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Pramiracetam


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#31 thedevinroy

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Posted 18 June 2011 - 05:23 PM

What's the oral bioavailability of pramiracetam?

I wasn't able to track down the source, but I'm confident in saying pramiracetam's oral bioavailability is quite high, between 97% and 100%. I believe the same is true for the other core racetams as well.

I would still say that there is some time release effect in the digestive system that other forms don't have that would increase the safety of taking pramiracetam at its optimal 427mg dose (6.5mg/kg). And NO activity isn't the end of the world. Body builders increase NO production all the time by supplementing with arganine and its precursors. As someone mentioned earlier, taking omega 3, garlic, and ginkgo will reverse NO toxicity. There's probably a slew of antioxidants that do the same thing and haven't been tested. I feel better now. Yall had me scared with that rat study.

I think I saw a study that said that the mammals excrete about 30% of pramiracetam in a 72 hour period. I guess the rest is broken down and used up. Does anyone know what it is metabolized into?
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#32 Duster

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Posted 28 July 2011 - 04:22 PM

What's the oral bioavailability of pramiracetam?

I wasn't able to track down the source, but I'm confident in saying pramiracetam's oral bioavailability is quite high, between 97% and 100%. I believe the same is true for the other core racetams as well.

I would still say that there is some time release effect in the digestive system that other forms don't have that would increase the safety of taking pramiracetam at its optimal 427mg dose (6.5mg/kg). And NO activity isn't the end of the world. Body builders increase NO production all the time by supplementing with arganine and its precursors. As someone mentioned earlier, taking omega 3, garlic, and ginkgo will reverse NO toxicity. There's probably a slew of antioxidants that do the same thing and haven't been tested. I feel better now. Yall had me scared with that rat study.

I think I saw a study that said that the mammals excrete about 30% of pramiracetam in a 72 hour period. I guess the rest is broken down and used up. Does anyone know what it is metabolized into?


Don't know how much this will help, but, from a review paper (Gouliaev 2004): "Chang et al. suggest that the clearnace values are relatively small compared to the hepatic blood flow, suggesting that little or no first-pass metabolism will occur, provided that the drug is not metabolised in the gut. Unidentified metabolites, together with unchanged pramiracetam which is mainly excreted through the urine have, however, previously been observed by Young and Chang in rats and monkeys"

I don't know enough about renal clearance to give you an exact number, but this seems to indicate that 30% is a bit off... Also, the metabolites are "unknown" lol. Also, from that study: "...complete absorption was assumed. The validity of this assumption is supported by animal data that have shown that orally administered (14)C-labeled pramiracetam is promptly and efficiently absorbed relative to equivalent intravenous doses," so the oral bioavailability does seem to be quite high.

Chang (1985) Pharmacokinetics of oral pramiracetam in normal volunteers
Young, Chang (1982) Metabolic disposition of pramiracetam in rhesus monkeys and rats

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#33 X_Danny_X

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Posted 28 July 2011 - 11:10 PM

okay good. i was scared for a moment since Pramiracetam is something that i sometimes buy. i was scared even more for a moment that Bacopa increases NOS activity as well to a dangerous level. but it seems that it is in high dosage and it can be reverse very easily by some antioxidants and Fish Oil.

#34 nito

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Posted 29 July 2011 - 04:52 PM

has anyone tried snorting pramiracetam or any racetam for that matter?

#35 Audiomajik

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Posted 03 August 2011 - 06:23 PM

Just sharing results:
used Pram a couple of days ago (just 1 cap @ 200mg) and boy did it zombie me out! I read about the zombie effect from others but I almost didn't believe it. I found myself sitting in my chair comtemplating on why I was not working. Then I realized that I was completely still and started to evaluate how long I had remained completely still and whether or not anyone else in the room had noticed that I hadn't moved. When I finally started working, I realized that I hadn't said a word for two and a half hours. It was a weird prisoner-in-my-own-head type of experience. This was my second time taking pram. The first time i took pram, I ended up falling asleep for four hours in the middle of the day (something I almost never do). Good thing it was a weekend. I think pram is going to be a once-in-a-while thing for me. So far, Piracetam seems to be the most effective racetam I've used.

