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Nootropics (Template:Pron-en), also referred to as smart drugs, memory enhancers, and cognitive enhancers as well as intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that are purported to improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration.[1][2] The word nootropic was coined in 1972[3][4] 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.

Nootropics vs. cognitive enhancers

Cognitive enhancers are drugs, supplements, nutraceuticals, and functional foods that enhance concentration and memory[5][6]. 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.

The word nootropic was coined in 1972 by the Romanian Dr. Corneliu E. Giurgea[4], derived from the Greek words nous, or "mind," and trepein meaning "to bend/turn". 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.

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 which are illegal, or not completely illegal, but are controlled or exempt under a Drug schedule.

Traditional herbs

A 2007 survey online databases for herbs used in traditional herbal medicine to treat cognitive decline found over 150 plant species.[7]

Availability and prevalence

At present, there are several drugs on the market that improve memory, concentration, planning, and reduce impulsive behavior. Many more are in different stages of development.[8] The most commonly used class of drug is stimulants.[9]

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.[10] 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.[8] Stimulants such as methylphenidate are being used on college campuses, and by an increasingly younger group.[8] 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%.[9]

Hazards

The main concern with pharmaceutical drugs is adverse effects, and these concerns apply to cognitive-enhancing drugs as well. Cognitive enhancers are often taken for the long-term when little data is available.[8]

Dr. Corneliu E. Giurgea originally coined the word nootropics for brain-enhancing drugs with very few side effects. Racetams are sometimes cited as an example of a nootropic with few effects and wide therapeutic window;[11] 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.[12] (This mainly applies to the USA, but may not apply in the EU or elsewhere.)

Vitamins and Supplements

  • B Vitamins—may influence cognitive function through an effect on methylation and homocysteine levels, as excess homocysteine has been associated with cognitive impairment and the B vitamins work to reduce homocysteine[13] 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.[14] A systematic review of trials found "little evidence of a beneficial impact" from supplements on cognitive function later in life.[15]
  • Omega-3—linked to the maintenance brain function[citation needed]. A study done in Norway,[16] demonstrated a potential link between Omega-3 consumption during pregnancy and child intelligence test scores.[17]

Racetams

The word nootropic was coined upon discovery of the effects of piracetam, developed in the 1960s.[19] Although piracetam is the most commonly taken nootropic,[19] there are many relatives in the family that have different potencies and side effects. Other common racetams include pramiracetam, oxiracetam, and aniracetam. There is no generally-accepted mechanism for racetams. In general, they show no affinity for the most important receptors, although modulation of most important central neurotransmitters, including acetylcholine and glutamate, have been reported.[20] Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.[11]

Other substances sometimes classified as nootropics include hydergine, vinpocetine, bifemelane, huperzine A (cholinergic activator below), and dimethylaminoethanol (DMAE).[11]

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.[citation needed] 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 methylphenidate and amphetamines by the general population to increase brain power.[9][21]

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 methylphenidate (Ritalin) or amphetamine. Dopaminergic nootropics include dopamine synthesis precursors, dopamine reuptake inhibitors, monoamine oxidase inhibitors, and other compounds:


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. Acetylcholine 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:

GABA blockers

The GABAA α5 receptor site has recently displayed memory improvements when inverse agonized.

Glutamate activators

The AMPA 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 Ampakines. Although there are many Ampakines 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

  • CX-717—pending FDA approval for memory-impairing illnesses
  • IDRA-21—believed to improve memory by significantly enhancing long-term potentiation but used only in animals; incredibly potent
  • LY-503,430—under development for Parkinson's but showing increase in BDNF, specifically in areas of memory and higher cognitive skills

cAMP

Cyclic adenosine monophosphate 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.

  • Propentofylline—nonselective phosphodiesterase inhibitor with some neuroenhancement
  • Rolipram—PDE4 inhibitor, shows alertness enhancement, long term memory improvement and neuroprotection
  • Mesembrine—PDE4-inhibitor with possible serotonergic activity

Other

α2A 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.[35]

  • Guanfacine is an α2A receptor agonist, FDA approved for and frequently used to treat ADHD symptoms.[1][2] 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.[36]

Serotonergics

Serotonin is a neurotransmitter with various effects on mood and possible effects on neurogenesis. Serotonergics 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:

Anti-depression, adaptogenic (antistress), and mood stabilization

Stress, depression, and depressed mood negatively affect cognitive performance.[citation needed] It is reasoned that counteracting and preventing depression and stress may be an effective nootropic strategy.[citation needed] The term adaptogen applies to most herbal anti-stress claims.[citation needed]

The substances below may not have been mentioned earlier on the page:

Blood flow and metabolic function

Brain function is dependent on many basic processes such as the usage of ATP, 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
  • Creatine—protects ATP during transport
  • Lipoic acid—improves oxygen usage and antioxidant recycling, possibly improving memory
  • Pyritinol—Drug similar to B vitamin Pyridoxine
  • Marijuana— Studies show an increase in blood flow to the cerebellum.
  • Picamilon—GABA activity and blood flow improver
  • Ginkgo biloba—vasodilator. Acts as an NRI.[48]
  • Vinpocetine—increases blood circulation (vasodilator) and metabolism in the brain; also shown to inhibit voltage-sensitive Na+ channels—however, through a similar mechanism to reserpine, Vinpocetine may temporarily deplete the monoamines serotonin, dopamine and norepinephrine by inhibiting VMAT, thus preventing them from reaching the synapse.[49] Vinpocetine may therefore induce or exasperate depressive symptoms as an adverse effect.

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 stress and cell death, therefore exerting a neuroprotective effect.

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.

  • Vasopressin—memory hormone that improves both memory encoding and recall
  • Pregnenolone—increases neurogenesis
  • Orexin—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.

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:

Other nootropics

These substances have been linked to better cognitive function, but may not be the cause. See correlation does not imply causation

See also

References

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