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Piracetam
Piracetam is the parent compound of the Racetam class of Nootropic supplements. When
supplemented, it provides a mild boost to brain function.
This page features 111 unique references to scientific papers.

Summary (All Essential Benefits/Effects/Facts & Information)

Piracetam is the prototype for Racetam supplements, which are a group of synthetic
supplements intended to provide a cognitive boost.
Piracetam has a history of being used to treat cognitive impairment. According to a metaanalysis on human studies, piracetam improves general cognition when supplemented by
people in a state of cognitive decline, such as the kind that comes with aging. Though
piracetam may be a useful supplement for improving longevity, it offers limited benefits for
healthy people.
Healthy people supplementing piracetam do experience little to no cognitive benefit. Though
piracetam supplementation in healthy people is understudied, preliminary evidence suggests

that piracetam is most effective for older people. Piracetam supplementation has also been
found to reduce the chances of a breath-holding spell in children.
Piracetam enhances cellular membrane fluidity. This mechanism explains why piracetam is
able to improve cognition, particularly in elderly people.
Piracetam is as effective as aspirin when it comes to preventing blood clotting, which makes
it a useful supplemental intervention after cardiovascular trauma.

Things to Know
Also Known As
Pyracetam, Pyrrolidone acetamide, 2-Oxo-1-pyrrolidine, Memotopril, Fezam (with
cinnarizine), UCB6215

Things to Note

Piracetam is water-soluble, and does not need to be taken with food

Many studies note a high inter-individual variability

It is (anecdotally) reported to be non-stimulatory and non-sedative

Is a Form of

Racetam

Nootropic

Caution Notice
Examine.com Medical Disclaimer

How to Take (recommended dosage, active amounts, other details)

The standard piracetam dose for children is between 40-100mg per kilogram of bodyweight.
This dose is intended for the treatment of breath-holding spells, though it has also been used
for children with dyslexia. The lower end of the range (40-50mg/kg) is used most often.
The standard piracetam dose for adults is between 1,200-4,800mg a day. The largest effective
dose is 1,600mg, taken three times a day for a total of 4,800mg.

Editors' Thoughts on Piracetam

In regards to the mechanisms of Piracetam, I am personally leaning more towards Piracetam
being an agent that can preserve mitochondrial membrane potential.
This sort of downplays it from a cognitive enhancer to a cognitive preserver. It does interact
with mechanisms that can induce cognitive enhancement in otherwise healthy persons
(AMPA modulation and Calcium Channel inhibition) but these effects, at best, are weak.
Other racetams are more likely to be cognitive enhancers (For AMPA modulation and
Calcium channel 2.2 inhibition respectively; this would be Aniracetam and Leviracetam) If it
does enhance cognition significantly, it is possible that this is just from reversing small states
of cognitive deficit.
That being said, it is a non-discriminate membrane fluidity preservative. This may also
underlie how Piracetam is as effective as Aspirin at preventing blood clotting in older persons
when taken as daily preventative medicine.
I believe Piracetam is not so much a Cognitive enhancer as it is a minor Longevity-enhancing
agent; delaying age-related pathology in a non-specific and relatively weak manner. It is
surprisingly non-toxic, so it might be a good health preserving agent if you have excess
money to burn.
Kurtis Frank

Human Effect Matrix

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to
tell you what effect Piracetam has in your body, and how strong these effects are.
Grade
A
B
C

Level of Evidence
Robust research conducted with repeated double blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double blind study or multiple cohort studies

Grade
D
Level of
Evidence

Level of Evidence
Uncontrolled or observational studies only
Magnitude of
Scientific
Change
EFFECT
Effect Size
Consensus

Cognitive Decline

Breath Holding
Spells

Aggression

Memory

100%
Notable

See all 6 studies

100%
Strong

See all 3 studies

100%
Minor

See study

Minor

See 2 studies

Comments
There appears to
be a notable
reduction in the
rate of cognitive
decline (or
rehabiliation of
aged cognition)
associated with
high dose
Piracetam over
time and in a
general ... show

Remarkably
effective in
reducing breath
holding spells in
infants at
feasible
dosages, nearly
absolutely
reducing the
presence of
breath holding
spells with no
apparent ... show

In persons with
cognitive
decline,
supplementation
of Piracetam
was able to
reduce
aggression and
agitation
symptoms.