Edited by Audiomajik, 03 August 2011 - 06:25 PM.


#36 MenDis

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Posted 29 August 2011 - 02:25 AM

I'm pretty sure that I overdosed on Pramiracetam and Choline Bitrate and I havent been the same since. I had taken a little pramiracetam a few times before this and it didn't seem to have any noticable affect. I took 800 mg once and it just made me tired. I decided to try it again for a week at a higher dose to see if I could notice an effect. I starting taking 1000 mg of pramiracetam (admittedly a high dose and thus a dumb decision) along with 1000 mg of choline bitrate. The first two days I didn't feel anything. About 2 hours after the third dose, it hit me. I got really sweaty and all of a sudden all of my higher functions starting slipping. I couldn't read or follow a conversation and I'd forget things that I had done just minutes before. It was really hard to formulate thoughts and make logical connections. After a few days I started getting really scared. The fear turned into severe depression and I'm lucky to have lived through that. The last time I took it was five months ago and I've been struggling mentally ever since. I saw the doctor the other day and he was pretty much stumped - he referred me to the psychiatry department, but I know that won't help me. I'm still really forgetful and its really hard to hold onto a train of thought. I've resorted to making excel spreadsheets of things that I need to do so that I won't forget. One of the "action items" is to figure out what happened to me and try to reverse it. From what I've read so far, it seems that NO induced brain damage is what may have happened to me. My only advice is know what you are doing before you do it. I didn't.
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#37 Geovicsha

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Posted 29 August 2011 - 05:51 AM

I'm rather worried now. I purchased 50g of Pramiracetam, 50g of Aniracetam, 25g of CDP Choline and 25g of Alpha GPC. I purchased Pramiracetam rather than Piracetam for two main reasons: (i) Piracetam is now a Schedule IV drug in Australia. To import it without ap prescription is ostensibly illegal (I say ostensibly due to the fact there has been conflicting notions about it online, but it sitll wasn't worth the risk. (ii) Pramiracetam has been described as being Piracetam but 8-20x stronger.

Now I'm not so sure. I'm also scared for my friend: he has been taken 1800mg of Pram a day for the past few weeks.

#38 nezxon

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Posted 29 August 2011 - 02:12 PM

I don't think the amount your friend is taking is a dangerous amount at 1.8g, but I think it's likely they could achieve the same effect with a lower dose (150 - 600 mg upto twice per day). You could suggest an antioxidant (R-ALA, vitamin C, CoQ10) or just good old-fashioned fruits or pure juices (citrus, grapes, pomegranate) to cleanup free radical generation. As I understand Australian law regarding these supplements, the four supplements you purchased are unscheduled and can be imported without a problem. I think the potency of pramiracetam seems to be interpreted to mean you can take a dose 8-20x lower than Piracetam, effective doses being reportedly as low as 150mg for Pramiracetam compared to 2-4g for Piracetam. I don't believe its potency in relation to Piracetam affects its legal status. Does that address some of your concerns?

#39 hav

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Posted 29 August 2011 - 07:02 PM

Been trying without success to pull up the original poster's reference #3 which poses the proposition that NO can cause neuron death. But I did find this paper:

http://www.ncbi.nlm....pubmed/15032712

Nitric oxide and its role in ischaemic brain injury.
Keynes RG, Garthwaite J., Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6BT, UK.

Abstract
The role of the neural messenger nitric oxide (NO) in cerebral ischaemia has been investigated extensively in the past decade. NO may play either a protective or destructive role in ischaemia and the literature is plagued with contradictory findings. Working with NO presents many unique difficulties and here we review the potential artifacts that may have contributed to discrepancies and cause future problems for the unwary investigator. Recent evidence challenges the idea that NO from neurones builds up to levels (micromolar) sufficient to directly elicit cell death during the post-ischaemic period.

Concomitantly, the case is strengthened for a role of NO in delayed death mediated post-ischaemia by the inducible NO synthase. Mechanistically it seems unlikely that NO is released in high enough quantities to inhibit respiration in vivo; the formation of reactive nitrogen species, such as peroxynitrite, represents the more likely pathway to cell death.


