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Racing Ahead With The ‘Racetams’!

Racing Ahead With The ‘Racetams’!

Dr Corneliu E. Giurgea

And that’s why he invented nootropics, the ‘smart drugs’ that improve cognitive functioning. Racetams belong to a group of synthetic nootropics. The oldest known racetam is Piracetam that was discovered by Dr Giurgea in 1964. Currently, there are various racetams available in the market. 

However, the basic chemical structure of all these racetams is more or less the same because each new racetam variant was developed by giving a little tweak to the original structure. The difference between the racetams lies in their functionality, dosage, half-life (duration of drug action in the plasma) and strength of each racetam.

Let’s take a look at some of the features of these incredible cognitive enhancers… 

Features of Racetams

  • Racetams are cognitive enhancers and take time to act on the body, and hence, one may begin to see the benefit only after a few days or weeks after starting them.
  • Racetams have reverse tolerance, meaning they give the same benefits even after the reduction in dosage.
  • Further, this reverse tolerance feature applies across the entire racetam family, meaning if one has swapped a particular variety of racetam for another, then one need not wait for the new drug to pick up, as it will continue to act on the body from the place where the earlier racetam left off. Hence additional time is not required for experiencing the benefit of new racetam.
  • Racetams are available in liquid, capsule or powder forms.
  • Racetams are fat-soluble and hence can be combined with fatty food sources, and they tend to get absorbed better in the body when so combined.

A word of caution, though… Racetams act as blood thinners and are eliminated by the kidneys. Hence the risks of blood thinners and using other medications that load the kidneys apply to racetams.

A Sneak Peek into the Popular Racetams in the Market

1. Piracetam – The Beginner’s Nootropic

Piracetam is an excellent nootropic for beginners as it is supposed to have very mild side effects. Piracetam was developed to enhance the cognitive function among the elderly. Piracetam also promotes the cellular membrane fluidity required for memory enhancement, thereby promoting better learning. Piracetam prevents blood clotting on the lines of aspirin, and hence, it is used in patients post cardiovascular trauma. [1]

Mechanism of Action

Piracetam is the cyclical derivative of the inhibitory GABA neurotransmitter (GABA promotes a calming and relaxing effect in mind due to its inhibitory nature. Piracetam does not occur naturally in any plant or food source, nor does the body produce it.  [1]

Characteristics

It is water-soluble, and  the safest among all known racetams due to its mild side effects that include short-term anxiety, insomnia, nervousness, etc.  [2]

Dosage

For adults, the recommended dosage is 1,200-4,800 mg per day. [3]

Half-life 

Half-life is approximately 5 hours. [4]

Stacking

Piracetam can be stacked (combined) with other racetams like Aniracetam as well as with other nootropics like choline for improved benefits like enhanced memory. [5]

Benefits

Piracetam is neuroprotective and prevents age-related decline in cognition. [6] Hence, it is used in certain European countries for Dementia and Alzheimer’s. Its neuroprotective properties have been successful in treating patients suffering from stroke,[7] as well as those facing cerebrovascular trauma [8] 

Piracetam helps to sustain mitochondria (powerhouses of energy for the body cells) by assisting the destruction of damaged mitochondria cells (that releases free radicals causing oxidation and cell damage) and helps to start the growth of new mitochondria cells. [9] Piracetam also helps in verbal learning in dyslexic children. [10]

2. Aniracetam – Creative Thinking and Mental Health (2-5 times potent than Piracetam)

Aniracetam that was developed in the 1970s is two to five times more potent than Piracetam. It helps in boosting creativity by acting on the right brain hemisphere.

Mechanism of Action

Aniracetam stimulates the AMPA and glutamate receptors, thereby improving memory storage and enhancing neuroplasticity. [11] 

Aniracetam reduces stress as it works with neurotransmitters like choline, serotonin, and dopamine that enhance brain health. Aniracetam, through its potent anxiolytic effect, helps to reduce anxiety levels. [12]

The presence of pyrrolidone nucleus (an anxiotropic agent)  in Aniracetam helps to lower anxiety and boost lateral thinking, thereby paving the way for better creativity. [13]

Characteristics

Aniracetam gets metabolized in the liver and is quickly transported throughout the body. Users can feel the effects of this nootropic as soon as 30 minutes after ingestion. [14]

Aniracetam is a fat-soluble compound. 