100%

Small increase
in backwards

Level of
Evidence

EFFECT

Change

Magnitude of
Effect Size

Scientific
Consensus

Comments
recall with
piracetam;
nothing
remarkable and
overall very
limited evidence
in otherwise
healthy
individuals to
draw from.

Stroke Recovery
Rate

Cognition

Scientific Research
Table of Contents:
1. Source and Structure
1. Origin
2. Structure

100%
See study

100%
See study

Ineffective in
the one study
where stroke
recovery rate
was assessed

No significant
influence on
cognition and
neural
functioning has
been noted in
otherwise
healthy persons
following
piracetam
ingestion.

2. Pharmacology
1. Serum
2. Excretion
3. Neurology
1. Mechanisms
2. Memory and Cognition
3. Dyslexia
4. Epilepsy and Seizure
5. Neuroprotection
6. Oxygenation and Stroke
7. Dependence
8. Analgesia
9. Stress, Anxiety, and Depression
10. Breath-Holding Spells
11. Ataxia
12. Tardive Dyskinesia
4. Cardiovascular Health
1. Platelets/Antithrombotic
2. Interventions
5. Inflammation and Immunology
1. Mechanisms
6. Interactions with Organ Systems
1. Ears and Audition
7. Interactions with Hormones
1. Mineralocorticoids

8. Nutrient-Nutrient Interactions
1. Choline
2. Alcohol
3. Cinnarizine
4. Morin
9. Comparative Studies
1. Asparagus Racemosus
2. Clitoria Ternatea
3. Ginger
10. Safety
1. General

1. Source and Structure

1.1. Origin
Piracetam (known as (2-oxo-1-pyrrolidine-acetamide) is a synthetic compound of the racetam
family, and shares the characteristic 5-carbon oxopyrrolidone ring structure.[3] Piracetam was
the first of the racetam family, and developed by UCB Pharma in Belgium,[4][3] and is also
known as Nootropyl or UCB6215.[5] It is a nootropic compound, derived from the greek word
noos (mind) and tropein (towards); ultimately meaning 'towards the mind'.[6]
Synthetic molecule designed to enhance brain function. Piracetam is the basic 'racetam'
molecule of a family of related compounds
1.2. Structure
Piracetam tends to share structural similarity to the neurotransmitter GABA, as it is a cyclical
derivative; as such it retains two nitrogens in its structure with one amine bearing the twocarbon side chain that has the other nitrogen within it. The skeleton structure and computed
minima via conformational analysis (PBE0/6-31G(d,p)) are depicted below; via this article.[7]

Piracetam does not occur naturally in any food or plant source.

2. Pharmacology
2.1. Serum
In youth given 1600mg Piracetam orally in a fasted state, a Cmax of 27.6+/-1.3ug/mL is
reached in 0.90+/-0.15 hours and a 24 hour AUC of 145ug/min/mL is achieved.[8]
In older individuals, the same fasted 1600mg dose yields a Cmax of 32.82+/-3.6ug/mL in a
similar (0.86+/-0.14h) Tmax, but the 24 hour AUC is extended to 188ug/mL/min; this is
thought to be due to a lower urinary excretion rate.[8]
2.2. Excretion
Due to interactions with a cell membrane (particularily in blood cells), a possibility of
Piracetam not following linear excretion and following a loading prinicple is possible;[9] when
excreted, it is exclusively excreted in the urine via glomerular filtration.[10]

3. Neurology
3.1. Mechanisms
Increased brain oxygen consumption has been noted mostly during periods of insufficient
neuronal oxidation following Piracetam ingestion[11] or incubation with neurons.[12] As these
observations are indicative of glucose consumption, interactions with glucose oxidation were
ingestigated and found to be increased in rats[13] and replicated in humans following two 6g
infusions of Piracetam.[14]

