438 replies to this topic

[brain]

I'm leaning away from the aldosterone theory now-- it is still valid, of course, but I have a feeling (based upon the evidence) that most non-responders and negative-responders are that way because of something else (see earlier posts for current theories).

Why are you leaning away from it? We still have all of these theories floating up in the air. Why are you beginning to favor these other theories over this one? I'm just curious what it is that's changing your mind, here. for one, every other aspect of piracetam's pharmacology aside from its role with aldosterone seem less definitive - aldosterone is the one thing that it appears piracetam needs to work. Up until this point, I was under the impression the "aldosterone hypothesis" was created by noting and relating two distant facts: that many of us seem to have pupil fluctuations indicative of aldosterone deficiency, and also that piracetam is ineffective when certain adrenal hormones are not present, which would lead to the idea that aldosterone in specific may be what's altering and leading to a reduction in piracetam's effectiveness/negative symptoms, if not suggesting a deficiency further up in the hormone pathway. I only came across this study just now, which specifically isolates aldosterone in piracteam's function(I don't think it's been posted, apologies if it has):

Aldosterone receptors are involved in the mediation of the memory-enhancing effects of piracetam.

Mondadori C, Häusler A.

Pharmaceutical Research Department, CIBA-GEIGY Limited, Basel, Switzerland.

The blockade of the memory-enhancing effects of piracetam resulting from adrenalectomy can be abolished by substitution with either corticosterone or aldosterone. However, corticosterone substitution does not reinstate these effects if the aldosterone receptors are blocked by the aldosterone antagonist epoxymexrenon.

Conclusion = memory enhancing effects of piracetam are dependent on aldosterone. Other mental markers aren't tested here, so we can't say how much of a global role aldosterone plays. Given the multiple systems at hand (acetylcholine, glutamate), it would seem overly simplistic to believe it's merely aldosterone which the whole boat is floating on.

I'd be curious to hear if any others have noticed symptoms of electrolyte imbalance while on, or after coming off piracetam. I notice symptoms such as apparent dehydration minus the expected thirst, and very dark urine, which i rarely have otherwise. These symptoms are most marked directly after stopping the piracetam, though when I'm stopping it, I'm also usually stopping it for a reason, if that says something. I'll also leak urine after taking a piss in a way which is problematic and which doesn't happen normally. It almost definitely only happens while I'm on the piracetam. maybe the latter could have something more to do with acetylcholine?

The hormone aldosterone regulates kidney removal of sodium and potassium. Lack of aldosterone can result in hyperkalemia with an increase in total body potassium.

on hyperkalemia:

Increased extracellular potassium levels result in depolarization of the membrane potentials of cells. This depolarization opens some voltage-gated sodium channels, but not enough to generate an action potential. After a short while, the open sodium channels inactivate and become refractory, increasing the threshold to generate an action potential. This leads to the impairment of neuromuscular, cardiac, and gastrointestinal organ systems. Of most concern is the impairment of cardiac conduction which can result in ventricular fibrillation or asystole.

This sounds just like the sort of general malaise piracetam seems to cause after a while. It sounds like it can also cause dark urine and dehydration. I'm not saying this is IT, but it does seem like it needs further investigation, IMO.

If anyone really wanted to play guinea pig for the pack, Fludrocortisone, a synthetic aldosterone agonist, is widely available very cheaply over the internet. Extreme caution would be necessary, with a specialist's supervision, regular blood pressure testing, and aldosterone/electrolyte labwork being strongly advised. I'm not sure where I stand on the whole eye fluctuation matter, but if it really was a reliable indicator it would be very handy when trying to gauge Fludrocortisone dose. That and blood pressure. It'd be prudent to test blood pressure at baseline levels, followed by a low dose, perhaps a 1/4 dose of 0.025 mg. Doses used to treat Addison's are within the 0.1 - 0.2 mg range, whether for cat, dog, human, or god. The same dose might be tested every two days. Supposing a week passes without acquiring something like necrotizing angiitis, the dose might then be raised to 0.25 mg daily, followed by careful monitoring of blood pressure, which appears to be the first thing which can go wrong with this medication. If there is any indication of side-effect, it should be stopped immediately.

I'm sure you guys will love the favorable side effect profile:

Most adverse reactions are caused by the drug's mineralocorticoid activity (retention of sodium and water) and include hypertension, edema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis.

When fludrocortisone is used in the small dosages recommended, the glucocorticoid side effects often seen with cortisone and its derivatives are not usually a problem; however the following untoward effects should be kept in mind, particularly when fludrocortisone is used over a prolonged period of time or in conjunction with cortisone or a similar glucocorticoid.

Musculoskeletal-muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathologic fracture of long bones, and spontaneous fractures.

Gastrointestinal-peptic ulcer with possible perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis.

Dermatologic-impaired wound healing, thin fragile skin, bruising, petechiae and ecchymoses, facial erythema, increased sweating, subcutaneous fat atrophy, purpura, striae, hyperpigmentation of the skin and nails, hirsutism, acneiform eruptions, and hives; reactions to skin tests may be suppressed.

Neurological-convulsions, increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment, vertigo, headache, and severe mental disturbances.

Endocrine-menstrual irregularities; development of the cushingoid state; suppression of growth in children; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress (e.g., trauma, surgery, or illness); decreased carbohydrate tolerance; manifestations of latent diabetes mellitus; and increased requirements for insulin or oral hypoglycemic agents in diabetics.

Ophthalmic-posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos.

Metabolic-hyperglycemia, glycosuria, and negative nitrogen balance due to protein catabolism.

Allergic Reactions-allergic skin rash, maculopapular rash, and urticaria.

Other adverse reactions that may occur following the administration of a corticosteroid are necrotizing angiitis, thrombophlebitis, aggravation or masking of infections, insomnia, syncopal episodes, and anaphylactoid reactions.

anyway, I don't think anyone should try this, it seemed more viable until I looked into the side effects in more depth. I'll leave it here for information.


Thankfully I think i may have found a better option.

