Nootropic
Encyclopedia
Nootropics also referred to as smart drugs, brain steroids, memory enhancers, cognitive enhancers, and intelligence enhancers, are drug
s, supplement
s, nutraceutical
s, and functional food
s that improve mental functions such as cognition
, memory
, intelligence
, motivation
, attention
, and concentration. The word nootropic was coined in 1972 by the Romanian
Dr. Corneliu E. Giurgea
, derived from the Greek
words νους nous, or "mind," and τρέπειν trepein meaning "to bend/turn". Nootropics are thought to work by altering the availability of the brain's
supply of neurochemicals (neurotransmitters, enzymes, and hormones), by improving the brain's oxygen
supply, or by stimulating nerve growth. However the efficacy
of nootropic substances, in most cases, has not been conclusively determined. This is complicated by the difficulty of defining and quantifying cognition and intelligence.
s, supplement
s, nutraceutical
s, and functional food
s that enhance concentration
and memory
. Nootropics are cognitive enhancers that are neuroprotective or extremely nontoxic. Nootropics are by definition cognitive enhancers, but a cognitive enhancer is not necessarily a nootropic.
These drugs are used primarily to treat people with cognitive difficulties such as Alzheimer's disease
, Parkinson's disease
, and ADHD. However, more widespread use is being recommended by some researchers. These drugs have a variety of human enhancement
applications as well, and are marketed heavily on the Internet
. Nevertheless, intense marketing may not correlate with efficacy
; while scientific studies support some of the claimed benefits, it is worth noting that many of the claims attributed to most nootropics have not been formally tested.
In academia, modafinil
has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals. Stimulants such as methylphenidate
are being used on college campuses, and by an increasingly younger group. One survey found that 7% of students had used stimulants for a cognitive edge in the past year, and on some campuses the number is as high as 25%.
s, and these concerns apply to cognitive-enhancing drugs as well. Cognitive enhancers are often taken for the long-term when little data is available.
Dr. Corneliu E. Giurgea
originally coined the word nootropics for brain-enhancing drugs with very few side-effects. Racetam
s are sometimes cited as an example of a nootropic with few side-effects and wide therapeutic window
; however, any substance ingested could produce harmful effects. An unapproved drug
or dietary supplement
does not have to have safety or efficacy approval before being sold. (This mainly applies to the USA, but may not apply in the EU or elsewhere.)
is the most commonly taken nootropic, there are many relatives in the family that have different potencies and side-effects. Studies of the racetams have revealed that these structurally similar compounds often act via different mechanisms. These other common racetams include pramiracetam
, oxiracetam
, and aniracetam
. Their mechanisms of action are not fully understood, however, piracetam and aniracetam are known to act as positive allosteric modulator
s of AMPA receptor
s. They also appear to modulate acetylcholine
rgic systems. Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam
shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.
Other substances sometimes classified as nootropics include hydergine, vinpocetine
, bifemelane
, huperzine A
(cholinergic activator below), and dimethylaminoethanol (DMAE).
and amphetamine
s by the general population to increase brain power.
(Ritalin) or amphetamine
. Dopaminergic nootropics include dopamine synthesis precursors, dopamine reuptake inhibitors, monoamine oxidase inhibitors, and other compounds:
is a facilitator of memory formation. Increasing the availability of this neurotransmitter in the brain may improve these functions. Cholinergic nootropics include acetylcholine precursors and cofactors, and acetylcholinesterase inhibitors:
receptor site has recently displayed memory improvements when inverse agonized
.
transmitter and the AMPA receptors are currently being researched, and there are signs that significant memory improvement and possible alertness enhancement may occur when agonized. The drug class for AMPA system modulation is called Ampakine
s. Although there are many Ampakine
s currently in-research, those mentioned here are significantly notable, and/or show reasonable signs of coming to market.
Some racetams have shown this activity, such as aniracetam
is a secondary messenger that, if increased, has shown memory improvements. One common method is by decreasing the activity of phosphodiesterase
-4, an enzyme that breaks down cAMP. Typical effects include wakefulness and memory enhancement.
receptors are concentrated heavily in the prefrontal cortex
and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal cortex.
is a neurotransmitter with various effects on mood and possible effects on neurogenesis
. Serotonergic
s are substances that affect the neurotransmitter serotonin or the components of the nervous system that use serotonin. Serotonergic nootropics include serotonin precursors and cofactors, and serotonin reuptake inhibitors:
, and depressed mood
negatively affect cognitive performance. It is reasoned that counteracting and preventing depression and stress
may be an effective nootropic strategy. The term adaptogen
applies to most herbal anti-stress claims.
The substances below may not have been mentioned earlier on the page:
, removal of waste, and intake of new materials. Improving blood flow or altering these processes can benefit brain function. The list below contains only vasodilators that have shown at least probable mental enhancement.
and cell death, therefore exerting a neuroprotective effect.
Nootropics with proven or purported benefits:
.
.
Examples of adaptogens are plants like the ayurvedic "Holy Basil" or "Tulsi" which is commonly found in nootropic supplements like excelerol.
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s, supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
s, nutraceutical
Nutraceutical
Nutraceutical, a portmanteau of the words “nutrition” and “pharmaceutical”, is a food or food product that reportedly provides health and medical benefits, including the prevention and treatment of disease. Health Canada defines the term as "a product isolated or purified from foods that is...
s, and functional food
Functional food
Functional food is a food where a new ingredient has been added to a food and the new product has a new function ....
s that improve mental functions such as cognition
Cognition
In science, cognition refers to mental processes. These processes include attention, remembering, producing and understanding language, solving problems, and making decisions. Cognition is studied in various disciplines such as psychology, philosophy, linguistics, and computer science...
, memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
, intelligence
Intelligence
Intelligence has been defined in different ways, including the abilities for abstract thought, understanding, communication, reasoning, learning, planning, emotional intelligence and problem solving....
, motivation
Motivation
Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...
, attention
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
, and concentration. The word nootropic was coined in 1972 by the Romanian
Romanians
The Romanians are an ethnic group native to Romania, who speak Romanian; they are the majority inhabitants of Romania....
Dr. Corneliu E. Giurgea
Corneliu E. Giurgea
Corneliu E. Giurgea was a Romanian psychologist and chemist.In 1964, he synthetised Piracetam, which he has described as a nootropic.Giurgea coined the term nootropic in 1972.-Nootropic characteristics:...
, derived from the Greek
Ancient Greek
Ancient Greek is the stage of the Greek language in the periods spanning the times c. 9th–6th centuries BC, , c. 5th–4th centuries BC , and the c. 3rd century BC – 6th century AD of ancient Greece and the ancient world; being predated in the 2nd millennium BC by Mycenaean Greek...
words νους nous, or "mind," and τρέπειν trepein meaning "to bend/turn". Nootropics are thought to work by altering the availability of the brain's
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
supply of neurochemicals (neurotransmitters, enzymes, and hormones), by improving the brain's oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
supply, or by stimulating nerve growth. However the efficacy
Efficacy
Efficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...
of nootropic substances, in most cases, has not been conclusively determined. This is complicated by the difficulty of defining and quantifying cognition and intelligence.
