9 replies to this topic

[owls]

is there any potential negatives to consistent daily long term racetam usage..?

are there any other factors that may prevent racetams from working properly or actually cause them to behave counter-productively? such as a lack of choline or adrenal fatigue perhaps?

also, have you guys found that lower doses are a necessity after heavy longer term usage?

i've found that 2g of piracetam is about my maximum tolerable daily dosage now after about a year of use, whereas before, 6g a day was ideal.. now it seems that even 2g as a single dose will produce brainfog and negative effects

thanks for any thoughts guys and gals

Edited by owls, 05 March 2011 - 07:25 AM.

[FadingGlow]

Pretty much stopped working for me after 3 months, and then I was sort of addicted to it, it seemed. I felt very weird after stopping for about a week. I've remained off it.

[owls]

bump.. any ideas? i'm going to search the forum now for more answers

[brain]

I used it for about a year with only brief breaks. Everywhere from 2 - 8 g/day. You get rebound effects and 'withdrawal' effects when you stop. I've stopped piracetam after using for extended periods of time multiple times now, and I'll notice similar sides each time. The physical effects aren't particularly severe, but it messes with water retention and electrolytes, I'm pretty sure. I also noticed worse cognition than when I started, which lasted for several months. Potentially unrelated in some aspects. I also think it might burn out your adrenal glands after a while, or increase stress hormones. I took lots of rhodiola and eleuthero while I was using it, also loaded up on B vitamins. Eat a lot of protein, a lot of fat, and exercise a lot, and you should be ok. Also, take fish oil in high doses to keep serotonin levels high.

No one really understands how piracetam works or what the long term effects are. It's effects on the adrenal gland and neurosteroids are very unclear in particular. Keep that in mind.

[Ichoose2live]

I used it for about a year with only brief breaks. Everywhere from 2 - 8 g/day. You get rebound effects and 'withdrawal' effects when you stop. I've stopped piracetam after using for extended periods of time multiple times now, and I'll notice similar sides each time. The physical effects aren't particularly severe, but it messes with water retention and electrolytes, I'm pretty sure. I also noticed worse cognition than when I started, which lasted for several months. Potentially unrelated in some aspects. I also think it might burn out your adrenal glands after a while, or increase stress hormones. I took lots of rhodiola and eleuthero while I was using it, also loaded up on B vitamins. Eat a lot of protein, a lot of fat, and exercise a lot, and you should be ok. Also, take fish oil in high doses to keep serotonin levels high.

No one really understands how piracetam works or what the long term effects are. It's effects on the adrenal gland and neurosteroids are very unclear in particular. Keep that in mind.

Then Phosphatidylserine might be synergic with Piracetam since it reduces ACTH and cortisol.

http://www.ncbi.nlm....pubmed/15512856
http://www.livestron...drenal-fatigue/
http://www.springerl...8r3551t2235342/

Strangely Piracetam and his derivative (oxiracetam, aniracetam, pramiracetam) has no effects on rats with removed adrenal glands (Adrenalectomy).

Piracetam facilitates long-term memory for a passive avoidance task in chicks through a mechanism that requires a brain corticosteroid action.

Loscertales M, Rose SP, Daisley JN, Sandi C.

Brain and Behaviour Research Group, The Open University, Milton Keynes, UK.
Abstract