Lets take a look at corticosterone:



Corticosterone itself doesn't seem to do much, mostly being an intermediate between progesterone and aldosterone while possessing minor glucocorticoid and mineralocorticoid activity. One supplement which has been shown to increase corticosterone levels, and hence aldosterone levels, is carnosine:

Effect of central administration of carnosine and its constituents on behaviors in chicks.

Tomonaga S, Tachibana T, Takagi T, Saito ES, Zhang R, Denbow DM, Furuse M.

Laboratory of Advanced Animal and Marine Bioresources, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan.

Even though their contents in the brain are high, the function of brain carnosine and its constituents has not been clarified. Both carnosine and anserine inhibited food intake in a dose dependent fashion when injected intracerebroventricularly. The constituents of carnosine, beta-alanine (beta-Ala) and l-histidine (His), also inhibited food intake, but their effects were weaker than carnosine itself. Co-administration with beta-Ala and His inhibited food intake similar to carnosine, but also altered other behaviors. Injection of carnosine induced hyperactivity and increased plasma corticosterone level, whereas beta-Ala plus His induced hypoactivity manifested as sleep-like behavior. This later effect seemed to be derived from beta-Ala, not His. These results suggest that central carnosine may act in the brain of chicks to regulate brain function and/or behavior in a manner different from its constituents.

aside from increasing corticosterone levels, it seems to be a useful and safe supplement in itself:

http://en.wikipedia.org/wiki/Carnosine

http://en.wikipedia....cetyl-carnosine

I'm not sure which would be preferred, but I might guess the latter, unless it is one of the carnosine metabolites which produces the effects (the acetyl version producing less of these metabolites, sustaining its form, and thus being considered better by some people. I'm not sure how to interpret the reports of carnosine causing hyperactivity in humans. I feel this may either be offset by the piracetam, or that this just might seem to go along with what piracetam does to begin with. When piracetam is really working, it wouldn't seem to be a stretch to label the feeling as being somewhat hyperactive, IMO. Not saying corticosterone/aldosterone are involved in this.

we then have magnesium:
Effect of Magnesium Deficiency on Corticosterone in Rats
C. L. RICHER, R. VEILLEUX and P. BOIS

Départmént d’Anatomie, Université de Montréal Montréal Québec, Canada

Abstract

Corticosterone in adrenal glands and plasma was measured by a fluorometric method in rats fed a magnesium-deficient diet, in 2 control groups receiving the same diet supplemented with different quantities of magnesium, and finally in animals fed regular laboratory chow. Eosinophils in blood were also counted. Corticosterone in the magnesium-deficient group showed a statistically significant decrease that was already apparent after 15 hr on the diet and persisted throughout the 20 days of the experiment. The control diet containing the smaller supplement of magnesium was sufficient to maintain body weight gain and to prevent erythema and eosinophilia but corticosterone levels were decreased also in this group. The animals receiving the larger magnesium supplement showed corticosterone levels similar to those of the rats fed laboratory chow. These findings suggest that the reduction of corticosterone is a sensitive index of suboptimal magnesium intake. (Endocrinology 82: 954, 1968)

This seems interestng, considering magnesium's interaction with NMDA/glutamate. It is possible excess ca++ from increased glutamatergic activity is suppressing corticosterone via magnesium reduction? Would someone more knowledgeable than I like to try to dissect the possible relationship here? Whether or not it's a good adjunct to piracetam is another question, considering its NMDA antagonism. This could help or hurt, I'm not sure.

then we've got this:

Changes in Rat Serum Corticosterone After Treatment with Metabotropic Glutamate Receptor Agonists or Antagonists
M. P. Johnson , G. Kelly and M. Chamberlain
Neuroscience Research, Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN, USA.
Correspondence to: Michael P. Johnson, Neuroscience Research DC0510, Lilly Corporate Center, Indianapolis, IN 46285, USA (e-mail: johnson_michael_p@lilly.com).
Copyright British Neuroendocrine Group
KEYWORDS
mGlu • DHPG • LY393675 • corticosterone • glutamate.
ABSTRACT

Abstract

From previous work, it appears that glutamate can activate the hypothalamic-pituitary-adrenocortical (HPA) axis by an interaction at either ionotopic or metabotropic (G-protein coupled) receptors. For example, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD), a metabotropic glutamate (mGlu) receptor agonist, has been shown to increase the levels of serum corticosterone in rats. The present study was undertaken to further characterize which of the mGlu receptors are substantially involved in control of the HPA axis. The group I mGlu receptor agonists, 3,5-dihydroxyphenylglycine (DHPG), 1S,3R-ACPD, and 2-chloro-5-hydroxyphenylglycine (CHPG) but not the inactive isomer 1R,3S-ACPD were found to dose-dependently increase serum corticosterone 1 h after intracerebroventricular (i.c.v.) injection in male rats. The relative potency, DHPG (EC50 = 520 nmol) > 1S,3R-ACPD (1.4 µmol) = CHPG (2.7 µmol) ≫ 1R,3S-ACPD (≫ 3 µmol) is consistent with activation of group I (mGlu1/5) receptors. The effects of DHPG were long lasting with substantial elevations in corticosterone remaining for at least 3 h. In a similar manner, the group III mGlu receptor agonists, L-AP4 (4-phosphono-2-aminobutyric acid) and L-SOP (serine-O-phosphate), were found to increase serum corticosterone levels at 1 h. In contrast, the mGlu group II selective agonists LY354740 (10 mg/kg, i.p.) and subtype-selective doses of the group II antagonist LY341495 (1 mg/kg, i.p.) did not significantly elevate serum corticosterone. Given the group I agonists results, it was surprising to find that group I selective and mGlu1 selective antagonists given alone also increased serum corticosterone. As with the agonists, the rise in serum corticosterone with LY393675 (an mGlu1/5 antagonist, EC50 = 20 nmol, i.c.v.) and LY367385 (an mGlu1 antagonist, 325 nmol, i.c.v.) were dose-dependent and consistent with their relative affinity for the group I mGlu receptors. The selective mGlu5 antagonist MPEP [2-methyl-6-(phenylethylnyl)pyridine] increased serum cortocosterone but only at high doses (> 30 mg/kg, i.p.). A model involving the high glutamatergic tone on GABAergic interneurons in the paraventricular nucleus of the hypothalamus is discussed as a possible explanation for these results.

