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'''Nootropics''', popularly referred to as "'''smart drugs'''", "'''smart nutrients'''", "'''cognitive enhancers'''" and "'''brain enhancers'''", are a class of [[drugs]] that improve impaired [[human]] [[cognitive abilities]] (the functions and capacities of the [[brain]]).<ref>{{Dorlands|n_10|12577719}}</ref>
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'''Nootropics''' ({{IPAc-en|icon|n|oʊ|.|ə|ˈ|t|r|ɒ|p|ɨ|k|s}} {{respell|noh-ə|TROP|iks}}), also referred to as ''smart drugs'', ''memory enhancers'', ''neuro enhancers'', ''cognitive enhancers'', and ''intelligence enhancers'', are [[drug]]s, [[Dietary supplement|supplement]]s, [[nutraceutical]]s, and [[functional food]]s that purportedly improve mental functions such as [[cognition]], [[memory]], [[intelligence]], [[motivation]], [[attention]], and concentration.<ref>{{Cite web|url=http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_n_10zPzhtm |title=Dorlands Medical Dictionary |work= |accessdate= |archiveurl = http://web.archive.org/web/20080130031824/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_n_10zPzhtm |archivedate = 2008-01-30}}</ref><ref>{{Cite journal|author=Lanni C, Lenzken SC, Pascale A, ''et al.'' |title=Cognition enhancers between treating and doping the mind |journal=Pharmacol. Res. |volume=57 |issue=3 |pages=196–213 |year=2008 |month=March |pmid=18353672 |doi=10.1016/j.phrs.2008.02.004 |url=}}</ref> The word ''nootropic'' was coined in 1972 by the [[Romanians|Romanian]] Dr. [[Corneliu E. Giurgea]],<ref name="isbn0-06-088473-8">{{Cite book|author=Gazzaniga, Michael S. |title=The Ethical Brain: The Science of Our Moral Dilemmas (P.S.) |publisher=Harper Perennial |location=New York, N.Y |year=2006 |pages=184 |isbn=0-06-088473-8 |oclc= |doi= |accessdate=}}</ref><ref name="pmid4541214">{{Cite journal|author=Giurgea C |title=[Pharmacology of integrative activity of the brain. Attempt at nootropic concept in psychopharmacology] ("Vers une pharmacologie de l'active integrative du cerveau: Tentative du concept nootrope en psychopharmacologie") |language=French |journal=Actual Pharmacol (Paris) |volume=25 |issue= |pages=115–56 |year=1972 |pmid=4541214 |doi= |url=}}</ref> derived from the [[Ancient Greek|Greek]] words νους ''nous'', or "mind," and τρέπειν ''trepein'' meaning "to bend/turn". Nootropics are thought to work by altering the availability of the [[human brain|brain's]] supply of neurochemicals ([[neurotransmitters]], [[enzymes]], and [[hormones]]), by improving the brain's [[oxygen]] supply, or by stimulating nerve growth.
   
The word '''nootropic''' was coined in 1964 by the [[Romanian people|Romanian]] Dr. [[Corneliu E. Giurgea]], derived from the [[Ancient Greek|Greek]] words ''noos'', or "mind," and ''tropein'' meaning "to bend/turn". Typically, nootropics are alleged 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 alleged nootropic substances in most cases has not been conclusively determined. This is complicated by the difficulty of defining and quantifying [[cognition]] and [[intelligence]].
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==Nootropics vs. cognitive enhancers==
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{{Expert-subject|Pharmacology|section|date=February 2010}}
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Cognitive enhancers are [[drug]]s, supplements, nutraceuticals, and [[functional food]]s that enhance [[attentional control]] and memory.<ref>{{cite web |url=http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_n_10zPzhtm |title=Dorlands Medical Dictionary |work= |accessdate= |archiveurl = http://web.archive.org/web/20080130031824/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_n_10zPzhtm |archivedate = 2008-01-30}}</ref><ref>{{cite journal |author=Lanni C, Lenzken SC, Pascale A, ''et al.'' |title=Cognition enhancers between treating and doping the mind |journal=Pharmacol. Res. |volume=57 |issue=3 |pages=196–213 |year=2008 |month=March |pmid=18353672 |doi=10.1016/j.phrs.2008.02.004 |url=}}</ref> 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==
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'''Giurgea's Nootropic Criteria:'''
Nootropic drugs are generally only available by prescription or through personal importation. The other nootropic substances listed below are either nutritional supplements or plant components ([[herbs]], [[root]]s, [[beans]], [[bark]], etc.), and are generally available [[over-the-counter drug|over the counter]] at [[health food]] and [[grocery stores]], and are used as nutritional supplements.
 
   
The drugs are used to treat people with cognitive learning difficulties, neural degradation ([[Alzheimer's disease]] or [[Parkinson's disease]]), and for cases of oxygen deficit to prevent [[Hypoxia (medical)|hypoxia]]. 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.
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# Enhances learning and memory.
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# Enhance learned behaviors under conditions which are known to disrupt them. Example: hypoxia (oxygen deficiency).
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# Protect the brain from physical or chemical injury.
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# Enhance the tonic cortical/subcortical control mechanisms
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# Exhibit few side effects and extremely low toxicity, while lacking the pharmacology of typical psychotropic drugs (motor stimulation, sedation etc.).
   
==Therapy or enhancement==
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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 utilizes a metabolic approach, taking into account the pharmacological mode of action.
Nootropic drugs are primarily for therapeutic use, in the sense that they normalize an inhibited mental performance by various causes. In fact, some nootropic substances are ineffective unless there is a malfunction in the first place{{Fact|date=February 2008}}; replenishing neurotransmitters for instance, is only positively effective when there is a lack of the neurotransmitters in the first place.
 
   
On the other hand, many nootropics may theoretically be used as [[human enhancement]], boosting mental function in otherwise normal healthy people. This is physically problematic, however, e.g. since compensatory mechanisms of the brain prevents long-term enhancements{{Fact|date=December 2007}}. For instance, a short period of increased concentration and alertness of taking stimulants{{Fact|date=December 2007}}, e.g. caffeine, is compensated for by a period at least as long with decreased alertness etc. in order to avail for recovery. Furthermore, there is much controversy over such applications. This may contribute to the lacking research on such effects.
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'''Skondia's Nootropic Criteria:'''
   
Nevertheless, [[colostrinin]] may enhance long-term memory retention even in young, already healthy, individuals<ref>{{cite journal |author=Stewart MG, Banks D |title=Enhancement of long-term memory retention by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm |journal=Neurobiol Learn Mem |volume=86 |issue=1 |pages=66–71 |year=2006 |pmid=16473531 |doi=10.1016/j.nlm.2005.12.011}}</ref>.
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I. No direct vasoactivity
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:A. No vasodilation
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:B. No vasoconstriction
   
==Examples==
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II. EEG activity: No change in basic rhythm
The term "drug" here is used as a legal designation, and does not indicate greater [[efficacy]]. With nootropics, the effects, effectiveness, and potency differ from substance to substance and from individual to individual. See the substance descriptions below for more detail.
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:A. Quantitative EEG: Increased power spectrum (beta 2 and alpha)
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:B. Qualitative EEG: Decreased delta waves and cerebral suffering
   