I don't know if this is the paper the original poster's reference was based on but I note that the hole discussion above deals with the effect of nitric oxide in the brains of stroke victims, not healthy individuals. These are people who suffer brain damage when blood flow to the brain is interrupted. The question dealt with above is whether a treatment that increases the brain's nitric oxide levels and thus increases blood flow can make recovery more likely. This paper seems to be leaning towards concluding that it does.

Howard

edit: since the software update I can't seem to figure out how to quote an abstract without breaking it into multiple quotes

Edited by hav, 29 August 2011 - 07:05 PM.


#40 JChief

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Posted 05 September 2011 - 02:50 PM

One of the "action items" is to figure out what happened to me and try to reverse it. From what I've read so far, it seems that NO induced brain damage is what may have happened to me. My only advice is know what you are doing before you do it. I didn't.


One of the "action items" is to figure out what happened to me and try to reverse it? Seems a bit extreme. I see there's only one post from this person. So take it with a grain of salt.

#41 JChief

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Posted 07 September 2011 - 03:58 AM

has anyone tried snorting pramiracetam or any racetam for that matter?


No but I would advise against. Just a hunch ;)

#42 thedevinroy

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Posted 26 September 2011 - 06:06 PM

NO is used by T cells to break down cells. A side effect from increased NOS activity is increased citrulline, which isn't really a good thing past a certain limit. Citrullinated proteins, under certain biological circumstances can trigger neurodegeneration. This is a hypothesis in development for understanding Multiple Sclerosis and Rheumatoid Arthritis.

Citrulline is a very common thing, and under low acetic acid levels, it is a healthy thing that the urea cycle can use to get rid of aspartate. However, under high acetic acid levels, aspartate becomes N-Acetyl-Aspartate and ruins the cycle, possibly causing Citrulline damage. Ouch.

I suggest to take Pramiracetam with citrus fruit, vinegar, malic acid, or fumaric acid. The citric acid cycle is what removes excess acetic acid. Cholinergics may help remove acetic acid (by making acetylcholine), but a choline source also may increase methylation which could increase NOS activity in the long run.

Been trying without success to pull up the original poster's reference #3 which poses the proposition that NO can cause neuron death. But I did find this paper:

http://www.ncbi.nlm....pubmed/15032712

Nitric oxide and its role in ischaemic brain injury.
Keynes RG, Garthwaite J., Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6BT, UK.

Abstract
The role of the neural messenger nitric oxide (NO) in cerebral ischaemia has been investigated extensively in the past decade. NO may play either a protective or destructive role in ischaemia and the literature is plagued with contradictory findings. Working with NO presents many unique difficulties and here we review the potential artifacts that may have contributed to discrepancies and cause future problems for the unwary investigator. Recent evidence challenges the idea that NO from neurones builds up to levels (micromolar) sufficient to directly elicit cell death during the post-ischaemic period.

Concomitantly, the case is strengthened for a role of NO in delayed death mediated post-ischaemia by the inducible NO synthase. Mechanistically it seems unlikely that NO is released in high enough quantities to inhibit respiration in vivo; the formation of reactive nitrogen species, such as peroxynitrite, represents the more likely pathway to cell death.


I don't know if this is the paper the original poster's reference was based on but I note that the hole discussion above deals with the effect of nitric oxide in the brains of stroke victims, not healthy individuals. These are people who suffer brain damage when blood flow to the brain is interrupted. The question dealt with above is whether a treatment that increases the brain's nitric oxide levels and thus increases blood flow can make recovery more likely. This paper seems to be leaning towards concluding that it does.

Howard

edit: since the software update I can't seem to figure out how to quote an abstract without breaking it into multiple quotes


Edited by devinthayer, 26 September 2011 - 06:21 PM.

