There are several options for brain-boosting drugs in the nootropics space. One of the most recommended nootropics, especially for diagnosable brain conditions, are racetams.

For people who are just learning about nootropics, the word “racetams” might sound significantly more like a conventional medicine than other natural nootropics like Gingko Biloba and Ashwagandha herbs.

Racetams aren’t found in nature but were instead developed specifically to help enhance brain function. The term “smart drugs”* was originally used to refer to racetams and was only later used to refer to all nootropics.

There are several classes of nootropics in the racetam family, and each have slightly different effects on the brain. Here, we will review the four most common racetams: piracetam, aniracetam, oxiracetam, and pramiracetam.

We will review their effects and known mode of action, and any points of caution to consider.

*Note: the term “smart drugs” can be misleading, because the term drugs is most often used to refer to substances that are meant to cure or treat disease. While there is evidence that nootropics can have a positive impact on the wellbeing of people with specific brain diseases, whether they are considered medicines depends on the country in which they are sold.

Types of Nootropics

Before we get into the details of the racetam group of nootropics, let’s review the types of nootropics, classified by origin and form. Nootropic drugs are made in a lab and are known to have isolated chemicals that produce a pharmacological effect on the brain.

Medicines and Drugs

The FDA defines drugs as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.” In other words, they are used for therapeutic purposes.

Most nootropic medicines and drugs are available by prescription, but it depends on the country. In some cases, the same nootropic is classified as a drug in some countries and as a supplement in others, as is the case for some racetams.

Some of the conditions nootropic drugs and medicines are used for include:

• Alzheimer’s
• Dementia
• Depression
• Epilepsy
• Memory impairments
• Vertigo
• Adverse blood flow

Natural Nootropics

Natural nootropics are herbs and foods that contain components that benefit certain aspects of brain activity. Thousands of natural nootropics have been used for centuries, and are only very recently classified as nootropics or adaptogens.

Some of these include:

• Ginkgo Biloba
• St. John’s Wort
• Lion’s Mane mushroom
• Rhodiola Rosea
• Ashwagandha
• Bacopa monnieri
• Cocoa
• Cinnamon
• Coconut oil
• Almond oil
• Coffee and teas

An Introduction to the Racetam Family

Racetams are a class of nootropics that are specifically designed to improve memory. Piracetam, the “original” racetam, was discovered in the late 1960s, but now there are more than twenty substances in the racetam family.

They are synthetic, meaning that they aren’t found in nature, but rather were developed specifically for their effects on the brain.

Because they are synthetic doesn’t meant that they are more or less effective, or that they are more or less risky than nootropics found in nature. It does mean, however, that they are more thoroughly studied than most other nootropics available on the market – both synthetic and natural.

How Racetams Work

Even though racetams were developed synthetically, their mechanisms of action are not fully understood. They are grouped together because they have similar chemical structures.

It appears that racetams, especially piracetam and aniracetam, modulate Glutamate and AMPA receptors in the brain. AMPA receptors mediate synaptic transmission in the central nervous system in milliseconds. More specifically, they pay key roles in plasticity, which allow the brain to uptake and process new information.

In other words, they are responsible for most of the excitatory brain wave transmission, or the messages that encourage neurons to act and adapt to changing situations, including retaining new information. This is as opposed to inhibitory neurotransmitters, which are responsible for discouraging neuron action.

Racetams also seem to modulate acetylcholinergic systems, which are involved in the processing of complex information. Alterations and changes in the cholinergic systems are linked to neurological aging and Alzheimer’s disease.

Unlike other nootropics and some brain-altering drugs, racetams don’t have a single mode of action. This means that there are many complex pathways through which they impact the brain which is why they are not easily understood.

Even though the pathways of action are complex, researchers have determined two main pathways through which the substances act on the brain:

1. They positively impact cognitive function and intelligence
2. They are linked to nervous activity in the right and left hemispheres and in brainwaves

Most racetams are considered “pharmacologically safe”, nontoxic, and almost free of side effects. In fact, they are considered neuroprotective (protective of the brain), with the exception of nefriracetam (not discussed here) may have some serious negative effects in males.

Why Racetams Are Used

Racetams are used specifically for cognitive improvement or, in some cases, to treat cognitive impairment and nervous system disorders. They are classified as nootropics, which are components that improve brain function.

