Piracetam (also known by the name Nootropil, among others) is an extremely popular nootropic when it comes to brain health. Nootropics are defined as nutritional or dietary-based cognitive enhancers. They’re also known as “smart drugs” and are available in prescription or supplemental form, basically focusing on improvement of cognitive functions, motivation, memory, as well as creativity capabilities in healthy individuals.
Nootropics as a term has been used since the early 1970s. Only a few drugs have been scientifically studied and determined to be effective in treating a number of cognitive disorders, and one of those is piracetam. It’s been researched extensively for its potential to be used in a variety of treatments, mainly focusing on cognitive function and in relieving symptoms and memory loss in cognitive disorders and diagnoses.
Piracetam is a nootropic drug that is considered among the racetams group of drugs. Racetams are defined as a class of drugs that share a pyrrolidone nucleus. This structure means that piracetam can produce or influence a large variety of diverse actions and activities in biological processes and systems. It is not exactly understood how racetams perform in general, at least in regard to their mechanism of action, although it has been determined that they can influence not only cognitive function without the simulative or sedative effect of many prescription drugs, but may also influence neuron and vascular functions.
Things To Know
Racetams like piracetam are mainly used to improve cognition, and share similar chemical structures. They focus on improving mood, energy levels, focus, learning capabilities, and memory, hence their popularity with those looking to enhance brain function and perhaps even to stave off age-related conditions such as dementias. The most common racetams include:
These racetams contain oxygen, nitrogen, and hydrogen, with a 2-pyrrolidone nucleus.
Racetams function through the stimulation of cellular receptors for a neurotransmitter called acetylcholine. Some are effective in enhancing glutamate uptake by activating two additional receptors: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA).
Piracetam is derived from GABA or gamma-aminobutyric acid, an amino acid that behaves as a neurotransmitter in the central nervous system. It’s also vital for brain metabolism as well as optimal brain function. In turn, GABA is formed from another amino acid – glutamate acid. The function of glutamate acid is to decrease neuron activity and prevent the excitability of nerve cells. When taken together with niacinamide and inositol, GABA can reduce stress and anxiety messages from reaching the motor centers of the brain. It does this by literally occupying their receptor sites. However, piracetam does not affect GABA brain metabolism or receptors.
GABA, therefore, is often taken by individuals to calm the body and the senses. It acts much like the prescription drugs Valium (diazepam) and Librium (chlordiazepoxide) as well as other types of tranquilizers, without fears of addiction. In some cases, GABA has been used in the treatment of hypertension and epilepsy.
Glutamate acid is defined as an “excitatory” neurotransmitter. This amino acid increases neuron activity or firing in the central nervous system as well as the spinal cord. Glutamate acid is vital in the metabolism of lipids and glucose and aids in potassium transportation within the spinal fluid and across the blood-brain barrier.
Glutamine is more effective in passing through the blood-brain barrier, but so too can glutamate acid when found in high levels in the blood. The brain utilizes glutamate acid as a form of fuel. Glutamate acid is also under research for its ability to adjust personality disorders and has been used in the treatment of muscular dystrophy, hypoglycemic coma, epilepsy, and ulcers.
Glutamate acid is also a component of folate, a vitamin that belongs to the B family of vitamins that enhances the body’s ability to break down amino acids. Amino acids, in turn, provide the foundation for protein synthesis.
The chemical name of piracetam is 2-oxo-1-pyrrolidine acetamine.
Chemical formula: C6H10N2O2
Also known as:
Mechanism Of Action
Both AMPA (ɑ-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors have been studied for their ability to improve cognitive function. One study, “NMDA receptor function, memory, and brain aging,”has been linked to memory as well as learning impairments, as well as psychosis, and some types of brain injury (excitotoxic) (1). It’s believed that due to aging processes, the function of the NMDA receptors declines, which can contribute to a decline in learning performance as well as memory. This decline can also be worsened by the development of certain types of dementia including Alzheimer’s disease, which is believed to increase hypofunction or decline in NMDA function in the brain (2).