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#43 PurpleCow

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Posted 02 October 2011 - 01:37 AM

I have used Pram for three weeks now at 2400mg per day. I noticed that my short term memory is suddenly awesome. I started coaching soccer, and I not only remembered all of the players names without trying to make an effort of it, but suddenly, I am no longer forgetting adult names of people I have met over the last week with this new soccer endeavor. I also noticed a large increase in my reading speed and a higher accuracy when doing things like typing a quick email. I notice a tingly stimulant effect an hour after taking 1200mg. This effect lasts about an hour. No serious headaches. I had one that was mild but I use lecithin as with other racetams. I am not, currently, taking other racetams.

I did not notice these things when taking Piracetam for four months at 7600mg/day. i did notice the blood thinning effect when I cut my finger (while taking Piracetam).

Edited by PurpleCow, 02 October 2011 - 01:39 AM.

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#44 impdaddee

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Posted 09 October 2011 - 05:15 PM

ohmygods

Just tasted pramiracetam for the first time. Ooo, ooo, it's vile! Still quivering with revulsion half an hour later.

#45 manic_racetam

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Posted 09 October 2011 - 06:56 PM

ohmygods

Just tasted pramiracetam for the first time. Ooo, ooo, it's vile! Still quivering with revulsion half an hour later.


Yeah, the sensation it causes is very strange as well. It burns, but it feels like a spicy chemical burn, or something like that. And the flavor... it's not exactly bitter, more like a completely alien and almost gag-worthy. Almost impossible to describe but definitely unpleasant.

#46 Geovicsha

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Posted 10 October 2011 - 10:07 AM

Haha, at first tasting it I, too, was repulsed by the peculiar taste. It tasted nothing like anything I have had before. But I'm an experimental individual by nature, and whenever I am capping, if I get some left over Pram on my fingers, I feel inclined to lick it up. The more I've done this, the more I become familiar with the taste. Obviously it isn't something I'd opt to spread on my chips, but I've become more familiar with it.

I gave my dad a taste and he seemed to like it. Weird man.

#47 impdaddee

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Posted 10 October 2011 - 06:01 PM

Geovicsha, "De gustibus non est disputandum," and all that.

I'd read the reports, but the reality far exceeded anything I'd primed mysef for (and I'm familiar with some pretty awful tasting Ayurvedic and Chinese herbal concoctions). My body couldn't decide whether to retch, or laugh in amused disgust.

Subjectively, I felt a mild "zoom" after about 10 minutes, then a settled calm, and sense of utter command and competence after about an hour. I don't think its best use is to enhance one's culinary skills, but our Canadian Thanksgiving meal was never so smoothly prepared, and with as few dirty dishes. Everything fell into place effortlessly, everything seemed to be exactly where I needed it to be when I needed it, and time to tidy up the kitchen magically appeared between all the precisely orchestrated chopping and peeling and steaming and roasting. The complex tasks became trivial, even ludic to accomplish. Nootropics as a kitchen aid! Oh, the absurdity.

I can hardly wait to see what effect a month of taking pramiracetam will have on my reading of Longchenpa and Mipham.

One thing is certain--next time, I'll encapsulate its potent vileness. That experience was comically horrible.

#48 topsykretts

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Posted 27 January 2012 - 08:33 PM

I hate to bump an old thread, but as I've just started taking pramiracetam and came across this discussion about NO induced cell death, I'm just wondering what the general consensus is. Should I keep taking it, stop, or only take it with antioxidants?

#49 Baten

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Posted 27 January 2012 - 10:05 PM

At sub 1g doses it shouldn't be a problem at all. At doses involving grams, you shouldn't take it long-term.
If anything, I believe drinking alcohol is worse for your brain than taking a couple of grams of pramiracetam a day.

#50 jillin

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Posted 28 January 2012 - 03:07 AM

NO toxicity has been pushed to the side lines in regards to scientific research on validating said effects and its mechanisms [albeit, it's still being looked into in other fields like Oncology]. It should be known that NO concentration readily increases with consumption of a lot of compounds that have been deemed healthy, i.e. resveratrol; and there have been both positive and negative results that have been documented which usually proliferate through cascades of complicated extracellular/intercellular modality modulations. As it is, if you're worried about NO toxicity, then just stop taking Pram. Resveratrol has antioxidant effects yet it increases endogenous NO concentration, so you can't just look for easy solutions with research chemicals as there are no easy solutions. I am sure there has been multiple research papers in the past couple of years that obviate the NO neuro-toxicity worry and shift the scope to a wider understanding and categorization of free radicals. However, as with anything regarding self-experimentation, if you have can't be bothered to read up on the vast amounts of research information about the subject and would rather rely on inferences from people of the internet -- self-experimentation can be detrimental rather than helpful.
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#51 zeroskater6979

