Piracetam study depository

[Mauritio]

Piracetam is a great substance and has so many uses ,yet its still not fully understood how it works .

Let us collect some studies to paint a better picture on what it does.
@Hans @Razvan @Charger @Ismail

Here are some studies from my notes: :


Here's a very interesting study concerning piracetam for cancer treatment.

"Tumor remissions were observed in several male animals. "

"All animals treated in this manner for 7 months remained tumor-free."
([Antineoplastic activity of drugs affecting the central nervous system against chemically induced tumors in the rat (author's transl)] - PubMed)


Piracetam and phenotropil increase the dopamine and noradrenaline content in the brain [1, 4].

7-fold administrations of phenotropil induced an increase indensities of NMDA receptors in the hippocampus, nicotinic receptors in the cortex, and D3-dopamine receptors in the striatum [3]

Piracetam is an agonist of
glutamate quisqualate autoreceptors [7]

The affinity of phenylpiracetam to the nicotinitic acetylcholine (nACh) receptor, but not the glutamate NMDA subtype, was demonstrated in ligand-binding experiments in vitro. However, injection of this drug (100 mg/kg, intraperitoneally) to rats increases the numbers of both nACh and NMDA receptors, but decreases serotonin and dopamine
receptors in the brain tissue.[40]"
(Piracetam and Piracetam-Like Drugs - Drugs)

It lowers glutamate .
(Activation of quisqualate metabotropic receptors reduces glutamate and GABA-mediated synaptic potentials in the rat striatum - PubMed)

different effects depending on the dosage . With low/medium doses beeing more nootropic and high doses more anxiolytic.
([The nootropic and anxiolytic properties of different doses of piracetam] - PubMed)

Long term safe. This study administered up to 20g per day for 18 months .
(Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy - PubMed)


In this study they took 8g/d for 1 year and the drug was well tolerated .
(Long‐term and high‐dose piracetam treatment of Alzheimer's disease)


Piracetam, an analog of GABA, improves
learning, increases resistance to toxins or oxygen
deprivation, and increases bilateral symmetry of
function in the cerebral hemispheres (Giurgea,
1973)."
-RP
(A Biophysical Approach To Altered Consciousness, Ray Peat)

It increases BDNF.
([Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy] - PubMed)

 

[Charger]

What's interesting about it's effects is that it feels like it lowers prolactin as effectively as something like caber or meter with regards to its effects on libido but without making me feel as mentally stimulated or spaced out, which is a good thing.

Basically feels like getting the benefits of drugs like Cabergoline and Selegiline but much more sustainable and safe (afaik). It's effects on cognition and verbal fluency definitely make it feel like it could/should be a staple 'antiaging' nootropic.

 

[Ismail]

Piracetam is a great substance and has so many uses ,yet its still not fully understood how it works .

Let us collect some studies to paint a better picture on what it does.
@Hans @Razvan @Charger @Ismail

Here are some studies from my notes: :


Here's a very interesting study concerning piracetam for cancer treatment.

"Tumor remissions were observed in several male animals. "

"All animals treated in this manner for 7 months remained tumor-free."
([Antineoplastic activity of drugs affecting the central nervous system against chemically induced tumors in the rat (author's transl)] - PubMed)


Piracetam and phenotropil increase the dopamine and noradrenaline content in the brain [1, 4].

7-fold administrations of phenotropil induced an increase indensities of NMDA receptors in the hippocampus, nicotinic receptors in the cortex, and D3-dopamine receptors in the striatum [3]

Piracetam is an agonist of
glutamate quisqualate autoreceptors [7]

The affinity of phenylpiracetam to the nicotinitic acetylcholine (nACh) receptor, but not the glutamate NMDA subtype, was demonstrated in ligand-binding experiments in vitro. However, injection of this drug (100 mg/kg, intraperitoneally) to rats increases the numbers of both nACh and NMDA receptors, but decreases serotonin and dopamine
receptors in the brain tissue.[40]"
(Piracetam and Piracetam-Like Drugs - Drugs)

It lowers glutamate .
(Activation of quisqualate metabotropic receptors reduces glutamate and GABA-mediated synaptic potentials in the rat striatum - PubMed)

different effects depending on the dosage . With low/medium doses beeing more nootropic and high doses more anxiolytic.
([The nootropic and anxiolytic properties of different doses of piracetam] - PubMed)

Long term safe. This study administered up to 20g per day for 18 months .
(Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy - PubMed)


In this study they took 8g/d for 1 year and the drug was well tolerated .
(Long‐term and high‐dose piracetam treatment of Alzheimer's disease)


Piracetam, an analog of GABA, improves
learning, increases resistance to toxins or oxygen
deprivation, and increases bilateral symmetry of
function in the cerebral hemispheres (Giurgea,
1973)."
-RP
(A Biophysical Approach To Altered Consciousness, Ray Peat)

It increases BDNF.
([Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy] - PubMed)

Thank you for this, very concise and beneficial ???