A variety of metabolic conditions, including diabetes, may also have an adverse effect on AMPA (3).
Some of these conditions may be temporary or transient while others are more long-term in nature.
Piracetam, at its most basic definition, stimulates acetylcholine receptor systems that encourage more release of neurotransmitters into the brain, which may perhaps enhance long-term health of the brain as well as in boosting “brain power”, focus, and attention.
Additional effects and benefits of piracetam can include but are not limited to increased neuroplasticity of the brain cells, which is essential for optimal function (4). Increased neuroplasticity coincides with increased focus, memory, and cognitive abilities.
Piracetam, although defined as a GABA derivative, has a mechanism of action that may not be particularly related to that neurotransmitter’s properties. One of the major effects of piracetam is its ability to restore the fluidity of cellular membranes, which is neither organ nor cellular specific. A number of studies have reported and demonstrated the influence of piracetam on this fluidity, especially when normal levels are compromised, as is typical during aging processes. Studies involving piracetam and elderly mouse brain membranes showed improvement in fluidity, but the same effect was not noted in younger mice.
According to another study, the same observation was made in the hippocampal membranes of patients diagnosed with Alzheimer’s disease. It was noted that the improvement of fluidity was also significantly linked to and coincided with the reduction of avoidance learning, but that piracetam didn’t have an effect on either membrane fluidity or learning in younger rats receiving the supplement.
Piracetam is also important in neurotransmission processes, although not limited to any specific neurotransmitter type. Some studies have determined its influence on cholinergic, serotoninergic, glutamatergic, and noradrenergic systems in the body. These studies aren’t new, with many occurring from the early 1980s through the early 2000s.
Piracetam is also believed to have a neuroprotective effect, effect on neuroplasticity (in aged rats), and anticonvulsant effects (5). It’s also believed (as determined in early animal studies) to provide vascular effects and have an impact on blood vessels. It was also noted that piracetam may influence coagulation. In humans, one dose of piracetam reduced fibrinogen and plasma levels and von Willebrand factors by up to 40% (3.2 to 9.6 g dosage).
What Is Piracetam Used For?
Piracetam has been used in a number of medical environments including in the treatment of dementia. Additional uses of piracetam are currently under study for:
- Treatment of peripheral vascular issues including vertigo, sickle cell anemia, and dyslexia
- Exploration in its use to reduce symptoms of autism in children
Piracetam may have the ability (noted in animal research) to increase blood circulation, carrying vital oxygen to certain portions of the brain that increase brain activity, although this aspect of the nootropic has been explored as a side effect of the piracetam rather than a specific mechanism of action of the drug (6).
Piracetam has also been used for relieving muscle twitching and jerking in the extremities. It is often combined with other drugs (prescription or over-the-counter) for optimal efficacy in the treatment and relief of symptoms in such disorders.
Research and attention have been focused on the ability of piracetam to improve cognitive decline, especially those associated with age. A number of studies in this aspect can be reviewed:
- “Clinical efficacy of piracetam and cognitive impairment: a meta-analysis” used a very small group (19 individuals) in a double-blind, placebo-controlled study on individuals diagnosed with cognitive impairment or dementia (7). While the study did show some benefits in improvement, further study is required.
- “Piracetam for dementia or cognitive impairment” reports that a 2001 study that focused on the clinical efficacy of prescribing piracetam for cognitive impairment associated (or not) with dementia (8). The study analyzed the clinical efficacy of piracetam for many of the features associated with cognitive impairment and dementia, with vascular dementia, Alzheimer’s disease, or a combination of Alzheimer’s disease and vascular dementia. The conclusion was that the limited data available from the study and literature failed to support the use of piracetam in those diagnosed with dementia or cognitive impairment, at least with regard to specific and consistent results.