The original definition of nootropics, developed by Giurgea and Salama in 1977 is as follows:

A nootropic drug is characterized by a direct functional activation of the higher integrative brain mechanisms that enhances cortical vigilance, a telencephalic functional selectivity, and a particular efficiency in restoring deficient higher nervous activity.

More simply put, nootropics, including racetams are substances that improve human cognitive abilities.

There are hundreds of studies that examine the different uses of racetams. Below we summarize a few of the most outstanding impacts of racetams on the human brain.

1. Improvements in cognitive deficits after traumatic brain injuries.

Several studies have been carried out on the effects on racetams to improve cognition after traumatic brain injuries.

One study conducted with 42 adolescents who had suffered traumatic disorders were divided into two groups; one group was given piracetam for one month, and the other group was examined as controls.

In the study, piracetam was found to have a positive therapeutic effect on cognition, including memory, attention, and executive functions, and on motor coordination, speed and performance.

Another study looked at the effects of pramiracetam, another racetam, in young men who suffered cognitive effects of head injuries. The placebo-controlled study found significant improvements in memory, especially delayed recall, that were maintained for 18-months that pramiracetam was continued to be administered, and one month after it was discontinued.

2. Neuroprotective effects when undergoing surgery

During cardiac surgery, it is possible that patients experience a reduction in cognitive function. In one 2008 study, patients who were scheduled for coronary bypass surgery received piracetam or a placebo. Those who received piracetam experienced a protective effect on brain functions and reduced the potential decline of neuropsychological activities that can result from the surgery.

Then, a meta-analysis (a study of studies) came to the same conclusion: piracetam may have been effective in improving the short-term cognitive performance of people who were undergoing bypass surgery.

3. Lowering depression and anxiety

There are two main types of racetams that have studies show may be effective against symptoms of depression and anxiety.

Levetiracetam has mood stabilizing properties, and in a preliminary study was administered to patients who had partial seizures and depressive symptoms. It suggested that treatment of patients with Levetiracetam improved depression and anxiety in patients.

These results were confirmed by a systematic review of studies, and found that the incidence of depression and anxiety in people taking Levetiracetam was even lower than in people taking antiepileptic drugs.

But how about the use of levetiracetam for general social anxiety disorder not linked to epilepsy? A pilot study suggests that the use of levetiracetam is not only safe, but effective. Larger, controlled studies are needed to confirm the results, however.

Aniracetam also may have antidepressive effects. Most of the studies that have been carried out for this have been conducted on mice and rats, but they have found that it also has antidepressive and anti-anxiety effects. Interestingly enough, they are more pronounced when combined with the effects on the aging brain.

In other words, if the results can be transferred to adults, aniracetam could help to mediate depressive symptoms in people who are experiencing the negative effects of brain aging.

4. Improving memory

Piracetam and pramiracetam are the most-studied nootropics for their memory-improving effects. Both animal studies and human trials have been conducted that show similar results.

A classic study, published in 1981, showed that when choline and piracetam were combined, rather than using only one or the other, it had a profound effect on the memory of aged rats. Another study that administered both piracetam and pramiracetam to rats found improvements in information retention.

Another animal study carried out with zebrafish found parallel results, where the fish that were given piracetam had significantly better results in a maze test than fish not given piracetam.

Clinical trials with humans have also demonstrated the positive effects of piracetam on memory. A 1984 double-blind study published in Psychiatry Journal administered piracetam to dyslexic boys, and found that it helped to improve their verbal learning after treatment.

Other studies have demonstrated the positive effects of piracetam in treating learning and memory disorders in elderly people. This is good news regarding the identification of new and novel treatment for memory impairment that can take place in people with senile dementia.

5. Antiepileptic activity (leveracetam, seletracetam, brivaracetam)

Levetiracetams were discovered precisely because of their ability to protect the brain against different phases of seizures. Levetiracetams have opened the door for a whole new class of antiepileptic treatments because no adverse effects have been identified.

Researchers understand that it is because levetiracetam has a highly selective action against abnormal patterns of brain activity, rather than generalized effects on neurotransmitters.

Seletracetam and brivaracetam are both recently developed racetam nootropics (considered second-generation to existing antiepileptic racetams).

6. Improvements in symptoms of Alzheimer’s disease, dementia and cognitive impairment

Initial research carried out prior to clinical trials have suggested that piracetams, when administered over long periods of time, may slow the progression of cognitive deterioration in people diagnosed with Alzheimer’s disease, with no adverse effects.