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Posted 28 January 2012 - 03:20 AM

i think racetams are a huge waste of money for such minimal effects, plus most of them were sedative for me anyway, especially pram
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#52 brunotto

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Posted 28 January 2012 - 11:46 AM

NO is used by T cells to break down cells.


But it act also as a negative feedback to TH17 (worst type)...
so IMHO Arginine and others that stimulate a little more NO production are usually ok.

Studies carried out in the Institute of Infection, Immunity and Inflammation, show that Nitric Oxide can stop the development and function of a type of white blood cell, known as TH17 which can attack the body tissue through excessive inflammation.

http://medicalxpress...ne-disease.html
http://www.ncbi.nlm....pubmed/22280236

More... NO tends to shift the immunitary system towards TH1 (reducing both T-regs and Th17)

http://www.ncbi.nlm....pubmed/21555530

IMHO T-regs are big friends with autoimmune, but enemy with cancer.

NO is detrimental in TH1 autoimmunity but benefitial in TH17 one... the opposite of interferone.

http://www.ncbi.nlm....pubmed/22231516

In relapsing remitting multiple sclerosis (RRMS), type I interferon (IFN) is considered immuno-modulatory, and recombinant forms of IFN-β are the most prescribed treatment for this disease. However, within the RRMS population, 30-50% of MS patients are nonresponsive to this treatment, and it consistently worsens neuromyelitis optica (NMO), a disease once considered to be a form of RRMS. In contrast to RRMS, type I IFNs have been shown to have properties that drive the inflammatory pathologies in many other autoimmune diseases. These diseases include Sjögren's syndrome, system lupus erythematosus (SLE), neuromyelitis optica (NMO), rheumatoid arthritis (RA) and psoriasis. Historically, autoimmune diseases were thought to be driven by a TH1 response to auto-antigens. However, since the discovery of the TH17 in experimental autoimmune encephalomyelitis (EAE), it is now generally thought that TH17 plays an important role in MS and all other autoimmune diseases. In this article, we will discuss recent clinical and basic research advances in the field of autoimmunity and argue that IFN-β and other type I IFNs are immuno-modulatory in diseases driven predominantly by TH1 but in contrast are inflammatory in diseases that have a predominant Th17 response.

http://www.ncbi.nlm....pubmed/22265273

Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Th17 cells reportedly play important roles in the development of inflammatory and autoimmune diseases. In this study, we investigated the contributions of circulating Th17 cells and plasma Th17-associated cytokines to carotid artery plaques: CONCLUSION: These results suggest that increased frequencies of circulating Th17 cells and Th17-associated cytokines are correlated to the severity and progression of carotid artery plaques.

Edited by brunotto, 28 January 2012 - 12:44 PM.


#53 hooter

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Posted 28 January 2012 - 12:33 PM

Who cares about neuronal death? This will most likely affect your erectile function long term. Weiner

#54 MenDis

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Posted 24 July 2012 - 12:37 AM

I realize that I am responding to an old thread, but I think its important that I share the difficulties that I have experienced with Pramiracetam:

Onset: I took 1000mg of pramiracetam on 3/24/2011 (Ordered in bulk form (50 g) from Cerebral Health) and didn't notice anything. On 3/28, I took 1200mg of Pramiracetam and 1200mg of Choline Bitartrate (ordered in bulk (50g) from superiornutraceuticals.com) at the same time and didn't notice anything. Next day, I did the same dose and nothing noteworthy. Next day, I worked out and did the same dose of both immediately afterward. Ten minutes later, I felt nauseous, sweaty, dizzy, and confused. I was unable to understand spoken language or written text and had short term memory loss. Also was unable to carry on a train of thought - felt like I was in a "zombie" state, unable to formulate any ideas. Difficulties continued for months, leading to depression. Difficulties continue to this day, as stated below.