===Replenishing and increasing neurotransmitters===
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III. Must pass blood-brain barrier
As the brain ages, its ability to produce and maintain youthful levels of neurotransmitters declines.<ref name="Stancheva et al. 1991">{{cite journal | author = Stancheva, S.L., Petkov, V.D., Hadjiivanova, C.I., and Petkov, V.V. | title = Age-related changes of the effects of a group of nootropic drugs on the content of rat brain biogenic monoamines. | journal = Gen. Pharmacol. ''(Department of Experimental Pharmacology, Bulgarian Academy of Sciences, Sofia)' | date= 1991 | volume = 22 | issue = 5 | pages = 873–7 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1761194&dopt=Citation}}</ref> There are various reasons for such an insufficiency. For instance, there might be a lack of [[enzymes]] involved in the neurotransmitter synthesis. Nevertheless, in many cases, providing the brain with ample raw materials necessary to make neurotransmitters can restore them to more youthful levels and thus help maintain cognitive function at vigorous youthful levels.{{Fact|date=December 2007}} Furthermore, there are declines in immune and endocrine functioning. <ref name="Arai et. al.">{{cite journal | author = Milton Hideaki Arai, Alberto JS Duarte, and Valeria Maria Natale, Disciplina de Clínica Geral do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil | title = The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones | journal = Immunity & Ageing | date= 25 August 2006 | volume = 3 | issue = 9 | pages = | url =http://www.worldhealth.net/p/the-effects-of-long-term-endurance-training-on-the-immune-and-endocrine-systems-of-elderly-men-the-role-of-cytokines-and-anabolic-hormones-2006-10-09.html }}</ref> Certain nootropics enhance immune and endocrine functioning.
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:A. Under normal conditions
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:B. Under pathological conditions
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IV. Must show metabolic activity in:
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:A. Animal brain metabolism
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::1. Molecular
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::2. Physiopathological
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:B. Human brain metabolism (clinical evaluation)
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::1. A-V differences
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:::a. Increased extraction quotients of O2
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:::b. Increased extraction quotients of glucose
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:::c. Reduced lactate pyruvate ratio
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::2. Regional cerebral metabolic rates (rCMR)
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:::a. Increased ICMR of O2
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:::b. Increased rCMR of glucose
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::3. Regional cerebral blood flow: Normalization
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V. Minimal side effects
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VI. Clinical trials must be conducted with several rating scales designed to objectify metabolic cerebral improvement.
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==Availability and prevalence==
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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.<ref name=NatureProfessor>{{Cite journal|author1=Sahakian B|author1-link=Barbara Sahakian|author2=Morein-Zamir S |title=Professor's little helper |journal=Nature |volume=450 |issue=7173 |pages=1157–9 |year=2007 |month=December |pmid=18097378 |doi=10.1038/4501157a |url=}}</ref> The most commonly used class of drug is [[stimulants]].<ref name=Nature2008/>
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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.<ref>{{Cite web|url=http://blogs.dnalc.org/2009/09/21/smart-drugs-and-should-we-take-them/|title=Smart Drugs and Should We Take Them?|publisher=[[Dolan DNA Learning Center]]|accessdate=2012-11-04}}</ref> 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.
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In academia, [[modafinil]] has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals.<ref name=NatureProfessor/> Stimulants such as [[methylphenidate]] are being used on college campuses, and by an increasingly younger group.<ref name=NatureProfessor/> 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%.<ref name=Nature2008/>
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==Hazards==
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The main concern with [[pharmaceutical drug]]s is [[adverse effect]]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.<ref name=NatureProfessor/>
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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 a wide [[therapeutic window]].<ref name=BetterBrain>{{Cite journal|author=Malik R, Sangwan A, Saihgal R, Jindal DP, Piplani P |title=Towards better brain management: nootropics |journal=Curr. Med. Chem. |volume=14 |issue=2 |pages=123–31 |year=2007 |pmid=17266573 |doi= 10.2174/092986707779313408|url=http://www.bentham-direct.org/pages/content.php?CMC/2007/00000014/00000002/0001C.SGM}}</ref> In the United States, [[Approved drug|unapproved drugs]] or dietary supplements do not have to have safety or efficacy approval before being sold.<ref>{{Cite journal|author=Goldman P |title=Herbal medicines today and the roots of modern pharmacology |journal=Ann. Intern. Med. |volume=135 |issue=8 Pt 1 |pages=594–600 |year=2001 |pmid=11601931 |doi=}}</ref>
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==Drugs==
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===Racetams===
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The word ''nootropic'' was coined upon discovery of the effects of piracetam, developed in the 1960s.<ref name=McDaniel2002>{{Cite journal| author = McDaniel, M.A., Maier, S.F., and Einstein, G.O. | title = Brain-Specific Nutrients: A Memory Cure? | journal = Psychological Science in the Public Interest |publisher=American Psychological Society | volume = 19 | issue = 11 | url =| doi = 10.1016/S0899-9007(03)00024-8 | year = 2002 | pages = 957–75 | pmid=14624946}}</ref> Although [[piracetam]] is the most commonly taken nootropic,<ref name=McDaniel2002/> (depending on one's definition of nootropic, which can sometimes include more popular substances such as caffeine and nicotine) 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.<ref>{{Cite journal|author=Gualtieri F, Manetti D, Romanelli MN, Ghelardini C |title=Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs |journal=Curr. Pharm. Des. |volume=8 |issue=2 |pages=125–38 |year=2002 |pmid=11812254 |doi=10.2174/1381612023396582 |url=}}</ref> Although aniracetam and nebracetam show affinity for muscarinic receptors, only [[nefiracetam]] shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.<ref name=BetterBrain/>
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===Vitamins and supplements===
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{{Cleanup|section|date=July 2010}}
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* [[B Vitamins]]&mdash;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.<ref name=Selhub2000>{{cite journal |author= Selhub J, Bagley L, Miller J, Rosenberg I |title=B vitamins, homocysteine, and neurocognitive function in the elderly |journal=American Journal of Clinical Nutrition |volume=71 |issue=2 |pages=614S–620s |year=2000 |pmid=10681269}}</ref> 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.<ref name=Huskisson2007>{{cite journal |author=Huskisson E, Maggini S, Ruf M |title=The influence of micronutrients on cognitive function and performance |journal=J. Int. Med. Res. |volume=35 |issue=1 |pages=1–19 |year=2007 |pmid=17408051}}</ref> In 2008 a systematic review of trials found "little evidence of a beneficial impact" from supplements on cognitive function later in life.<ref>{{cite journal |author=Jia X, McNeill G, Avenell A |title=Does taking vitamin, mineral and fatty acid supplements prevent cognitive decline? A systematic review of randomized controlled trials |journal=J Hum Nutr Diet |volume=21 |issue=4 |pages=317–36 |year=2008 |month=August |pmid=18721399 |doi=10.1111/j.1365-277X.2008.00887.x |url=}}</ref> A randomized, placebo-controlled trial in 168 70 year olds with mild cognitive impairment showed that a mix of B vitamins slowed the rate of brain atrophy; the slowing was related to a decrease in homocysteine levels.<ref>{{cite journal |author=Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H |title=Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. |journal=PLoS ONE |volume=8 |issue=5(9) |pages= |year=2010 |month=September |pmid=20838622 |doi= 10.1371/journal.pone.0012244|url= |pmc=2935890}}</ref>
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* [[Omega-3]]&mdash;linked to the maintenance of brain function. A study done in Norway<ref>Pediatrics. 2003 Jan;111(1):e39-44</ref> demonstrated a potential link between Omega-3 consumption during pregnancy and child intelligence test scores.<ref>Prevention [0032-8006] Chillot yr.2004 vol.56 iss.1 pg.122 -9</ref> A cross-sectional population-based study of 1,613 subjects found an association between [[PUFA]] intake and decreased risk for impairment of cognitive function & cognitive speed.<ref>{{cite journal |author=Kalmijn S, van Boxtel MP, Ocké M, Verschuren WM, Kromhout D, Launer LJ |title=Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. |journal=Neurology |volume=62 |issue=2 |pages=275–80 |year=2004 |month=January |pmid=14745067 |url=http://www.ncbi.nlm.nih.gov/pubmed/14745067}}</ref>
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* [[Isoflavone]]s&mdash;may be related to cognitive function.<ref>{{cite journal |author=Wong MC, Emery PW, Preedy VR, Wiseman H |title=Health benefits of isoflavones in functional foods? Proteomic and metabonomic advances |journal=Inflammopharmacology |volume=16 |issue=5 |pages=235–9 |year=2008 |month=October |pmid=18815737 |doi=10.1007/s10787-008-8023-x |url=}}</ref> A double-blind, placebo-controlled study showed improvement in spatial working memory after administration of an isoflavone combination containing [[daidzein]], [[genistein]] & [[glycitin]].<ref>{{cite journal |author=Thorp AA, Sinn N, Buckley JD, Coates AM, Howe PR |title=Soya isoflavone supplementation enhances spatial working memory in men. |journal=Br J Nutr |volume=102 |issue=9 |pages=1348–54 |year=2009 |month=November |pmid=19480732 |url=http://www.ncbi.nlm.nih.gov/pubmed/19480732 |doi=10.1017/S0007114509990201}}</ref> In a randomized, double-blind, placebo-controlled study of older, non-demented men & women, soy isoflavone supplementation improved performance on 6 of 11 cognitive tests, including visual-spatial memory and construction, verbal fluency and speeded dexterity; unexpectedly, the placebo group performed better on 2 tests of executive function.<ref>{{cite journal |author=Gleason CE, Carlsson CM, Barnet JH, Meade SA, Setchell KD, Atwood CS, Johnson SC, Ries ML, Asthana S |title=A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women |journal=Age Ageing |volume=38 |issue=1 |pages=86–93 |year=2009 |month=January |pmid=19054783 |pmc=2720778 |doi=10.1093/ageing/afn227}}</ref>
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* [[Vitamin D]]&mdash;has positive effects on cardiovascular health and may have positive effects on cognitive function separately; the active form of Vitamin D seems to be involved in brain development and in adult brain function. In particular, metabolic pathways for Vitamin D in the hippocampus and cerebellum have been found. Epidemiological data show that higher Vitamin D levels (>20&nbsp;ng/mL or 50nmol/L) are associated with better cognitive function, but do not seem to be associated with better memory performance.<ref>{{cite journal |author=Buell JS, Scott TM, Dawson-Hughes B, Dallal GE, Rosenberg IH, Folstein MF, Tucker KL |title=Vitamin D is associated with cognitive function in elders receiving home health services. |journal=J Gerontol A Biol Sci Med Sci. |volume=64 |issue=8 |pages=888–95 |year=2009 |month=Aug |pmid=19377013 |url= |doi=10.1093/gerona/glp032 |pmc=2981461}}</ref>
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* A 2007 survey of online databases for herbs used in traditional herbal medicine to treat cognitive decline - without any proof of safety or efficacy - found over 150 plant species, such as [[Ginkgo biloba]].<ref>{{cite journal |author=Adams M, Gmünder F, Hamburger M |title=Plants traditionally used in age related brain disorders--a survey of ethnobotanical literature |journal=J Ethnopharmacol |volume=113 |issue=3 |pages=363–81 |year=2007 |month=September |pmid=17720341 |doi=10.1016/j.jep.2007.07.016 |url=}}</ref>
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===Dopaminergics===
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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:
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* Metabolic precursors&mdash;raise levels
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** [[Phenylalanine|L-Phenylalanine]]&mdash;purported cognitive improvement
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** [[Tyrosine|L-Tyrosine]] (or N-Acetyl-L-Tyrosine, more bioavailable form)&mdash;purported cognitive improvement
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** [[L-DOPA]] (L-3,4-dihydroxyphenylalanine)&mdash;[[precursor (chemistry)|precursor]] to [[catecholamine]]s ([[dopamine]]); neurotoxic effects documented<ref>{{Cite journal | last1 = Cheng | first1 = N. | last2 = Maeda | first2 = T. | last3 = Kume | first3 = T. | last4 = Kaneko | first4 = S. | last5 = Kochiyama | first5 = H. | last6 = Akaike | first6 = A. | last7 = Goshima | first7 = Y. | last8 = Misu | first8 = Y. | title = Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal neurons. | journal = Brain Res | volume = 743 | issue = 1-2 | pages = 278–83 | month = Dec | year = 1996 | doi = 10.1016/S0006-8993(96)01056-6| pmid = 9017256 }}</ref><ref>{{Cite journal | last1 = Maeda | first1 = T. | last2 = Cheng | first2 = N. | last3 = Kume | first3 = T. | last4 = Kaneko | first4 = S. | last5 = Kouchiyama | first5 = H. | last6 = Akaike | first6 = A. | last7 = Ueda | first7 = M. | last8 = Satoh | first8 = M. | last9 = Goshima | first9 = Y. | title = L-DOPA neurotoxicity is mediated by glutamate release in cultured rat striatal neurons. | journal = Brain Res | volume = 771 | issue = 1 | pages = 159–62 | month = Oct | year = 1997 | doi = 10.1016/S0006-8993(97)00908-6| PMID = 9383020 }}</ref><ref>{{Cite journal | last1 = Lee | first1 = JJ. | last2 = Kim | first2 = YM. | last3 = Yin | first3 = SY. | last4 = Park | first4 = HD. | last5 = Kang | first5 = MH. | last6 = Hong | first6 = JT. | last7 = Lee | first7 = MK. | title = Aggravation of L-DOPA-induced neurotoxicity by tetrahydropapaveroline in PC12 cells. | journal = [[Biochem Pharmacol]] | volume = 66 | issue = 9 | pages = 1787–95 | month = Nov | year = 2003 | doi = 10.1016/S0006-2952(03)00421-0| PMID = 14563489 }}</ref>
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** [[Biopterin]]&mdash;a rare [[vitamin]] ([[coenzyme]]) that is synthesized in the [[pineal gland]]<ref>{{Cite journal | last1 = Kapatos | first1 = G. | last2 = Kaufman | first2 = S. | last3 = Weller | first3 = JL. | last4 = Klein | first4 = DC. | title = Biosynthesis of biopterin: adrenergic cyclic adenosine monophosphate-dependent inhibition in the pineal gland. | journal = Science | volume = 213 | issue = 4512 | pages = 1129–31 | month = Sep | year = 1981 | doi = 10.1126/science.6168019| PMID = 6168019 }}</ref> & crucial to the [[biosynthesis]] of dopamine
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** [[Pyridoxal-phosphate]] (or PLP, pyridoxal-5'-phosphate, P5P, active form of [[Vitamin B6]])&mdash;plays a role in the conversion of L-DOPA into dopamine (via the enzyme [[aromatic L-amino acid decarboxylase]])
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* Reuptake inhibitors&mdash;stabilize/improve levels
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** [[Amineptine]]&mdash;mild stimulant
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** [[Methylphenidate]]&mdash;stimulant approved for ADHD; strong [[Dopamine reuptake inhibitor|DAT inhibition]]
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** [[Bupropion]]&mdash;atypical antidepressant; moderate [[Dopamine reuptake inhibitor|DAT inhibition]]
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* [[Monoamine oxidase inhibitor|MAO-B inhibitors]]&mdash;prevent breakdown
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** [[Selegiline]]&mdash;Mild stimulant; irreversible
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** [[Rasagiline]]&mdash;Mild stimulant; irreversible
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** ''[[Rhodiola rosea]]''&mdash;Adaptogenic herb; reversible<ref name="Diermen2009">{{Cite journal | last1 = van Diermen | first1 = D. | last2 = Marston | first2 = A. | last3 = Bravo | first3 = J. | last4 = Reist | first4 = M. | last5 = Carrupt | first5 = PA. | last6 = Hostettmann | first6 = K. | title = Monoamine oxidase inhibition by Rhodiola rosea L. roots. | journal = J Ethnopharmacol | volume = 122 | issue = 2 | pages = 397–401 | month = Mar | year = 2009 | doi = 10.1016/j.jep.2009.01.007 | PMID = 19168123 }}</ref>
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* [[Dopamine agonists]]
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** [[Ropinirole]]&mdash;agonist at D2, D3, and D4 receptors
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** [[Pramipexole]]&mdash;agonist at D2, D3 and D4 receptors
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** [[Amisulpride]] &mdash;blocks dopamine autoreceptors at low doses generating more dopamine in the CNS.
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* Others
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** [[Mucuna pruriens]] (Velvet Bean)&mdash;natural source of L-DOPA
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** [[Modafinil]]&mdash;purported dopaminergic activity
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** [[Citicoline]] ([[International Nonproprietary Name|INN]]) (aka: [[cytidine diphosphate]]-choline (CDP-Choline) & cytidine 5'-diphosphocholine)&mdash;studies suggest CDP-choline supplements increase dopamine receptor densities,<ref>{{cite journal |author=Giménez R, Raïch J, Aguilar J |title=Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice |journal=British Journal of Pharmacology |volume=104 |issue=3 |pages=575–8 |year=1991 |month=November |pmid=1839138 |pmc=1908237}}</ref> and suggest that CDP-choline supplementation can ameliorate memory impairment caused by environmental conditions.<ref>{{cite journal |author=Teather LA, Wurtman RJ |title=Dietary CDP-choline supplementation prevents memory impairment caused by impoverished environmental conditions in rats |journal=Learning & Memory |volume=12 |issue=1 |pages=39–43 |year=2005 |pmid=15647594 |pmc=548494 |doi=10.1101/lm.83905}}</ref> 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.<ref>{{cite news |url=http://www.smh.com.au/articles/2008/02/24/1203788130776.html |title=Supplement naturally boosts ageing brain power |date=2008-02-25 |work=[[Sydney Morning Herald]] |accessdate=2009-07-28}}</ref><ref>{{cite journal |author=Silveri MM, Dikan J, Ross AJ, ''et al.'' |title=Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy |journal=NMR in Biomedicine |volume=21 |issue=10 |pages=1066–75 |year=2008 |month=November |pmid=18816480 |doi=10.1002/nbm.1281}}</ref>
  +
  +
===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|date=July 2010}} 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 [[amphetamine]]s by the general population to increase brain power.<ref name=Nature2008>{{Cite web|url=http://www.nature.com/nature/journal/vaop/ncurrent/full/456702a.html |title="Towards responsible use of cognitive-enhancing drugs by the healthy" in ''Nature: International Weekly Journal of Science'' |work= |accessdate=December 2008}}</ref><ref>{{Cite news|url=http://www.time.com/time/health/article/0,8599,1869435,00.html |title=Popping Smart Pills: The Case for Cognitive Enhancement - TIME |work= Time|accessdate= 2010-05-20| date=2009-01-06 | first=Maia | last=Szalavitz}}</ref>
  +
* [[Amphetamine]]s
  +
** [[Amphetamine]] ([[Adderall]], [[Dextroamphetamine|Dexedrine]])&mdash;adrenergic, dopaminergic
  +
** [[Lisdexamfetamine]] (Vyvanse)&mdash;dextroamphetamine [[prodrug]]
  +
** [[Methamphetamine]] (Desoxyn)&mdash;adrenergic, dopaminergic
  +
* [[Adrenergic]]s
  +
** [[Atomoxetine]]&mdash;[[norepinephrine reuptake inhibitor]]; approved for ADHD
  +
** [[Reboxetine]]&mdash;Norepinephrine reuptake inhibitor; approved in Europe for [[clinical depression]] but may also be used off-label to treat ADHD
  +
** [[Synephrine]] (found in [[Bitter orange]])&mdash;agonist at [[alpha-1 adrenergic receptor|α<sub>1</sub> adrenergic receptor]]s
  +
* [[Cholinergic]]s
  +
** [[Arecoline]]
  +
** [[Nicotine]] A meta-analysis of 41 [[double-blind]], [[placebo]]-controlled studies concluded that [[nicotine]] or smoking had [[health effects of tobacco|significant positive effects]] on fine motor, alerting attention-accuracy and response time (RT), orienting attention-RT, short-term episodic memory-accuracy, and working memory-RT.<ref>{{cite journal |title=Meta-analysis of the acute effects of nicotine and smoking on human performance |author=Heishman SJ, Kleykamp BA, Singleton EG |journal=[[Psychopharmacology (Berl).]] |volume=210 |issue=4 |pages=453–69 |date=2010-06 |accessdate=2012-03-23 |pmid=20414766 |pmc=3151730 |doi=10.1007/s00213-010-1848-1}}</ref>
  +
* [[Eugeroics]] ("Wakefulness Enhancers")&mdash;unproven primary mechanisms but proven efficacy
  +
** [[Adrafinil]]
  +
** [[Armodafinil]]
  +
** [[Modafinil]]
  +
* [[Xanthine]]s&mdash;reduces [[fatigue (medical)|fatigue]] perception
  +
** [[Caffeine]]&mdash;shown to increase alertness, performance, and in some studies, memory.<ref>{{Cite journal| author = Rogers, P. |title = Caffeine, mood and mental performance in everyday life.|journal = Psychology Today| volume = 32|issue = 1| pages = 84–89|year = 2007| accessdate = 2009–11- 01| doi = 10.1111/j.1467-3010.2007.00607.x}}</ref> Children and adults who consume low doses of caffeine showed increase alertness, yet a higher dose was needed to improve performance.<ref name=Kiefer2007>{{Cite journal| author = Kiefer, I.|title = Brain Food|journal = Scientific American Mind| volume = 18|issue = 5| pages = 58–63|year = 2007| url = http://www.nature.com/scientificamericanmind/journal/v18/n5/full/scientificamericanmind1007-58.html| accessdate = 2009–11- 01 | doi = 10.1038/scientificamericanmind1007-58
  +
}}</ref> Caffeine has also been shown to have more of an effect on improving cognitive performance and sustaining attention in older adults.{{Citation needed|date=September 2010}} Chronic pretreatment of caffeine in animals has shown to reduce ischaemic brain damage, in addition to reducing the risk of Parkinson's disease.{{Citation needed|date=September 2010}}
  +
** [[Paraxanthine]]
  +
** [[Theobromine]]
  +
** [[Theophylline]]
  +
  +
===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====
[[Cholinergics]] are substances that affect the neurotransmitter acetylcholine or the components of the nervous system that use acetylcholine. Acetylcholine facilitates memory, concentration, focus, and high-order thought processes (abstract thought, calculation, innovation, etc.).{{Fact|date=December 2007}} Increasing the availability of this neurotransmitter in the brain may improve these functions and increase the duration in which they may be engaged without slowing down or stopping. Oversupplying the brain with acetylcholine may have the opposite effect, temporarily reducing rather than improving mental performance.{{Fact|date=December 2007}} Cholinergic nootropics include acetylcholine precursors and cofactors, and [[acetylcholinesterase inhibitors]]:
+
[[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]]:
  +
  +
* Precursors
  +
** [[Choline]]&mdash;precursor of acetylcholine and [[phosphatidylcholine]]
  +
** [[DMAE]]&mdash;precursor of acetylcholine
  +
** [[Meclofenoxate]]&mdash;probable precursor of acetylcholine, approved for [[Dementia]] and [[Alzheimer's]]
  +
** [[Alpha-GPC]]&mdash;thought to be the only cholinergic that delivers choline to the brain across the [[Blood–brain barrier]]; sold under its chemical name
  +
* Cofactors
  +
** [[Acetylcarnitine]]&mdash;amino acid that functions in acetylcholine production by donating the acetyl portion to the acetylcholine molecule
  +
** [[Vitamin B5|Vitamin B<sub>5</sub>]]&mdash;cofactor in the conversion of choline into acetylcholine
  +
* [[Acetylcholinesterase]] inhibitors
  +
** [[Galantamine]]
  +
** ''[[Lycoris radiata]]'' (Red Spider Lily)&mdash;natural source for [[galantamine]]
  +
** [[Huperzine A]]&mdash;also shown to act as an [[NMDA antagonist]] and appears to increase [[nerve growth factor]] levels in rats<ref>{{Cite journal|author = Tang, L., Wang, R., Tang, X.|title = Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells|journal = Acta Pharmacologica Sinica|year = 2005|volume = 26|pages = 673–678|doi = 10.1111/j.1745-7254.2005.00130.x|pmid = 15916732|issue = 6}}</ref>
  +
** [[Donepezil]]
  +
** [[Rosemary]]
  +
** [[Salvia officinalis|Sage]]
  +
** [[Cannabis]] Due to its AChE-inhibiting properties, studies suggest it as a treatment for Alzheimer's.<ref>{{Cite journal | last1 = Eubanks | first1 = LM. | last2 = Rogers | first2 = CJ. | last3 = Beuscher | first3 = AE. | last4 = Koob | first4 = GF. | last5 = Olson | first5 = AJ. | last6 = Dickerson | first6 = TJ. | last7 = Janda | first7 = KD. | title = A molecular link between the active component of marijuana and Alzheimer's disease pathology. | journal = Mol Pharm | volume = 3 | issue = 6 | pages = 773–7 | month = | year = 2006| doi = 10.1021/mp060066m | pmid = 17140265 | pmc = 2562334 }}</ref> [[Anxiolytic]] and [[analgesic]] found in [[cannabis]]. Neuroprotectant, possible Alzheimer's prevention and possible [[neurogenesis]] inducer.<ref>{{cite journal |url=http://www.jci.org/articles/view/25509 |title=Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects |author=Wen Jiang; Yun Zhang; Lan Xiao; Jamie Van Cleemput; Shao-Ping Ji; Guang Bai; Xia Zhang |journal=[[Journal of Clinical Investigation]] |volume=115 |issue=11 |pages=3104–16 |date=2005-11-01 |doi=10.1172/JCI25509 |pmc=1253627 |accessdate=2011-03-02 |pmid=16224541}}</ref>
  +
* [[Reuptake]] inhibitors and enhancers
  +
** [[Coluracetam]]&mdash;choline uptake enhancer
  +
** [[Ginsenosides]] [https://docs.google.com/viewer?a=v&q=cache:fVLpyWFpff0J:escholarship.org/uc/item/7sn5s2h5.pdf+&hl=en&gl=us&pid=bl&srcid=ADGEESi593MEqEh8naj8CAS441JIVE-ePEr_zWnRmUN3UwWwGKQKs--RQstboibqO2Z6Lv3X92EZTrS2OGPUCf6oll-mx9BomIAShvEVmOcMBmfIMZhEn3CxiB0Zc2lsLN5gbxSStVfT&sig=AHIEtbSlWtmzuFc0oha8ubvKY2pesJVamg&pli=1 Source]
  +
* Agonists
  +
** [[Ispronicline]]
  +
** [[Nicotine]]
  +
** [[Arecoline]]
  +
  +
====GABA blockers====
  +
The [[GABAA|GABA<sub>A</sub>]] [[GABRA5|α5]] receptor site has recently displayed memory improvements when [[inverse agonist|inverse agonized]].
  +
  +
*[[α5IA|α<sub>5</sub>IA]]&mdash;α5 inverse agonist. A number of α5IA analogues exist that, like α5IA, selectively and partially agonize some GABA receptor subtypes while inverse agonizing others, which may provide a nootropic effect without the associated anxiogenic effects of general GABA inverse agonism.
  +
*[[Suritozole]]&mdash;α5 partial inverse agonist
  +
  +
====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 [[Ampakine]]s. 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]]&mdash;pending FDA approval for memory-impairing illnesses
  +
* [[IDRA-21]]&mdash;believed to improve memory by significantly enhancing [[long-term potentiation]] but used only in animals; incredibly potent
  +
* [[LY-503,430]]&mdash;under development for Parkinson's but showing increase in [[BDNF]], specifically in areas of memory and higher cognitive skills
   
