Racetams are a class of drugs that modulate a variety of neurotransmitters in the brain including acetylcholine and glutamate, since their discovery they have become a favorite amongst biohackers for their nootropic properties. However the sheer size of the drug family has resulted in a great deal of confusion in the nootropic community as each analogue holds a unique effect profile. To be clear, there is no “best” individual of any drug class, this guide simply serves as a reference for those looking to find the ideal racetam for their needs.

Before we go any further, it’s important for us to understand how racetams work and why they are as effective as they are. There is contention in the biochemical community regarding racetams’ exact mechanism of action, though it’s generally accepted that while most show little affinity for central nervous system receptors, they do in fact function as strong modulators of both acetylcholine and glutamate (as previously mentioned). More specifically, they function by activating glutamate receptors that are colocalized with cholinergic receptors, ultimately increasing the activation frequency of said receptors and enhancing both the formation and retention of memory.


piracetam racetam guide nootropics cognitive enhancement comprehensive acetylcholine choline memory focus

The most popular and widely used racetam is Piracetam. While it was first synthesized in the 1950’s for the purpose of mitigating epilepsy, it has since been found to be suitable for treating a variety of other neurological issues such as cognitive decline, bipolar disorder and anxiety. Piracetam in particular functions by allosterically modulating the AMPA receptor. It is also suspected that its effect on ion channels/carriers also contributes to the compound’s cognitive enhancing effects, though there’s yet to be conclusive evidence.

Piracetam is one of the most heavily studied among nootropic agents, namely for the purpose of investigating its efficacy as a treatment for memory degenerative disorders such as Alzheimer’s or dementia. The majority of the studies pertaining to piracetam have had positive results, though not sufficiently so for it to be recognized as a pragmatic treatment. For this reason, piracetam is generally marketed as an off-label health supplement. However in various countries including Russia and China, it has been deemed viable for pharmaceutical use, and as such can only be obtained via prescription.

Piracetam has a very broad effect profile, while each individual will experience different results, these are the most commonly reported effects among nootropic users.

  • Improved Memory
  • Increased Learning Retention
  • Improved Focus
  • Heightened Sensory Perception
  • Reduced Anxiety
  • Improved Vasodilation
  • Mitigated Effects of Brain Trauma

Users find that not only is the formation of memory discernibly improved, but also residual memory and general recollection. For this reason, piracetam has become increasingly popular over the past few decades among students as an alternative to more potentially dangerous cognitive enhancers such as prescription stimulants.

The enhancement of sensory perception is likely attributed to piracetam’s effect on acetylcholine, as it not only increases its neurological abundance but also it’s reception efficiency. Acetylcholine has a variety of functions in the body, the most notable of which is what enables the communication between motor neurons and muscular tissue. However, it’s role in cognitive function lies in its ability to govern how brain structures process information. There are numerous regions of the brain that rely on cholinergic modulation to function, most notably for the roles of arousal, attention and motivation.

The effect of racetams’ function of acetylcholine will be elaborated further later on. The following table details the properties of piracetam.

Typical Dose:800-2400mg
Metabolism:Renal
Half-Life:4-5 hours
Bioavailability:>97% taken orally, ~100% taken sublingually
LogP (water/lipid solubility):-1.75 (Water Soluble)
Solubility in Water (at 25C):72mg/ml
Melting Point:152°C
Formula:C6H10N2O2

Piracetam, in many studies, has been cited as a neuroprotective agent, however it’s efficacy as such has yet to be determined. Ideally if this is a property you’re seeking in a nootropic, there are many that have been shown to be much more promising in this regard. The basis for piracetam’s assumed neuroprotective traits involves its induction of vasodilation. It is believed to reduce the abundance of molecular radicals that cause oxidative stress, ultimately mitigating the cholinergic damages believed to be, in part, responsible for Alzheimer’s and dementia (as well as a handful of other neurological disorders).

The following rating has been derived from the frequency of keywords in a wide sample of user reviews, while this is far from an objective measurement, it should give you a rough idea of the magnitude of common effects in comparison to other racetams.

Memory3
Focus4
Motivation4
Energy7
Anxiolysis6

As a final note on piracetam, like any other racetam, since it functions as a modulator of acetylcholine, it is highly recommended that you take it with a choline source (e.g. choline bitartrate or CDP-choline) for the most effective results.


phenylpiracetam racetam guide nootropics cognitive enhancement comprehensive acetylcholine choline memory focus

Phenylpiracetam is, as you may have guessed, the phenylated analogue of piracetam. It was first synthesized in 1983 by a Russian pharmaceutical company as a treatment for organic cognitive decline. While there have been very few studies involving the usage in healthy individuals, it has been shown to have much greater cognitive enhancing and neuroprotective properties than that of piracetam, this is likely attributed to its additional phenyl group, as it enables the compound to pass through the blood-barrier much more efficiently, and in doing so, has been determined to be nearly 60 times more potent.