Interestingly, the aforementioned study divided dementia patients into those with Alzheimer's
and those without and only in the Alzheimer's group (where glucose consumption is
significantly perturbed) was there a statistically significant increase of 8-10% glucose
consumption,[14] suggesting a mechanism unique to cognitively impaired persons.
Piracetam (and Leviracetam) have been found to antagonize an inhibition of glucose uptake
into erythrocytes induced by hypnotic drugs (including Melatonin)[15] which is likely related
to membrane fluidity.[16][15] A possible connection between membrane fluidity and glucose
consumption exists, although plausible mechanisms also exist for glucose consumption being
enhanced downstream of modulating ion currents and action potentials.[3]
Overall, Piracetam increases glucose and oxygen consumption in brains which precedes
cognitive improvement (as these benefits are global (not favoring certain brain regions) and
more significant in cognitively impaired persons, both of which are in accordance with
interventions in humans).
The exact mechanisms underlying the enhancement of glucose and oxygen consumption are
currently not established
Influences on neurons may be mediated by positively modulating AMPA-gluatmate receptors,
which can increase calcium influx into neurons and increase the density of AMPA receptor
binding sites.[17] This mechanism of action is similar to Aniracetam and Oxiracetam[17] and
like those two, Piracetam does not significantly act on or modulate the other two glutamate
receptor subtypes, NMDA and Kainate receptors,[17][3] although 500mg/kg to aged mice for 2
weeks may increase the amount of NMDA receptors expressed.[18] Increased receptor
expression has been noted with acetylcholine receptors as well only in aged mice (no effect in
youth), suggesting that this is a basic mechanism not unique to glutaminergic receptors.[19]
Piracetam appears to bind to Glu2 and Glu3 subunits of AMPA receptors, of which
Aniracetam binds to Glu3 mostly; binding to Glu2 is a unique site for Piracetam.[20]
Piracetam shows affinity for two subsets of AMPA (glutamate) receptors, Glu2 and Glu3, and
may attenuate the rate of action potentials. It does not appear to directly act upon the other
two glutamate receptors (Kainate and NMDA) although the ability of piracetam to possibly
increase receptors in general in aged mice may influnce these two receptor classes
Piracetam was initially shown to reduce high voltage-dependent calcium influx into
neurons[21] has been found to inhibit CAV2.2 calcium channels in some peripheral and central
neurons with an IC50 value of 3.4umol/L and a maximal efficacy of 94+/-2% inhibition at
2000umol/L.[22] The effects of Piracetam were independent of a G-Protein Coupled Receptor
(GPRC), were reversible, and were not occluded by noradrenaline (which had some additive
benefits with Piracetam).[22] These effects were noted in superior cervical ganglion cells (large
percentage of CAV2.2 channels) and in CA1 hippocampal neurons, where Piracetam at
10umol/L reduced action potential frequency from 133+/-11% (action potential on regular
neurons, with 100% resting levels) to 97+/-10%, excitatory post-synaptic potentials were
reduced from 80+/-7% in control to 18+/-5% with Piracetam.[22] These mechanisms are
similar to that of Leviracetam.[23]
The authors noted a reduction of resting membrane potential after action potential, and
suggested that other ion channels could be getting modified by Piracetam.[22]