=====Piracetam=====
+
====cAMP====
{{Main|Piracetam}}
+
[[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.
[[Piracetam]] (Nootropil) - [[Prescription drug]] (in Europe). The original (first),<ref name="McDaniel et al. 2002">{{cite journal | author = McDaniel, M.A., Maier, S.F., and Einstein, G.O. | title = Brain-Specific Nutrients: A Memory Cure? | journal = Psychological Science in the Public Interest ''(American Psychological Society)' | volume = 3 | issue = 1 | url = http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TB0-4B0KTYF-C&_coverDate=12%2F31%2F2003&_alid=448998985&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5128&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=f99a155c658f3be9a94cc485fbf37262| date = 2002}}</ref> and most commonly taken<ref name="Goldman et al., 1999 cited in McDaniel et al. 2002">{{cite book | author = Goldman, R., Klatz, R., and Berger, L. | title = Brain fitness | location = New York | publisher = Doubleday | year = 1999}}</ref><ref name="McDaniel et al. 2002"/> nootropic drug. It is a cholinergic agent, synergistic with [[DMAE]], [[Centrophenoxine]], choline, and [[Hydergine]]. Increases brain cell metabolism and energy levels,<ref name="Gabryel & Trzeciak 1994, cited in McDaniel et al. 2002">{{cite journal | author = Gabryel, B. and Trzeciak, H.I. | title = Nootropics: Pharmacological properties and therapeutic use. | journal = Polish Journal of Pharmacology | year = 1994 | volume = 46 | pages = 383–394 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7894524&dopt=Citation}}</ref><ref name="McDaniel et al. 2002"/> and speeds up interhemispheric flow of information (left-right brain hemisphere communication).<ref> url = http://en.wikipedia.org/wiki/Piracetam</ref> Increases [[alertness]],<ref name="Saletu & Grunberger 1985">{{cite journal | author = Saletu, B. and Grunberger, J. | title = Memory dysfunction and vigilance: neurophysiological and psychopharmacological aspects. | journal = Annals of the New York Academy of Sciences | volume = 444 | issue = 1 | pages = 406–27 | url = http://www.annalsnyas.org/cgi/content/abstract/444/1/406 | date= 1985}}</ref> improves concentration, and enhances memory. Protects neurons from hypoxia,<ref name="McDaniel et al. 2002"/> and stimulates growth of acetylcholine receptors. May also cause nerves to regenerate. Piracetam markedly decreases the formation of neuronal lipofuscin.<ref name="Paula-Barbosa et al. 1991">{{cite journal | author = Paula-Barbosa, M.M., Brandao, F., Pinho, M.C., Andrade, J.P., Madeira, M.D., and Cadete-Leite, A. | title = The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study. | journal = Alcohol Clin. Exp. Res. | date= 1991-10-01 | volume = 15 | issue = 5 | pages = 834–8 | url = http://www.blackwell-synergy.com/doi/abs/10.1111/j.1530-0277.1991.tb00610.x}}</ref> It improves posture in elderly people.<ref name="Riedel et al. 1998">{{cite journal | author = Riedel, W.J., Peters, M.L., Van Boxtel, M.P.J., and O'Hanlon, J.F. | title = The influence of piracetam on actual driving behaviour of elderly subjects | journal = Human Psychopharmacology: Clinical & Experimental | volume = 13 | issue = S2 | pages = S108–14 | url = http://www3.interscience.wiley.com/cgi-bin/abstract/4292/ABSTRACT?CRETRY=1&SRETRY=0 | date= 1998-12-04}}</ref> It is not regulated in the US. It is a [[pyrrolidone]] derivative.
 
