Piracetam is a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

that has efficacy in

cognitive disorders Neurocognitive disorders (NCDs), also known as cognitive disorders (CDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem-solving. Neurocognitive disorders in ...

vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

, cortical myoclonus,

dyslexia Dyslexia (), previously known as word blindness, is a learning disability that affects either reading or writing. Different people are affected to different degrees. Problems may include difficulties in spelling words, reading quickly, wri ...

, and

sickle cell anemia Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...

; sources differ on its usefulness for

dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

. Piracetam is sold as a medication in many European countries. Piracetam in the United States is not approved for general use. Piracetam is in the racetams group, with chemical name ''2-oxo-1-pyrrolidine acetamide''. It is a cyclic derivative of the neurotransmitter

GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

and shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid. Related drugs include the anticonvulsants

levetiracetam Levetiracetam, sold under the brand name Keppra among others, is a novel antiepileptic drug. (medication) used to treat epilepsy. It is used for Focal seizure, partial-onset, Myoclonic epilepsy, myoclonic, or tonic–clonic seizures, and is ta ...

and

brivaracetam Brivaracetam, sold under the brand name Briviact among others, is a chemical analog of levetiracetam, a racetam derivative with anticonvulsant (antiepileptic) properties. It has been approved since 2016. It is marketed by the pharmaceutical co ...

, and the putative nootropics aniracetam and

phenylpiracetam Phenylpiracetam, also known as fonturacetam () and sold under the brand names Phenotropil, Actitropil, and Carphedon among others, is a psychostimulant, stimulant and nootropic medication used in Russia and certain other Eastern European countr ...

Efficacy

Dementia

A 2001

Cochrane review Cochrane is a British international charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes ...

concluded that there was not enough evidence to support piracetam for

or cognitive problems. A 2005 review found some evidence of benefit in older subjects with cognitive impairment. In 2008, a working group of the British

Academy of Medical Sciences The Academy of Medical Sciences is an organisation established in the UK in 1998. It is one of the four UK National Academy, National Academies, the others being the British Academy, the Royal Academy of Engineering and the Royal Society. Its ...

noted that many of the trials of piracetam for dementia were flawed. There is insufficient evidence of piracetam as a treatment for

vascular dementia Vascular dementia is dementia caused by a series of strokes. Restricted blood flow due to strokes reduces oxygen and glucose delivery to the brain, causing cell injury and neurological deficits in the affected region. Subtypes of vascular dement ...

Depression and anxiety

Some sources suggest that piracetam's overall effect on lowering depression and

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

is higher than on improving memory. However, depression is reported to be an occasional adverse effect of piracetam.Nootropil®
Arzneimittel-Kompendium der Schweiz. 2013-09-12. Retrieved 2013-10-27.

Attention deficit hyperactivity disorder (ADHD)

Several clinical trials have looked at piracetam's efficacy as a treatment for

ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple ...

. Many of these have found that the drug fails to deliver the same therapeutic effects as current standard treatments for the disorder. However, more than one study has found piracetam to be highly synergistic with standard ADHD therapies, accelerating and potentiating their therapeutic effects. One 2008 clinical trial found that the combination of piracetam and

atomoxetine Atomoxetine, formerly sold under the brand name Strattera, is a selective norepinephrine reuptake inhibitor (sNRI) medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, cognitive disengagement syndr ...

was more effective than atomoxetine alone. While piracetam may be an effective adjuvant therapy for ADHD (when used with specific medications), there is no evidence that it is effective when used in isolation.

Other

Piracetam may facilitate the deformability of erythrocytes in

capillary A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the inn ...

which is useful for cardiovascular disease. Peripheral vascular effects of piracetam have suggested its use potential for

Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which the spasm of small arteries causes episodes of reduced blood flow to end arterioles. Typically the fingers, and, less commonly, the toes, are involved. Rare ...

and

. There is no evidence to support piracetam's use in sickle cell crisis prevention or for fetal distress during childbirth. There is no evidence for benefit of piracetam with ''acute'' ischemic stroke, though there is debate as to its utility during stroke rehabilitation.

Anti-vasospasm

Piracetam has been found to diminish

erythrocyte Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...

adhesion Adhesion is the tendency of dissimilar particles or interface (matter), surfaces to cling to one another. (Cohesion (chemistry), Cohesion refers to the tendency of similar or identical particles and surfaces to cling to one another.) The ...

to vascular wall

endothelium The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...

, making any

vasospasm Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia (insufficient blood flow) and tissue death (necrosis). Along with physical resistance, vasospasm is a main cause of ischemi ...

in the

less severe. This contributes to its efficacy in promoting

microcirculation The microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. ...

, including to the brain and kidneys.