Corticosterone has AMPA activity:

Corticosterone Slowly Enhances Miniature Excitatory Postsynaptic Current Amplitude in Mice CA1 Hippocampal Cells
Henk Karst and Marian Joëls

Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands

Submitted 10 February 2005; accepted in final form 13 July 2005

Corticosteroid hormones are released in high amounts after stress and bind to intracellular receptors in the brain, which in activated form function as transcription factors. We here tested the effect of a high dose of corticosterone on AMPA-receptor–mediated transmission in the CA1 hippocampal area, which is enriched in corticosteroid receptors. To focus on slow gene-mediated effects of the hormone, excitatory postsynaptic currents were measured at least 1 h after a brief application of 100 nM corticosterone to slices from adrenally intact adult mice. The amplitude but not frequency of miniature postsynaptic excitatory currents was found to be significantly enhanced. These effects were mimicked by 100 nM RU 28362, a selective agonist for intracellular glucocorticoid receptors. Evoked AMPA responses at the single cell were significantly enhanced when measured 2–4 h after application of 100 nM corticosterone, but not at earlier moments nor with a longer delay. In summary, the present results show that activation of hippocampal glucocorticoid receptors induces a slow enhancement of AMPA-receptor–mediated responses, at the single-cell level.

In conclusion, I'd predict that carnosine or acetyl-carnosine would be a safe/effective means to increase corticosterone, and hence aldosterone. This would lead to either a reduction or elimination of any aldosterone deficiency, and could potentially have very profound effects when combined with piracetam. Unlike some of the other hormones, Corticosterone is far enough down the pathway to not metabolize into anything other than aldosterone and it's intermediate, preventing risk for hormone imbalance.

I pulled an all nighter last night and I still haven't slept, so excuse any typos, etc.

Edited by brain, 03 February 2010 - 01:50 AM.

[mulvena312]

Piracetam is one of the most well studied supplements. On piracetam.com they have linked 141 studies to piracetam. An obvious connection is that it helps those that have any form of cognitive impairment the most. Studies also show that it speeds up EEGs.

If you are already operating at a fast EEG, are a superior elegant verbal communicator, have tons of mental energy, and very creative.. then there is a higher chance that it will not do anything for you or at least anything that will be very noticeable to you.

I have been a heavy binge drinker in college, I have had a serious concussion, and I am an average verbal communicator. That is most likely the reason why I respond so well. It's strengths are my exact weaknesses!!! That is the definition of a God-send. I believe it also addressed Isochroma's exact weaknesses. (It is not sending me into mania though, haha)

Despite all the above I have a 130 IQ, graduated college, and have a good job through hard work. Piracetam enhances the areas I need help.

For some, they may think they are non-responders, when in reality the benefits are only slightly enhancing their strengths. Of course there are far more variables or theories. Below I will take a stab at it.

Here are groups of people I am noticing (please add groups as you see fit)
1) Non-responders - who are actually responders but dont notice it because they are already strong in the areas of piracetam's strengths
2) Non-responders - who do not have sufficient glutamate but would benefit from piracetam's strengths. (try supplementing with glutamine. glutamine glutamate are in the same cycle)
http://www.jneurosci...hort/27/34/9192
The glutamate–glutamine cycle is thought to be integral in continuously replenishing the neurotransmitter pool of glutamate. Inhibiting glial transfer of glutamine to neurons leads to rapid impairment in physiological and behavioral function; however, the degree to which excitatory synaptic transmission relies on the normal operation of this cycle is unknown. In slices and cultured neurons from rat hippocampus, we enhanced the transfer of glutamine to neurons, a fundamental step in this cycle, by adding exogenous glutamine. Although raising glutamine augments synaptic transmission by increasing vesicular glutamate, access to this synthetic pathway by exogenously applied glutamine to neurons is delayed and slow, challenging mechanisms linking the rapid effects of pharmacological inhibitors to decreased vesicular glutamate. We find that pharmacological inhibitors of glutamine synthetase or system A transporters cause an acute depression of basal synaptic transmission that is rapidly reversible, which is unlikely to be attributable to the rapid loss of vesicular glutamate. Furthermore, release of vesicular glutamate remains robust even during the prolonged removal of glutamine from pure neuronal cultures. We conclude that neurons have the capacity to store or produce glutamate for long periods of time, independently of glia and the glutamate–glutamine cycle.
3) Responders long term - have perfect ratios of sufficient glutamate with no excitotoxcity
4) Responders who get brain fog - address glutamate excitotoxcity (green tea, vinpocentine, curcumin)
5) Responders who lose response and have no brain fog - 1st try glutamine with piracetam (easy solution) if it doesnt work then 2nd option is to strengthen adrenals (more difficult)



If all of the above fail.. then try aniracetam. Some people respond to aniracetam rather than piracetam.

An even better option... Figure out your weaknesses and find a nootropic/supplement to address it. Or pinpoint the strengths you wish to maximize and pinpoint ways to address..

Edited by mulvena312, 03 February 2010 - 01:43 AM.

[babcock]

Piracetam is one of the most well studied supplements. On piracetam.com they have linked 141 studies to piracetam. An obvious connection is that it helps those that have any form of cognitive impairment the most. Studies also show that it speeds up EEGs.

If you are already operating at a fast EEG, are a superior elegant verbal communicator, have tons of mental energy, and very creative.. then there is a higher chance that it will not do anything for you or at least anything that will be very noticeable to you.

I have been a heavy binge drinker in college, I have had a serious concussion, and I am an average verbal communicator. That is most likely the reason why I respond so well. It's strengths are my exact weaknesses!!! That is the definition of a God-send. I believe it also addressed Isochroma's exact weaknesses. (It is not sending me into mania though, haha)

Despite all the above I have a 130 IQ, graduated college, and have a good job through hard work. Piracetam enhances the areas I need help.

For some, they may think they are non-responders, when in reality the benefits are only slightly enhancing their strengths. Of course there are far more variables or theories. Below I will take a stab at it.