Many studies suggest that phenylpiracetam is highly effective in mitigating the effects of both anxiety and depression, as well as the cognitive degradation induced by such disorders. In addition to acetylcholine, there is evidence that phenylpiracetam also modulates a multitude of neurotransmitters (along with their respective receptor sites), the most notable of which being GABA, NDMA and dopamine. Save for acetylcholine, these transmitters are all understood to be in part responsible for the regulation of mood and motivation.

While phenylpiracetam does encompass the majority of piracetam’s effect profile, it does also have some unique effects, these are the most common among them.

  • Improved Motivation
  • Improved Mood
  • Mental Stimulation
  • Reduced Anxiety
  • Increased Wakefulness
  • Increased Physical Stamina
  • Improved Vasodilation
  • Increased Cold Tolerance

The stimulating properties of phenylpiracetam are not caused by the racetam/pyrrolidine component of the molecule but rather by the phenyl group and its affinities for both dopamine and norepinephrine. Conversely, the exact cause for phenylpiracetam’s cold tolerant traits are not well understood, though it’s speculated to be a result of the compound effects of mental stimulation and increased vasodilation.

The following table details important information for the consumption of phenylpiracetam.

Typical Dose:100-200mg
Metabolism:Renal
Half-Life:3-5 hours
Bioavailability:>98% taken orally, ~100% taken sublingually
LogP (water/lipid solubility):0.16 (Fat Soluble)
Solubility in Water (at 25C):1.5mg/ml
Melting Point:151°C
Formula:C12H14N2O2

As previously mentioned, the ratings are derived from the frequency of keywords in a wide sample of user reviews, while this is far from an objective measurement, it should give you a rough idea of the magnitude of common effects in comparison to other racetams.

Memory4
Focus6
Motivation5
Energy8
Anxiolysis8

As a final note on phenylpiracetam, it should be considered that the supplementation of this drug is considered illegal by many athletics associations due to its stamina increasing nature.


aniracetam racetam guide nootropics cognitive enhancement comprehensive acetylcholine choline memory focus

Aniracetam is an analogue of piracetam that contains a para-anisoyl component group. This compound was first synthesized in the mid-1970’s by a Swiss pharmaceutical company and, much like phenylpiracetam, was developed for the purpose of combating neurodegenerative diseases. Aniracetam is one of the most extensively studied ampakines and over the years has been shown to be extremely promising as a more wide-spread clinical treatment. Neuroprotection, anxiolysis and general cognitive enhancement are only a handful of aniracetam’s traits that have been studied since it’s introduction.

Aniracetam’s action mechanism is almost identical to that of piracetam, however, it’s non-sedating anxiolytic effects are caused by a process seen in very few drugs. This property has been studied heavily in animal models, the general consensus being that it is caused by the activation of both D2 and D3 dopamine receptors. Though this could also be attributed to aniracetam’s unique activation of nicotinic ACh receptors, which is believed to be responsible for many of its other nootropic effects. Additionally, Aniracetam has been seen to interact with the 5-HTP(2a) receptor which plays a critical role in the serotonergic system and, as a result, may further promote anxiolytic/antidepressant functions.

As such a unique compound, Aniracetam has a much wider effect profile than piracetam which includes, but is by no means limited to:

  • Improved Mood
  • Reduced Anxiety
  • Increased Wakefulness
  • Increased Physical Stamina
  • Improved Lingual Fluidity
  • Increased Attention Span
  • Improved Mental Clarity

Other more anecdotal effects include improved creativity, alertness, imagination, analytical abilities and even better musical discernment (supposedly).

While aniracetam has many enticing benefits, it is also capable of producing significantly more adverse effects in comparison to other racetams. Common side effects include nausea, stomach cramps, headaches and, for some, brain fog. Do note that these are only acute effects, long term use of aniracetam (or any racetam for that matter) has not been observed to be in any sense mentally detrimental. Being a racetam, it is highly recommended to take a choline based supplement 20-30 minutes before consumption and experiment with dosages to minimize side effects and ultimately determine what works best for you.

The following table details important information for the consumption of aniracetam.

Typical Dose:700-1500mg
Metabolism:Hepatic
Half-Life:1-3 hours
Bioavailability:>98% taken orally, ~100% taken sublingually
LogP (water/fat solubility):1.11 (Fat Soluble)
Solubility in Water (at 25C):2.47mg/ml
Melting Point:122°C
Formula:C12H13NO3

As previously mentioned, the ratings are derived from the frequency of keywords in a wide sample of user reviews, while this is far from an objective measurement, it should give you a rough idea of the magnitude of common effects in comparison to other racetams.