May interact with Calcium Channels, where it attenuates excessive neuronal firing
Piracetam is initially formed via using Gamma-Amino Butyric Acid (GABA) and, after
losing a molecule, assuming a cyclical shape.[24] That being said, Piracetam does not appear to
interact with GABA receptors.[25][22]
No significant interactions with GABA receptors despite its origin being a GABA derivative
Piracetam can interact with phospholipid structures due to having high affinity for the polar
head of the phospholipid,[26] which may underlie changes (increases) in membrane fluidity[27]
that may act in a therapeutic manner, as it had no apparent benefit to membrane fluidity in
otherwise healthy young brain slices (independent of species tested).[28]
Membrane fluidity is lessened (rigidity promoting) in instances of oxidative and lipid
peroxidative stress, where Piracetam appears to act to normalize fluidity.[29] A normalization
of mitochondrial function secondary to preserving fluidity is noted in instances of excessive
oxidative stress[16] and perturbed fluidity in the mitochondria is associated with states of
cognitive decline.[30][31] As Piracetam is implicated in increasing mitochondrial membrane
fluidity in aged brain only[28] and this preservation of mitochondrial membrane potential is
associated with improvements in A142 levels and preserving neurite outgrowth in animals.[32]
Appears to preserve membrane fluidity, which may be due to increasing membrane fluidity in
states where fluidity is compromised. These benefits correlate better to instances of cognitive
improvement in cognitive degeneration than do AMPA or Calcium channel
modulation/inhibition
Piracetam may enhance glutamate release from neuronal synapses, but this effect has not
been established in vivo.[33][25]
3.2. Memory and Cognition
One study in 16 otherwise healthy subjects (3:1 male) using 400mg Piracetam taken thrice a
day (1200mg total) for a period of 14 days conducted in a matched pair manner (8 given the
drug in double-blind manner) noted that while no differences existed at baseline or 7 days in,
that 14 days in the Piracetam group was significantly better at a test of backwords word
recall; suggesting improvements to short-term working memory.[34]
One study has noted that, using non-dyslexic persons as a control to test the efficacy of
Piracetam in dyslexics, that the apparently healthy controls experienced an 8.6%
improvement relative to placebo on measures of verbal learning; this was seen with 4.8g
Piracetam over 21 days.[35]
One study has been conducted on 18 persons aged 50 or above but with no salient signs of
cognitive decline, which noted that thrice daily doses of 1600mg (4800mg daily) was
associated with general improvement in cognition on a battery of tests, with no specific
subset showing a large magnitude of benefit.[36] This study was single blind and lasted 8
weeks, and the blinding may have failed due to the majority of the subjects receiving
Piracetam properly guessing so.

In young and otherwise healthy adults, some (quite weak) cognitive enhancement is
apparent. These benefits are more pronounced in populations where cognitive impairment
may not be present but optimal cognition is likely not present either (such as 'organic'
cognitive decline associated with healthy aging)
A meta-analysis on Piracetam assessing 19 double-blind trials noted a significant benefit
associated with Piracetam when it came to persons with some manner of cognitive ailment.[37]
This study built of a 1997 Cochrane Meta-Analysis that assessed 5 studies and found benefit
with an Odds Ratio of 2.89 (95% CI of 1.01-8.24) barely showing statistical significance with
limited studies,[38] and noted that when assessing 19 studies that met the inclusion criteria of
double-blind and parallel studies (54 in total, excluding 35 including cross-over) noted that in
1,488 persons the Odds Ratio for improvement with Piracetam over Placebo was 3.35 (95%
CI of 2.70-4.17) using fixed effects model, and a similar OR and CI were noted for Mantel
Haenszel and random effects model.[37] Excluding the two most statistically influencing
studies (one of which is located online[39]) reduce the OR to 2.50 (95% CI 1.96-3.17).[37]
Numerically, this meta-analysis concluded that the amount of people reporting improvement
is 112% higher (60.9% in piracetam and 32.5% in placebo) with piracetam relative to placebo
and no effects on cognitive or worsening thereof is reduced 34.4-37.9% relative to placebo
(magnitude of improvement not assessed due to hetergeneity of the data).[37]
This aforemented Meta-Analysis excluded 3 double-blind trials (only one of which is located
online[40]) despite reporting benefit due to note reporting categorical data that could not be put
into meta-analysis.[37] Studies included in meta-analysis that can be located online are cited as
follows.[41][42][43][44][45][39]
In a self-report survey from outpatients of cerebrovascular disorders, Piracetam showed a
modest memory improvement,[46][3] a much greater response was seen in in vivo models of
traumatic brain injury.[47]
There appears to be sufficient evidence to indicate that an improvement in cognitive function
exists in persons with degenerating cognitive function. Lots of studies not published online
or otherwise just presented at symposiums, however, Piracetam may have slightly more
benefit in instances of neural trauma when compared to its benefits in organic cognitive
decline
3.3. Dyslexia
One review exists on Dyslexia in particular when it comes to Piracetam[48] where 4 doubleblind crossover studies and 7 double blind studies (encompassing 591 dyslexic or learning
disordered boys aged 8-13 and one study with 30 16-21 year old dyslexics) and overall
tended to note improvements to verbal learning and comprehension associated with 1.2-3.3g
Piracetam daily for up to 8 weeks while other non-verbal parameters measured were much
less constant.[48]
When dyslexic studients are given Piracetam and paired against otherwise healthy peers, a
greater increase appears to be apparent with Dyslexic students (15% more than placebo) than
with non-dyslexic counterparts (8.6% more than placebo) over a period of 21 days.[35]
Is associated with improvements to verbal learning and performance in Dyslexics