Symptoms:
1.) Difficulty understanding and remembering what I read
2.) Difficulty understanding and remembering what has been said to me, especially if there are long monologues where I am not interjecting.
3.) Scrambled thoughts. Never able to carry on extensive train of thought without writing or talking and it is very difficult to remember previous trains of thought. Hard for me to plan and execute simple multistep plans. Forget the steps, don't understand the logic behind the steps.
4.) Small working memory.
5.) Severe concentration problems.
6.) Extremely difficult to recall things...takes a long time and there isn't much detail.
7.) Learning problems.
8.) Forgetting what I am doing when I'm doing it every 20 seconds.
9.) Sporadic Ringing in the ears.
10.) Executive dysfunction: http://en.wikipedia....ive_dysfunction. Specifically impulsive and disorganized.
11.) Very difficult to access knowledge for normal thought processes without speaking or writing. Often surprise myself with things that I am able to recall when speaking or writing.
12.) Inability to remember previous events in the day or previous days.
13.) Constantly abandoning trains of thought due to distraction and not being able to remember them.
14.) I can never remember what I thought about on previous days...I would describe it as conceptual memory impairment. Im thinking about the same things everyday, but they are new to me everyday. Realizations and conclusions that I have made in my head are gone the next day, so it is extremely hard to build a time expansive working memory to make decisions.
15.) I have these attacks in the afternoons where I have a bombardment of half formed thoughts that causes me to be really irritable and uncomfortable. The best term would be extreme restlessness. It may be linked to eating carbs, but I'm not sure. It definitely seems worse when I eat sugar. This may be due to an imbalance in neurotransmitters (i.e. more excitatory ones (glutamate) that inhibitory ones (GABA).
Summary: What I would imagine ADD to be like. My consciousness is disjointed and non-fluid.

Theory:
The Pramiracetam increased the activity of Nitric oxide synthase, which increased the production of nitric oxide in the cortex and lead to neuronal damage.


Comments:
It should be noted that at the time that this reaction occured, I was only taking the two supplements mentioned above. I still have the difficulties listed above to varying degress and still haven't found any clear answers about what exactly happened. I'm not sure if it was the NO induced cell death that caused the reaction or a contaminant in one (or both) of the supplements. Unfortunately, in the aftermath and panic of the first week after this happened, I threw away what remained of both supplements....so I can't test them to find out their purity. I did find evidence that Cerebral Health received at least one warning from the FDA for not testing their source materials. Anyways, I went to a neurologist several times and had a CTscan and MRI, which showed nothing. I tried hyperbaric oxygen therapy a couple times because the research I did indicated that it could increase growth hormones and heal parts of the brain, but found that it made the mental confusion worse. Anyways, I've kind of run out of options to try to correct this. I'll do hair testing for heavy metals toxicity and try to get involved in an fMRI study to try to at least pinpoint the area of my cortex that isn't working correctly, but beyond that there isn't much I can do. I've read the thread on DHA+uridine+choline for neural regeneration, but I'm a little scared considering what happened the first time I tried cognitive supplements. Anyways, any insight would be really really appreciated as I have trouble analyzing things myself. I would really LOVE to hear from MrHappy, as he seems to have some very good insights into many different topics discussed here at Longecity, as does JChief and many others. I hope that at some point in the future, I will be able to correct things somewhat...its really quite torturous living like this.
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#55 8bitmore

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Posted 25 July 2012 - 03:42 PM

I realize that I am responding to an old thread, but I think its important that I share the difficulties that I have experienced with Pramiracetam:
[...]
...its really quite torturous living like this.


I must admit I quite enjoyed reading your post: it is well formulated, correctly spelled and structurally sound - if you compare that to the mildly delusional ramblings that go on in these and other forums it seems that your neural health may well be, despite whatever toxic reaction you had to Pramiracetam, considerably above average.

