Nootropic

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Nootropics, also referred to as smart drugs, memory enhancers, and cognitive enhancers, are drugs, nutraceuticals, and functional foods that are purported to improve human cognitive abilities.[1][2] The term covers a broad range of substances including drugs, nutrients and herbs with claimed cognitive enhancing effects.

The word nootropic was coined in 1964 by Dr. Corneliu E. Giurgea, derived from the Greek words noos, or "mind," and tropein meaning "to bend/turn". Typically, 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.

Contents

[edit] Availability and prevalence

Currently there are several drugs on the market that improve memory, concentration, planning, and reduce impulsive behavior. Many more are in different stages of development.[3] The most commonly used class of drug are the stimulants.[4]

These drugs are used primarily to treat people with cognitive difficulties: Alzheimer's disease, Parkinson's disease, ADHD. However, more widespread use is being recommended by some researchers.[5] These drugs have a variety of human enhancement applications as well and are marketed heavily on the World Wide Web. 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.[3] Stimulants such as methylphenidate and atomoxetine are being used on college campuses, and by an increasingly younger group.[3] 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%.[4]

[edit] 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 for which little data is available.[3]

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;[6] 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.[7] (this mainly applies to the U.S.A., but may not apply in the E.U. or elsewhere) This nootropic list is not meant to be sufficient to determine the safety of a substance or mixture. Second, any efficacy described on this page should be demonstrated by references in the respective article, and if the claims are not referenced, at minimum in a clinical study, the claim or claims should not be taken seriously.

Some dangers of nootropics include, but are not limited to:

This list is not exhaustive. Any non-essential substances should only be taken after consideration from a doctor or otherwise legally competent physician.

[edit] Examples

The term "drug" here is used as a legal designation. Although some of the effects of these substances may be similar to others, only those substances that have shown cognitive effects are included.

[edit] Nootropics and racetams

The word nootropic was coined upon discovery of the effects of piracetam, developed in the 1960s.[8] Although piracetam is the most commonly taken nootropic,[8] there are many relatives in the family which have different potencies and side effects. Other commom racetams include pramiracetam, oxiracetam, and aniracetam. 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 glutamate have been reported.[9] Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.[6]

Other substances sometimes classified as nootropics include hydergine, vinpocetine, bifemelane, huperzine A (cholinergic activator below), and dimethylaminoethanol.[6]

[edit] Stimulants

Stimulants are often seen as smart drugs. These typically improve concentration and 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.[4]

[edit] 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 ritalin or amphetamine. Dopaminergic nootropics include dopamine synthesis precursors, dopamine reuptake inhibitors, monoamine oxidase inhibitors, and other compounds:

  • Metabolic precursors - raise levels
  • Reuptake inhibitors - stabilize/improve levels
  • MAO-B inhibitors - prevent breakdown
  • Others
    • cocaine and the relatives - multiple mechanisms that amplify dopamine release
    • amphetamine and relatives
    • Yohimbe - purported dopaminergic activity

[edit] Memory Enhancement

Memory can come from many different processes, but is dependent on the ability to store and recall information.

[edit] 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:

[edit] GABAergics

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

[edit] Glutamate activators

The AMPA transmitter and the AMPA receptors are currently being researched with significant memory improvements and possible alertness enhancement when agonized. The drug class for AMPA system modulation is called Ampakines. Although there are many in-research ones, the main ones mentioned will be the ones possibly coming to market or are significantly notable.

Some racetams have shown this activity

  • CX-717 - Going through FDA approval for memory-impairing illnesses
  • IDRA-21 - believed to improve memory by significantly enhancing long term potentiation but only used in animals - incredibly potent
  • LY-503,430 - Being developed for Parkinsons but showing increase in BDNF, specifically in areas of memory and higher cognitive skills

[edit] cAMP

Cyclic adenosine monophosphate is a secondary messenger which 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 - Drug. shows alertness enhancement, long term memory improvement and neuroprotection
  • Mesembrine - PDE4-inhibitor with possible serotonergic activity

[edit] 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:

  • 5-HTP - precursor
  • Tryptophan - Essential amino acid
  • SSRIs - Class of antidepressants that increase active serotonin levels by inhibiting its reuptake. Have also been shown to promote Neurogenesis in the hippocampus.
  • Tianeptine - paradoxical antidepressant, improves mood and reduces anxiety
  • Methamphetamine - some serotonin activity

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

Stress, depression, 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:

[edit] 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. Vasodilators mentioned are only this which have shown, at minimum, probable mental enhancement.

  • Coenzyme q-10 - 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
  • Vinpocetine - increases blood circulation (vasodilator) and metabolism in the brain
  • Picamilon - GABA activity and blood flow improver
  • Ginkgo biloba - vasodilator

[edit] 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 are frequently used to prevent oxidative stress, but do not improve brain function if that is their only activity.

[edit] Recreational drugs

Many recreational substances which 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. These drugs are assumed to have significant dependency or abuse potential, either physically, psychologically, or both. Note that this list is not intended to be exhaustive. This list include substances which are illegal, or not completely illegal, but are controlled or exempt under a Drug schedule.

See also: Controlled substances act and Misuse of Drugs Act 1971

[edit] Dietary nootropics

Diet can have the greatest effect on cognition and the brain, as there are many necessary things which must be consumed. However, other substances have been linked to certain benefits, and may be predominant in certain foods.