3.4. Epilepsy and Seizure

Piracetam seems to be an effective adjunct therapy to valproate in models of myoclonus
epilepsy.[49]
At least one study noted benefit to Tardive Dyskinesia symptoms, but the benefits were only
seen as long as treatment was maintained.[50]
3.5. Neuroprotection
Piracetam seems to have clinical efficacy, relative to placebo, in reducing the cognitive
impairment/dementia seen with aging in vivo,[37] although many trials are of short duration.[38]
Acutely, Piracetam seems to have efficacy in alleviating the reduction of cognitive function
seen with coronary bypass surgery.[51][52]
One trial assessing the neuroprotective effects of an acute dose of Piracetam prior to openheart surgery failed to find a benefit relative to placebo when cognition was assessed 3 days
after surgery,[53] this is in contrast to apparent neuroprotective effects on coronary bypass
surgery, which has been noted previously.[52][54][51]
3.6. Oxygenation and Stroke
Piracetam shows promise in alleviating damage done from strokes in animal models,[55] but
according to one systematic review, Piracetam has minimal human evidence to support this
claim.[56]
One study on ischemic cerebrovascular disease in persons suffering from aphasia
(impairment of language ability, in this case due to brain hypoxia) using 4.8g Piracetam daily
for 6 months after stroke noted that, after assessment via the GAT, NIHSS, mRS and BI
rating scales, that while there was significant improvement in regards to auditory
comprehension there was no significant influence on the other measured parameters of
spontaneous speech, reading fluency, reading comprehension, repetition, and naming when
compared to placebo.[57] These null results are in contrast to previous research, where 6 weeks
of 4800mg Piracetam was associated with improvements in 6 languages tests whereas
placebo only improved in three,[58] and one other study assessing brain waves which
suggested improvements.[59]
Mixed evidence on the benefits of Piracetam on recovery of language function after Stroke,
with either significant improvement existing or minor trends towards improvement
3.7. Dependence
One study assessing the effects of 4.8g Piracetam on whether or not it could reduce Cocaine
dependence found that, after 10 weeks, the Piracetam group was associated with more
Cocaine use than placebo and was rated as worse than both placebo and the other tested
group, Ginkgo biloba, which had no effect.[60]
The lone study assessing cocaine dependence has noted an increased dependency of cocaine
dependence associated with Piracetam usage

3.8. Analgesia
Piracetam appears to have analgesic properties in response to acute inflammatory
hyperalgesia at 30-300mg/kg oral intake (in rats) an hour prior to testing, with dosedependent reductions in pain reaching up to 41% inhibition of acetic acid induced writhing.[61]
These benefits were thought to be secondary to the antiinflammatory properties of Piracetam.
[61]

There appears to be analgesic properties against acute inflammatory pain

3.9. Stress, Anxiety, and Depression
Piracetam has been shown, via self-report, to be somewhat effective at reducing depression
associated with cerebrovascular disorders.[46] These have not been investigated in otherwise
healthy persons.
3.10. Breath-Holding Spells
Breath Holding Spells (BHSs) are periods of episodic apnea that sometimes occur in
otherwise healthy children (starting at 6-28 months, usually fading by 5-9 years old), where
most of the time it is benign yet causes distress to the parent of the unbreathing child (with
only 21% of parents, being told it is benign, find relief[62]); it is thought to be due to the
autonomous nervous system[63] with a relationship between symptoms and diffuse cerebral
anoxia.[25][64][65]
Piracetam is tested for alleviating BHS in children. One study of 40 children (5-60 months;
average 32.5) using 50mg/kg Piracetam daily via Stimulan syrup for a period of 4 months
was associated with significantly improved symptoms. While both groups had 5-5.5 attacks
per month at baseline, placebo maintained at an average 4-5 attacks per month while
Piracetam was assocaited with 0-1 attacks, with 72.08% symptoms reduction within one
month and 83.85% symptom reduction after 4 months; 5-6 patients seemed to have a delayed
response, taking two months to be affected.[66] This study builds off previous non-blinded
studies where Piracetam (50-100mg/kg daily, only 100mg/kg was used if no effect was
observed at 4 weeks) over 3-6 months (with supplemental Iron is too low, as that is tied to
pathology; no differences between iron treated and untreated groups) abolished BHS in 81%
of children, attenuated attacks in 9%, and had no significant effect on 10%.[67] A much earlier
double-blind study with 40mg/kg (divided into two doses daily) Piracetam where 92.3% of
children reported benefit; compared to 29.7% of placebo.[68]
These studies do not seem to report any significant difference between cyanotic or pallid
BHS symptoms, benefitting both to equal degrees.[66][67] Some case studies suggest this may
extend to Leviracetam, another Racetam compound.[69] Additionally, in these studies on
children, the doses (50-100mg/kg bodyweight) used for the specified durations are not
associated with any observed side effects.[66][67][68]
Piracetam appears to be highly effective and safe in the treatment of Breath Holding Spells
(BHSs) in children, and has not been associated with toxic effects at the dose range of 40100mg/kg bodyweight
3.11. Ataxia