Memory5
Focus4
Motivation4
Energy7
Anxiolysis9

oxiracetam racetam guide nootropics cognitive enhancement comprehensive acetylcholine choline memory focus

Oxiracetam is the hydroxylated analogue of piracetam and is one of the most well-known compounds among the ampakine family. Oxiracetam exhibits many of the same effects as piracetam however it is approximately 5 times as potent and triggers an array of unique neurological mechanisms that appear to be exclusive to this particular analogue. Much like Aniracetam, many studies exist exploring it’s cognitive enhancing and neuroprotective properties as well as the safety of chronic administration.

The most promising research results pertain to logical performance, concentration, memory and spatial orientation. Tests have been conducted on patients with moderate dementia and ADHD, each individual was given 800–2400 mg orally twice a day for one to six months. During this period, significant improvements in logic and recollection tests were observed. Improvement has also been seen in patients with exogenic post-concussion syndrome, organic brain syndromes and other forms of dementia.

Research shows oxiracetam improves hippocampally-mediated learning by increasing the efficacy of membrane-bound protein kinase C (PKC). When compared to untreated mice, oxiracetam-treated DBA mice demonstrated an impressive increase in spatial learning performance. This increase in performance was correlated to an increase in membrane-bound PKC.

While oxiracetam has not been observed to affect any neurotransmitters other than acetylcholine and glutamate, it has mildly stimulating effects. No conclusive research exists exploring what mechanism is responsible for this.

The most common effects of Oxiracetam include:

  • Improved Logical Thinking
  • Improved Learning Ability
  • Increased Memory Retention
  • Improved Analytical Reasoning
  • Improved Focus

Oxiracetam was the first racetam to be studied as a chronic treatment, so far no data has emerged indicating the long term or even daily use of oxiracetam (and quite likely any racetam) to be in any way detrimental. Additionally, studies conducted in pregnant mice given varying dosages of oxiracetam failed to find teratogenic effects of supplementation when assessing the youth, instead, there was an improved performance on a radial maze test (choice accuracy) and grooming behavior when compared to control.

The following table details important information for the consumption of oxiracetam.

Typical Dose:500-1000mg
Metabolism:Hepatic/Renal
Half-Life:3-7 hours
Bioavailability:~80% taken orally, >86% taken sublingually
LogP (water/fat solubility):-1.29 (Water Soluble)
Solubility in Water (at 25C):31mg/ml
Melting Point:163°C
Formula:C6H10N2O3

As previously mentioned, the ratings are derived from the frequency of keywords in a wide sample of user reviews, while this is far from an objective measurement, it should give you a rough idea of the magnitude of common effects in comparison to other racetams.

Memory9
Focus10
Motivation4
Energy8
Anxiolysis2

Final note on oxiracetam, many reports say that this analogue should, ideally, be taken with more choline to avoid adverse effects. Users of more potent choline sources (such as A-GPC or CDP) are less likely to encounter this issue.


pramiracetam racetam guide nootropics cognitive enhancement comprehensive acetylcholine choline memory focus

Pramiracetam is a complex racetam that was first synthesized in the 1970’s by Warner-Lambert for the purpose of combating Alzheimer’s and other neurodegenerative conditions, while it is one of the lesser studied racetams, medical trials have found it to be effective in restoring cognitive function from prior brain trauma. Like most racetams, pramiracetam is largely non-prescription, save for a few European countries, as a result, it has recently exploded in popularity within the nootropic community for it’s often reported “clean energy” and it’s convenient half-life.

Clinical trials organized by Cambridge Neuroscience found that the drug is rather effective in mitigating the effects of concussions and cerebrovascular disease, though it should be noted that the sample size of this particular study was limited to only 4 people. A larger study held in Italy posited that pramiracetam was able to partially reverse the effects of scopolamine-induced amnesia.

In spite of its many cognitive benefits, pramiracetam is more often used for its physical stimulation and sensory effects. The most common effects of pramiracetam include:

  • Improved Focus
  • Improved Memory
  • Marginally Improved Motivation
  • Wakefulness/Physical Stimulation
  • Increased Physical Stamina
  • Enhanced Visual Acuity
  • Enhanced Auditory Acuity

Due to the lack of scientific studies, recommendations on the ideal dose vary considerably. Of the various studies done on testing the effectiveness of pramiracetam, the general consensus was that a total daily intake of ~800 mg was optimal, divided into two or three doses per day. This is a good starting point and on an individual level should be adjusted to find what works best for you. While there are very few adverse side effects associated with this supplement, like any nootropic, it is always wise to start with the lowest effective dose and increase gradually as needed.