Here are groups of people I am noticing (please add groups as you see fit)
1) Non-responders - who are actually responders but dont notice it because they are already strong in the areas of piracetam's strengths
2) Non-responders - who do not have sufficient glutamate but would benefit from piracetam's strengths. (try supplementing with glutamine. glutamine glutamate are in the same cycle)
http://www.jneurosci...hort/27/34/9192
The glutamate–glutamine cycle is thought to be integral in continuously replenishing the neurotransmitter pool of glutamate. Inhibiting glial transfer of glutamine to neurons leads to rapid impairment in physiological and behavioral function; however, the degree to which excitatory synaptic transmission relies on the normal operation of this cycle is unknown. In slices and cultured neurons from rat hippocampus, we enhanced the transfer of glutamine to neurons, a fundamental step in this cycle, by adding exogenous glutamine. Although raising glutamine augments synaptic transmission by increasing vesicular glutamate, access to this synthetic pathway by exogenously applied glutamine to neurons is delayed and slow, challenging mechanisms linking the rapid effects of pharmacological inhibitors to decreased vesicular glutamate. We find that pharmacological inhibitors of glutamine synthetase or system A transporters cause an acute depression of basal synaptic transmission that is rapidly reversible, which is unlikely to be attributable to the rapid loss of vesicular glutamate. Furthermore, release of vesicular glutamate remains robust even during the prolonged removal of glutamine from pure neuronal cultures. We conclude that neurons have the capacity to store or produce glutamate for long periods of time, independently of glia and the glutamate–glutamine cycle.
3) Responders long term - have perfect ratios of sufficient glutamate with no excitotoxcity
4) Responders who get brain fog - address glutamate excitotoxcity (green tea, vinpocentine, curcumin)
5) Responders who lose response and have no brain fog - 1st try glutamine with piracetam (easy solution) if it doesnt work then 2nd option is to strengthen adrenals (more difficult)



If all of the above fail.. then try aniracetam. Some people respond to aniracetam rather than piracetam.

An even better option... Figure out your weaknesses and find a nootropic/supplement to address it.

I am adding myself to group 1 as I know I am experiencing the effects of Piracetam because I get the minor headaches but I do not see many improvements to my daily activities. I consider myself to be pretty quick mentally already and it was one of my concerns from the start as to how much more I could actually gain.

[brain]

thought I'd post my updated hypothetical stack, all revolving around piracetam, which I will be trying soon, possibly in various combinations:

1. magnesium chelate, before sleep - normalization of corticosterone secretion, potential for preventing "tolerance"/negative overexcitation/possible excitotoxicity, calmer sleep.

2. 5HTP, before sleep - normalization of serotonin, preventing depression, aldosterone synthesis/regeneration.

Both of these are taken before sleep out of a hunch that essentially counterbalancing piracetam for half the day will prevent its effects from progressing into a deleterious zone. It seems piracetam's effects are best when it's still gaining force - after reaching full intensity it seems to fall right of the top of its peak, in my experience.

3. L-carnosine, morning/afternoon, dose undecided. - synthesis of corticosterone/aldosterone, prevention of excitotoxicity.

4. 3 eggs, morning. 210% RDA cholesterol - precursor for all hormones

5. L-deprenyl, oral, 5 - 10 mg/morning - preventing potential antagonism by acetylcholine upregulation + synergy

6. glutamine, still contemplating/researching, concerned about increasing excitation/toxicity, as well as increasing depression risk

I won't be using any acetylcholine supplement/precursor. I don't see why more acetylcholine should be needed after receptors are upregulated. I'll let the eggs cover this. The result here, I'm hoping, would be an initial increase in headaches/fogginess, followed by satisfactory upregulation and clearing of symptoms.

I'll let you guys know how it goes

Edited by brain, 03 February 2010 - 04:33 AM.

[stephen_b]

First, transdermal application is a horrible idea. It would be pointless, as piracetam is not metabolized and passes straight into the urine... defeating the purpose of skipping the digestive system. Piracetam is cheap and you can dose as high as you want (as is evidenced).

Your sentence is a bit confusing. You seem to be saying that transdermal piracetam is a "horrible" idea because it wouldn't be metabolized and instead would pass into the urine, and implying conversely that oral piracetam is metabolized and doesn't pass straight into the urine. What are you claiming this process of metabolization does to piracetam? How is it chemically altered in the gut?

[cogitoergosum]

A very interesting thread! My pupils fluctuate a little and I actually had unpleasant results from a week piracetam intake. I'm sure this was not placebo; it was a really negative experience with my memory worsening noticeably and headaches occuring. But I'm not sure about adrenal fatigue. My sodium and potassium levels are within normal ranges. And I got my cortisol measured (in 9 a.m.) and it was on the top of the range...

[gwen]

From my ignorance...maybe glycine agonists could help as a co-neurotransmitter in NMDA piracetam function suposing low glycine or d-serine levels are implicates in piracetam response.

[chrono]

Do you guys think his experience was genuine, perhaps fabricated claims or simply placebo(or perhaps attributable some other factor)?

To me, he always sounded like someone who read a lot of eastern philosophy and/or had done a bunch of psychedelics, and wrote in an impressionistic way using florid language and excessively amplified metaphor. And he obviously enjoyed playing with people who took it all at face value. I have trouble believing that his descriptions can be taken literally, or that the way he presented himself was indicative of his real personality, but I suppose it's possible—sounded a bit like he was playing a game to me. But with the threatening stuff, there was probably something unbalanced going on as well. Maybe a bit of both.

[viltro]

Thanks for the answers guys, I guess we'll never know for sure how exaggerated his experience was though.

An update on my response to piracetam (hope it doesn't detract too far from the topic), I'm continuing with eggs until my choline arrives, which has kept the headaches I got last weekend at bay. Today I decided to try reducing my dose (it is so easy to think "more is better"). I took ~400mg then had a shower. The effects were more subtle than my first time, no difference in colour, etc, but boy was I focused. About 40 minutes later I had lots of ideas buzzing and I wrote the beginning of a new short story and I think it's my best one so far. Words flowed easily and I didn't have to play them out as much in my mind as I normally do.