Nootropics vs. cognitive enhancers
Cognitive enhancers are drugDrug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s, supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
s, nutraceutical
Nutraceutical
Nutraceutical, a portmanteau of the words “nutrition” and “pharmaceutical”, is a food or food product that reportedly provides health and medical benefits, including the prevention and treatment of disease. Health Canada defines the term as "a product isolated or purified from foods that is...
s, and functional food
Functional food
Functional food is a food where a new ingredient has been added to a food and the new product has a new function ....
s that enhance concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
and memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
. Nootropics are cognitive enhancers that are neuroprotective or extremely nontoxic. Nootropics are by definition cognitive enhancers, but a cognitive enhancer is not necessarily a nootropic.
Availability and prevalence
At present, there are several drugs on the market that improve memory, concentration, and planning, and reduce impulsive behavior. Many more are in different stages of development. The most commonly used class of drug is stimulants.These drugs are used primarily to treat people with cognitive difficulties such as Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, and ADHD. However, more widespread use is being recommended by some researchers. These drugs have a variety of human enhancement
Human enhancement
Human enhancement refers to any attempt to temporarily or permanently overcome the current limitations of the human body through natural or artificial means...
applications as well, and are marketed heavily on the Internet
Internet
The Internet is a global system of interconnected computer networks that use the standard Internet protocol suite to serve billions of users worldwide...
. Nevertheless, intense marketing may not correlate with efficacy
Efficacy
Efficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...
; while scientific studies support some of the claimed benefits, it is worth noting that many of the claims attributed to most nootropics have not been formally tested.
In academia, modafinil
Modafinil
Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals. Stimulants such as methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
are being used on college campuses, and by an increasingly younger group. One survey found that 7% of students had used stimulants for a cognitive edge in the past year, and on some campuses the number is as high as 25%.
Recreational drugs
Many recreational substances that are currently illegal or heavily controlled have effects on the brain or long-term functions that are typically considered secondary to their effects on perception. Note that this list is not intended to be exhaustive. This list includes substances that are illegal, or not completely illegal, but are not controlled or exempt under a Drug schedule.- TetrahydrocannabinolTetrahydrocannabinolTetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ1-THC , or dronabinol, is the main chemical psychoactive substance found in the cannabis plant. It was first isolated in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed...
- AnxiolyticAnxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
and analgesicAnalgesicAn analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
found in cannabisCannabisCannabis is a genus of flowering plants that includes three putative species, Cannabis sativa, Cannabis indica, and Cannabis ruderalis. These three taxa are indigenous to Central Asia, and South Asia. Cannabis has long been used for fibre , for seed and seed oils, for medicinal purposes, and as a...
. Neuroprotectant, possible Alzheimer's prevention and possible neurogenesisNeurogenesisNeurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
inducer. - AmphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
-type stimulants are described above - 4-methylaminorex - similar to modafinilModafinilModafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
but significantly more abuse potential - Most entheogens, including hallucinogens - drugs or substances that have shown value in psychotherapyPsychotherapyPsychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...
, like psilocybin mushrooms, mescalineMescalineMescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....
, MDMA, LSDLSDLysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
and DMTDMTDMT may refer to:In chemical substances:* Dimethyltryptamine, a psychedelic tryptamine* Dimethyl terephthalate, a polyester precursor* Desoxymethyltestosterone, a designer anabolic steroid...
. - MDPVMDPVMethylenedioxypyrovalerone is a psychoactive drug with stimulant properties which acts as a norepinephrine-dopamine reuptake inhibitor . Reportedly, it has been sold since around 2004 as a designer drug. It is also known as MDPK, MTV, Magic, Maddie, Black Rob, Super Coke and PV...
- designer drug, 4x as potent as methylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
, greater abuse potential - TobaccoTobaccoTobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
- Contains nicotineNicotineNicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
and also has significant MAOI activity
Traditional herbs
A 2007 survey online databases for herbs used in traditional herbal medicine to treat cognitive decline found over 150 plant species, such as Ginkgo biloba.Hazards
The main concern with pharmaceutical drugs is adverse effectAdverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s, and these concerns apply to cognitive-enhancing drugs as well. Cognitive enhancers are often taken for the long-term when little data is available.
Dr. Corneliu E. Giurgea
Corneliu E. Giurgea
Corneliu E. Giurgea was a Romanian psychologist and chemist.In 1964, he synthetised Piracetam, which he has described as a nootropic.Giurgea coined the term nootropic in 1972.-Nootropic characteristics:...
originally coined the word nootropics for brain-enhancing drugs with very few side-effects. Racetam
Racetam
Racetams are a class of nootropic drugs that share a pyrrolidone nucleus.-Mechanism:There is no generally accepted mechanism for racetams. They generally show no affinity for the most important receptors, although modulation of most important central neurotransmitters, including acetylcholine and...
s are sometimes cited as an example of a nootropic with few side-effects and wide therapeutic window
Therapeutic window
The Therapeutic window of a drug is the range of drug dosages which can treat disease effectively while staying within the safety range. In other words, it is the dosages of a medication between the amount that gives an effect and the amount that gives more adverse effects than desired effects...
; however, any substance ingested could produce harmful effects. An unapproved drug
Approved drug
In the United States, the FDA approves drugs. Before a drug can be prescribed, it must undergo an extensive FDA approval process. This process involves first testing the drug on animals or in medical labs. If found to be safe by the FDA and approved for the next phase of study, the drug is then...
or dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
does not have to have safety or efficacy approval before being sold. (This mainly applies to the USA, but may not apply in the EU or elsewhere.)
Vitamins and supplements
- B VitaminsB vitaminsB vitamins are a group of water-soluble vitamins that play important roles in cell metabolism. The B vitamins were once thought to be a single vitamin, referred to as vitamin B . Later research showed that they are chemically distinct vitamins that often coexist in the same foods...
—may influence cognitive function through an effect on methylationMethylationIn the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
and homocysteineHomocysteineHomocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
levels, as excess homocysteine has been associated with cognitive impairment and the B vitamins work to reduce homocysteine. However, although epidemiological evidence shows an association, two studies did not find B vitamin supplementation improves cognitive function, and another that found an association was criticized. A systematic review of trials found "little evidence of a beneficial impact" from supplements on cognitive function later in life.
- Omega-3—linked to the maintenance brain function. A study done in Norway, demonstrated a potential link between Omega-3 consumption during pregnancy and child intelligence test scores.
- IsoflavoneIsoflavoneIsoflavones comprise a class of organic compounds, often naturally occurring, related to the isoflavonoids. Many act as phytoestrogens in mammals...
s—may be related to cognitive function
Racetams
The word nootropic was coined upon discovery of the effects of piracetam, developed in the 1960s. Although piracetamPiracetam
Piracetam is a nootropic drug. Piracetam's chemical name is 2-oxo-1-pyrrolidine acetamide; it shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid . Piracetam is a cyclic derivative of GABA. It is one of the group of racetams...
is the most commonly taken nootropic, there are many relatives in the family that have different potencies and side-effects. Studies of the racetams have revealed that these structurally similar compounds often act via different mechanisms. These other common racetams include pramiracetam
Pramiracetam
Pramiracetam is a nootropic dietary supplement derived from piracetam, and is more potent . It belongs to the racetam family of nootropics....