Aniracetam regulates several neurotransmitters located in the brain like acetylcholine, glutamate, serotonin, and dopamine. These neurotransmitters are responsible for cognition, mood, and memory aspects.  [15]

Few side effects include vertigo, nausea, and headaches. 

Dosage 

The recommended dosage is 750-1500 mg per day. [16]

Half-life 

About 1-3 hours. [18] 

Stacking

It can be stacked well with Choline, Noopept, or go for the PAO (Piracetam, Aniracetam, and Oxiracetam) stack. [19]

Benefits

  • Decreases Anxiety: Aniracetam helps to reduce stress. A trial on dementia patients showed that those patients Aniracetam experienced less anxiety. [20]
  • Works as an Antidepressant. [21]
  • Helps in treating Dementia. [22]
  • Reverses Memory Impairment: Aniracetam has not only the capacity to boost memory, but it can also reverse impairment of memory as well. [23] 

3. Oxiracetam  - Logical Thinking, Good for Studies

Oxiracetam is a synthetic derivative of Piracetam bearing the same chemical structure and mode of operation. However, this nootropic is more potent than Piracetam. [24]

Mechanism of Action

Oxiracetam modulates the release of cholinergic and glutamatergic neurotransmitters, acetylcholine and glutamate. Oxiracetam also enhances neuronal communication by acting on the hippocampus part of the brain responsible for memory and emotion by stimulating the release of D-aspartic acid. [25], [26]  

Characteristics

Oxiracetam being an ampakine (stimulants that act with the AMPA glutamatergic receptors and do not have side effects associated with other known stimulants) acts as a mild central nervous system stimulator. [27]

Oxiracetam is excreted through the renal system.

Few side effects include brain fog, over-excitability, and headaches.

Dosage 

The recommended dosage in adults is 400mg to 2400mg.

Half-life  

The half-life is 8 hours.

Stacking

Stacking with choline helps to eliminate the headaches associated with racetams.

When Oxiracetam is stacked with Pramiracetam, it doubles the cognitive enhancement and promotes alertness.

When coupled with Aniracetam, it enables a gentle stimulant effect and also better cognitive enhancement.

Benefits

Research among dementia patientsproved that Oxiracetam could enhance learning by augmenting memory recall. [28]

Supplementation with Oxiracetam on elderly patients with multi-infarct dementia helped to improve verbal fluency as well as verbal learning. [29]

Oxiracetam is a powerful memory booster, and hence, it aids logical reasoning, thereby making it an essential kit for students taking up mathematics or other logical exams. [30]

Oxiracetam is said to help and protect the brain from altitude sickness, as proved by a study by a Military Medical University in China. [31]

4. Pramiracetam – The Strongest of Racetams

Pramiracetam was discovered during the late 1970s by Parke-Davis and is supposed to be the strongest among all members of the racetam family. It is helpful in the treatment of memory loss associated with Alzheimer's as it is also an excellent potential nootropic to treat various disorders of the central nervous system. [32],[33]

Mechanism of Action

Pramiracetam increases the choline uptake in the hippocampus part of the brain (indirectly sparking the neurotransmitter acetylcholine that aids cognition and learning). Further, it also increases the blood flow to the brain and thereby reduces the mind chatter or monkey mind experienced by people when dealing with multiple tasks and focusing on too many projects in hand.

Characteristics

Sharper focus and long-term memory. Hence it is useful for people working on big long-term projects. It is fat-soluble.

Minor side effects include headache,  gastrointestinal pain, and nervousness. [37]

Dosage

The typical dosage in adults is 400-600 mg.

Half-life 

The half-life is 4.5 to 6.5 hours. 

Stacking

Pramiracetam stacks well with Adrafinil, Oxiracetam, CDP Choline, and Aniracetam.