   
=====Aniracetam=====
+
* [[Propentofylline]]&mdash;nonselective phosphodiesterase inhibitor with some neuroenhancement
{{Main|Aniracetam}}
+
* [[Rolipram]]&mdash;PDE4 inhibitor, shows alertness enhancement, long term memory improvement and neuroprotection
Aniracetam is a pyrrolidone derivative drug, analogous of piracetam, and considered more potent{{Fact|date=February 2008}}. Like piracetam, aniracetam protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.<ref name="Genkova-Papasova & Lazarova-Bakurova 1988">{{cite journal | author = Genkova-Papasova, M. and Lazarova-Bakurova, M. | title = Influence of nootropic drugs on the memory-impairing effect of diethyldithiocarbamate and clonidine in "step down" passive avoidance in albino rats. | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2854355&dopt=Citation | journal = Acta Physiol. Pharmacol. Bulg. ''(Institute of Physiology, Bulgarian Academy of Sciences)' | date= 1988 | volume = 14 | issue = 4 | pages = 36–41}}</ref> Also like piracetam, aniracetam may enhance memory in aging adults by increasing levels of brain biogenic monoamines, which are beneficial to learning and memory.<ref name="Stancheva et al. 1991"/> Both racetams have possible therapeutic use in treating [[fetal alcohol syndrome]].<ref name="Vaglenova & Petkov 2001">{{cite journal | author = Vaglenova, J. and Petkov, V.V. | title = Can nootropic drugs be effective against the impact of ethanol teratogenicity on cognitive performance? | journal = European Neuropsychopharmacology | date= February 2001 | volume = 11 | issue = 1 | pages = 33–8 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11226810&dopt=Citation}}</ref> Aniracetam increases [[vigilance]]<ref name="Saletu & Grunberger 1985"/>. Aniracetam has shown to positively potentiate [[AMPA receptor]]s.
+
* [[Mesembrine]]&mdash;PDE4-inhibitor with possible serotonergic activity
   