, oxiracetam
Oxiracetam
Oxiracetam is a nootropic drug of the racetam family.Several animal studies suggest that the substance is safe even when high doses are consumed for a long period of time...
, and aniracetam
Aniracetam
Aniracetam is an ampakine and nootropic of the racetam chemical class purported to be considerably more potent than piracetam. It is lipid-soluble and has possible cognition-enhancing effects. It has been tested in animals extensively, Alzheimer's patients, and temporarily-impaired healthy subjects...
. Their mechanisms of action are not fully understood, however, piracetam and aniracetam are known to act as positive allosteric modulator
Positive allosteric modulator
A positive allosteric modulator is a drug which increases the activity of a receptor indirectly via activation of an allosteric site on the protein. PAMs are similar to agonists in that they contribute to overall receptor activation, but they are different because they do so in a functionally...
s of AMPA receptor
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
s. They also appear to modulate acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
rgic systems. Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam
Nefiracetam
Nefiracetam is a nootropic antidementia drug of the racetam family.Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, and monoaminergic neuronal systems that give antiamnesia effects to the Alzheimer's type and cerebrovascular type of dementia.Nefiracetam...
shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.
Other substances sometimes classified as nootropics include hydergine, vinpocetine
Vinpocetine
Vinpocetine is a semisynthetic derivative alkaloid of vincamine , an extract from the periwinkle plant....
, bifemelane
Bifemelane
Bifemelane is a pharmaceutical drug used in the treatment of senile dementia in Japan. It has nootropic, neuroprotective, and antidepressant effects, and acts through the cholinergic system in the brain. Bifemelane is also useful for the treatment of glaucoma....
, huperzine A
Huperzine A
Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the plant firmoss Huperzia serrata. and in varying quantities in other Husperzia spp.including H. elmeri, H. carinat, H. aqualupian,...
(cholinergic activator below), and dimethylaminoethanol (DMAE).
Stimulants
Stimulants are often seen as smart drugs, but may be more accurately termed productivity enhancers. Some stimulants can enhance cognition and memory in some people, but cause psychosis in others. They generally have a very substantial side-effect profile and are not considered classical "nootropic" drugs. These typically improve concentration and a few areas of cognitive performance, but only while the drug is still in the blood. Some scientists recommend widespread use of stimulants such as methylphenidateMethylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
and amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
s by the general population to increase brain power.
- AmphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
s- AmphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
(AdderallAdderallAdderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
, DexedrineDextroamphetamineDextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
)—adrenergic, dopaminergic - Lisdexamfetamine (Vyvanse)—dextroamphetamine prodrugProdrugA prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
- MethamphetamineMethamphetamineMethamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
(Desoxyn)—adrenergic, dopaminergic
- Amphetamine
- AdrenergicAdrenergicAn adrenergic agent is a drug, or other substance, which has effects similar to, or the same as, epinephrine . Thus, it is a kind of sympathomimetic agent...
s- Atomoxetine—norepinephrine reuptake inhibitorNorepinephrine reuptake inhibitorA norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
; approved for ADHD - ReboxetineReboxetineReboxetine is a drug marketed as an antidepressant for use in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia . Its mesylate salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra...
—Norepinephrine reuptake inhibitorNorepinephrine reuptake inhibitorA norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
; approved in Europe for clinical depressionClinical depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
but may also be used off-label to treat ADHD - SynephrineSynephrineSynephrine is a drug commonly used for weight loss. While its effectiveness is widely debated, synephrine has gained significant popularity as an alternative to ephedrine, a related substance which has been made illegal or restricted in many countries due to health risks and its use as a precursor...
(found in Bitter orangeBitter orangeThe name "bitter orange", also known as Seville orange, sour orange, bigarade orange, and marmalade orange, refers to a citrus tree and its fruit. Many varieties of bitter orange are used for their essential oil, which is used in perfume and as a flavoring...
)—agonist at α1 adrenergic receptorAlpha-1 adrenergic receptorThe alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...
s
- Atomoxetine—norepinephrine reuptake inhibitor
- CholinergicCholinergicThe word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...
s- ArecolineArecolineArecoline is an alkaloid natural product found in the areca nut, the fruit of the areca palm . It is an odourless oily liquid volatile in steam, miscible with most organic solvents and water, but extractable from the latter by ether in presence of dissolved salts. The salts are crystalline, but...
- NicotineNicotineNicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
- Arecoline
- Eugeroics ("Wakefulness Enhancers")—unproven primary mechanisms but proven efficacy
- AdrafinilAdrafinilAdrafinil is a mild central nervous system stimulant drug used to relieve excessive sleepiness and inattention in elderly patients...
- ArmodafinilArmodafinilArmodafinil is a stimulant-like drug produced by the pharmaceutical company Cephalon Inc., which was approved by the FDA on June 15, 2007...
- ModafinilModafinilModafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
- Adrafinil
- XanthineXanthineXanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....
s—reduces fatigue perception- CaffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
—shown to increase alertness, performance and in some studies memory. Children and adults who consume low doses of caffeine showed increase alertness, yet a higher dose was needed to improve performance. Caffeine has also been shown to have more of an effect on improving cognitive performance and sustaining attention in older adults. Chronic pretreatment of caffeine in animals has shown to reduce ischaemic brain damage, in addition to reducing the risk of Parkinson’s disease. - ParaxanthineParaxanthineParaxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine. Like caffeine, paraxanthine is a psychoactive central nervous system stimulant...
- TheobromineTheobromineTheobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...
- TheophyllineTheophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
- Caffeine
Dopaminergics
Dopaminergics are substances that affect the neurotransmitter dopamine or the components of the nervous system that use dopamine. Attributable effects of dopamine are enhancement of attention, alertness, and antioxidant activity. Dopamine is the primary activity of stimulants like methylphenidateMethylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(Ritalin) or amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
. Dopaminergic nootropics include dopamine synthesis precursors, dopamine reuptake inhibitors, monoamine oxidase inhibitors, and other compounds:
- Metabolic precursors—raise levels
- L-PhenylalaninePhenylalaninePhenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
—purported cognitive improvement - L-TyrosineTyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
(or N-Acetyl-L-Tyrosine, more bioavailable form)—purported cognitive improvement - L-DOPA (L-3,4-dihydroxyphenylalanine)—precursorPrecursor (chemistry)In chemistry, a precursor is a compound that participates in the chemical reaction that produces another compound. In biochemistry, the term "precursor" is used more specifically to refer to a chemical compound preceding another in a metabolic pathway....
to catecholamineCatecholamineCatecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
s (dopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
); neurotoxic effects documented - BiopterinBiopterinBiopterin is a coenzyme that is produced within the body.It is an oxidized degradation product of tetrahydrobiopterin.Defects in biopterin synthesis or regeneration can cause a form of hyperphenylalaninemia ....
—a rare vitaminVitaminA vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
(coenzyme) that is synthesized in the pineal glandPineal glandThe pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...
& crucial to the biosynthesisBiosynthesisBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of dopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their... - Pyridoxal-phosphatePyridoxal-phosphatePyridoxal-phosphate is a prosthetic group of some enzymes. It is the active form of vitamin B6, which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine.-Role as a coenzyme:...