Side effects

Symptoms including

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

irritability Irritability is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimul ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, agitation,

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

, and hyperkinesia are occasionally reported. Other reported side effects include

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...

weight gain Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition. Description Weight gain occurs ...

clinical depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...

weakness Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...

, increased

libido In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...

, and

hypersexuality Hypersexuality is a proposed medical condition said to cause unwanted or excessive sexual arousal, causing people to engage in or think about sexual activity to a point of distress or impairment., according to the website of ''Psychology Toda ...

. According to a 2005 review, piracetam has been observed to have the following side effects: hyperkinesia,

, anxiety, somnolence, depression, and weakness. Piracetam reduces

platelet aggregation Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytop ...

as well as

fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

concentration, and thus is contraindicated to patients with cerebral hemorrhage.

Toxicity

The for oral consumption in humans has not been determined. The LD₅₀ is 5.6 g/kg for rats and 20 g/kg for mice, indicating extremely low

acute toxicity Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...

. For comparison, in rats the LD₅₀ of vitamin C is 12 g/kg and the LD₅₀ of table salt is 3 g/kg.

Mechanisms of action

Piracetam's

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

, as with racetams in general, is not fully understood. The drug influences neuronal and vascular functions and influences cognitive function without acting as a

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

. Piracetam is a positive allosteric modulator of the

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitator ...

, although this action is very weak and its clinical effects may not necessarily be mediated by this action. It is hypothesized to act on ion channels or ion carriers, thus leading to increased neuron excitability.

brain metabolism and

GABA receptors The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...

are not affected by piracetam Piracetam increases the action of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

via muscarinic cholinergic (ACh) receptors, which are implicated in

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...

processes. Furthermore, piracetam may have an effect on NMDA

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

receptors, which are involved with

learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, Attitude (psychology), attitudes, and preferences. The ability to learn is possessed by humans, non-human animals, and ...

and

processes. Piracetam is thought to increase cell membrane permeability. Piracetam may exert its global effect on brain neurotransmission via modulation of

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s (''i.e.'', Na⁺, K⁺). It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brains. Piracetam, while in the brain, appears to increase the synthesis of

cytochrome b5 Cytochromes ''b''5 are ubiquitous electron transport hemoproteins found in animals, plants, fungi and purple bacteria, purple phototrophic bacteria. The microsome, microsomal and mitochondrial variants are membrane-bound, while bacterial and tho ...

, which is a part of the electron transport mechanism in

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

. But in the brain, it also increases the permeability of some intermediates of the

Krebs cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of biochemical reactions that release the energy stored in nutrients through acetyl-CoA oxidation. The e ...

through the mitochondrial outer membrane. Piracetam inhibits

N-type calcium channel N-type calcium channels, also called Cav2.2 channels, are voltage gated calcium channels that are localized primarily on the nerve terminals and dendrites as well as neuroendocrine cells. The calcium N-channel consists of several subunits: the prim ...

s. The concentration of piracetam achieved in

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

after a typical dose of 1200 mg (about 100 μM) is much higher than the concentration necessary to inhibit

s ( IC50 of piracetam in rat neurons was 3 μM).

History

Piracetam was first made some time between the 1950s and 1964 by Corneliu E. Giurgea. There are reports of it being used for epilepsy in the 1950s.

Society and culture

In 2009 piracetam was reportedly popular as a cognitive enhancement drug among students.

Legal status

Piracetam is an uncontrolled substance in the United States, meaning it is legal to possess without a license or prescription. Use of piracetam in food, supplements, medical devices,

insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, i ...

s, infant formula, cosmetics, animal feed, animal drugs, tobacco products, and drugs is unlawful and constitutes an act of misbranding.

Regulatory status

In the United States, piracetam is not approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

. Piracetam is not permitted in compounded drugs or dietary supplements in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

. Like most research chemicals, it has been available over-the-counter, self-regulated, and third-party lab tested by many U.S. companies for decades. Nonetheless it is still, for the purposes of U.S. law, a "New Drug" as defined by 21 U.S. Code § 321(p)(1). In the United Kingdom, piracetam is approved as a prescription drug for adults with myoclonus of cortical origin, irrespective of cause, and should be used in combination with other anti-myoclonic therapies. In Japan, piracetam is approved as a prescription drug. In the Czech Republic, piracetam is available without prescription. Piracetam has no DIN in Canada, and thus cannot be sold, but can be imported for personal use in Canada. In Hungary, piracetam was a prescription-only medication, but as of 2020, no prescription is required and piracetam is available as an

over-the-counter drug Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

under the name Memoril Mite, and is available in 600 mg pills.

References

External links

* {{Ionotropic glutamate receptor modulators Acetamides AMPA receptor positive allosteric modulators Drugs with unknown mechanisms of action Nootropics Racetams