=====Other cholinergic=====
+
====Other====
{{Refimprovesect|date=December 2007}}
+
[[Alpha-2A adrenergic receptor|α<sub>2A</sub>]] receptors are concentrated heavily in the [[prefrontal cortex]] and the [[locus coeruleus]], with the potential to improve attention abilities via modulating post-synaptic α<sub>2A</sub> receptors in the prefrontal cortex.<ref name=Kolar>{{cite journal | last1 = Kolar | first1 = D. | last2 = Keller | year = 2008 | first2 = A | last3 = Golfinopoulos | first3 = M | last4 = Cumyn | first4 = L | last5 = Syer | first5 = C | last6 = Hechtman | first6 = L | title = Treatment of adults with attention-deficit/hyperactivity disorder | url = | journal = Neuropsychiatric Disease and Treatment | volume = 4 | issue = 2| pages = 389–403 | pmid = 18728745 | pmc = 2518387}}</ref>
* [[Acetylcarnitine|Acetyl-L-carnitine (ALCAR)]] - Amino acid. Precursor of acetylcholine (donating the acetyl portion to the acetylcholine molecule). It is synergistic with [[lipoic acid]].<ref>Liu J, Killilea DW, Ames BN. "Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid." Proc Natl Acad Sci U S A. 2002 February 19; 99(4): 1876–1881.</ref>
 