We investigated the effects of piracetam, a nootropic, on learning and memory formation for a passive avoidance task in day-old chicks. To test for the possible cognitive-enhancing properties of piracetam, a weak learning version of this task--whereby chicks maintain a memory to avoid pecking at a bead coated in a diluted aversant for up to 10 h--was used. Post-training (5, 30 or 60 min), but not pretraining, injections of piracetam (10 or 50 mg/kg, i.p.) increased recall for the task when the chicks were tested 24 h later. Because previous studies showed that long-term memory for the passive avoidance task is dependent upon a brain corticosteroid action, and because the efficacy of piracetam-like compounds is also modulated by corticosteroids, we tested whether the facilitating effect of piracetam was dependent upon a corticosteroid action through specific brain receptors (mineralocorticoid receptor and glucocorticoid receptor). First, increased plasma levels of corticosterone were found 5 min after piracetam injection. In addition, intracerebral administration of antagonists for each receptor type (RU28318, for mineralocorticoid receptors, and RU38486 for glucocorticoid receptors; i.c.) given before the nootropic inhibited the facilitative effect of piracetam on memory consolidation. These results give further support to a modulatory action of piracetam on the mechanisms involved in long-term memory formation through a neural action that, in this learning model, requires the activation of the two types of intracellular corticosteroid receptors.

http://www.ncbi.nlm.nih.gov/pubmed/9749752

Elevated corticosteroid levels block the memory-improving effects of nootropics and cholinomimetics.

Abstract

Oral pretreatment of mice with aldosterone or corticosterone blocked the memory-enhancing effects of piracetam, pramiracetam, aniracetam and oxiracetam in a dose-related manner, without, however, impairing the animals' learning performance. The improvement of memory induced by physostigmine, arecoline, and tacrine (THA) was similarly inhibited. The fact that elevated steroid levels suppress the memory-enhancing effects of entirely different substances could indicate that these substances have a common site of action. In the light of new observations showing increased cortisol concentrations in Alzheimer patients, this steroid dependency of the effects of memory enhancers might explain why only a limited number of these patients respond to therapy with nootropics or cholinomimetics.

http://www.ncbi.nlm.nih.gov/pubmed/1410129

Abstract

The mechanism through which nootropics of the piracetam type (i.e., piracetam itself and its analogues oxiracetam, pramiracetam, and aniracetam) improve memory is still uncertain. Its elucidation will, however, not only mark an advance in the treatment of cognitive disorders, but also shed light on the basic processes of memory storage. Although the great majority of the findings available so far seem to suggest cholinergic mechanisms, divergent results are obtained whenever parallel experiments are performed with two or more of these compounds. More recent observations indicate that interactions with steroids take place. All four compounds are inactive in adrenalectomized laboratory animals; chemical blockade of the adrenal cortex with aminoglutethimide and pretreatment which epoxymexrenon, a potent mineralocorticoid antagonist, eradicated the memory-enhancing effect of all four substances.

http://www.ncbi.nlm.nih.gov/pubmed/2690149

Too much Corticosteroids releases from the adrenal cortex = No effects
No Adrenal cortex activity = No effects
Rats with no Adrenal glands = No effects

Edited by Ichoose2live, 08 March 2011 - 03:16 AM.

[Justchill]

I used it for about a year with only brief breaks. Everywhere from 2 - 8 g/day. You get rebound effects and 'withdrawal' effects when you stop. I've stopped piracetam after using for extended periods of time multiple times now, and I'll notice similar sides each time. The physical effects aren't particularly severe, but it messes with water retention and electrolytes, I'm pretty sure. I also noticed worse cognition than when I started, which lasted for several months. Potentially unrelated in some aspects. I also think it might burn out your adrenal glands after a while, or increase stress hormones. I took lots of rhodiola and eleuthero while I was using it, also loaded up on B vitamins. Eat a lot of protein, a lot of fat, and exercise a lot, and you should be ok. Also, take fish oil in high doses to keep serotonin levels high.

No one really understands how piracetam works or what the long term effects are. It's effects on the adrenal gland and neurosteroids are very unclear in particular. Keep that in mind.

So Mr Brain, how are you feeling/doing today? Do you still experience negative fx from piracetam use?
Maybe it's wise to cycle piracetam with something similar? How should that be done?

[Ichoose2live]

I would just like to correct some small mistake I made.

1 - Too much corticosteroid from drugs = No effect.

2 - Anti-steroid drugs = No effect.

3 - Animals with adrenal gland removed by surgery = No effect.