A pilot study in Ataxia where 8 patients were given intravenous doses of 30-60g Piracetam
daily (escalating dose) for 14 days (based off a previous case study with high dose
Piracetam[70]) noted improvements in clinician assessment of Ataxia via the International
Cooperative Ataxia Rating Scale (ICARS) where score was dropped from 39.4+/-17 to
30.9+/-14.9, a 21% improvement on average.[1] Significant improvement was seen globally
and on posture/gait subscales, but not kinetic functions, speech and oculomotor disorders
where it trended to improve the former two with no effect on oculomotor disorders; no side
effects were reported by the patients.[1]
3.12. Tardive Dyskinesia
At least one study existed in Schizophrenic patients (n=40) where 4.8g of Piracetam daily for
4 weeks in addition to standard antipsychotic therapy noted minor decreases in global rating
of symptoms while a more significant decrease was noted in the subscales of Tardive
Dyskinesia; this apparent benefit was mediated by unknown mechanisms.[50]

4. Cardiovascular Health
4.1. Platelets/Antithrombotic
Anti-platelet effects of Piracetam have been known to occur in humans for quite some time
(1975[71]) that are apparent in rats at 200mg/kg[72] and in humans at 4.8-9.6g daily (three doses
of 1.6g) with no practically significant efficacy with 1.6 or 3.2g in a day.[73]
Mechanisms underlying these effects are somewhat elusive, and at least one study has noted
that the IC50 values (concentration required to exert 50% effects) are 10-fold higher outside
the body in vitro than they are achieved in vivo when measuring extracted serum.[72]
In hyperactive disorders (acute stroke, Type II Diabetes, Raynaud's phenomenon), a
normalization of platelet function occurs.[74][75] One possibility is the rheological effects of
Piracetam (increasing membrane fluidity) normalizing cell function, but other possibilities
that have not been excluded are reducing the sensitivity of platelets to ADP or inhibition of
Thromboxane A2 synthesis (a proinflammatory prostaglandin).[72][73]
Appears to inhibit blood clotting at doses in the higher range for those used in cognitive
enhancement (4.8g or above), with the mechanisms currently unknown
4.2. Interventions
One large intervention that was comparative between Piracetam at 4.8g (1600mg thrice a
day) and Aspirin (Acetylsalicyclic Acid; ASA) at 200mg thrice a day over the course of 2
years followup in persons who suffered a stroke (n=563) noted that there were no significant
differneces between the two groups in regards to preventing death and stroke, but that
Piracetam was significantly better tolerated (with 12.5% of persons in Piracetam reporting
adverse events, and 21.8% with ASA).[76] That being said, the apparent non-response to ASA
that occurs in some persons[77] also appears to apply to Piracetam.[76]

4.8g daily (in three doses of 1.6g) appears to be optimal due to peak efficacy at 1-4 hours post
consumption and declining efficacy 8-12 hours after consumption.[73]
May be effective as prophylaxis after strokes to maintain blood flow, with one study
suggesting no significant differences when compared to Aspirin (commonly the first choice
for prophylaxis after stroke)