Was recently reading the works of Thomas Seyfried, he mentions how cancer feeds on glutamine via some type of fermentable fuel process. Wonder if piracetams wonders are linked to cancer benefits via this pathway perhaps ??‍

 

[Mauritio]

Piracetam increases prolactin

(Effects of piracetam on brain monoamine metabolism and serum prolactin levels in the rat - PubMed)

Piracetam lowers morphine induced prolactin

Modulating effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin secretion in male rats - PubMed

1. The effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin (PRL) secretion was investigated in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein...

pubmed.ncbi.nlm.nih.gov

 

[Mauritio]

Today I took 1200mg of piracetam and it had more of a calming effect than I remembered. I slept not great, after which I felt kind of stressed and piracetam brought the stress down a lot . I also felt more social .
I feel like piracetam works as a adaptogen. When you're already stressed additional stimulation might make you feel worse ,so it calms you down . When I feel normal it has more of a stimulating effect on me.

 

[Charger]

Piracetam increases prolactin

(Effects of piracetam on brain monoamine metabolism and serum prolactin levels in the rat - PubMed)

I know these are from large doses and probably don't apply to much smaller doses, but I'll add that since starting Piracetam, even if I ejaculate several times, I don't get anything like the POIS/high prl type symptoms I normally would without it. There is no 'brain fog' or loss of sharpness, drive, or an increase in fatigue or anxiety the following day which is what led me to believe that it's effects were probably anti-prolactin.

Another thing I've noticed since starting, and have read similar anecdotes, are random flashbacks to previously forgotten memories from childhood.

 

[Mauritio]

Piracetam effect on prolactin seems to follow a U-shaped curve with high and low doses beeing ineffective. The most effective dose for prolactin lowering was 100mg/kg ,which is about 1,2-1,5g for a human .
The first study showing doses of 6/12g increasing prolactin.


"Piracetam had no effect on basal plasma PRL concentration. "

"...especially in the group given 100 mg kg-1 piracetam, where plasma PRL concentration was not significantly different from basal values. The dose-response relationship showed a U-shaped curve; the smallest dose had a minor inhibitory effect and the highest dose had no further effect on the PRL rise."

(Modulating effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin secretion in male rats.)




"Piracetam activated pituitary prolactin cells."

[Ultrastructure of the liver and endocrine system in aging rats: effect of piracetam] - PubMed

Lipogenic pigmentation is described in thyroid follicular, parathyroid, and pineal cells, as well as in adrenocortical macrophages. Piracetam activated pituitary prolactin cells and increased paracrystals in thyroid follicular cells; smooth endoplasmic reticulum was increased and glycogen...

pubmed.ncbi.nlm.nih.gov

 

[Mauritio]

"In a 12-week double-blind study, piracetam at two dose levels (2.4 and 4.8 g/day) was compared to placebo in the treatment of 60 elderly psychiatric patients with mild diffuse cerebral impairment, but no signs of focal brain lesion. The psychiatric illness, schizophrenia or affective disorder, of patients selected was in remission at the time of the study. Monthly evaluations by the nurse revealed that piracetam improved overall functioning, particularly alertness, socialization, and cooperation, relative to the control group. Patients treated with 2.4 g/day piracetam also showed significant improvement in scores for the full IQ and the memory quotient on the Wechsler Adult Intelligence and Memory Scales; greater response was seen in those with lower initial scores. Piracetam at 4.8 g/day had a more rapid onset of action on behavioral variables than 2.4 g/day, but its therapeutic effect tended to diminish at 12 weeks, possibly as the result of overstimulation. Piracetam did not appear to interfere with concomitant psychotropic maintenance medication or affect the psychiatric illness itself."
(Piracetam in elderly psychiatric patients with mild diffuse cerebral impairment - PubMed)