All the same of course I trust that something is awry; otherwise you would undoubtedly not have spend the time writing here! So, on that note: I would suggest a course of mildly neuro-generative/protective herbs and mushrooms like Ashwagandha, Ginkgo Biloba and Lion's Mane, these are consistent in their effect if you do the research and get good organic sources (I would personally recommend Mountain Rose Herbs as a really consistent and ethical supplier) and are very unlikely to do further damage. Alongside with the physical/herbal intervention I would suggest therapy of one kind or another, often physical/chemical trauma can be a potential gateway to look at older auto-biographical problems that may well be holding up resources that you could very well do with to facilitate the healing of your present condition (that's speaking from my personal experience of dealing with physical impairment that down the road turned out to be heavily entwined in an emotional pattern/experience from childhood).

Edited by 8bitmore, 25 July 2012 - 03:48 PM.


#56 MenDis

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Posted 25 July 2012 - 05:14 PM

Thanks 8bitmore, I appreciate your input. There are definitely some odd characteristics about this situation, particularly that by writing and speaking I am able to think much more clearly. Its almost like by doing those, I close a feedback loop that helps me understand and remember things better. However, even when doing so, I am significantly slower at understanding things. It is the "thinking in my head" that is really difficult. Most of the time when I try to do this, there are scrambled bits of thoughts that I can never piece together in a coherent string. I've been taking ALCAR, phosphatidylserine, ginko biloba, alpha lipoic acid, CoQ10 and haven't seen much improvement. However, I will research Lion's Mane and Ashwagandha. And I will start being more consistent with exercise...was finding the motivation hard to come by for awhile. I'll definitely consider therapy, too. Your suggestions are much appreciated.

#57 choqueiro

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Posted 26 July 2012 - 11:52 AM

I was thinking in trying "Brain Octane Pramiracetam" formula from Superior Nutraceuticals but some comments (posts #53 or #54 for example) really scare me. Is Pramiracetam safe in the long term?? Objectively could be any problem taking this substance daily according to the NO toxicity?? Can it really affects my erectile function?? (I´m trying to "ba a father").


Thanks

#58 renfr

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Posted 27 July 2012 - 10:50 AM

I realize that I am responding to an old thread, but I think its important that I share the difficulties that I have experienced with Pramiracetam:

Onset: I took 1000mg of pramiracetam on 3/24/2011 (Ordered in bulk form (50 g) from Cerebral Health) and didn't notice anything. On 3/28, I took 1200mg of Pramiracetam and 1200mg of Choline Bitartrate (ordered in bulk (50g) from superiornutraceuticals.com) at the same time and didn't notice anything. Next day, I did the same dose and nothing noteworthy. Next day, I worked out and did the same dose of both immediately afterward. Ten minutes later, I felt nauseous, sweaty, dizzy, and confused. I was unable to understand spoken language or written text and had short term memory loss. Also was unable to carry on a train of thought - felt like I was in a "zombie" state, unable to formulate any ideas. Difficulties continued for months, leading to depression. Difficulties continue to this day, as stated below.

Symptoms:
1.) Difficulty understanding and remembering what I read
2.) Difficulty understanding and remembering what has been said to me, especially if there are long monologues where I am not interjecting.
3.) Scrambled thoughts. Never able to carry on extensive train of thought without writing or talking and it is very difficult to remember previous trains of thought. Hard for me to plan and execute simple multistep plans. Forget the steps, don't understand the logic behind the steps.
4.) Small working memory.
5.) Severe concentration problems.
6.) Extremely difficult to recall things...takes a long time and there isn't much detail.
7.) Learning problems.
8.) Forgetting what I am doing when I'm doing it every 20 seconds.
9.) Sporadic Ringing in the ears.
10.) Executive dysfunction: http://en.wikipedia....ive_dysfunction. Specifically impulsive and disorganized.
11.) Very difficult to access knowledge for normal thought processes without speaking or writing. Often surprise myself with things that I am able to recall when speaking or writing.
12.) Inability to remember previous events in the day or previous days.
13.) Constantly abandoning trains of thought due to distraction and not being able to remember them.
14.) I can never remember what I thought about on previous days...I would describe it as conceptual memory impairment. Im thinking about the same things everyday, but they are new to me everyday. Realizations and conclusions that I have made in my head are gone the next day, so it is extremely hard to build a time expansive working memory to make decisions.
15.) I have these attacks in the afternoons where I have a bombardment of half formed thoughts that causes me to be really irritable and uncomfortable. The best term would be extreme restlessness. It may be linked to eating carbs, but I'm not sure. It definitely seems worse when I eat sugar. This may be due to an imbalance in neurotransmitters (i.e. more excitatory ones (glutamate) that inhibitory ones (GABA).
Summary: What I would imagine ADD to be like. My consciousness is disjointed and non-fluid.