A systematic review set out to analyze and compare the results of several studies that tested whether piracetam was effective for the treatment of dementia and cognitive impairment.

Unfortunately, the systematic review concluded that piracetam wasn’t effective as a treatment for people with dementia or cognitive impairment, but that positive evidence is enough to support further research in to piracetam for such a use.

Oxiracetam is another racetam that has been identified as potentially having a positive effect on the symptoms of dementia, especially for the first months of a 12-month treatment. The effects were measured based on the application of several tests, including: Mini Mental State Examination, Auditory Continuous Performance Test, Rey’s 15 Words Test, Block Tapping Test, Mattis Word Fluency, Luria Alternating Series and Instrumental Activities of Daily Living.

A Review of 4 Popular Racetams

Piracetam

Piracetam is “the original” racetam discovered in 1964 by Dr. Corneliu Giurgea, the same researcher who later names and defined the concept of nootropics. Piracetam continues to be the most popular one. It is similar in composition to the naturally-occurring GABA neurotransmitter, but is functionally unrelated.

 

It boosts cognitive potential by improving:

• Mental alertness and concentration
• Boosting brain metabolism and brain oxygenation
• Improving mental energy
• Promoting effective communication between neurons in the brain
• Promoting effective communication between the two sides of the brain
• Boosting attention, learning potential, memory, ability to process information and others
• Protecting the brain from oxidative damage due to Piracetam’s antioxidant qualities
• Reversing the effects of aging

What it used for

It was originally used to treat Alzheimer’s disease, ADHD and other attention-deficit disorders, and the cognitive effects caused by Down Syndrome.

Now, while it is still used for its therapeutic effects, is more commonly used by generally healthy people to boost cognitive potential.

Piracetam can be used to treat:

• Clotting disorders
• Cognitive issues that result from brain trauma
• The effects of aging on cognition
• Depression and anxiety

Side effects and interactions

One of the reasons for Piracetam’s popularity is that several studies claim that there are virtually no side effects identified at recommended doses. This discovery has made researchers look to Piracetam and other racetams as alternatives to current cognitive treatments. It is also non-addictive which is very important when used for different cognitive disorders.

However, more generic reports do list several potential side effects to taking piracetam. These include:

• Psychomotor agitation
• Dysphoria
• Tiredness
• Dizziness
• Memory loss
• Headache
• Diarrhea

Piracetam has no known severe interactions with other drugs, but some mild to moderate interactions can take place with the following drugs:

• cilostazol
• clopidogrel
• dipyridamole
• eptifibatide
• prasugrel
• ticlopidine
• tirofiban
• levothyroxine
• liothyronine
• thyroid desiccated

Aniracetam

Aniracetam is one of the more controversial racetam nootropics. While it is approved in Europe, it is not approved by the FDA. Aniracetam acts as both a stimulant and cognitive enhancer, including improving memory and concentration.

Like other racetams, aniracetam positively modulates AMPA-sensitive glutamate receptors and possibly facilitates cholinergic transmission. Cholinergic transmission is directly related to cognitive function and brain response, and its mode of action results in a prolonged stimulation effect. By some reports it is more potent than piracetam.

What it used for

Aniracetam is used for the following conditions and states:

• Improved creativity and holistic thinking
• Reduction in anxiety and depression
• To reduce symptoms of Alzheimer’s Disease and Dementia
• Cognitive deficits onset by Fetal Alcohol Syndrome (FAS)

It is important to note, however, that there is still a lack of human studies for many of these conditions.

Aniracetam is fat-soluble, meaning that it should need to be taken with foods with fats for it to be absorbed by the body. However, it appears to be absorbed even when users are fasting.

Side effects

There are two main reasons why the FDA hasn’t approved the use of aniracetam in the United States. First, is because there is a lack of clinical studied that demonstrate its effectiveness for its many potential and actual uses. Second is because evidence is lacking regarding its efficacy and potential side effects, some of which are significantly greater than for other racetams.