(or PLP, pyridoxal-5'-phosphate, P5P, active form of Vitamin B6Vitamin B6Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
)—plays a role in the conversion of L-DOPA into dopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
(via the enzyme aromatic L-amino acid decarboxylaseAromatic L-amino acid decarboxylaseAromatic L-amino acid decarboxylase is a lyase enzyme.-Reactions:It catalyzes several different decarboxylation reactions:* L-DOPA to dopamine - a neurotransmitter* 5-HTP to serotonin - also a neurotransmitter...
)
- L-Phenylalanine
- Reuptake inhibitors—stabilize/improve levels
- AmineptineAmineptineAmineptine was developed by the French Society of Medical research in the 1960s. Under the trade-names is used as an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting...
—mild stimulant - MethylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
—stimulant approved for ADHD; strong DAT inhibitionDopamine reuptake inhibitorA dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter... - BupropionBupropionBupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
—atypical antidepressant; moderate DAT inhibitionDopamine reuptake inhibitorA dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...
- Amineptine
- MAO-B inhibitorsMonoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
—prevent breakdown- SelegilineSelegilineSelegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...
—Mild stimulant; irreversible - RasagilineRasagilineRasagiline is an irreversible inhibitor of monoamine oxidase used as a monotherapy in early Parkinson's disease or as an adjunct therapy in more advanced cases. It is selective for MAO type B over type A by a factor of fourteen....
—Mild stimulant; irreversible - Rhodiola roseaRhodiola roseaRhodiola rosea is a plant in the Crassulaceae family that grows in cold regions of the world. These include much of the Arctic, the mountains of Central Asia, the Rocky Mountains, and mountainous parts of Europe, such as the Alps, Pyrenees, Carpathian Mountains, Scandinavia, Iceland, Great...
—Adaptogenic herb; reversible
- Selegiline
- Dopamine agonists
- RopiniroleRopiniroleRopinirole is a non-ergoline dopamine agonist. It is manufactured by GlaxoSmithKline , Cipla and Sun Pharmaceutical. It is used in the treatment of Parkinson's disease...
—agonist at D2, D3, and D4 receptors - PramipexolePramipexolePramipexole is a non-ergoline dopamine agonist indicated for treating early-stage Parkinson's disease and restless legs syndrome...
—agonist at D2, D3 and D4 receptors
- Ropinirole
- Others
- Mucuna pruriensMucuna pruriensMucuna pruriens is a tropical legume known as velvet bean or cowitch and by other common names , found in Africa, India and the Caribbean. The plant is infamous for its extreme itchiness produced on contact, particularly with the young foliage and the seed pods...
(Velvet Bean)—natural source of L-DOPA - ModafinilModafinilModafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
—purported dopaminergic activity - CiticolineCiticolineCiticoline , also known as cytidine diphosphate-choline & cytidine 5'-diphosphocholine is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline...
(INNInternational Nonproprietary NameAn International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
) (aka: cytidine diphosphateCytidine diphosphateCytidine diphosphate, abbreviated CDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside cytidine. CDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase cytosine....
-choline (CDP-Choline) & cytidine 5'-diphosphocholine)—studies suggest CDP-choline supplements increase dopamine receptor densities, and suggest that CDP-choline supplementation can ameliorate memory impairment caused by environmental conditions. Preliminary research has found that citicoline supplements help improve focus and mental energy and may possibly be useful in the treatment of attention deficit disorder.
- Mucuna pruriens
Concentration and memory enhancement
The nootropics in this section are purported or shown to enhance concentration or the recollection and formation of memories.Cholinergics
Cholinergics are substances that affect the neurotransmitter acetylcholine or the components of the nervous system that use acetylcholine. AcetylcholineAcetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
is a facilitator of memory formation. Increasing the availability of this neurotransmitter in the brain may improve these functions. Cholinergic nootropics include acetylcholine precursors and cofactors, and acetylcholinesterase inhibitors:
- Precursors
- CholineCholineCholine is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
—precursor of acetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
and phosphatidylcholinePhosphatidylcholinePhosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically... - DMAE—precursor of acetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
- Meclofenoxate—probable precursor of acetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
, approved for DementiaDementiaDementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
and Alzheimer's - Alpha-GPCAlpha-GPCL-Alpha Glycerylphosphorylcholine is a natural choline compound found in the brain and in milk. It is also a parasympathomimetic acetylcholine precursor which may have potential for the treatment of Alzheimer's disease and is used as a nootropic dietary supplement to enhance memory and...
—thought to be the only cholinergic that delivers choline to the brain across the Blood-brain barrierBlood-brain barrierThe blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
; sold under its chemical name
- Choline
- Cofactors
- AcetylcarnitineAcetylcarnitineAcetyl-L-carnitine or ALCAR, is an acetylated form of L-carnitine. It is a dietary supplement and naturally occurs in plants and animals.- Biochemical Production and Action :ALCAR is an acetylated derivative of L-carnitine...
—amino acid that functions in acetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
production by donating the acetyl portion to the acetylcholine molecule - Vitamin B5—cofactor in the conversion of choline into acetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
- Acetylcarnitine
- AcetylcholinesteraseAcetylcholinesterase"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
inhibitors- GalantamineGalantamineGalantamine is used for the treatment of mild to moderate Alzheimer’s disease and various other memory impairments, in particular those of vascular origin...
- Lycoris radiata (Red Spider Lily)—natural source for galantamineGalantamineGalantamine is used for the treatment of mild to moderate Alzheimer’s disease and various other memory impairments, in particular those of vascular origin...
- Huperzine AHuperzine AHuperzine A is a naturally occurring sesquiterpene alkaloid compound found in the plant firmoss Huperzia serrata. and in varying quantities in other Husperzia spp.including H. elmeri, H. carinat, H. aqualupian,...
—also shown to act as an NMDA antagonist and appears to increase nerve growth factorNerve growth factorNerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
levels in rats - DonepezilDonepezilDonepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include...
- RosemaryRosemaryRosemary, , is a woody, perennial herb with fragrant, evergreen, needle-like leaves and white, pink, purple or blue flowers, native to the Mediterranean region. It is a member of the mint family Lamiaceae, which includes many other herbs, and is one of two species in the genus Rosmarinus...
- Sage
- Marijuana Due to marijuana's AChE-inhibiting properties, studies suggest it as a treatment for Alzheimer's.
- Galantamine
- ReuptakeReuptakeReuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
inhibitors and enchancers- ColuracetamColuracetamColuracetam is a nootropic drug of the racetam family. It may also have potential use in prevention and treatment of ischemic retinopathy and retinal and optic nerve injury....
—choline uptake enhancer
- Coluracetam
- Agonists
- IsproniclineIsproniclineIspronicline is a drug which acts as a partial agonist at neural nicotinic acetylcholine receptors. It is subtype-selective, binding primarily to the α4β2 subtype. It has antidepressant, nootropic and neuroprotective effects, and is under development for the treatment of dementia and Alzheimer's...
- NicotineNicotineNicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
- ArecolineArecolineArecoline is an alkaloid natural product found in the areca nut, the fruit of the areca palm . It is an odourless oily liquid volatile in steam, miscible with most organic solvents and water, but extractable from the latter by ether in presence of dissolved salts. The salts are crystalline, but...