Bit of background, I've always enjoyed a bit of fiction writing. About 18 months ago I decided to collate my work and form a proper novel. However, my ideas come and go and the plots are often weak, which has so far resulted in 4 separate stories in various stages of completion (I seem to go through phases where my mood changes, two are comedy, one is about suicide, one is a detective novel). I have a good feeling about this new one, it's my first science-fiction and I reckon the plot is pretty solid. So, I'll see where it leads.

I took the same amount with my lunch and did some dissertation work, didn't get much done but I believe I was working more efficiently.


The more I think about it, the more I wonder if have been seeing the effects of piracetam without realising it. For example, I have been waking more easily and it has been affecting the influence alcohol has. Interesting you mention verbal communication mulvena, I'm a pretty good communicator IMO, great at presentations and free from anxiety, but I have been known to stammer, slur and trip over my words. As a child it was debilitating and I had some sort of therapy/training for it. I don't keep track since it's not significant anymore and people rarely mention it, but I can't remember doing it at all since I started piracetam. Perhaps I'm just seeing benefits because I want the piracetam to work, but I will pay closer attention.

Edited by viltro, 04 February 2010 - 02:04 AM.

[What'sAllThisThen]

What are the affects of piracetam with alcohol?

Does it make you drunk more easily or cause dizziness, etc? I want to know if I have to be careful.

[babcock]

What are the affects of piracetam with alcohol?

Does it make you drunk more easily or cause dizziness, etc? I want to know if I have to be careful.

I've read some people say that they feel they get drunk "faster" while on piracetam. I actually went to a party this weekend and got the most drunk I've been since college. First time I've heavily consumed alcohol while on piracetem as well. However, I also hadn't eaten very much all day and would attribute that and slamming 3 car bombs in a row to my state of drunkeness more than piracetem. :-P

Edit: spelling errors

Edited by babcock, 04 February 2010 - 02:19 AM.

[viltro]

I've read some people say that they feel they get drunk "faster" while on piracetam.

Yeah, I'd say that. I also thought I had more of a body drunk feeling and my head was pretty clear, but drunk people are prone to thinking that anyway. Regardless, I was drunk on a lot less than I usually drink, I also feel like drinking less (I think that's because I find the drunk body/clear head thing frustrating).

[acantelopepope]

This is my second night having took 700mg Cerebral Health piracetam. There are a lot of posts that I want to respond to but I don't have enough time right now. I just wanted to say that I'm unable to classify my response as negative right now. Sometimes I feel like there are (abnormal) gaps in my thinking but it's hard to say.

One thing I have noticed, though, is that my "creative humor" is on fire... which is one of the most unfunny things to say, I know, but I'm just throwing it out there

Out.

[cogitoergosum]

Sometimes I feel like there are (abnormal) gaps in my thinking but it's hard to say.

That is exactly the same thing I experienced! Though it was subtle but noticeable indeed.

[jackj]

Ahh a loss "creative humour" might be a good way of describing how I felt on my old source of piracetam and alpha GPC.

I still haven't switched back to my old piracetam or choline source. I was thinking about adding my choline source to the new piracetam to see if that changed anything as another thread mentions issues with extra choline supplementation and piracetam over time.

One question do you guys ever take a few days off piracetam? Or should it be taken regularly?

Edited by jackj, 06 February 2010 - 02:52 AM.

[jackj]

Well first day on my new piracetam source and a 300mg dose of my old alpha GPC and I've definitely had a major mood crash. Might see if the same thing happens sometime next week but I really don't want to put myself in this mood again. So yeah, maybe it isn't my 'bulk' supply of piracetam after all.

[Getting High On Life]

So I have not had time to read the whole thread yet, but where would mematine fit into all this? could it provide just enough antagonism to block excitotoxic effects of piracetam (if that is what we assume is causing issues) or will it just block it out all together?

I'm trying some now.

[Animal]

Well first day on my new piracetam source and a 300mg dose of my old alpha GPC and I've definitely had a major mood crash. Might see if the same thing happens sometime next week but I really don't want to put myself in this mood again. So yeah, maybe it isn't my 'bulk' supply of piracetam after all.

I have that response regardless of the Piracetam/Choline source, hence I utterly avoid the stuff. Do you have a predisposition to low mood in general?

[brain]

Well first day on my new piracetam source and a 300mg dose of my old alpha GPC and I've definitely had a major mood crash. Might see if the same thing happens sometime next week but I really don't want to put myself in this mood again. So yeah, maybe it isn't my 'bulk' supply of piracetam after all.

I have that response regardless of the Piracetam/Choline source, hence I utterly avoid the stuff. Do you have a predisposition to low mood in general?

I already gave this it's own thread, but here's an excellent overview on the interaction between acetylcholine and affect. I'm starting to think more and more that excess acetylcholine is the real problem here, not excitoxicity or hormone imblance.

http://www.acnp.org/...1000095/CH.html

[recitative]

I already gave this it's own thread, but here's an excellent overview on the interaction between acetylcholine and affect. I'm starting to think more and more that excess acetylcholine is the real problem here, not excitoxicity or hormone imblance.

http://www.acnp.org/...1000095/CH.html
[/quote]


Brain,

That is an interesting idea, but I have never had an adverse reaction when taking CDP-Choline, or Alpha GPC, or Centro, or Huperzine-A without Priacetam. And, I am prone to depression.

[jackj]

I have that response regardless of the Piracetam/Choline source, hence I utterly avoid the stuff. Do you have a predisposition to low mood in general?

Perhaps.

I read some of the choline study, nice find. It would explain it for me but I'm not sure what that means.. I'm a possible depressive/manic/skitzo?? Or just choline sensitive?

Exercise/diet/fish oil/royal jelly and some piracetam now and then seems to be working out for me. I'm going to give this combo another month and hope I don't start getting headaches or moody.

Edited by jackj, 10 February 2010 - 03:47 AM.

[P. Bonkers]

I think what we may be lacking in this discussion, (at least as the thread began) is that we may be missing the forest for the trees. Looking for the right chemical tweak, to consistently produce good effects with racetams, may not be the solution we are seeking, (although, if sound concepts emerge, I’m all for it.) But the solution may be right in front of our faces, yet counterintuitive, nevertheless. (These are the kinds of insights I get from Piracetam, which is why I love it.)