I found new stuff:

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

Abstract

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.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYR-483SN6N-N3&_user=10&_coverDate=08%2F06%2F1990&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_searchStrId=1669596740&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=82f85fb7299e14df1056a2b5c354b85f&searchtype=a

Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics

Abstract

Since adrenalectomy abolishes the memory-enhancing effects of piracetam and its derivatives, oxiracetam, aniracetam and pramiracetam, the question arises whether endogenous steroids play a role in their mechanism of action. We show that inhibition of steroid biosynthesis by aminoglutethimide and blockade of the aldosterone receptors by epoxymexrenone completely suppress the memory-improving effects of the nootropics. These results indicate that steroids, or more precisely, activities mediated by the aldosterone receptors, might be involved in the mechanism of action of this class of nootropics. Blockade of aldosterone receptors, however, does not block the effects of cholinomimetics on memory, indicating the involvement of another mechanism of action.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYR-483SM18-K8&_user=10&_coverDate=01%2F01%2F1990&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_searchStrId=1669596318&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=dae4c18c8047f130b5409093929dfdc4&searchtype=a

That's very intriguing, I suggest we should keep are Corticosteroids at a regular level.

Edited by Ichoose2live, 08 March 2011 - 09:58 AM.

[owls]

any possible chance you could summarize the findings? i don't have time to go look through each specific article right now..

[Duster]

I used it for about a year with only brief breaks. Everywhere from 2 - 8 g/day. You get rebound effects and 'withdrawal' effects when you stop. I've stopped piracetam after using for extended periods of time multiple times now, and I'll notice similar sides each time. The physical effects aren't particularly severe, but it messes with water retention and electrolytes, I'm pretty sure. I also noticed worse cognition than when I started, which lasted for several months. Potentially unrelated in some aspects. I also think it might burn out your adrenal glands after a while, or increase stress hormones. I took lots of rhodiola and eleuthero while I was using it, also loaded up on B vitamins. Eat a lot of protein, a lot of fat, and exercise a lot, and you should be ok. Also, take fish oil in high doses to keep serotonin levels high.

No one really understands how piracetam works or what the long term effects are. It's effects on the adrenal gland and neurosteroids are very unclear in particular. Keep that in mind.

The effect on adrenal glands makes sense. Piracetam is supposed to improve the function of acetylcholine receptors, and according to my endocrinology professor, acetylcholine is what triggers the release of epinepherine and norepinepherine from the adrenal medulla.

However, this doesn't have very much to do with Ichoose2live's articles. Epinepherine and norepinepherine are catecholamines, not steroids, and they are (as far as I know) the only adrenal products whose release is controlled directly by nerve impulses. I'll have to read that stuff...

In any case, from my experience, whenever I take a day off (very rarely, usually when I unexpectedly don't have access to my noots), I find I can still function fine, I just feel sluggish relative to being on the racetams. I believe the "withdrawal" effects have more to do with people developing a different idea of "normal function" than an actual negative effect of discontinuation of piracetam.

[Methodician]

I know this is pretty old but thought it was about time I chimed in...

 

I've been using an increasing variety of *racetams and other nootropics pretty much daily for >2 years and have a few takeaways to share...

 

 

 

A few words on dosage:

I will refrain from specifying dosage since it varies from person to person and drug to drug. It should always be just enough, 'nuff said.

 

Reading around the web I gather that most users play around with pretty high dosages, often claiming super-human feats of cognition or learning. The few times I've tried more than my usual, I've come away disappointed. I get pretty dramatic benefits from taking just enough for it to work. Doubling or even tripling that "just enough" dosage can be interesting but it's not particularly helpful... *Racetams are subtle so you can't expect to really "feel it kick in" like caffeine or amphetamines. If you take enough to feel a solid kick in that probably means you took too much and you're wasting your money. Does drinking 8 cups of coffee improve your productivity? Not really, and taking several grams of oxiracetam won't either, especially long term.