Some regular food items contain substances with alleged nootropic benefits:

[edit] 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

[edit] Secondary enhancers

These are substances which by themselves may not improve brain function, but may have benefits for those lacking them (in the case of hormones) or may alter the balance of neurotransmitters.

[edit] Unknown enhancement

Other agents purported to have nootropic claims but do not have (as of yet) attributable mechanisms or have clinically insignificant effects (but may upon refinement of administration) to warrant inclusion into other sections are mentioned here.

Nootropics with proven or purported benefits:

[edit] Other nootropics

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

  • Moderate use of alcohol - Moderate drinkers tend to have better cognitive function than both abstainers and heavy drinkers.[13][14][15][16][17]

[edit] See also

[edit] Brain and neurology

[edit] Thought and thinking (what nootropics are used for)

[edit] Health

[edit] References

  1. ^ "Dorlands Medical Dictionary". http://web.archive.org/web/20080130031824/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_n_10zPzhtm. 
  2. ^ Lanni C, Lenzken SC, Pascale A, et al (March 2008). "Cognition enhancers between treating and doping the mind". Pharmacol. Res. 57 (3): 196–213. doi:10.1016/j.phrs.2008.02.004. PMID 18353672. 
  3. ^ a b c d Sahakian B, Morein-Zamir S (December 2007). "Professor's little helper". Nature 450 (7173): 1157–9. doi:10.1038/4501157a. PMID 18097378. 
  4. ^ a b c ""Towards responsible use of cognitive-enhancing drugs by the healthy" in Nature: International Weekly Journal of Science". http://www.nature.com/nature/journal/vaop/ncurrent/full/456702a.html. Retrieved on December 2008. 
  5. ^ "Scientists back brain drugs for healthy people - Yahoo! News". http://news.yahoo.com/s/ap/20081207/ap_on_he_me/med_brain_pills_1. 
  6. ^ a b c Malik R, Sangwan A, Saihgal R, Jindal DP, Piplani P (2007). "Towards better brain management: nootropics". Curr. Med. Chem. 14 (2): 123–31. PMID 17266573. http://www.bentham-direct.org/pages/content.php?CMC/2007/00000014/00000002/0001C.SGM. 
  7. ^ Goldman P (2001). "Herbal medicines today and the roots of modern pharmacology". Ann. Intern. Med. 135 (8 Pt 1): 594–600. PMID 11601931. 
  8. ^ a b McDaniel, M.A., Maier, S.F., and Einstein, G.O. (2002). "Brain-Specific Nutrients: A Memory Cure?". Psychological Science in the Public Interest (American Psychological Society) 3 (1). doi:10.1016/S0899-9007(03)00024-8. 
  9. ^ Gualtieri F, Manetti D, Romanelli MN, Ghelardini C (2002). "Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs". Curr. Pharm. Des. 8 (2): 125–38. doi:10.2174/1381612023396582. PMID 11812254. 
  10. ^ Soman, I., Mengi, S.A., and Kasture, S.B. (2004). "Effect of leaves of Butea frondosa on stress, anxiety, and cognition in rats". Pharmacology, Biochemistry & Behavior (C.U. Shah College of Pharmacy, SNDT University Santacruz, Mumbai, Maharashtra, India) 79 (1): 11–6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15388278&dopt=Citation. 
  11. ^ Singh, H.K. and Dhawan, B.N. (1997). "Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monniera Linn. (Brahmi)". Indian Journal of Pharmacology 29 (5): 359–65. http://ijp-online.com/article.asp?issn=0253-7613;year=1997;volume=29;issue=5;spage=359;epage=365;aulast=Singh;type=0. 
  12. ^ Brahmi rasayana Improves Learning and Memory in Mice
  13. ^ Britton, A., Singh-Manoux, A., Marmot, M. Alcohol consumption and cognitive function in the Whitehall II Study. American Journal of Epidemiology,2004 Aug 1;160(3):240-7.
  14. ^ Launer LJ, Feskens EJ, Kalmijn S, Kromhout D Smoking, drinking, and thinking. The Zutphen Elderly Study American Journal of Epidemiology 1996 Feb 1;143(3):219-27
  15. ^ Galanis, DJ; Joseph C, Masaki KH, Petrovitch H, Ross GW, White L A longitudinal study of drinking and cognitive performance in elderly Japanese American men: the Honolulu-Asia Aging Study American Journal of Public Health Vol 90, Issue 8 1254-1259
  16. ^ Dufouil, Carole; Ducimetière, Pierre; Ducimetière, Pierre Sex Differences in the Association between Alcohol Consumption and Cognitive Performance American Journal of Epidemiology Vol. 146, No. 5: 405-412
  17. ^ Rodgers, B., et al. Non-linear relationships between cognitive function and alcohol consumption in young, middle-aged and older adults: The PATH Through Life Project. Addiction, 2005, 100(9), 1280-1290; Anstey, K. J., et al. Lower cognitive test scores observed in alcohol are associated with demographic, personality, and biological factors: The PATH Through Life Project. Addiction, 2005, 100(9), 1291-1301.

[edit] External links

v • d • e
Psychoanaleptics: psychostimulants, agents used for ADHD and nootropics (N06B)
Centrally acting sympathomimetics
Xanthine derivatives
Glutamate receptor
CX-516 • CX-546 • CX-614 • CX-691 • CX-717 • IDRA-21 • LY-404,187 • LY-503,430 • PEPA
Eugeroics / Benzhydryl compounds
Histamine H3 receptor antagonists
GABAA α5 inverse agonists
Other psychostimulants and nootropics
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