First we need to differentiate between non-responders, and responders who then become non-responders. (Non-responders who never become responders may have expectations that are unfulfilled, or perceptual insufficiency or, perhaps, more likely, a bio-chemical predisposition negating racetams, that is simply beyond our scope of knowledge at this time.)

So, I am going to assume, for many of you (myself included), that you are responders who have become non-responders over time. We feel like we have achieved cognitive nirvana one day, and then the next day, we merely feel normal; then every day after that, using racetams.

I am currently experimenting with a possible solution that I will call, for a lack of a better term: Reverse Titration Dosing

Doctors will titrate a dose of medicine lower, if the desired effect is too high, or if the effect is insufficient, increase the dose. (With hypertension meds, for example, he will titrate the dose upwards, until acceptable blood pressure levels are attained, and titrate downwards if side effects are overwhelming, or blood pressure goes too low.)

This is the approach that I am guessing most racetam users here have tried. You’re no longer on cloud nine? The solution? Take more. Titrate upwards. At some point, no matter how much you take, it just doesn’t work. You have become a non-responder.

Prior to this point, Reverse Titration Dosing comes into play. When the effects from racetams lessen. I stop. They still might be working, but instead of titrating up, I just stop taking them. My body is trying to tell me something. It is a brilliant automated thing. It’s wise to listen to it. While there has been speculation about various chemical imbalances and how to jury rig them, to fix the issue, perhaps we already know how. Hence, the forest for the trees reference. Our body/mind has spoken, if only we could listen.

One of the things I have noticed is that for my whole life (I am 51) I needed 7 hours of sleep and maybe even a power nap/meditation session -- as my circadian rhythm dictated, and situation allowed -- sometime during the day. On racetams, I get 5 hours sleep. Brain is working too fast; Can stay in bed all I want. Doesn’t matter.

Now, I don’t mean to suggest sleep deprivation as the sole source of racetams’ bell-curve response. However, cycling is a well-discussed strategy on these boards for effectively using racetams. Cycling, among other benefits, may allow normal sleep patterns to emerge. (However, what I am suggesting is different than cycling.) And this may be part of the reason for racetams working again down the line. Something is depleted inside that needs recharging. But sleep is especially important for memory retention, and a host of health reasons that are well understood and researched. Even if you feel like you don’t need as much sleep. Like on racetams. You still do.

Also you will hear references to exercise helping. As a drug that has such an impact on the CNS (Central Nervous System), this is logical.

The point I am trying to make is that whatever is occurring to defeat the effectiveness of racetams, our bodies tell us that it is happening and then we are left with coming up with the strategy to overcome this.

Here’s what I am thinking, as regards to Reverse Titration Dosing. As mentioned, first, you stop. Now, for me the day of stopping introduces the Creeping Fear; A general feeling of anxiety. If I feel this, I throw back a small amount of piracetam (.5 gm with appropriate choline chaser) to ward this off. You won’t feel any effect, but you are just allowing homeostasis to occur, without too much of a jar. Or, tapering for several days, as necessary, depending on the length of a racetam run.

Next step, listen to your body. Get a good night’s sleep (even if your sleep cycles are screwed up and you need to use an OTC sleep aid). Exercise. Do you feel at the top of your game? If the answer is no. Take more time away. Do a maintenance dose again if the Creeping Fear emerges. Wait till you body tells you, you are good to go.

Then go. Try a dose (determining what that is, is an individual matter). If it works, keep doing it.

Until the day it doesn’t work as well as it did.

Then do not take more (even if taking more would still work – but not taking you to the previous day’s level of effectiveness). Stop (if you can stop cold turkey with no effects, great, do that; apparently, most people can.)

Recuperate. Before you completely burn out, wondering where the magic went. Nip it in the bud.

This is the essence of my idea. When your body/mind tells you that racetams are not working anymore for whatever reason, listen to it immediately. Determine your recharge needs (again by listening to your body). Then jump back on the bandwagon.

Maybe this should be a separate thread for people to post their results if they try doing it this way? Or, has anyone tried this specific method? Haven’t seen it discussed anywhere.

[acantelopepope]

Two things:

1) You're completely right about the title "non-responders". It is not an adequately descriptive term to cover the range of possible unfavorable responses. The reason I originally titled the thread this was because, back then, the idea of people actually responding negatively to piracetam was very rarely spoke of, and I didn't know that the number of people who fit this group were so large. There were short posts here and there about fatigue and confusion, but no general recognition that a large number of people experienced substantially negative effects when taking piracetam. Because of this, I wanted anyone who didn't feel that they were getting positive effects from piracetam to try my pupil test. That's how this all started. Now, it's become clear that a great number of people are responding negatively to piracetam. Technically this isn't "non-response" but "negative-response". I'm curious about anyone and everyone who does not experience positive effects from piracetam. Perhaps it's time to begin a new thread with a more focused question and a summation of the research we've put together in this thread so far.

Personally, I fit into the group of people who experienced profoundly positive effects from piracetam for a period of about five months. After that, I experienced (and continue to experience) profoundly negative effects. Last week I tried piracetam for a couple of evenings after I was free of any serious obligations. I would characterize my response as "mixed" because I definitely experienced fatigue and confusion, but I also seemed to be having some exciting, creative ideas, too. I believe that the theanine, magnesium, fish oil, and various other supplements I took helped facilitate the positive effects. Overall, the negatives outweighed the positives, so I won't be trying any more piracetam for another few weeks, at least.

2) With that in mind, your strategy of basically taking a break applies directly to me. To put it simply, it hasn't worked for me yet. I have been "off" of piracetam for over 6 months now, and I still do not experience unequivocally positive effects after taking piracetam.

[acantelopepope]

I have that response regardless of the Piracetam/Choline source, hence I utterly avoid the stuff. Do you have a predisposition to low mood in general?

Perhaps.

I read some of the choline study, nice find. It would explain it for me but I'm not sure what that means.. I'm a possible depressive/manic/skitzo?? Or just choline sensitive?