5. Inflammation and Immunology

5.1. Mechanisms
It is known that mediators in the inflammatory pain response (hyperalgesia) are prooxidative
molecules, as inflammatory cytokines (such as TNF-) can cause intracellular increases in
prooxidants such as H2O2,[78] peroxynitrate,[79] and superoxide[80] mediate the subsequent pain
response. Preventing these oxidative molecules either directly (antioxidants) or indirectly via
preventing the actions of inflammatory cytokines can reduce hyperalgesia.[81]
Oral ingestion of 30-300mg/kg Piracetam to rats prior to inflammatory stimuli (carrageenin)
was able to reduce myeloperoxidase (MPO) activity at 100mg/kg, and this effect was
replicated with localized treatment.[61] When looking at mechanisms, it appears that piracetam
failed to reduce TNF- levels in serum but prevented TNF- from inducing secretion of IL1 and MPO and reducing prooxidative changes.[61]
Piracetam appears to prevent TNF- from causing an inflammatory response, which underlies
the pain reducing effects of Piracetam by preserving intracellular oxidant status

6. Interactions with Organ Systems

6.1. Ears and Audition
One study has been conducted in Acute Acoustic Trauama (AAT) with Piracetam (dose not
specified) paired with steroid therapy (Prednisone at 25mg IV thrice daily) noted that the
combination therapy was able to preserve hearing function in persons dependent on time of
intervention; 65% of persons with intervention in under an hour experinced benefit compared
to 23.3% (1-24h) and 13.3% (over 24 hours later), with the early intervention outperfoming
the latter two groups on auditory tests.[82] This study investigated Piracetam as the pathology
of AAT involves hypoxia in the cochlea,[83] which Piracetam is though to preserve.

7. Interactions with Hormones

7.1. Mineralocorticoids

Inhibition of steroid synthesis in general[84] and an adrenalectomy (removal of the adrenal

glands) appears to abolish the memory-enhancing effects of Piracetam[85] and this learning
inhibition is fully reversed when optimal circulating levels of corticosterone (3ug/mL) and
aldosterone (30ng/mL) are maintained; suggesting their importance in the signalling of
Piracetam.[86]
Partial restoration of effects are noted with either aldosterone or corticosterone, both of which
signal through the mineralocorticoid type I receptor (as blocking with epoxymexrenon
abolishes the effects of Piracetam regardless of serum hormone levels)[87][88] which also
appears to exist when the glucocorticoid receptor is selectively blocked.[87] and the
interactions of Racetam compounds and corticosteroids appear to follow a U curve, with
higher doses of cortisol attenuating the benefits of Piracetam, with 30-100mg/kg
Corticosterone in otherwise normal mice abolishing the effects of Piracetam with no apparent
inhibition at 3mg/kg; same effects were noted with supraphysiological levels of 100300mcg/kg aldosterone.[89]
One study in chicks that injected Piracetam noted an increase in corticosterone, where a
50mg/kg injection increased corticosterone levels 24.9% after training.[87]
This inhibition of actions applies to most basic Racetam compounds including Aniracetam,
Oxiracetam, and Pramiracetam.[90][85][89]
Corticosteroids and Aldosterone are critical for the memory enhancing effects of Piracetam,
probably via the Mineralocorticoid Type I receptor; excessive levels of either hormone
abolish the benefits in a similar manner as does no circulating levels

8. Nutrient-Nutrient Interactions
8.1. Choline
Racetam compounds are typically supplemented alongside Cholinergic compounds as their
mechanisms are highly interrelated.[91] Administration of Piracetam causes a decrease in
acetylcholine levels in the hippocampus[92] with unknown mechanisms.[93]
In a few animal models, choline supplementation has been noted to increase the memory and
cognitive effects of Piracetam when coingested.[94][95] These effects seem to be greatest in
models of slight cognitive impairment, such as aging.[96]
These studies on Piracetam and choline synergism have not been tested in humans.
May augment the relatively poor memory enhancing effects of Piracetam in otherwise healthy
animals, but administration of choline alongside Piracetam is not a prerequisite to its efficacy
and has not been tested in humans
8.2. Alcohol
Chronic alcohol consumption is related to build-up of lipofuscin in brain tissue[97] of which
piracetam has been implicated in reversing (both in rats)[98] after cessation of alcohol and

treatment of piracetam. Piracetam is also implicated in increasing synaptic reorganization[99]