- Another study involving a slightly larger group (162 subjects), “Drug therapy and memory training programs: a double-blind, randomized trial of general practice patients with age-associated memory impairment”, did note some improvement following use of 4.8 g of piracetam on a daily basis with or without cognitive therapy (9). Results showed that such individuals not given the placebo did enjoy a higher cognitive improvement when compared with the placebo group.
- Another small study involving 30 subjects, “Long-term and high-dose piracetam treatment of Alzheimer’s disease” in a double-blind study determined that individuals diagnosed with Alzheimer’s disease and given 8 g of piracetam for one year did not result in noticeable significance (10). However, some improvement was a noted in the study regarding the recall of image series as well as recent and remote memory processes.
While studies in this area involving the use of piracetam to treat cognitive decline caused by dementia conditions continues, there is also exploration in the overall benefits of piracetam in improving the cognitive function in individuals dealing with a normal age-related decline in memory, focus, attention, etc. It is still believed that long-term dosage protocols of piracetam may help reduce the progression of cognizant deterioration in patients diagnosed with Alzheimer’s disease.
Another area where piracetam has been reported to have the greatest efficacy, in addition to its potential in reducing cognitive decline, is in infants diagnosed with breath-holding spells.
Breath-holding spells (BHS) are often associated with seizure disorders, including epilepsy. These breath-holding spells in infants and children are involuntary and reflexive in nature. They may be triggered by extreme emotion. Severe breath-holding can contribute to cyanosis, loss of awareness, and consciousness. According to the Epilepsy Foundation, the prevalence averages 0.1% to just over 4% and tends to run in families (11). Most infants diagnosed with BHS experience onset before they are two years old (over 90%). In most cases, infants and children diagnosed with breath-holding spells generally overcome the condition by four years of age, although some cases have been noted in children as old as eight.
Several studies in this area have been small, ranging from approximately 40 to 79 subjects, but the efficacy of piracetam was noted in infants from weeks of age to five years old in reducing breath holding spells.
“Piracetam in severe breath-holding spells” is just one such study. It’s interesting to note that approximately 63 patients of the 91 involved in the study were found to be iron deficient and diagnosed with iron deficiency anemia (12). These patients were given 6 mg per kilogram per day of iron for three months, while other children in the study were not. The combination of iron and piracetam appeared to be more effective than those who received the placebo (84.1% versus 21.4%).
Studies regarding the use of piracetam for infants in fetal distress during labor have also been conducted. One study “Piracetam for fetal distress and labor” reported that the randomized trial involving 96 women showed that treatment with piracetam tended to reduce the need for Cesarean section dependent on respiratory issues as well as signs of hypoxia (insufficient oxygen supply) in infants during labor (13). However, the study was too small and provided insufficient conclusions. Further research is acquired in determining the efficacy of the use of piracetam for fetal distress during labor.
Piracetam is often prescribed for the treatment of dementia and cognitive impairments in continental Europe. As stated in a 2012 article, “Evidence for the efficacy of piracetam for dementia or cognitive impairment is inadequate for clinical use but sufficient to justify further research” defines the continued interest and encouragement for research regarding piracetam in the treatment of cognitive issues (14).
Dosage recommendations for piracetam or Nootropil tablets or oral solutions depend on the reason they are being taken. Some find that it can be taken with or without food, although some prefer taking it with food to reduce the risk of upset stomach. Tablets should be taken with liquid. Piracetam oral solutions can be taken with soft drinks or water to reduce the bitter aftertaste.
Dosage recommendations vary between individuals. Age, weight, health status, and the reason for which the medication is being taken will also differ depending on case-by-case scenarios. It is always important to follow instructions provided by the physician or a pharmacist.
When it comes to dosage recommendations, always refer to a physician or pharmacist. Unless recommended by a physician, piracetam is not recommended for children under 16 years of age. However, depending on diagnosis and treatment plan, piracetam dosage for children may approximate roughly 40 to 100 mg per kilogram of body weight.