Exercise/diet/fish oil/royal jelly and some piracetam now and then seems to be working out for me. I'm going to give this combo another month and hope I don't start getting headaches or moody.

This was my original theory explaining negative responses to piracetam (see my thread in the research forum about acetylcholine and depression). It may be part of the equation, but there are a lot of questions it leaves unanswered. Like: why was I able to take DMAE and Centrophenoxine at high dosages and feel fine?

Until about a month ago, I was extremely sensitive to choline in any form. Whether it was eggs or choline citrate, choline sent me into an immediate downward mood spiral. However, I am now able to eat eggs freely and I've even taken some A-GPC without any problem. I haven't tried taking a high dosage of choline citrate, but I'm not in any hurry. If choline/acetylcholine were the culprit in the piracetam negative-response mystery, once I was able to deal with choline normally again, shouldn't I have been able to take piracetam without negative effects? Such has not been the case, as I said above.

What confuses me is that even leading choline researchers I've personally communicated with have told me that choline shouldn't produce any sort of dysthymia, even in excess.

Here's what one researcher on choline homeostasis wrote to me. As you can see by his "nocebo", he didn't give any real credit to my assertion that choline was eliciting a negative response.

I do not know of any good and serious studies showing that high choline is either particularly beneficial or toxic to the body. Also, I would never follow advice on internet pages (better be careful). Most people have no response to choline (although they smell vaguely of fish). Considering that you have taken large amounts of choline, it seems possible that you have experienced some negative mental effects – at least it can be envisioned although I would not expect it. My obvious advice is NOT to take huge amounts of choline any more but stick to a regular diet rich in fruit and vegetables.



As for your current indisposition with taking anything that contains choline, let me tell you that this is a classical “nocebo” effect, similar to people who develop high blood pressure when they see a doctor. This happens to all of us: if we expect something unpleasant to happen, we fall sick. This has been substantiated in numerous clinical studies. In your case, you experienced bad responses to high-dose choline, and now you respond with sick feelings every time you are aware (!) that you ingest choline. But let me tell you, choline is in all foods, usually not in free form but so-called phospholipids, and it is really a normal constituent in our body. The only advice I have is (a.) not to bother about normal choline in food, it does not hurt you; and (b.) to avoid cauliflower which is one of the few foodstuffs known to contain high levels of free choline.



Hope this helps, and sorry I have no better answer. Yours, J. Klein



--

Jochen Klein, Ph.D.

Professor of Pharmacology and Clinical Pharmacy

University of Frankfurt College of Pharmacy

Max-von-Laue-Str. 9

D-60438 Frankfurt



Tel. +69 798 29366

FAX +69 798 29374

http://www.pharmazie...lein/index.html



In other words, "sorry kid, I can't help ya."

...So that's why I gave up on the choline hypothesis for awhile.

[P. Bonkers]

acantelopepope, that is a dilemma. Since it has worked for you in the past, I find it a difficult problem as to why it would not agai,n after such an extended break. I salute your diagnostic efforts so far.

Something has changed. The detective work would obviously begin at what has changed in your life, from them until now. A thousand situation variables could come into play (e.g. relationship changes, sleep changes, job/school/money changes, hidden disease expressing itself, diet changes, substance abuse, depression in general, etc., etc.,etc., etc.)

My long experience, from the Cheech and Chong generation, has taught me that whatever you bring to a substance, emotionally/physically/intellectually, is what you get out the other end. No substance is plug and play. (Although, I suppose, the breadth of the pharmacological industry would beg to differ.)

Unless, there is a darker side to racetams. Perhaps they exact long-term alterations to a person, physiologically. Although, from what I’ve seen of the literature, the long-term benefits have always been considered beneficial, or benign at worst.

However, I do wonder about the effect this substance has on one’s CNS. So far, both the literature, and my personal experience, leaves me not particularly concerned. But, I like to keep my eyes open for other’s experiences as well.

As for negative responding. I have felt the fog. For sure. For me, it was during initial uses of Aniracetam. It is much more powerful. (For me, 750 mg is a tiger dose; more than that and my brain seems to overload – unless, I am on the other side of the bell curve.)

I think most people have experienced the fog at one point or another. It would be interesting to know what their doses were, first off.

For others, (not yourself, as I recall) I frequently see people using massive stacks. Who knows what the hell is happening, if you can’t isolate the racetams out of the stack.

[brain]

Adenosine seems to have a role in regulating tyrosine hydroxylase. Increased levels of adenosine seem to upregulate tyrosine hydroxylase, so we might hypothesize that decreased levels down-regulate tyrosine hydroxylase. This might explain why I've experienced some benefits while combining piracetam and deprenyl, but which itself down-regulates tyrosine hydroxylase over time.

[outsider]

Ok I think I can help by giving my own experience.

The only time I tried 500 mg choline I experienced a manic and then a very deep depression the same day, something that I never experienced before. Then I was scared of choline sources. But then there is a funny thing, I ordered a bottle of Pyritinol and got centrophenoxine instead. With some fear of the consequence I tried 500 mg centrophenoxine (knowing it was quite different than choline) and got good results. From then on it became my source of acethylcholine to experiement with.

After 3 days of piracetam I got a headach, took centro and never had headach again. The first day pir and centro was very good but after that I can't say it helped much except that it improved my mood.

I tried oxy, ani and pyritinol together the first day and experienced great speed of thoughts but the next day I experienced brain fog for the first time after 2 months of pir and centro.

The best cognitive improvement (comprehension, deep understanding) was with the piracetam 6g and pyritinol 800mg for a couple of weeks but after an experience of intense throwing up after drinking I never took pyritinol again.

Then the combo vinpo, centro, bacopa and piracetam gave me good memory improvement. At some points I was quite impressed.

If I took 6g pir and centrophenoxine together I felt it was the same as oxy alone, oxy and centro together gave me intense brain fog to the same extent as aniracetam alone.

Right now (after 2 years) I can take centrophenoxine and Aniracetam and have good improvement short term but I stoped experimenting long term.

If I take celastrus and shankapushpi with aniracetam right now I experience a feeling of being dumb, this combo without ani is great, I can't mix these three together. Celastrus works on nmda too. One interesting thing is that the shankhapushpi herb has several pyrrolidine alkaloides and is said to be the best brain herb ayurveda has to offer. I experienced strong cognitive improvement with shankhapushpi and bacopa (with guduchi and licorice as support herbs).