The following table details important information for the consumption of pramiracetam.

Typical Dose:600-1200mg
Metabolism:Renal
Half-Life:5 hours
Bioavailability:>97% taken orally, ~100% taken sublingually
LogP (water/fat solubility):ACD LogP -1.4, ALogP 0.49 (Both water/fat soluble)
Solubility in Water (at 25C):180mg/ml
Melting Point:48°C
Formula:C14H27N3O2

As previously mentioned, the ratings are derived from the frequency of keywords in a wide sample of user reviews, while this is far from an objective measurement, it should give you a rough idea of the magnitude of common effects in comparison to other racetams.

Memory6
Focus8
Motivation3
Energy9
Anxiolysis4

coluracetam racetam guide nootropics cognitive enhancement comprehensive acetylcholine choline memory focus

One of the newer and less investigated racetams is coluracetam. Research suggests that it has an action mechanism that is distinct from other racetams. Coluracetam speeds the process of choline uptake, which is usually the factor that inhibits the neuronal synthesis of acetylcholine. Increasing the HACU (high-affinity choline uptake) rate ultimately improves the rate of communication between cholinergic neurons, increasing the efficiency of the acetylcholinergic system as a whole.

Coluracetam has been observed to attenuate learning deficits seen with choline uptake inhibitors in the assessment of water maze tests, generally being active orally at doses ranging from 1-10mg/kg in rats. The effects of doses ranging from 300-3,000mcg have not been detected after single administration but were present in maze testing after 12 days. Benefits to cognition have been noted at 1-3mg/kg to extend for up to two days after cessation despite no detectable coluracetam in the brain.

The most commonly reported effects include:

  • Increased Focus
  • Enhanced Memory
  • Improved Visual Acuity
  • Improved Color Perception
  • Dream Potentiation
  • Mild Stimulation
  • Minor Anxiolysis

The following table details important information for the consumption of coluracetam.

Typical Dose:20-40mg
Metabolism:Hepatic
Half-Life:30-45 minutes
Bioavailability:Unknown, likely poor taken orally. Sublingual administration is highly recommended.
LogP (water/fat solubility):1.98 (fat soluble)
Solubility in Water (at 25C):<1mg/ml
Melting Point:232°C
Formula:C19H23N3O3

As previously mentioned, the ratings are derived from the frequency of keywords in a wide sample of user reviews, while this is far from an objective measurement, it should give you a rough idea of the magnitude of common effects in comparison to other racetams.

Memory5
Focus7
Motivation4
Energy8
Anxiolysis5

fasoracetam racetam guide nootropics cognitive enhancement comprehensive acetylcholine choline memory focus

Fasoracetam is arguably the least studied among racetams. Very little information exists regarding its exact pharmacology, though it is speculated to be similar to that of aniracetam. In vitro studies on mice, fasoracetam was observed to have modulated mGluR II/III activity. Similar studies in rats found that it blocked memory disruptions caused by baclofen, a GABA(B) agonist and upregulated production of GABA(B) receptors after consistent consumption.

An interesting trait of Fasoracetam is, anecdotally, there is no discernible tolerance buildup as a result of daily use.

Of the few user reviews out there, the most commonly reported effects include:

  • Increased Energy
  • Increased Focus
  • Increased Physical Stamina
  • Eliminated Brain Fog
  • Minor Anxiolysis

The following table details important information for the consumption of fasoracetam.

Typical Dose:20-40mg
Metabolism:Hepatic/Renal
Half-Life:2-3 hours
Bioavailability:80-90% taken orally, >94% taken sublingually
LogP (water/fat solubility):-1.37 (water soluble)
Solubility in Water (at 25C):50mg/ml
Melting Point:152°C
Formula:C10H16N2O2

Unfortunately, insufficient reviews exist to rate the effect profile with an adequate degree of certainty.

As a final note on fasoracetam, despite racetams being regarded as generally safe for extended use, we cannot recommend this for fasoracetam due to the lack of research and clinical testing.

Summary

Being nearly as effective in healthy individuals as they are in those with cognitive deficiencies, racetams are one of the most popular classes of smart drugs, and rightly so. Each racetam analogue has unique traits, there is no “best” individual of any drug class, as every nervous system will respond to foreign compounds differently. Ultimately, finding what racetam is best for you will require experimentation, this includes what type, dose, choline source, amount of choline, etc. If you are looking for cognitive enhancement in any capacity, given the low toxicity, good safety profile and positive human trials, each analogue is as good a start as any other as they all possess both mentally and physically enhancing properties.

References