutamine by addition of NH4 (ammonia). If excess ammonia is not present then no amount of MSG taken orally can cause problems.

#359 SuperjackDid_

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Posted 03 December 2012 - 03:07 AM

My mood really better this morning .

I have much more energy + very much clear head effect .

Piracetam help my brain again ,that why i very much need to using it everyday ,this happen on large dose .


Lower dose still give some benefit but not like large dose .

large dose give effect next last to today ,i have notice several times before .


I still have one more puzzle is that can i still using Piracetam everyday ?

Might because of Piracetam give benefits beyond next day ,and maybe not need to re-dose again to avoid so much stress to body (good to brain anyway )

and switch to another Noot ,such as Coffee and enjoy motivation and do work coffee give .

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#360 Isochroma

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Posted 03 December 2012 - 04:21 AM

Sorry to disappoint you Nootropix but caffeine is NOT a nootropic.

It is a depleting stimulant that will exhaust your Adrenal glands and slowly make you more and more tired.

Like all stimulants, caffeine sends a false signal to the brain - telling it that it should run faster than its base energy conversion systems can handle.

This kind of sabotage causes already stressed, aged or damaged mitochondria to burn out even faster.

Rather than solutions looking for problems, stimulants are problems looking for solutions to destroy.

Even racetams can't recover the damage caused by them.
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