Also I think James south said that magnesium could help people with racetam side effects. I found in a study that magnesium was the "gate keeper" of nmda receptor if I remember correctly and they said it was very important for brain plasticity. Basically from what I could find we live in a world of magnesium deprivation.

Edited by outsider, 16 February 2010 - 10:21 AM.

[EvertonP]

Hey Guys i'm new around here but I've just read your posts all the way from the beginning. You have some great information here seem to be following the most logical path to a resolution.

I would be in the category of responders that became non-responder with no negative effects. But here is where I seem to be different than all of your experiences: i bought a 250g jar from 1FAST400 and my first dose ever of piracetam was two years ago of about 3-4g and I felt the full effects (clear thinking, memory, colors, verbal, math...) in about 30 minutes or so (I was 23 at the time and had never taken any nootropics before, except maybe for some occasional ginko biloba). I don't remember exactly if i took some again the very next day, but within the following weeks I never took it daily and always felt an effect every time I took a dose. I soon realized that piracetam made me more sensitive to caffeine, so I quickly laid off coffee and eventually settled on a half tsp dose (about 700mg). Sometimes I would go without taking it for a whole week, take a single 700mg dose before an exam at school and had full effects that lasted 4-6hrs.

This last summer though, my brother-in-law came to visit from Brazil and stayed a whole month, during which I introduced him to piracetam and he seemed to respond the same way I did: I actually gave him a 700mg dose in OJ without telling him what it was and asked him how he felt an hour later and he loved the stuff! During that month, him, his brothers and I averaged 3-5 beers a day for at least 21 days straight and ever since piracetam stopped working for me.

At firts I though my 250g original supply might've reacted with water in the air and become some inactive substance, so I tried the little I had left in random doses to no avail. Then I ordered a 500g tub by prima force on medco.com to no different results.

I've tried up to 8g doses, I've tried 3-6g daily in 3 divided doses for up to 10 days, and now that I think of it, one of my trials gave me what I'd call a 10% of the old efficacy of piracetam, but because I was used to only taking it sporadically and having it always work, I was too lazy to keep taking it every single day and decided to research how to get the results back.

When it did work, I got the minor headaches whenever I took it for a few days in a row, and occasionally I would take a 1400 or 2100 mg dose for a higher effect, but now, nothing works.


I tried the pupil test and while simply staring at my pupil in the mirror with the lights on, my pupil seems to fluctuate a bit (diameter varied by about 1mm). Early this morning on my way to class my eyes were very bothered by the sunlight reflecting off the bright snow and did not adjust, even though my walk was about 12 minutes long. But a few minutes ago I took my fluorescent flashlight as a portable source of soft light into my dark closet with a mirror and my pupil seemed to contract and stay contracted, although I wonder if I didn't stare at it long enough (I might not have watched it for a whole 30 seconds).

I haven't excercised at all lately, and I have a desk job, so I'm going to try the exercises first, in fact i'll start right now with maybe 20 minutes on the my stationary bike. In the past 10 years or so (since I was 15) i've come to notice that exercise always makes me feel better, so maybe it'll bring back the balance my body and brain need to make piracetam work again (although I was not exercising either while piracetam did work for me before).

When I started writing this post I took about a 3g dose and by now I usually would've felt something. I feel alright, and can think somewhat clearer than before I took it, but then again I took some advil at the same time because I had a headache which has now gone away, so the clearer thinking could just be from the headache being gone.

I'm glad I found this website and thread, as you are clearly on a pathway way to figure this out, it just seems to be a matter of time, specially with so many different people reporting results and experiences.

One last thing I forgot, after my 21 days of binge drinking in aug-09, I kept drinking on average one beer/day every single day and eventually thought the alcohol could be the issue and have stopped that as well, I went for a whole 7 days without a single drink and piracetam still did not work (it might've been then that I felt a very very weak effect) and now I only drink 2-3 beers per week.

I'll try the exercise now and let post my results in a couple of days.

Also, my wife was sensitive to it the same way I was (700mg dose was enough), but as she only took it recreationally (once a month if that to show off to her in laws) I expect it to still work for her, so I'll have her have a dose of the prima force source in the morning and report back here as well. She liked the effects of it and will definitely be able to tell if and how strong the effects are, and I think she'll be a good benchmark to lay to rest the questions of quality that have been brought up.

edit: spelling

Edited by EvertonP, 19 February 2010 - 01:41 AM.

[EvertonP]

Also, the other thing I forgot to mention, is that, as weird as it may sound, and I have NEVER met anyone else (besides my brother) with this reaction from alcohol: it seems to increase my cognitive abilities just as piracetam does. For me taking a physics or any other hard exam right after a couple of beers with a nice buzz going has the same effect on memory and cognition as piracetam, but the effects go away with the buzz and the main difference I notice between the effect of alcohol and piracetam on me is that while alcohol allows me to remember things and think clearly, it inhibits new memory formation, so I can just as well have a few beers to do homework with calculations, but not to study for biology or chemistry. Although, I do not recall piracetam specifically increasing my memory creating abilities, it definetely increased my ability to recall things, which still comes out in the wash as a more positive effect than the beer.

[outsider]

Also, the other thing I forgot to mention, is that, as weird as it may sound, and I have NEVER met anyone else (besides my brother) with this reaction from alcohol: it seems to increase my cognitive abilities just as piracetam does. For me taking a physics or any other hard exam right after a couple of beers with a nice buzz going has the same effect on memory and cognition as piracetam, but the effects go away with the buzz and the main difference I notice between the effect of alcohol and piracetam on me is that while alcohol allows me to remember things and think clearly, it inhibits new memory formation, so I can just as well have a few beers to do homework with calculations, but not to study for biology or chemistry. Although, I do not recall piracetam specifically increasing my memory creating abilities, it definetely increased my ability to recall things, which still comes out in the wash as a more positive effect than the beer.

Yes I heard someone saying something like that about cognition and beer a couple of years ago on this board.