* [[Choline]] - precursor to acetylcholine (an essential component of the acetylcholine molecule).
 
** [[Alpha-GPC]] ([[L-alpha glycerylphosphorylcholine]], [[Choline alfoscerate]]) - most effective choline precursor, readily crosses the blood-brain barrier.
 
** [[CDP-Choline]] ([[Cytidine Diphosphate Choline]]) - choline precursor, tends to be less expensive and similar in effect to Alpha GPC.
 
** [[Choline|Choline bitartrate]] - precursor of acetylcholine, anti-depressant.
 
** [[Choline|Choline citrate]] - precursor of the neurotransmitter acetylcholine, anti-depressant.
 
** [[Citicoline]] The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory.<ref name="McDaniel et al. 2002">{{cite journal | author = McDaniel, M.A., Maier, S.F., and Einstein, G.O. | title = Brain-Specific Nutrients: A Memory Cure? | journal = Psychological Science in the Public Interest ''(American Psychological Society)' | volume = 3 | issue = 1 | url = http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TB0-4B0KTYF-C&_coverDate=12%2F31%2F2003&_alid=448998985&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5128&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=f99a155c658f3be9a94cc485fbf37262| date = 2002}}</ref>
 
* [[DMAE]] - approved treatment for [[Attention-deficit hyperactivity disorder|ADD/ADHD]]{{Fact|date=November 2007}}, precursor of acetylcholine, [[Cholinergic|cholinergic agent]], removes [[lipofuscin]] from the brain, anti-depressant.
 
* [[Galantamine]] - acetylcholinesterase inhibitor made from chemical synthesis or extract from plants such as Red Spider Lily (Lycoris radiata).
 
* [[Huperzine A]] - potent acetylcholinesterase inhibitor derived from Chinese club-moss.
 
* [[Lecithin]] - contains [[phosphatidylcholine]], precursor of acetylcholine.
 
* Other pyrrolidone derivatives:
 
** [[Etiracetam]] - It increases vigilance.<ref name="Saletu & Grunberger 1985"/>
 
** [[Nefiracetam]] - Drug. Analog of piracetam, and facilitates hippocampal neurotransmission.<ref name="Nomura & Nishizaki 2000">{{cite journal | author = Nomura, T. and Nishizaki, T. | title = Nefiracetam facilitates hippocampal neurotransmission by a mechanism independent of the piracetam and aniracetam action. | journal = Brain Res. ''(Department of Physiology, Kobe University School of Medicine. Kobe, Japan)' | date= 2000-07-07 | volume = 870 | issue = 1–2 | pages = 157–62 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10869513&dopt=Citation}}</ref>
 
** [[Oxiracetam]] - Drug. Analog of piracetam, and 2 to 4 times stronger. Improves memory, concentration, and vigilance. When fed to pregnant rats, the offspring of those rats were more intelligent than the offspring of rats fed a saline solution placebo.
 
** [[Pramiracetam]] - Drug. Analog of [[piracetam]].
 
** In animal studies, nootropics such as piracetam, oxiracetam and aniracetam are known to facilitate the formation of long term memory traces and to restore object recognition in aging rats. <ref name="Zdenek Hlinak and Ivan Krejci">{{cite journal | author = Zdenek Hlinak and Ivan Krejci | title = Oxiracetam prevents the MK-801 induced amnesia for the elevated plus-maze in mice | journal = Behavioral Brain Research | date= 18 July 2000| volume = 117 | issue = | pages = 147-151| url = http://dx.doi.org/doi:10.1016/S0166-4328(00)00298-9 }}</ref> There is evidence that the beneficial effect of racetams may result from an interaction with the central glutamatergic receptor function. <ref name="Zdenek Hlinak and Ivan Krejci">{{cite journal | author = Zdenek Hlinak and Ivan Krejci | title = Oxiracetam prevents the MK-801 induced amnesia for the elevated plus-maze in mice | journal = Behavioral Brain Research | date= 18 July 2000| volume = 117 | issue = | pages = 147-151| url = http://dx.doi.org/doi:10.1016/S0166-4328(00)00298-9 }}</ref>
 
* [[Vitamin B5]] - cofactor in the conversion of choline into acetylcholine, cholinergic agent, increases [[stamina]] (including mental stamina).
 