- Ispronicline
GABA blockers
The GABAA α5GABRA5
Gamma-aminobutyric acid A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene.-Function:...
receptor site has recently displayed memory improvements when inverse agonized
Inverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....
.
- α5IA—α5 inverse agonist
- SuritozoleSuritozoleSuritozole is an investigational cognition enhancer. It acts as a partial inverse agonist at the benzodiazepine receptor site on the GABAA ion channel compex, but does not have either anxiogenic or convulsant effects, unlike other BZD inverse agonists such as DMCM...
—α5 partial inverse agonist
Glutamate activators
The AMPAAMPA
AMPA is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate....
transmitter and the AMPA receptors are currently being researched, and there are signs that significant memory improvement and possible alertness enhancement may occur when agonized. The drug class for AMPA system modulation is called Ampakine
Ampakine
Ampakines are a class of compounds known to enhance attention span and alertness, and facilitate learning and memory. The ampakines take their name from the glutamatergic AMPA receptor with which they strongly interact...
s. Although there are many Ampakine
Ampakine
Ampakines are a class of compounds known to enhance attention span and alertness, and facilitate learning and memory. The ampakines take their name from the glutamatergic AMPA receptor with which they strongly interact...
s currently in-research, those mentioned here are significantly notable, and/or show reasonable signs of coming to market.
Some racetams have shown this activity, such as aniracetam
Aniracetam
Aniracetam is an ampakine and nootropic of the racetam chemical class purported to be considerably more potent than piracetam. It is lipid-soluble and has possible cognition-enhancing effects. It has been tested in animals extensively, Alzheimer's patients, and temporarily-impaired healthy subjects...
- CX-717—pending FDA approval for memory-impairing illnesses
- IDRA-21IDRA-21IDRA-21 is an ampakine drug derived from aniracetam. IDRA-21 is a chiral molecule, with -IDRA-21 being the active form.IDRA-21 shows nootropic effects in animal studies, significantly improving learning and memory...
—believed to improve memory by significantly enhancing long-term potentiationLong-term potentiationIn neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
but used only in animals; incredibly potent - LY-503,430LY-503,430LY-503,430 is an ampakine drug developed by Eli Lilly.LY-503,430 produces both nootropic and neuroprotective effects, reducing brain damage caused by 6-hydroxydopamine or MPTP and also increasing levels of the neurotrophic factor BDNF in the brain, particularly in the substantia nigra, hippocampus...
—under development for Parkinson's but showing increase in BDNF, specifically in areas of memory and higher cognitive skills
cAMP
Cyclic adenosine monophosphateCyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
is a secondary messenger that, if increased, has shown memory improvements. One common method is by decreasing the activity of phosphodiesterase
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
-4, an enzyme that breaks down cAMP. Typical effects include wakefulness and memory enhancement.
- PropentofyllinePropentofyllinePropentofylline is a xanthine derivative with purported neuroprotective effects.-Pharmacology:It is a phosphodiesterase inhibitor.It also acts as an adenosine reuptake inhibitor.-Uses:...
—nonselective phosphodiesterase inhibitor with some neuroenhancement - RolipramRolipramRolipram is a PDE4-inhibitor. Like most PDE4-inhibitors, it is an anti-inflammatory drug. Rolipram is being studied as a possible alternative to current antidepressants. Recent studies show that rolipram may have antipsychotic effects...
—PDE4 inhibitor, shows alertness enhancement, long term memory improvement and neuroprotection - MesembrineMesembrineMesembrine is an alkaloid present in Sceletium tortuosum. Mesembrine acts as a serotonin reuptake inhibitor. Mesembrine may contribute to the antidepressant effects of kanna....
—PDE4-inhibitor with possible serotonergic activity
Other
α2AAlpha-2A adrenergic receptor
The alpha-2A adrenergic receptor , also known as ADRA2A, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.-Role in Central Nervous System:...
receptors are concentrated heavily in the prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal cortex.
- GuanfacineGuanfacineGuanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
is an α2A receptor agonist, FDA approved for and frequently used to treat ADHD symptoms. Studies have shown guanfacine to strengthen working memory, reduce distractibility, improve response inhibition, increase regional cerebral blood flow, reduce locomotor hyperactivity, and improve attentional control in animal models, as well as enhance memory function in humans.
Serotonergics
SerotoninSerotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
is a neurotransmitter with various effects on mood and possible effects on neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
. Serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...
s are substances that affect the neurotransmitter serotonin or the components of the nervous system that use serotonin. Serotonergic nootropics include serotonin precursors and cofactors, and serotonin reuptake inhibitors:
- Precursors
- 5-HTP—precursor (intermediate between tryptophanTryptophanTryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
and serotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
) - TryptophanTryptophanTryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
—essential amino acid precursor
- 5-HTP—precursor (intermediate between tryptophan
- Cofactors
- Pyridoxal-phosphatePyridoxal-phosphatePyridoxal-phosphate is a prosthetic group of some enzymes. It is the active form of vitamin B6, which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine.-Role as a coenzyme:...
(or PLP, pyridoxal-5'-phosphate, P5P, active form of Vitamin B6Vitamin B6Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
)—plays role in conversion of 5-HTP into serotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(via the enzyme aromatic L-amino acid decarboxylaseAromatic L-amino acid decarboxylaseAromatic L-amino acid decarboxylase is a lyase enzyme.-Reactions:It catalyzes several different decarboxylation reactions:* L-DOPA to dopamine - a neurotransmitter* 5-HTP to serotonin - also a neurotransmitter...
).
- Pyridoxal-phosphate
- Reuptake inhibitors
- SSRIs—class of antidepressants that increase active serotonin levels by inhibiting reuptake, also shown to promote NeurogenesisNeurogenesisNeurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
in the hippocampus - Sceletium tortuosumSceletium tortuosumSceletium tortuosum is a succulent herb commonly found in South Africa, which is also known as Kanna, Channa, Kougoed - which literally means, 'chew things/goodies' or 'something to chew'...
—active constituent mesembrineMesembrineMesembrine is an alkaloid present in Sceletium tortuosum. Mesembrine acts as a serotonin reuptake inhibitor. Mesembrine may contribute to the antidepressant effects of kanna....
shown to act as an SSRI and PDE4 inhibitorPDE4 inhibitorA phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 on cyclic adenosine monophosphate . It is a member of the larger family of PDE inhibitors. The PDE4 family of enzymes are the most prevalent PDE in...
. (Half-life unknown) - Hypericum perforatum—inhibits reuptake of serotonin (as well as Norepinephrine, Dopamine, GABA and Glutamate) via activation of TRPC6TRPC6Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential ion channel...
- SSRIs—class of antidepressants that increase active serotonin levels by inhibiting reuptake, also shown to promote Neurogenesis
- MAO-A inhibitorsMonoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
- ResveratrolResveratrolResveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi....
- CurcuminCurcuminCurcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family . The other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are natural phenols and are responsible for the yellow color of turmeric...