It should be noted that the use of piracetam in children is relatively uncommon, although it may be used for those diagnosed with dyslexia or a condition that exhibits breath-holding spells. In such cases, a 40 to 50 mg dose per kilogram is often recommended.
Adult dosage recommendations can range 1,200 mg to nearly 5,000 mg a day, again depending on the situation. An average dose of 1,600 mg taken three times a day (morning, afternoon, evening), may prove effective. But the dosage must not exceed that unless medically supervised.
A general therapeutic dose range for cognitive disorders as well as vertigo recommends 2.4 to 4.8 g daily.
For dyslexia – 3.2 g daily
Cortical myoclonus – 7.2 to 24 g daily
Cognitive disorders – Age-related and associated memory impairment may offer recommendations in the dosage ranging anywhere from 2.4 g daily to 4.8 g daily. One study involved 162 patients who were treated with such dosage and enrolled in a memory training program. There was a positive improvement in memory testing, delayed, and global recall.
Efficacy and dosage recommendations and the use of piracetam for dementia treatments has been limited and continues to be limited by underlying pathologies. However, some studies over the years have reported that patients diagnosed with dementia may experience greater improvements in psychometric as well as clinical assessment scales with piracetam than those who were on the placebo.
Potential Side Effects And Cautions
Most of the side effects associated with piracetam are relatively mild. Among the most common side effects of piracetam include:
- Weight gain
- Increased anxiety or nervousness
- An increase in hyperkinesia or increased body movement or jerkiness
- An overall feeling of weakness
Some users also experience a number of additional side effects:
- Erratic sleep cycles or insomnia
- Dizziness or vertigo
- Nausea (with or without vomiting)
- Skin rashes
- Balance issues
- Pain in the abdomen
If you experience any of these side effects, discuss with your physician. Adjusting the milligram dosage may help reduce the side effects.
Some users complain of a drowsy feeling, but again, this effect is not the same for everyone. It should be used cautiously by the elderly, as well as anyone diagnosed with decreased liver or kidney function.
Individuals diagnosed with bleeding disorders or increased risk of bleeding such as a clotting disorder or hemophilia, as well as peptic ulcers, should also use cautiously. This is especially true if a person is taking prescribed medications known as blood thinners or anticoagulants or antiplatelet drugs.
Piracetam can interact with other medications, even over-the-counter medications and herbal medicines and remedies. Certain drugs taken with piracetam can increase the risk of bleeding. They include but are not limited to:
- Warfarin/Coumadin (anticoagulant)
- Heparin (anticoagulant)
- Antiplatelet medicine (including low-dose aspirin or dipyridamole)
Consumers should be aware that piracetam (Nootropil) oral solutions as well as tablets do contain sodium so they should not be consumed for anyone recommended to follow a low-sodium diet, including cardiac patients.
Contraindications against use:
- Pregnant or breastfeeding women – It has not been determined whether the use of piracetam can affect a developing fetus or a nursing infant, so it’s best to avoid. In cases where a doctor recommends the drug, carefully and thoroughly discuss the risks as opposed to the benefits. Piracetam can pass into breast milk.
- Anyone diagnosed with Huntington’s chorea
- Anyone diagnosed with a brain bleed
- A person diagnosed with decreased kidney function
- Use by children under 16 years of age without the knowledge and guidance of physician
- Use by someone who is allergic to one or more than one of its ingredients
The contraindications require the dosage to be adjusted for patients diagnosed with renal insufficiency. It is contraindicated in patients diagnosed with end-stage renal disease. It is also contraindicated to any patient diagnosed with a cerebral hemorrhage.
While the risk of drug interactions with piracetam are low because neither does it bind to plasma albumin nor is it metabolized in the liver, caution is always advised in the presence of a medical condition.
All in all, piracetam is classified as a well-tolerated drug with numerous documented clinical benefits in the treatment of a variety of disorders not only related to cognitive decline caused by aging processes. Efficacy in some of these studies is dependent upon its vascular and neuronal effects, which are often related to the aforementioned membrane fluidity.
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