 

All this said, most of the research I've done indicates that it's not particularly dangerous to mega dose. Long-term daily megadosing is another story. While the drug itself poses little/no risk of toxicity, you will end up with other problems like adrenal fatigue, anxiety, antisocial behaviors, insomnia, malnutrition, etc... maybe even psychosis. Perhaps most important you'll be wasting your time and money because you aren't likely to notice any super-human benefits that can't be dismissed as placebo and you'll be developing serious tolerance and/or dependence. Which reminds me...

 

 

Let's talk about tolerance.

If you're the kind of person who needs to feel a "kick" from whatever drug/supplement you're using to be satisfied, you will surely encounter tolerance. This can be remedied with cycling (look it up) and AFAIK tolerance is not permanent unless you've actually damaged your brain, which you'd have to be an idiot to do with *racetams. A few weeks or months away from the drug and you should be able to get your old results again.

 

However if, like me, you're quite satisfied with the minimum effective dose, you won't likely develop significant tolerance. I've only seen tolerance to a couple of the stronger ones such as pramiracetam and phenylpiracetam and even then only a tiny bit. It levels off and I continue to receive ample benefit from a steady dose as long as I'm not looking for a "kick".

 

If you must get your kicks, have a cup of coffee or 5-10 mg of amphetamines (AKA Adderall) or methylphenidate (AKA Ritalin) along with your *racetam. Mix the *racetams with caffeine and Ritalin and you'll be able to get your kicks on dosages well below what could lead to tolerance and experience a smooth, steady flow of cognitive surplus. Which leads us to...

 

 

Stacks, waves, and it all comes together...

My "nootropic" stack consists of little more than *racetams, CDP Choline, and L-Theanine. You might count magnesium, the occasional fish oil, b-vitamin, or other nutritional supplement.

 

I also eat very healthy (somewhat "paleo") and exercise several times per day.

 

However, I tend to consume 1-3 stimulants along with my stack. Some combo of coffee and tea, ginseng, Ritalin, and Adderall. Always in fairly small dosages. The combination is where I get any "kick" I need to feel. This keeps things safe, smooth, and minimizes risk of side effects or tolerance.

 

It doesn't stop there. I've used a variety of mildly psychoactive substances every day for many years now and really fine-tuned my approach. I was prescribed Ritalin for ADHD as a child and have been on and off of it for about 20 years. At one point I was taking 40-60 mg per day which, IMHO, is absurd, especially for a child. Today, I take about 5 mg of either Adderall or Ritalin 1-3 times per day almost every day of my life. At this dosage I never develop tolerance or any notable side effects. I know, this isn't about Ritalin, but it plays into my approach.

 

I've also used marijuana for about 15 years and alcohol for about 12. These days I use them almost daily. So, what of it?

 

Waves people. Waves. My mood and energy levels persist in a pretty predictable sine wave every day. I wake up slowly and stretch and do a little groggy exercise with a cup of coffee, some kind of *racetam, and usually and a little Ritalin/Adderall. I'll usually take a second *racetam dose around noon +/- 2 hours, along with some tea and perhaps more Ritalin/Adderall. In the evening some time between 3:30 and 7 I start to calm myself with some Kava, marijuana, or alcohol (or a combo) and then take no drugs for at least 2-3 hours before bed time.

 

The wave ensures predictable, smooth effects while reducing the risk of some of the side effects mentioned above: adrenal fatigue, anxiety, sleepless nights, etc... Anyone taking nootropics to try and work 16 hour days and sleep as little as possible is doing life wrong. You cannot do that long term. Long term safe, effective use of these and any drugs requires balance and harmony.

 

The idea is to give yourself a predictable cycle of mania and depression that never peaks too high or dips too low. Psychoactive thrill seeking is not sustainable. If you want to keep at it safely, daily, and for many years to come then just forget about the rush and embrace the wave. Enjoy the wave. Ride the wave. Surf the wave of life day after day. Get your thrills from experience, not substance.