- PiperinePiperinePiperine is the alkaloid responsible for the pungency of black pepper and long pepper, along with chavicine . It has also been used in some forms of traditional medicine and as an insecticide. Piperine forms monoclinic needles, is slightly soluble in water and more so in alcohol, ether or...
- HarmalHarmalHarmal is a plant of the family Nitrariaceae, native from the eastern Mediterranean region east to India. It is also known as Wild Rue or Syrian Rue because of its resemblance to plants of the rue family....
- Rhodiola roseaRhodiola roseaRhodiola rosea is a plant in the Crassulaceae family that grows in cold regions of the world. These include much of the Arctic, the mountains of Central Asia, the Rocky Mountains, and mountainous parts of Europe, such as the Alps, Pyrenees, Carpathian Mountains, Scandinavia, Iceland, Great...
- Resveratrol
- Reuptake enhancers
- TianeptineTianeptineTianeptine was discovered by The French Society of Medical Research in the 1960s. Under the trade-names it is a drug used for treating major depressive episodes ....
—paradoxical antidepressant (considered to be a selective serotonin reuptake enhancerSelective serotonin reuptake enhancerA selective serotonin reuptake enhancer is a type of drug which enhances the plasmalemmal reuptake of the neurotransmitter serotonin, leading to a decrease in its synaptic concentrations and therefore a decrease in serotonergic neurotransmission....
(SSRE) (note that no widely known proof of direct SSRE action exists)), improves mood and reduces anxiety; action on the NMDANMDA receptorThe NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
and AMPA receptorAMPA receptorThe α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
, a hypothesized mechanism of action, based on tianeptine's effect of promoting stress-associated impaired neuroplasticityNeuroplasticityNeuroplasticity is a non-specific neuroscience term referring to the ability of the brain and nervous system in all species to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in...
; it enhances the extracellular concentration of dopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
in the nucleus accumbensNucleus accumbensThe nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
and modulates the D2Dopamine receptor D2Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
and D3Dopamine receptor D3D dopamine receptor is a protein that in humans is encoded by the DRD3 gene.This gene encodes the D3 subtype of the dopamine receptor. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that...
dopamine receptors, but this effect is modest and almost certainly indirect.
- Tianeptine
Anti-depression, adaptogenic (antistress), and mood stabilization
Stress, depressionClinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, and depressed mood
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
negatively affect cognitive performance. It is reasoned that counteracting and preventing depression and stress
Stress management
Stress management is the alteration of stress and especially chronic stress often for the purpose of improving everyday functioning.Stress produces numerous symptoms which vary according to persons, situations, and severity. These can include physical health decline as well as depression. According...
may be an effective nootropic strategy. The term adaptogen
Adaptogen
An adaptogen is a herbal product claimed to increase resistance to stress, trauma, anxiety and fatigue. The term is used mainly by herbalists who also refer to adaptogens as rejuvenating herbs, qi tonics, rasayanas, or restoratives...
applies to most herbal anti-stress claims.
The substances below may not have been mentioned earlier on the page:
- Beta blockers—reduce somatic symptoms of anxietyAnxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
- Lemon BalmLemon balmLemon balm , not to be confused with bee balm, Monarda species, is a perennial herb in the mint family Lamiaceae, native to southern Europe and the Mediterranean region....
—displays adaptogenAdaptogenAn adaptogen is a herbal product claimed to increase resistance to stress, trauma, anxiety and fatigue. The term is used mainly by herbalists who also refer to adaptogens as rejuvenating herbs, qi tonics, rasayanas, or restoratives...
properties; also shown to possess GABA transaminase inhibitorGABA transaminase inhibitorA GABA transaminase inhibitor is an enzyme inhibitor that acts upon GABA transaminase.Examples include vigabatrin and ethanolamine-O-sulfate .Certain members of this class are used as anticonvulsants....
properties - Passion FlowerPassion flowerPassiflora, known also as the passion flowers or passion vines, is a genus of about 500 species of flowering plants, the namesakes of the family Passifloraceae. They are mostly vines, with some being shrubs, and a few species being herbaceous. For information about the fruit of the passiflora...
—possible MAOI and neurotransmitter reuptake activity - Rhodiola RoseaRhodiola roseaRhodiola rosea is a plant in the Crassulaceae family that grows in cold regions of the world. These include much of the Arctic, the mountains of Central Asia, the Rocky Mountains, and mountainous parts of Europe, such as the Alps, Pyrenees, Carpathian Mountains, Scandinavia, Iceland, Great...
—adaptogenAdaptogenAn adaptogen is a herbal product claimed to increase resistance to stress, trauma, anxiety and fatigue. The term is used mainly by herbalists who also refer to adaptogens as rejuvenating herbs, qi tonics, rasayanas, or restoratives...
; possible MAOI activity - St John's WortSt John's wortSt John's wort is the plant species Hypericum perforatum, and is also known as Tipton's Weed, Chase-devil, or Klamath weed....
—herbal supplement approved (in Europe) to treat mild depression. Method of action is unproven but exhibits effects similar to both MAOIs and SSRIs. - GinsengGinsengGinseng is any one of eleven species of slow-growing perennial plants with fleshy roots, belonging to the genus Panax of the family Araliaceae....
(including Siberian ginseng)—adaptogenAdaptogenAn adaptogen is a herbal product claimed to increase resistance to stress, trauma, anxiety and fatigue. The term is used mainly by herbalists who also refer to adaptogens as rejuvenating herbs, qi tonics, rasayanas, or restoratives...
ic effects shown - Sutherlandia frutescensSutherlandia frutescensSutherlandia frutescens is a southern African legume shrub with bitter, aromatic leaves. Red-orange flowers appear in spring.-External links:*...
—possible anti-inflammatory, reducing pain from those illnesses - KavaKavaKava or kava-kava is a crop of the western Pacific....
—anxiolytic herb - TeaTeaTea is an aromatic beverage prepared by adding cured leaves of the Camellia sinensis plant to hot water. The term also refers to the plant itself. After water, tea is the most widely consumed beverage in the world...
—contains many different adaptogens - TheanineTheanineTheanine , also gamma-glutamylethylamide or 5-N-ethyl-glutamine, is an amino acid and a glutamic acid analog commonly found in tea , primarily in green tea, and also in the basidiomycete mushroom Boletus badius and in guayusa. More specifically, this compound is called L-theanine, being the...
—GABAergic activity producing relaxation, also increases brain serotonin and dopamine levels - Grape seed extractGrape seed extractGrape seed extracts are industrial derivatives from whole grape seeds that have a great concentration of vitamin E, flavonoids, linoleic acid, and OPCs...
—has shown some efficacy in reducing bodily stress - AdafenoxateAdafenoxateAdafenoxate is a compound related to centrophenoxine, that has been found to act as a nootropic in rats....
—possible anxiolyticAnxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
effect - ValerianValerian (herb)Valerian is a hardy perennial flowering plant, with heads of sweetly scented pink or white flowers which bloom in the summer months. Valerian flower extracts were used as a perfume in the sixteenth century....
