The racetam family is quite frankly the origin of nootropics as we know them. The term "racetams" refers to a class of drugs that share a common pyrrolidone nucleus in their chemical structure. Many racetams exist, but only a select few are found in nootropic supplements.
Despite their long history of use and a growing body of scientific research, racetams remain somewhat misunderstood from a physiological standpoint. There is still no widely accepted mechanism of action for racetams .
However, racetams are undoubtedly promising nootropics for enhancing cognitive function, improving long-term memory recall, and reducing the risk of brain-related health conditions like dementia, Alzheimer's disease, epileptic seizures, and stroke . They also appear to have an exceptional safety profile when used in appropriate dosages .
Read on as this comparison of racetams will explain the potential uses of this class of drugs and determine which is the best racetam for your needs.
Scientists have yet to elucidate the primary mechanism of action of racetams fully. Current evidence suggests that racetams appear to exert at least some of their effects by increasing blood flow (and thus, oxygen delivery) to the brain and targeting synaptic vesicle 2 (SV2) proteins in neurons .
Racetams are also putative modulators of AMPA receptors — which mediate the effects of glutamate —and cholinergic transmission . In simpler terms, racetams ostensibly augment the activity of glutamate and acetylcholine, two neurotransmitters that play a crucial role in arousal, memory formation, verbal fluency, focus, and concentration. As such, racetams may restore/bolster cognitive function and protect against memory loss, neurodegenerative diseases, and stroke.
However, the restorative and protective effects of racetams do not seem relevant to cognitive impairment caused by hazardous organic solvents such as chlorinated hydrocarbons and formaldehyde . These substances are present in degreasers, paint thinners, paint, refrigerants, varnish removers, and lacquers. (We are indirectly exposed to noxious organic solvents daily through household dust particles and public water contamination.)
What’s particularly intriguing about racetams is that they have a reliable safety profile and rarely cause side effects when used in proper dosages. That characteristic is atypical for some nootropics, like phenibut and kratom.
Now that we have a general overview out of the way let’s take a look at the science behind the racetam family of nootropics.
The benefits of piracetam in healthy individuals are somewhat limited. However, research has demonstrated a therapeutic effect of piracetam in individuals with memory loss and cognitive disorders arising from aging or drug use . These benefits appear to extend to aniracetam, oxiracetam, and pramiracetam (discussed below) [8, 9].
A meta-analysis that included 19 human studies — patients with dementia — concluded that piracetam effectively restored cognitive function in elderly subjects . Other studies report similar findings .
Piracetam may also be helpful for younger adults and children. For example, one study found that both non-dyslexic and dyslexic boys taking 1,600 mg of piracetam daily for 21 days experienced notable improvements in verbal fluency and memory recall compared to those taking a placebo . The researchers note that the benefits of piracetam on verbal fluency were almost immediate.
Another study noted a reduction of depressive symptoms in otherwise healthy individuals taking 2,400 mg of piracetam daily for two months, along with improvements in blood flow to the brain . Some evidence also suggests that piracetam affects spontaneous electrical activity in the brain in a dose-dependent manner in healthy human subjects . Thus, piracetam use may confer an increase in cooperativity of functional brain processes.
Lastly, a review of piracetam use in stroke patients found no statistically significant benefits or drawbacks compared to a placebo . More long-term human studies are necessary to confirm if piracetam (and other racetams) are prudent for treating/preventing strokes.
Aniracetam is posited to be a more potent analog of piracetam, possessing stronger therapeutic effects on memory and a lower risk of side effects . Unfortunately, conflicts of interest are rife in human studies of aniracetam.
As with other racetams, the benefits of aniracetam supported by literature are mainly applicable to individuals with cognitive decline and result from greater blood flow to the brain. Notably, one study of aniracetam did demonstrate enhanced memory formation in healthy subjects impaired via experimentally induced hypoxia, a state of low oxygen delivery to the brain .
Oxiracetam was produced after piracetam and aniracetam. The former appears more promising than other compounds in the racetam family despite oxiracetam having fewer available studies than piracetam.
Like piracetam, research suggests oxiracetam use produces enhancements in cognitive function and decreases in rates of cognitive decline in those impaired by dementia and other deleterious brain conditions [18, 19, 20]. These benefits are patent in tasks involving learning and memory recall.
Pramiracetam does not have much data supporting its nootropic benefits, and user anecdotes are underwhelming. It is thought that pramiracetam may increase acetylcholine synthesis and confer benefits such as increased motivation and focus.
However, take those suppositions with a grain of salt. Pramiracetam needs more compelling research to confirm its nootropic effects.
Phenylpiracetam is arguably the least compelling racetam, yet it's somewhat popular in nootropic supplements. Structurally, phenylpiracetam is quite similar to piracetam, differing only by the inclusion of a phenyl group.
However, phenylpiracetam is severely lacking empirical evidence to substantiate its purported benefits. It is also much harder to find over-the-counter since virtually no clinical data suggests it’s a useful nootropic.
Some nootropic supplements will include a small dosage of phenylpiracetam just to “dress the label” and give consumers a false sense of "synergy" among the other ingredients. Don’t fall for those tactics; phenylpiracetam doesn’t stack up well against the likes of piracetam, aniracetam, oxiracetam, and ostensibly other racetams.
Levetiracetam and brivaracetam are commonly used as adjunctive treatments for controlling epileptic seizures in clinical settings . These racetams are not sold over the counter in most countries and instead must be prescribed by a medical professional.
Many other racetams exist that have little to no evidence supporting their efficacy, nor do we know much about their safety profiles. Such racetams generally include nebracetam, nefiracetam, seletracetam, rolipram, fasoracetam, coluracetam, rolziracetam, and dimiracetam.
Most of those "other" racetams don’t appear to have nootropic properties, making them poor options for cognitive enhancement. They are, however, great for twisting your tongue if you want to practice pronouncing odd words.
Naturally, you’re probably left wondering which racetam is best? Is it aniracetam, piracetam, pramiracetam, oxiracetam, or something else?
In reality, the best racetam is relevant to your intended use and experience using nootropics. For those new to nootropics and the racetam family, it's sensible to start with one of the more commonly used options, such as piracetam or aniracetam, and see how you respond.
Oxiracetam holds promise as the most potent racetam, but more literature is necessary to understand how it works and verify the anecdotal benefits. That being said, piracetam and oxiracetam are good candidates for people looking to enhance memory formation and recall, focus, and concentration. Students may find these racetams beneficial for long studying sessions and fighting brain fog during the day.
Needless to say, racetams will likely continue to flourish as nootropics in the coming years. We can expect future research to help us learn more about how each racetam works physiologically. Until that time, you can't go wrong by taking nootropics with a little more research behind them, such as caffeine and L-theanine — found in the Transparent Labs Nootropic.