"P was ineffective in modifying either synthesis release, uptake or post- synaptic binding sites for GABA. Acute P injection decreased dose-dependently cGMP levels in the rat cerebellum. Moreover, this effect was not mediated through a GABAergic mechanism. An acute challenge with Piracetam 15 days after chronic treatment with the compound increased DOPAC levels in the striatum and counteracted haloperidol-induced PRL rise. Furthermore, chronic P administration increased normetanephrine levels in the cerebral cortex, an index of the release of norepinephrine at the synaptic level, and induced a desensitization of beta-adrenoceptors in this same brain area"
(Neurochemical studies on GABAergic and aminergic systems in the rat brain following acute and chronic piracetam administration - PubMed)


"Pyracetam in a dose of 100 mg/kg increased the DA level and decreased the 5-HT level in the striatum homogenates: DA- to 121% and 5-HT-to 81% (p < 0.05), respectively. "
([The effect of a low dose of piracetam on the activity of the dopaminergic system in the rat striatum] - PubMed)


"piracetam significantly increased the DA level in the cerebral cortex and in the striatum, as well as the 5-HT level in the cortex, reducing the 5-HT level in the striatum, brain stem and hypothalamus."
(Changes in the brain biogenic monoamines of rats, induced by piracetam and aniracetam - PubMed)


"The experimental data show that piracetam exerts a marked effect on cerebral hemodynamics producing a lowering of cerebral artery tonus and an increase of local blood flow. In addition, an increase of GABA content is noted, particularly following an experimentally-induced disorder of cerebral blood circulation."
([Mechanism of action of piracetam on cerebral circulation] - PubMed)

 

[Mauritio]

 

[Mauritio]

A case for simultaneous choline supplementation:

"Those subjects given only choline (100 mg/kg) did not differ on the behavioral task from control animals administered vehicle. Rats given piracetam (100 mg/kg) performed slightly better than control rats (p less than 0.05), but rats given the piracetam/choline combination (100 mg/kg of each) exhibited retention scores several times better than those given piracetam alone. In a second study, it was shown that twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not enhance retention nearly as well as when piracetam and choline (100 mg/kg of each) were administered together. Further, repeated administration (1 week) of the piracetam/choline combination was superior to acute injections."
(Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats - PubMed)


From my own experience I can confirm that. With both piracetam and phenylpiracetam after some time I needed a additional choline source, even my usual 1-2eggs per day didn't suffice i needed at least 4 eggs per day and even then the effect wasn't as pronounced as with a choline supplement .
I dont know why but for some reason I get much stronger effects from a choline (bitartate) supplement than from 4 eggs, even when the amount of choline in the eggs is higher then in the supplement ...

 

[Ismail]

From my own experience I can confirm that. With both piracetam and phenylpiracetam after some time I needed a additional choline source, even my usual 1-2eggs per day didn't suffice i needed at least 4 eggs per day and even then the effect wasn't as pronounced as with a choline supplement .
I dont know why but for some reason I get much stronger effects from a choline (bitartate) supplement than from 4 eggs, even when the amount of choline in the eggs is higher then in the supplement ...

How much choline bitartrate do you take? Do you also take the bitartrate in addition to the 4 eggs?

 

[Mauritio]

How much choline bitartrate do you take? Do you also take the bitartrate in addition to the 4 eggs?

No if I take the 4 eggs I dont take choline .
I Just have half a capsule ,which is 100mg choline and 250mg of bitartrate. And it increased my metabolism, concentration and mood a lot more than the eggs.

 

[Mauritio]

Today I took 1,2g again first thing in the morning . Ate 2 eggs with with . Shortly after I got tired and a hedonic . Typical side effects .
I took half a tablet of methylfolate ,which I still had lying around and now almost all the fatigue is gone .
It probably means I have a problem with converting dietary choline to acetylcholine, in which folate is involved . Or it has to do with the whole MTHFR under-/overmethylating stuff.

One could also try methylcobalamin or another form of supplemental choline .