Benefits

Pramiracetam acts as an anti-amnesic and helps to reduce forgetfulness. [34] Studies on patients with degenerative amnesia have shown that Pramiracetam has been effective in reversing amnesia and enhancing recall. [35] 

Many users of Pramiracetam have reported that it helps to reduce social anxiety and thereby enhance social fluency. However, there is no documented evidence on the same.

Various hypothesis claimed by researchers states that Pramiracetam acts on the external sites (located outside the brain) that depend on the adrenal glands, thereby increasing the scope of other modes of actions as well. [36] 

5. Coluracetam - The Ultra-HD Vision 

Japan's Mitsubishi Tanabe Pharma Corporation initially developed Coluracetam for treatment of Alzheimer's disease in 2005. However, as the trials were not successful, it was licensed to Brain Cells Inc, a US biotechnology company. This company successfully tested the usage of Coluracetam for treating Anxiety and Depression, thereby revealing a promising market for Major Depressive Disorder (MDD). However, the development was not taken to the next level, and BrainCells shut down its operations in 2014. 

Mechanism of Action

Coluracetam is a unique brain enhancer as it works by improving the choline uptake into the nerve cells through the high-affinity choline uptake mechanism, (HACU). HACU regulates the rate of choline that is taken into the neurons for getting converted into acetylcholine. Thus choline uptake enhances acetylcholine in the brain. Colucetram also helps to restore the choline uptake system post nerve cell damage.[39],[40],[41],[42]

Coluracetam safeguards the NMDA receptors from glutamate toxicity. Usually, certain diseases like Alzheimer’s, stroke, or any trauma to the brain post-injury, etc.may damage these NMDA receptors. Coluracetam also protects the NMDA receptors from the toxicity of the excitotoxin glutamate. Damage to these receptors occurs during a stroke, Alzheimer's, traumatic brain injury, and other brain diseases. [43]

Characteristics

Coluracetam is a choline uptake enhancer and helps to increase the levels of the acetylcholine neurotransmitter. The production of acetylcholine depends on choline. Acetylcholine is linked to memory and cognitive function, as a result of which Coluracetam helps in enhancing memory.

Coluracetam is very potent, and hence, a small dose will suffice. It is also fast-acting, as high levels in plasma are reached in less than half an hour upon ingestion; however, it also tends to drop down quickly within three hours. [44]

There are no documented side effects. Some Coluracetam users have reported nausea and sleepiness during the day, both of which have reduced upon a decrease in dosage. Another common side effect is a headache as with all racetams.

Dosage 

The typical dosage for normal adults is 5mg to 35 mg.

Half-life

The half-life of Coluracetam is 3 hours. 

Stacking

Coluracetam stacks well with Alpha GPC for better memory.

Benefits

Coluracetam helps to promote nerve growth in diseases linked to degeneration of the retina. [45]

Many users have confirmed that Coluracetam helps to make things look sharp, bright, and colourful, giving that Ultra-HD look, which is perfect for certain professions like that of an artist. [46] 

Coluracetam also helps with Schizophrenia by making the enzyme acetylcholine, that is often found at a reduced level in Schizophrenia patients. [47]

Animal studies have proved Coluracetam has helped to increase the activity acetylcholine enzyme in nerve cell damage. [48]

Coluracetam also helps in neurogenesis (promoting nerve cell growth) when dosed continuously for a few weeks. This might probably be due to the increase in hippocampal acetylcholine contributed by this racetam. [49]

6. Fasoracetam -  The Latest Racetam Kid

Fasoracetam was first created during the early 1990s in Japan for the treatment of vascular dementia. The drug, however, failed to move past phase 3 clinical trials and was hence abandoned. Later Fasoracetam was revived by another company in 2013 and currently phase 2 clinical trials are underway for its possible treatment in people with ADHD (Attention-Deficit Hyperactivity Disorder), Anxiety and Autism.  [50], [51]

Mechanism of Action

The modality of action is not fully documented yet. However, studies have shown that Fasoracetam works by modulating the release of three important neurotransmitters of the brain, namely GABA (gamma-aminobutyric acid), glutamate and acetylcholine. Fasoracetam has been proven to increase the number of receptors in the cortex for GABA and also regulate the activity of GABA-B receptors. [52],[53]

