Nootropic

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Nootropics (/n.əˈtrɒpɨks/ noh-ə-TROP-iks), also referred to as smart drugs, memory enhancers, neuro enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that purportedly improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration.[1][2] The word nootropic was coined in 1972 by the Romanian Dr. Corneliu E. Giurgea,[3][4] 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.

Nootropics vs. cognitive enhancers[edit]

Cognitive enhancers are drugs, supplements, nutraceuticals, and functional foods that enhance attentional control and memory.[5][6] Nootropics are cognitive enhancers that are neuroprotective or extremely nontoxic. Nootropics (such as Modafinil) are by definition cognitive enhancers, but a cognitive enhancer is not necessarily a nootropic.

Giurgea's nootropic criteria:

  1. Enhances learning and memory.
  2. Enhances learned behaviors under conditions which are known to disrupt them (e.g. hypoxia, sleep deprivation).
  3. Protects the brain from physical or chemical injury.
  4. Enhances the tonic cortical/subcortical control mechanisms
  5. Exhibits few side effects and extremely low toxicity, while lacking the pharmacology of typical psychotropic drugs (motor stimulation, sedation, etc.).

Since Giurgea's original criteria were first published, there has been little agreement as to what truly constitutes a nootropic compound. The most well defined criteria to date was established by Skondia in 1979. Skondia uses a metabolic approach, taking into account the pharmacological mode of action.

Skondia's nootropic criteria:

I. No direct vasoactivity

A. No vasodilation
B. No vasoconstriction

II. EEG activity: No change in basic rhythm

A. Quantitative EEG: Increased power spectrum (beta 2 and alpha)
B. Qualitative EEG: Decreased delta waves and cerebral suffering

III. Must pass blood-brain barrier

A. Under normal conditions
B. Under pathological conditions

IV. Must show metabolic activity in:

A. Animal brain metabolism
1. Molecular
2. Physiopathological
B. Human brain metabolism (clinical evaluation)
1. A-V differences
a. Increased extraction quotients of O2
b. Increased extraction quotients of glucose
c. Reduced lactate pyruvate ratio
2. Regional cerebral metabolic rates (rCMR)
a. Increased ICMR of O2
b. Increased rCMR of glucose
3. Regional cerebral blood flow: Normalization

V. Minimal side effects

VI. Clinical trials must be conducted with several rating scales designed to objectify metabolic cerebral improvement.

Availability and prevalence[edit]

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.[7] The most commonly used class of drug is stimulants.[8]

These drugs are used primarily to treat people with cognitive or motor function difficulties attributable to such disorders as Alzheimer's disease, Parkinson's disease, Huntington's disease and ADHD. However, more widespread use is being recommended by some researchers.[9] 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 not all of the claims from certain nootropics suppliers have been formally tested.

Academic doping[edit]

In academia a Nootropic called modafinil has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals.[7] Stimulants such as methylphenidate, a cognitive enhancer (which is not considered as a Nootropic according to the criteria above), are being used on college campuses, and by an increasingly younger group.[7] One survey found that 7% of students had used stimulants for a cognitive edge, and on some campuses use in the past year is as high as 25%.[8][10] The use of prescription stimulants is especially prevalent among students attending academically competitive colleges and students who are members of a fraternity/sorority.[10]

Surveys suggest that 3-11% of American students and 0.7-4.5% of German students have used cognitive enhancers in their lifetime.[11]

Hazards[edit]

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.[7]

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 side-effects and a wide therapeutic window.[12] In the United States, unapproved drugs or dietary supplements do not have to have safety or efficacy approval before being sold.[13]

Drugs[edit]

Racetams[edit]

The word nootropic was coined upon discovery of the effects of piracetam, developed in the 1960s.[14] Studies of the racetams have revealed that these structurally similar compounds often act via different mechanisms. Notable drugs include pramiracetam, oxiracetam, and aniracetam. Their mechanisms of action are not fully understood. Piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.[15] Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.[12]

Vitamins and supplements[edit]

Stimulants[edit]

Stimulants are often seen as smart drugs, but may be more accurately termed productivity enhancers. These typically improve concentration and a few areas of cognitive performance, but only while the drug is still in the blood at therapeutic concentrations. Some scientists recommend widespread use of stimulants such as methylphenidate and amphetamines by the general population to increase brain power.[8][35]

Concentration and memory enhancement[edit]

The nootropics in this section are purported or shown to enhance concentration or the recollection and formation of memories.

Cholinergics[edit]

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[edit]

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

Glutamate modulators[edit]

Ligands and modulators of the AMPA receptor, an ionotropic glutamate receptor, are being researched for a myriad of conditions, from Alzheimer's to ADHD. Although there are many AMPAkines being researched, those mentioned here show signs of entering the market in the near future. Other notable drugs with AMPA-modulating activity include aniracetam and tianeptine.

cAMP[edit]

Cyclic adenosine monophosphate is a secondary messenger that may improve certain aspects of memory if increased. Common research tools for this purpose include PDE4 inhibitors, which prevents cAMP catabolism, and forskolin, a stimulator of adenylate cyclase.

Other[edit]

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.[54]

Serotonergics[edit]

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:

Dopaminergics[edit]

Sleep[edit]

Sleep is known to be important in memory consolidation, mood, anxiety, appetite, and numerous other physiological processes. Drugs that improve sleep may therefore have an indirect nootropic effect.

Anti-depression, adaptogenic (anti-stress), and mood stabilization[edit]

Stress (specifically elevated levels of circulating corticosteroids) has been associated with the cognitive deficits seen in human aging.[92] Many studies show that stress and fatigue negatively impact cognitive functioning in young adults.[93][94] Some level of stress in the learning environment may aid the ability to focus and retain information. However, stress levels, especially high, sustained or traumatic stressors, hinder declarative memory, spatial reasoning, learning, attention and working memory. Fatigue is also a stressor that impedes attention, processing, retrieval, working memory and short term memory.[93] The effects of stress on cognitive performance seem to be controlled by the sympatho-adrenal system and the hypothalamic-hypophysial-adrenal axis.[94]

Depression and depressed mood negatively affect cognitive performance and memory.[95] Depression was found to increase false memory, especially with negative words or subjects.[95]

It is reasoned that counteracting and preventing depression and stress management may be an effective nootropic strategy.[93][94] Proper nutrition, adequate sleep, and mechanisms for coping with stress, such as meditation, have been shown to improve learning and cognitive functioning both in the short and long term.[93][94]

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[edit]

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.

Experimental histamine antagonists[edit]

The H3-receptor decreases neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin. Thus, H3-receptor-antagonists increases cognition, vigilance, and wakefulness.

Nerve growth stimulation and brain cell protection[edit]

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.

Hormones[edit]

These are hormones that have activity not necessarily attributable to another specific chemical interaction, but have shown effectiveness. Only specific nootropic effects are stated.

Unknown enhancement[edit]

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[edit]

Other substances sometimes classified as nootropics include jujube, mexidol, hydergine,[12] noopept, selank, semax and bifemelane.

See also[edit]

References[edit]

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