and alleviating further loss of neurons after alcoholism.[98]
May attenuate some pathology associated with excessive alcohol consumption (alcoholism)
8.3. Cinnarizine
Cinnarizine is an anti-histamine used for motion sickness and that is sometimes combined
with Piracetam as a combination product called Fezam (Phezam) or Omaron.[100][101] It is
touted that the ingredients are synergistic with each other in regards to increasing cerebral
oxygenation, although the synergism has not been shown experimentally. Both compounds in
isolation are effective at preventing hypoxia-related damages however.[102][103]
Said to be synergistic, this has not yet been demonstrated
8.4. Morin
Morin is a flavonoid compound found in Maclura pomifera (Osage Orange), tinctoria (Old
Fustic), Morus alba, and Psidium guajava (Guava) that serves as an inhibitor of CYP3A4 and
P-Gyp. A 10mg/kg Morin pretreatment for a period of 7 days in rats was able to increase the
AUC of a 50mg/kg Piracetam dose 1.5 and increase its Cmax by 1.45, but acute Morin
ingestion failed to mimic these results.[104] The authors suggested that a Morin-rich diet could
influence pharmacokinetics of Piracetam.
May increase apparent bioavailability when measured in serum due to enzyme inhibition

9. Comparative Studies
Due to Piracetam being the atypical memory enhancing standard, it is sometimes used as an
active control for other compounds to assess memory enhancing effects of those other
compounds; this section compiles those studies.
9.1. Asparagus Racemosus
Asparagus racemosus at oral doses of 50, 100, and 200mg/kg (an extract concentrated for
62.2% saponins) was not significantly different than 500mg/kg Piracetam in improving
spatial memory;[105] no dose-dependence was seen despite the acetylcholinesterase properties
of Asparagus Racemosus being dose-dependent.
9.2. Clitoria Ternatea
100mg/kg Clitorea Ternatea water extract is not significantly different than 50mg/kg
Piracetam in memory retention and spatial learning when measured after 9 days, although
Piracetam outperformed Clitoria after the first day.[106]
9.3. Ginger

After hypoxic injury to the brain, 100-200mg/kg Ginger appears to be as effective as

Piracetam at 250mg/kg in improving memory recovery over time; both underperformed
relative to Aricept (Donepezil).[107]

10. Safety
10.1. General
Adverse effects, although rare and of short duration[3] are limited to anxiety, insomnia,
drowsiness and agitation. It may be safe for up to 18 months in humans at doses of 3.2g
daily[49] with one year-long study in ambulatory patients with Alzheimer's using 8g daily
reporting no side effects.[45] Piracetam also appears to have clinical usage (and a lack of side
effects) when used in youth for the purpose of Breath Holding Spells at oral doses of 50100mg/kg bodyweight in children aged 5-60 months.[68][67][66]
In animal models (rodents, dogs, and marmoset), an LD50 failed to be established at the
dosage of 8-10g/kg bodyweight in those three species.[25][108]
Piracetam appears to be quite non-toxic at common doses used, and a few studies exceeding
recommended dose (4.8g daily) fail to find toxicity associated with Piracetam
In general, racetams (usually referring to Class I racetams; Pi-, Ani-, and Oxi-) are said to
have little side effects and low toxicity rates at commonly used dosages and up to 12g for up
to 8 weeks.[25][109][110] However, a possibility for adverse drug-drug interactions persists for
Piracetam due to it interacting with blood in an anti-clotting manner (and such, caution
should be taken when pairing Piracetam with pharmaceutical blood thinning agents such as
Warfarin or potent nutraceutical options).

Scientific Support & Reference Citations

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Piracetam - The original smart drug

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(Common misspellings for Piracetam include peracetam, pirasetam, pirasetam, pacetam)
(Common phrases used by users for this page include piracetam recommended dosage, piracetam, piracetam
review, calcium channel piracetam, piracetam, piracetam reviews)
(Users who contributed to this page include KurtisFrank, shrillthrill, Sol, dbarvinok )

Summary

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Editors' Thoughts

Human Effect Matrix

Scientific Research

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Piracetam is the parent compound of the Racetam class of Nootropic supplements. When
supplemented, it provides a mild boost to brain function.

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