—possible anxiolyticAnxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
effect through agonism at GABA-A receptors - Butea frondosa—possible anxiolyticAnxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
effect - Gotu Kola—adaptogenAdaptogenAn adaptogen is a herbal product claimed to increase resistance to stress, trauma, anxiety and fatigue. The term is used mainly by herbalists who also refer to adaptogens as rejuvenating herbs, qi tonics, rasayanas, or restoratives...
and anxiolyticAnxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
- Foti—adaptogenAdaptogenAn adaptogen is a herbal product claimed to increase resistance to stress, trauma, anxiety and fatigue. The term is used mainly by herbalists who also refer to adaptogens as rejuvenating herbs, qi tonics, rasayanas, or restoratives...
; possible MAOI activity - Many Chinese herbs such as Panax ginseng, Polygala tenuifoliaPolygala tenuifoliaPolygala tenuifolia is an herb in the family Polygalaceae which is hardy to USDA Zone 6.-Medicinal uses:Yuan Zhi is used primarily as an expectorant...
, Acorus gramineusAcorus gramineusAcorus gramineus Sol. Aiton is a botanical species belonging to the family of Acorus.-Origin:Native to Japan in eastern Asia, where it usually occurs in wetlands and shallow water.-Description:...
and Huperzia serrataHuperzia serrataHuperzia serrata is a plant known as a firmoss which contains the acetylcholinesterase inhibitor huperzine A. It is widely distributed over-the-counter as a nootropic and dietary supplement. It may also be used to treat Alzheimer's disease.This species is native to India and southeast Asia.-...
. - Bacopa monnieriBacopa monnieriBacopa monnieri is a perennial, creeping herb whose habitat includes wetlands and muddy shores...
Blood flow and metabolic function
Brain function is dependent on many basic processes such as the usage of ATPAdenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, removal of waste, and intake of new materials. Improving blood flow or altering these processes can benefit brain function. The list below contains only vasodilators that have shown at least probable mental enhancement.
- Blessed Thistle—increases blood circulation, improving memory
- Coenzyme q-10—antioxidant; increases oxygen usage by mitochondria
- CreatineCreatineCreatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of Adenosine triphosphate...
—protects ATP during transport - Lipoic acidLipoic acidLipoic acid , also known as α-lipoic acid and Alpha Lipoic Acid is an organosulfur compound derived from octanoic acid. LA contains two vicinal sulfur atoms attached via a disulfide bond and is thus considered to be oxidized...
—improves oxygen usage and antioxidant recycling, possibly improving memory - PyritinolPyritinolPyritinol also called pyridoxine disulfide or pyrithioxine is a semi-natural water soluble analog of vitamin B6 . It was produced in 1961 by Merck Laboratories by bonding 2 vitamin B6 compounds together with a disulfide bridge...
—Drug similar to B vitamin Pyridoxine - PicamilonPicamilonPicamilon is a dietary supplement formed by combining niacin with GABA. It was developed in the Soviet Union in 1969 by the All-Union Vitamins Scientific Research Institute and further studied in both Russia and Japan as a prodrug of GABA.Picamilon is sold in the United States as a dietary...
—GABA activity and blood flow improver - Ginkgo biloba—vasodilator. Acts as an NRINorepinephrine reuptake inhibitorA norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
. - VinpocetineVinpocetineVinpocetine is a semisynthetic derivative alkaloid of vincamine , an extract from the periwinkle plant....
—increases blood circulation (vasodilator) and metabolism in the brain; also shown to inhibit voltage-sensitive Na+ channels—however, through a similar mechanism to reserpineReserpineReserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...
, Vinpocetine may temporarily deplete the monoamines serotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, dopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and norepinephrineNorepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
by inhibiting VMAT, thus preventing them from reaching the synapse. Vinpocetine may therefore induce or exasperate depressive symptoms as an adverse effect. - VincamineVincamineVincamine is a peripheral vasodilator that increases blood flow to the brain . Generic drugs containing vincamine exist in specific regions. Most common drug preparations are in the sustained release forms...
—increases blood circulation (vasodilator) and metabolism in the brain; related to vinpocetine; used in sustained release (example of a brand is Oxybral SR) - NicergolineNicergolineNicergoline is an ergot derivative used to treat senile dementia and other disorders with vascular origins. It has been found to increase mental agility and enhance clarity and perception. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of...
—an ergotErgotErgot or ergot fungi refers to a group of fungi of the genus Claviceps. The most prominent member of this group is Claviceps purpurea. This fungus grows on rye and related plants, and produces alkaloids that can cause ergotism in humans and other mammals who consume grains contaminated with its...
derivative used to treat senile dementiaDementiaDementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
and other disorders with vascularBlood vesselThe blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
origins; it has been found to increase mental agility and enhance clarity and perception; it decreases vascular resistanceVascular resistanceVascular resistance is a term used to define the resistance to flow that must be overcome to push blood through the circulatory system. The resistance offered by the peripheral circulation is known as the systemic vascular resistance , while the resistance offered by the vasculature of the lungs...
and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells; it has been used for more than three decades for the treatment of cognitive, affective, and behavioral disorders of older people.
Experimental histamine antagonists
The H3-receptor decreases neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin. Thus, H3-receptor-antagonists increases cognition and wakefulness.- CiproxifanCiproxifanCiproxifan is an extremely potent histamine H3 inverse agonist/antagonist.The histamine H3 receptor is an inhibitory autoreceptor located on histaminergic nerve terminals, and is believed to be involved in modulating the release of histamine in the brain...
—produces wakefulness and attentiveness in animal studies, and produced cognitive enhancing effects without prominent stimulant effects at relatively low levels of receptor occupancy, and pronounced wakefulness at higher doses. - A-349,821A-349,821A-349,821 is a potent and selective histamine H3 receptor antagonist . It has nootropic effects in animal studies, although there do not appear to be any plans for clinical development at present and it is currently only used in laboratory research....
—It has nootropic effects in animal studies.
Nerve growth stimulation and brain cell protection
Nerves are necessary to the foundation of brain communication and their degeneracy, underperformance, or lacking can have disastrous results on brain functions. Antioxidants may prevent oxidative stressOxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
and cell death, therefore exerting a neuroprotective effect.
- IdebenoneIdebenoneIdebenone is an experimental drug, initially developed by Takeda Pharmaceutical Company for the treatment of Alzheimer's disease and other cognitive defects. This has been met with limited success. The Swiss company Santhera Pharmaceuticals has started to investigate it for the treatment of...
—antioxidant - MelatoninMelatoninMelatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
—antioxidant - GlutathioneGlutathioneGlutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
—chief antioxidantAntioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
- AcetylcarnitineAcetylcarnitineAcetyl-L-carnitine or ALCAR, is an acetylated form of L-carnitine. It is a dietary supplement and naturally occurs in plants and animals.- Biochemical Production and Action :ALCAR is an acetylated derivative of L-carnitine...
(Acetyl-L-Carnitine Arginate or HydrochlorideHydrochlorideIn chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
) neuroprotective - InositolInositolInositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol...
—implicated in memory function, deficit linked to some psychiatric illnesses—has been shown particularly efficacious in OCD patients - AnticonvulsantAnticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s—inhibit seizure related brain malfunction if a person has seizures - PhosphatidylserinePhosphatidylserinePhosphatidylserine is a phospholipid component, usually kept on the inner-leaflet of cell membranes by an enzyme called flippase...