It also enhances the discharge of acetylcholine from the cerebral cortex and activates particular glutamate receptors called metabotropic glutamate receptors – mGluRs that improve memory and learning. [54]

Characteristics

Fasoracetam works as a cholinergic (increases uptake of choline in the hippocampus part of the brain). [55]

Side effects include fatigue and headache. Large dosages (more than 1000 mg per day) have said to cause bradycardia (low heart rate). [56]

Dosage  

The suggested dosage is 20mg to 100 mg. However, there are no definite, documented guidelines. In the clinical trials involving ADHD patients, Fasoracetam dosages of 100, 200 as well as 400 mg was used twice daily. [57] However, some users have reported low doses of 20 mg taken twice daily to be very useful. 

Half-life

The estimated half-life is 1.5 hours.

Stacking

Stacks better with Alpha GPC, CDP Choline.

Benefits

Various animal studies have shown to reduce the effects of GABA-B activation, which is responsible for memory problems. Fasoracetam has also helped to increase acetylcholine. This combined impact has helped to reduce amnesia. [58] 

7. Noopept - ‘The Climate Acclimatizer Hero

Noopept is another synthetic nootropic molecule and a potential cognitive enhancer. Though there is a limited study of Noopept on humans, it is said that the effects of Noopept are significantly better than that of Piracetam in issues like emotional sensitivity, post vascular, or traumatic brain injuries.

Mechanism of Action

Though the exact modality of action of this racetam is not known clearly, animal studies on the single as well as long–term treatment with this drug have shown that Noopept has helped to enhance the nerve growth factor (NGF) as well as the BDNF (brain-derived neurotrophic factor) factor in the hippocampus and hypothalamus of rats. [59a], [59b]

Noopept primarily works by enhancing the activity of HIF1A, which is a DNA transcription factor. [60]

Characteristics

Noopept is approximately 1000 times stronger than Piracetam. While Piracetam helps in the early stage memory process, Noopept also aids in the consolidation and retrieval of memory as well. Further Noopept also has antioxidant, anti-inflammatory, and neuroprotective effects. [61]  

Side effects of Noopept include fatigue, headaches, giddiness, etc. These side effects occur as a result of high blood pressure building up in the arteries as a result of intake of this racetam. [62], [63]

Dosage 

The recommended dosage is 10-20 mg. Though many claimed to have extended up to 30 mg per day, there is evidence of a clinical trial using a 20 mg dosage. [64]

Half-life

The half-life of Noopept is 30-60 minutes. [65]

Stacking

Noopept stacks well with Alpha GPC, Aniracetam, CDP Choline, and Piracetam. [66]

Benefits

In a clinical trial on 53 patients suffering from emotional trauma post vascular and traumatic brain injury, Noopept (10 mg twice a day) performed considerably superior to Piracetam that was administered at 400mg three times a day. [67]

Noopept is shown to improve headache, nervousness, irritation, and disturbed sleep within the first week of intake. It is also shown to prevent drowsiness during the day and enhance the mood. [68]

Animal studies have proved that Noopept improves memory and averts amnesia. [69] 

In test tube-based clinical studies, Noopept was found to have neuroprotective properties by preventing the death of cells due to amyloid toxicity, which is the main symptom in case of diseases like Alzheimer’s and Parkinson’s. [70]

Another experiment found that Noopept also prevents oxidative cell damage as well as mitochondrial cell death, both of which are important for combating Alzheimer’s and Parkinson’s diseases.  [71], [72]

Another exciting benefit of Noopept is that it helps in acclimatization to hot or cold climates.

Studies conducted on 127 healthy volunteers, showed that Noopept improved their adaptation to extremities in climate, namely hot or cold environments and also increased their endurance to carry on physical work in hot climatic conditions. [73] 

Conclusion 

So, are you ready to try racetams in your next nootropic stack? Well then, we have various options you can choose from to find the one that best fits your goals.




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