I got the idea from this article:

My Experience with Piracetam - The Procrastination Killer - The Revisionist

In this article, I will be talking about my experience testing piracetam, the original Russian nootropic. Initially It was greatly stimulating, such that I couldn’t go to sleep at night. And later on it was sedating, such that I would start nodding off. I had to theorize & research what was...

www.therevisionist.org

 

[Mauritio]

"In the dose range from 50 to 300 mg/kg, piracetam improved the avoidance performance of both types and produced a dose-dependent increase in the TER amplitude, but did not affect the behavior of rats in conflict situations. As the drug dose was increased to 400-1000 mg/kg, the positive learning influence disappeared (sometimes the effect was even negative) and the TER increase changed to decrease. In contrast, the conflict situation tests revealed pronounced anxiolytic activity of piracetam at elevated doses."
([The nootropic and anxiolytic properties of different doses of piracetam] - PubMed)

 

[Charger]

Definitely noticing fatigue that only started once I began Piracetam. Sleep hasn't been as refreshing, also had symptoms I would attribute to serotonin, namely fatigue, diarrhea, and just feeling bitchy about work-related things which I'm usually pretty zen about.

Pros so far:
• Abolition of anxiety better than anything I've used aside from Androsterone, but without the low estro, mood blunting, antisocial effects that andro sometimes brings.
• More social and confident, mostly due to lack of anxiety.
• Higher libido, lower refractory period, and wider preference in females.
• Regained interest in previously old hobbies, but this was mainly noticeable with video games, which makes me think it's serotonin related rather than dopamine, that's just an assumption though.
• Flashbacks to previously forgotten memories, especially from childhood, more reminiscing and nostalgia... this could also be attributed to serotonin.

Cons:
• Fatigue.
• Mild headache.
• Irritability, worsened from lack of refreshing sleep.
• Lack of patience.

I've seen a post or two here and there when digging through nootropic forums and subreddit that Piracetam is supposedly serotonergic in small doses and dopaminergic in high doses, I don't know how much truth there is to this but I definitely feel more in a serotonergic state than I did before starting Piracetam.

I don't know if all of this could be attributed to Choline, but I see more anecdotes implying a better experience without attempting to supplement it.

If anyone has any recommendations that are as strong on anxiety and sociability without being serotonergic as Piracetam and can be used daily without issue or suppression, that would be awesome. Unfortunately, I don't think that's possible, even anti-serotonin drugs like Metergoline seemingly aren't sustainable daily.

 

[Mauritio]

I had similar symptoms after like 2 weeks of daily phenylpiracetam. Daily eggs just won't cut it . Try supplemental choline . Or other methyldonors worked for me.

Methyl b12 /folate and choline are all methyl donors. So by piracetam depleting choline it suggests that I was already low in choline/ methyldonors to begin with or have the MTHFR polymorphism that needs more choline .
I'm definitely going to experiment more with choline . I ordered alpha gpc.

 

[Charger]

You may be right, I wasn't aware but according to @redsun

The main antagonist to norepinephrine is acetylcholine.

If you sleep poorly all the time your norepinephrine and cortisol will be elevated. Also if you are significantly physically stressed like from exercise + your work or whatever else you do and you are not feeding properly, norepinephrine will be elevated beyond normal.

This would explain the high adrenaline symptoms like diarrhea, insomnia, etc.

I've been off Piracetam the past two days, took some Alpha GPC to see if it'll help balance out this edgy state I'm in.

 

[Mauritio]

You may be right, I wasn't aware but according to @redsun


This would explain the high adrenaline symptoms like diarrhea, insomnia, etc.

I've been off Piracetam the past two days, took some Alpha GPC to see if it'll help balance out this edgy state I'm in.

How's your experience with alpha GPC? Every choline source seems to have a supposedly different effect on me.

 

[Jayvee]

I took one single dose of Piracetam at 1g and not slept properly in 4 days, also I seem to have high histamine. I was super stressed after taking it and it made me a very angry driver. I'm annoyed with myself for trying it

 

[Mauritio]

Piracetam lowers inflammation and reactive oxygen species increased through endotoxin.

I also suspect it has a slight diuretic effect although i couldn't find any evidence for that.

Metabolic Enhancer Piracetam Attenuates the Translocation of Mitochondrion-Specific Proteins of Caspase-Independent Pathway, Poly [ADP-Ribose] Polymerase 1 Up-regulation and Oxidative DNA Fragmentation - PubMed

Piracetam, a nootropic drug, has been clinically used for decades; however, its mechanism of action still remains enigmatic. The present study was undertaken to evaluate the role of mitochondrion-specific factors of caspase-independent pathway like apoptotic-inducing factor (AIF) and...

pubmed.ncbi.nlm.nih.gov