—possible membrane stabilizer - Lion's Mane Mushroom—Stimulated myelination in an in vitro experiment and stimulated nerve growth factorNerve growth factorNerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
in an in vitro experiment with human astrocytomaAstrocytomaAstrocytomas are a type of neoplasm of the brain. They originate in a particular kind of glial-cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usually affect other organs...
cells. Also improved cognitive ability, in a double-blind, parallel-group, placebo-controlled trial. - SAM-e (S-Adenosyl methionine)—crucial for cellular regeneration (fuels DNA methylationDNA methylationDNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...
), also involved with the biosynthesis of dopamine & serotonin - Acetylcysteine (L-cysteine)—precursor to antioxidant glutathioneGlutathioneGlutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
- ApoaequorinAequorinAequorin is a photoprotein isolated from luminescent jellyfish and a variety of other marine organisms...
(Calcium-binding proteinCalcium-binding proteinCalcium-binding proteins are proteins that participate in calcium cell signalling pathways by binding to Ca2+.The most ubiquitous Ca2+-sensing protein, found in all eukaryotic organisms including yeasts, is calmodulin....
) (CaBP)—(Prevagen®) neuroprotective (note that orally ingested proteins are not generally bioavailable and are thus unlikely have any effect) - Uncaria tomentosaUncaria tomentosaUncaria tomentosa is a woody vine found in the tropical jungles of South and Central America, which derives its name from its claw-shaped thorns...
(Cat's Claw)—in an in vitro experiment with rats, Cat's Claw (PTI-00703™), inhibited formation of brain beta amyloid deposits - (DopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
enhancers)—dopamine is an antioxidant that can enhance dendrite extension
Direct hormones
These are hormones that have activity not necessarily attributable to another specific chemical interaction, but have shown effectiveness. Only specific nootropic effects are stated.- VasopressinVasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
—memory hormone that improves both memory encoding and recall - PregnenolonePregnenolonePregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. As such it is a prohormone. Pregnenolone sulfate is a GABAA antagonist and increases neurogenesis in the hippocampus.-Chemistry:Like other steroids,...
—increases neurogenesis - OrexinOrexinOrexins, also called hypocretins, are the common names given to a pair of excitatory neuropeptide hormones that were simultaneously discovered by two groups of researchers in rat brains....
—Significant wakefulness promoter
Secondary enhancers
These are substances that by themselves may not improve brain function, but may have benefits for those who lack them (in the case of hormones) or may alter the balance of neurotransmitters.- DHEA—precursor to estrogenEstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
and testosteroneTestosteroneTestosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
Unknown enhancement
Other agents purported to have nootropic effects but do not (yet) have attributable mechanisms or clinically significant effects (but may upon refinement of administration) are listed below.Nootropics with proven or purported benefits:
- Bacopa monniera (Brahmi)—shown to possess adaptogenAdaptogenAn adaptogen is a herbal product claimed to increase resistance to stress, trauma, anxiety and fatigue. The term is used mainly by herbalists who also refer to adaptogens as rejuvenating herbs, qi tonics, rasayanas, or restoratives...
ic properties and enhance memory and concentration. Folk use in Ayurvedic medicine purports "enhancement of curiosity"; Brahmi rasayana has been shown to improve learning and memory in mice - FipexideFipexideFipexide is a psychoactive drug of the piperazine chemical class which was developed in Italy in 1983. It was used as a nootropic drug in Italy and France, mainly for the treatment of senile dementia, but is no longer in common use due to the occurrence of rare adverse drug reactions including...
—drug for DementiaDementiaDementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging... - Gerovital H3—famous alleged anti-aging mixture, most effects disproven but some mind enhancement shown
- SulbutiamineSulbutiamineSulbutiamine is a synthetic derivative of thiamine . As a dimer of two modified thiamine molecules, it is a lipophilic compound that crosses the blood-brain barrier more readily than thiamine and increases the levels of thiamine and thiamine phosphate esters in the brain...
—fat soluble vitamin B1 derivative—caused mice to perform better on operant conditioning tests and object recognition tests - Royal JellyRoyal jellyRoyal jelly is a honey bee secretion that is used in the nutrition of larvae, as well as adult queens. It is secreted from the glands in the hypopharynx of worker bees, and fed to all larvae in the colony....
—Increases brain cell growth and diversity, only demonstrated in-vitro, improbable in-vivo - CurcuminCurcuminCurcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family . The other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are natural phenols and are responsible for the yellow color of turmeric...
—significant in-vitro activity, but in-vivo activity limited by low bioavailabilityBioavailabilityIn pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
Other nootropics
These substances have been linked to better cognitive function, but may not be the cause. See correlation does not imply causationCorrelation does not imply causation
"Correlation does not imply causation" is a phrase used in science and statistics to emphasize that correlation between two variables does not automatically imply that one causes the other "Correlation does not imply causation" (related to "ignoring a common cause" and questionable cause) is a...
.
- AlcoholEthanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
—moderate drinkers tend to have better cognitive function than abstainers or heavy drinkers
Adaptogens
Although not nootropics from the standpoint of cognitive enhancement, adaptogens are plants that help the body adapt to stress. By creating an environment whereby stress is reduced, cortisol (a degenerative hormone) release is impaired. These substances have been linked to better cognitive function, but may not be the cause. See correlation does not imply causationCorrelation does not imply causation
"Correlation does not imply causation" is a phrase used in science and statistics to emphasize that correlation between two variables does not automatically imply that one causes the other "Correlation does not imply causation" (related to "ignoring a common cause" and questionable cause) is a...
.
Examples of adaptogens are plants like the ayurvedic "Holy Basil" or "Tulsi" which is commonly found in nootropic supplements like excelerol.
See also
- Cognitive scienceCognitive scienceCognitive science is the interdisciplinary scientific study of mind and its processes. It examines what cognition is, what it does and how it works. It includes research on how information is processed , represented, and transformed in behaviour, nervous system or machine...
- Eidetic memoryEidetic memoryEidetic , commonly referred to as photographic memory, is a medical term, popularly defined as the ability to recall images, sounds, or objects in memory with extreme precision and in abundant volume. The word eidetic, referring to extraordinarily detailed and vivid recall not limited to, but...
- Human enhancementHuman enhancementHuman enhancement refers to any attempt to temporarily or permanently overcome the current limitations of the human body through natural or artificial means...
- Long-term potentiationLong-term potentiationIn neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
- Memory and agingMemory and agingOne of the key concerns of older adults is the experience of memory loss, especially as it is one of the hallmark symptoms of Alzheimer's disease. However, memory loss is qualitatively different in normal aging from the kind of memory loss associated with a diagnosis of Alzheimer's...
External links
- "A Pandora's box full of smart drugs" by Ann Robinson (The Guardian: February 23, 2010)
- "Brain Gain: The underground world of “neuroenhancing” drugs" by Margaret Talbot (The New Yorker: April 27, 2009)
- Business Week Online - "I Can't Remember" September 1, 2003 at Business Week
- List of Nootropic drugs at ErowidErowidErowid, also called The Vaults of Erowid, is an online library of information about psychoactive plants and chemicals and other topics on altered states of consciousness such as meditation and lucid dreaming. It provides information about legal and illegal substances, including their desired and...
- The Nootropics Database