Theory:
The Pramiracetam increased the activity of Nitric oxide synthase, which increased the production of nitric oxide in the cortex and lead to neuronal damage.


Comments:
It should be noted that at the time that this reaction occured, I was only taking the two supplements mentioned above. I still have the difficulties listed above to varying degress and still haven't found any clear answers about what exactly happened. I'm not sure if it was the NO induced cell death that caused the reaction or a contaminant in one (or both) of the supplements. Unfortunately, in the aftermath and panic of the first week after this happened, I threw away what remained of both supplements....so I can't test them to find out their purity. I did find evidencethat Cerebral Health received at least one warning from the FDA for not testing their source materials. Anyways, I went to a neurologist several times and had a CTscan and MRI, which showed nothing. I tried hyperbaric oxygen therapy a couple times because the research I did indicated that it could increase growth hormones and heal parts of the brain, but found that it made the mental confusion worse. Anyways, I've kind of run out of options to try to correct this. I'll do hair testing for heavy metals toxicity and try to get involved in an fMRI study to try to at least pinpoint the area of my cortex that isn't working correctly, but beyond that there isn't much I can do. I've read the thread on DHA+uridine+choline for neural regeneration, but I'm a little scared considering what happened the first time I tried cognitive supplements. Anyways, any insight would be really really appreciated as I have trouble analyzing things myself. I would really LOVE to hear from MrHappy, as he seems to have some very good insights into many different topics discussed here at Longecity, as does JChief and many others. I hope that at some point in the future, I will be able to correct things somewhat...its really quite torturous living like this.


You seem like you have a severe glutamate imbalance as you say. I suggest you take huge amounts of taurine (3000-5000mg) for a week to keep glutamate surge in control.
I already experienced nearly what you describe there from points 1 to 8. It happened to me when I had a benzo withdrawal, I solved that with massive magnesium, taurine intake. I guess pramiracetam is extremely glutamatergic and caused the same symptoms as a benzo withdrawal.
As well be sure to replenish your brain with vitamins, overall B1-B3-B6 in significant amounts.
Btw, do you have severe sleep problems? Like total insomnia, hard time sleeping or waking up all the times after pramiracetam use?

Personally I don't think your batch was contaminated but rather you took too much pramiracetam, starting doses are 100mg, you took 10 times more. Some people have a lot of sensitivity to glutamatergic substances and it might be your case.
Anyway good luck and don't wait, if it's glutamate then it's killer for your neurons and you can fully recover if you reduce glutamate flood asap.
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#59 MenDis

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Posted 28 July 2012 - 05:06 AM

Renfr, thanks for the recommendations. I just bought Taurine and will take it over the next week and see how it goes. Definitely need to get on a good multivitamin. No sleep problems at all, sleep 8-9 hours every night with no problems and didn't have any problems initially after the reaction, either. It does seem like a glutamate issue. I think any damage that could have been done due to excitoxicity is done by now since this happened about 16 months ago, but hopefully Taurine will at least make a small difference.

Edited by gthughes, 28 July 2012 - 05:07 AM.


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#60 renfr

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Posted 28 July 2012 - 04:32 PM

I guess you might be able to recover your cognitive abilities however glutamate excitotoxicity has probably destroyed some memory over 16 months, I had it for 3 days before I knew what to do and it was already severely destructive I forgot several things and concepts.
What I can suggest is bacopa to upregulate GABA and sustain the balance but also to impeach more neurons to be eliminated, you can also start a NGF therapy to renew your neurons Hericium Erinaceus, Noopept, Melatonin those are good sources of NGF stimulation. Neuroplasticity is stronger than what we think.
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