   
Excess acetylcholine is considered by many to be potentially harmful; see [[cholinesterase inhibitor]].
+
* [[Guanfacine]] is an α<sub>2A</sub> receptor agonist, FDA approved for and frequently used to treat ADHD symptoms.<ref>[http://www.freepatentsonline.com/y2009/0221610.html Compositions and Methods for Treating Cognitive Disorders.] United States Patent Application 20090221610.</ref><ref>{{Cite news |url=http://www.medicalnewstoday.com/articles/74898.php |title=Shire Receives FDA Approvable Letter For INTUNIV (guanfacine) ER, A Nonstimulant ADHD Treatment |date=24 June 2007 |work=Medical News Today}}</ref> 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.<ref>{{Cite journal
  +
| last1 = Arnsten | first1 = A. F.
  +
| last2 = Dudley | first2 = A. G.
  +
| title = Methylphenidate improves prefrontal cortical cognitive function through α2 adrenoceptor and dopamine D1 receptor actions: Relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder
  +
| journal = Behavioral and Brain Functions
  +
| volume = 1
  +
| issue = 1
  +
| pages = 2
  +
| doi = 10.1186/1744-9081-1-2
  +
| year = 2005
  +
| pmid = 15916700
  +
| pmc =1143775
  +
}}</ref> Another study found no effect on healthy male adult's executive functions and working memory, and small decrements on 2 tasks relating to the sedative effect of guanfacine.<ref>{{Cite journal |pmid=16078088|year=2005|last1=Müller|first1=U|last2=Clark|first2=L|last3=Lam|first3=ML|last4=Moore|first4=RM|last5=Murphy|first5=CL|last6=Richmond|first6=NK|last7=Sandhu|first7=RS|last8=Wilkins|first8=IA|last9=Menon|first9=DK|title=Lack of effects of guanfacine on executive and memory functions in healthy male volunteers|volume=182|issue=2|pages=205–13|doi=10.1007/s00213-005-0078-4|journal=Psychopharmacology}}</ref>
   
====Dopaminergics====
+
===Serotonergics===
[[Dopaminergic]]s are substances that affect the neurotransmitter [[dopamine]] or the components of the nervous system that use dopamine. Dopamine is produced in the synthesis of all [[catecholamine]] neurotransmitters, and is the rate limiting step for this synthesis. Dopaminergic nootropics include dopamine precursors and cofactors, and [[dopamine reuptake inhibitors]]:
+
[[Serotonin]] 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]]:
* [[Mucuna pruriens]] - Seed powder contains high concentrations of levodopa (L-dopa),<ref>
 
{{cite web
 
|url=http://books.google.com/books?id=qDf3AO8nILoC&pg=PA1679&lpg=PA1679&dq=%22mucuna+pruriens%22+alkaloids&source=web&ots=pTUo3Whq_r&sig=o70RMmOVZDTr7nCPPjzp8DuiN1cMedical
 
|title=Medical Toxicology - Google Book Search
 
|publisher=books.google.com
 
|accessdate=2008-03-15
 
|last=
 
|first=
 
}}
 
</ref> a direct precursor of the neurotransmitter dopamine.
 
* [[Lazabemide]] is a MAO-B inhibitor and has potent membrane lipid antioxidant activity. The antioxidant effects of lazabemide are attributed to its chemical structure and direct physicochemical interactions with the membrane lipid bilayer. It is a potent antioxidant, even more powerful than selegiline (deprenyl) or vitamin E, and is used to treat Alzheimer’s disease.<ref name="R. Preston Mason, Edwin G. Olmstead Jr., and Robert F. Jacob">{{cite journal | author = R. Preston Mason, Edwin G. Olmstead Jr., and Robert F. Jacob | title = Antioxidant Activity of the Monoamine Oxidase B Inhibitor Lazabemide | journal = Biochemical Pharmacology | date= 2000 | volume = 60 | issue = | pages = 709-716| url = http://dx.doi.org/doi:10.1016/S0006-2952(00)00374-9 }}</ref>
 
* [[L-dopa]] - Prescription drug and dietary supplement. Precursor to the neurotransmitter dopamine, anti-depressant.
 
* [[Phenylalanine]] (requires [[Vitamin B6]] and [[Vitamin C]]) - [[Essential amino acid]]. Precursor to dopamine, anti-depressant, sleep reducer.
 
* [[Theanine]] - Found in tea. Increases serotonin and dopamine levels in the brain. Increases alpha-wave based alert relaxation.
 
* '''[[Tyrosine]]''' (requires Vitamin B6 and Vitamin C) - [[Amino acid]]. Precursor to dopamine, anti-depressant, sleep reducer.
 
* [[Vitamin C]]- improves cardiovascular elasticity and integrity, membrane stabilizer and major anti-oxidant (protects brain cells and prevents brain cell death), cofactor in the production of the neurotransmitters dopamine and [[serotonin]].
 
* [[Vitamin B6]] - co-factor used by the body to produce dopamine.
 
* [[Yohimbe]] - Bark. Boosts dopamine levels, though how it does this is not yet understood. Aphrodisiac. Yohimbe poses some health risks through its side-effects: it is a neuro-paralytic which slows down breathing and induces [[acidosis]], some symptoms of which are malaise, nausea, and vomiting. Contraindicated for users of megadoses of acidic vitamins or nutrients.
 
* [[Deprenyl]] - (selegiline) L-Deprenyl is an irreversible MAO-B inhibitor, an enzyme that breaks down dopamine. Thus, it is used to treat Parkinson's disease, and to delay the progression of Alzheimer's disease. It protects against the genotoxin AraC, provides neuroprotection against growth factor withdrawal in PC12 cells, protects against oxidative stress in mesencephalatic neurons, and delays neuronal cell death in the hippocampus after global ischemia.<ref name="Suuronen et. al. ">{{cite journal | author = Tiina Suuronen, Petri Kolehmainen, and Antero Salminen, Department of Neuroscience and Neurology, University of Kuopio, Finland. | title = Protective Effect of L-Deprenyl against Apoptosis Induced by Okadaic Adic in Cultured Neuronal Cells | journal = Biochemical Pharmacology | date= 2000 | volume = 59 | issue = | pages = 1589-1595 | url = http://www.ihop-net.org/UniPub/iHOP/pm/8443936.html?pmid=10799657 }}</ref>
 
* [[Tolcapone]] - Inhibits [[COMT]] (an enzyme that breaks down the neurotransmitters dopamine, epinephrine, and norepinephrine) and increases performance in tasks depending on [[working memory]] in individuals with the val/val and val/met genotype of the val158Met polymorphism of the catechol-O-methyltransferase gene, while decreasing it in presence of the met/met version. Tolcapone presents the risk of deadly side effects.
 