Potential side effects for racetams include:

• Fertility damage
• Harm to unborn babies
• Jitteriness
• Irritability
• Insomnia
• Headaches
• Nausea
• Vomiting

Aniracetam may interact with several drugs, including:

• Warfarin
• 2,5-Dimethoxy-4-ethylthioamphetamine
• 4-Bromo-2,5-dimethoxyamphetamine
• Acenocoumarol
• Aceprometazine
• Adipiplon
• Bufotenine
• Bupropion

The list above is only a small sample of the dozens of drugs with which aniracetam could potentially have a negative interaction.

Oxiracetam

Oxiracetam was produced after both Piracetam and Aniracetam. It is technically derived from Piracetam and was designed to be a more potent form of Piracetam.

Oxiracetam works by mimicking the GABA neurotransmitter, that, like several other racetams, positively modulates AMPA receptors. It also helps to metabolize phospholipids and has an impact on neurotransmitter release.

Research shows that when used with amphetamine compounds, learning is improved, and when paired with phygostigmine, memory is improved.

What it used for

The research that has been done on oxiracetams reveals the following uses of the drug:

• Reduction in cognitive decline, including symptoms related to dementia
• Improvements in memory in healthy youth
• Improvements in quality of life in people with dementia
• Improvements in verbal fluency
• Increased functionality in elderly or injured
• Reduction in symptoms of Alzheimer’s

Studies have yet to find significant effectiveness of the oxiracetam for increased functionality and the reduction of symptoms of Alzheimer’s Disease, however.

Side effects and interactions

Side effects of oxiracetam are mild, if reported at all. Some of the reported side effects of oxiracetam include:

• Insomnia
• Nervousness
• Headaches
• Feeling antsy
• Nausea, when taking more than the recommended dosage
• Dizziness, when taking more than the recommended dosage, or due to drug sensitivity
• Restlessness and muscle tension, potentially linked to acetylcholine transmission
• Brain Fog, which may be addressed by changing dosage or adding more stimulating nootropics

If any of these side effects are experienced it is essential to report it to your doctor immediately, as they may be a sign of a more serious side effect or an interaction with another drug you are taking.

Pramiracetam

Pramiracetam was first synthesized by the pharmaceutical company Parke-Davis in the 1970s, first with the hopes of treating patients with Alzheimer’s. Results were mixed, so it was also tested for the treatment of depression (major depressive disorder).

Like other racetams, pramiracetam stimulates the central nervous system by promoting choline uptake and increasing activity in the hippocampus of the brain. The hippocampus is responsible for spatial processing and navigation, regulating emotional responses in the brain, and is linked to long-term memory. For these reasons it was thought to be an effective treatment for both Alzheimer’s and major depressive disorder.

Unlike some other racetams, pramiracetam is legal in the United States and can be purchased legally without a prescription as of now. However, it hasn’t been officially approved by the FDA so it is not yet regulated.

What it used for

Pramiracetam is used to treat issues related to concentration and memory that result from brain cell degeneration or blood supply issues to the brain. Some of the most common conditions for which pramiracetam is prescribed include:

• Increased concentration
• Improved memory (new memories and long-term memories)
• Increased brain fluidity that promotes communication between cells
• Treatment of symptoms of Alzheimer’s Disease
• Major depressive disorder (depression)
• Increased cognition

A small number of clinical studies have been carried out focused on the effects of pramiracetam, and most of the results have been consistent.

Side effects and interactions

The side effects associated with the consumption of pramiracetam, buy they are relatively mild. Side effects include:

1. Diarrhea
2. Weight gain
3. Drowsiness
4. Insomnia
5. Nervousness
6. Depression
7. Muscle spasm
8. Hyperactivity
9. Rash

Moderate and mild interactions between other drugs and pramiracetam include:

• cilostazol
• clopidogrel
• dipyridamole
• eptifibatide
• prasugrel
• ticlopidine
• tirofiban
• levothyroxine
• liothyronine
• thyroid desiccated

There are more interacting drugs, but these are some of the most common.

Conclusion

Racetams are one of the most powerful group of nootropics out there. They are one of the few groups of nootropics that are man made, derived from other chemical components. Interestingly enough, researchers aren’t exactly sure how they work because of the thoroughly complex processes by which they affect the brain.

Researchers can, however, see the effects of the racetams in clinical trials. Here, we see the profound effects racetams can have on the brain to improve a wide range of brain functions, from mood to memory and even for helping to improve the brain health of people experiencing cognitive decline.

Talk to your doctor if you are considering taking a racetam, and see if you can find one that fits your needs.