<!--If there's no cite for "contraindicated for", consider removing the last line -- wikipedia isn't a venue for health advice-->
 
   
====Serotonergics====
+
* Precursors
{{Unreferencedsection|date=December 2007}}
+
** [[5-HTP]]&mdash;precursor (intermediate between [[tryptophan]] and serotonin)
[[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]]:
+
** [[Tryptophan]]&mdash;essential amino acid precursor
*''[[Griffonia simplicifolia]]'' a natural source of [[5-HTP]] (an alternative in countries where 5-HTP not legal, freely available.)
+
* Cofactors
* [[Tryptophan]] (requires Vitamin B6 and Vitamin C) - Essential amino acid. Precursor to serotonin, found in high concentration in bananas and poultry (especially turkey), also in milk, promotes relaxed poise and sound sleep. 5-HTP is a form of Tryptophan.
+
** [[Pyridoxal-phosphate]] (or PLP, pyridoxal-5'-phosphate, P5P, active form of [[Vitamin B6]])&mdash;plays role in conversion of [[5-HTP]] into serotonin (via the enzyme [[aromatic L-amino acid decarboxylase]]).<ref>{{Cite journal | last1 = Calderón-Guzmán | first1 = D. | last2 = Hernández-Islas | first2 = JL. | last3 = Espitia-Vázquez | first3 = I. | last4 = Barragán-Mejía | first4 = G. | last5 = Hernández-García | first5 = E. | last6 = Santamaría-del Angel | first6 = D. | last7 = Juárez-Olguín | first7 = H. | title = Pyridoxine, regardless of serotonin levels, increases production of 5-hydroxytryptophan in rat brain. | journal = Arch Med Res | volume = 35 | issue = 4 | pages = 271–4 | month = | year = | doi = 10.1016/j.arcmed.2004.03.003 | PMID = 15325498 }}</ref><ref>{{Cite journal | last1 = Lee | first1 = NS. | last2 = Muhs | first2 = G. | last3 = Wagner | first3 = GC. | last4 = Reynolds | first4 = RD. | last5 = Fisher | first5 = H. | title = Dietary pyridoxine interaction with tryptophan or histidine on brain serotonin and histamine metabolism. | journal = Pharmacol Biochem Behav | volume = 29 | issue = 3 | pages = 559–64 | month = Mar | year = 1988 | doi = 10.1016/0091-3057(88)90020-2 | PMID = 3362950 }}</ref>
* 5HT<sub>2A</sub> agonists such as [[LSD]] and [[2C-T-7]] have been shown to produce nootropic effects when used at a dose much lower than a hallucinogenic dose. (e.g. 10 μg for LSD and 1 mg 2C-T-7, 1/25 of a normal recreational dose ){{Fact|date=December 2007}}
+
* [[Serotonin reuptake inhibitor|Reuptake inhibitors]]
* [[SSRI]]s - Class of antidepressants that increase serotonin levels in the brain by inhibiting its reuptake. Have also been shown to promote [[Neurogenesis]] in the hippocampus.
+
** [[SSRI]]s&mdash;class of antidepressants that increase active serotonin levels by inhibiting reuptake, also shown to promote Neurogenesis in the hippocampus
  +
** ''[[Sceletium tortuosum]]''&mdash;active constituent [[mesembrine]] shown to act as an [[SSRI]]<ref>{{Cite journal | last1 = Stafford | first1 = GI. | last2 = Pedersen | first2 = ME. | last3 = van Staden | first3 = J. | last4 = Jäger | first4 = AK. | title = Review on plants with CNS-effects used in traditional South African medicine against mental diseases. | journal = J Ethnopharmacol | volume = 119 | issue = 3 | pages = 513–37 | month = Oct | year = 2008 | doi = 10.1016/j.jep.2008.08.010 | PMID = 18775771 }}</ref> and [[PDE4 inhibitor]]. (Half-life unknown)
  +
** ''[[Hypericum perforatum]]''&mdash;inhibits reuptake of serotonin (as well as Norepinephrine, Dopamine, GABA and Glutamate) via activation of [[TRPC6]]
  +
* [[Monoamine oxidase inhibitor|MAO-A inhibitors]]
  +
** [[Resveratrol]]<ref>{{Cite journal | last1 = Yáñez | first1 = M. | last2 = Fraiz | first2 = N. | last3 = Cano | first3 = E. | last4 = Orallo | first4 = F. | title = Inhibitory effects of cis- and trans-resveratrol on noradrenaline and 5-hydroxytryptamine uptake and on monoamine oxidase activity. | journal = Biochem Biophys Res Commun | volume = 344 | issue = 2 | pages = 688–95 | month = Jun | year = 2006 | doi = 10.1016/j.bbrc.2006.03.190 | PMID = 16631124 }}</ref>
  +
** [[Curcumin]]<ref>{{Cite journal | last1 = Xu | first1 = Y. | last2 = Ku | first2 = BS. | last3 = Yao | first3 = HY. | last4 = Lin | first4 = YH. | last5 = Ma | first5 = X. | last6 = Zhang | first6 = YH. | last7 = Li | first7 = XJ. | title = The effects of curcumin on depressive-like behaviors in mice. | journal = Eur J Pharmacol | volume = 518 | issue = 1 | pages = 40–6 | month = Jul | year = 2005 | doi = 10.1016/j.ejphar.2005.06.002 | PMID = 15987635 }}</ref>
  +
** [[Piperine]]<ref>{{Cite journal | last1 = Rahman | first1 = T. | last2 = Rahmatullah | first2 = M. | title = Proposed structural basis of interaction of piperine and related compounds with monoamine oxidases. | journal = Bioorg Med Chem Lett | volume = 20 | issue = 2 | pages = 537–40 | month = Jan | year = 2010 | doi = 10.1016/j.bmcl.2009.11.106 | PMID = 19969454 }}</ref>
  +
** [[Harmal]]<ref>{{Cite journal | last1 = Herraiz | first1 = T. | last2 = González | first2 = D. | last3 = Ancín-Azpilicueta | first3 = C. | last4 = Arán | first4 = VJ. | last5 = Guillén | first5 = H. | title = beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). | journal = Food Chem Toxicol | volume = 48 | issue = 3 | pages = 839–45 | month = Mar | year = 2010 | doi = 10.1016/j.fct.2009.12.019 | PMID = 20036304 }}</ref> One of the major constituents of harmal, harmaline, has demonstrated acetylcholinesterase inhibition.
  +
** ''[[Rhodiola rosea]]''<ref name="Diermen2009"/>
  +
* Reuptake enhancers
  +
** [[Tianeptine]]&mdash;paradoxical antidepressant (considered to be a [[selective serotonin reuptake enhancer]] ([[SSRE]]) (note that no widely known proof of direct SSRE action exists)), improves mood and reduces anxiety; action on the [[NMDA receptor|NMDA]] and AMPA receptor, a hypothesized mechanism of action, based on tianeptine's effect of promoting stress-associated impaired [[neuroplasticity]];<ref name=mp09>{{cite doi|10.1038/mp.2009.80}}</ref><ref name=cns08>{{cite journal |author=Kasper S, McEwen BS |title=Neurobiological and clinical effects of the antidepressant tianeptine |journal=CNS Drugs |volume=22 |issue=1 |pages=15–26 |year=2008 |pmid=18072812 |doi=10.2165/00023210-200822010-00002}}</ref> it enhances the extracellular concentration of [[dopamine]] in the [[nucleus accumbens]]<ref>{{cite journal |author=Invernizzi R, Pozzi L, Garattini S, Samanin R |title=Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism |journal=Neuropharmacology |volume=31 |issue=3 |pages=221–7 |year=1992 |month=March |pmid=1630590 |doi=10.1016/0028-3908(92)90171-K}}</ref> and modulates the [[Dopamine receptor D2|D<sub>2</sub>]] and [[Dopamine receptor D3|D<sub>3</sub>]] dopamine receptors,<ref>{{cite web|url=http://www.tianeptine.com/dopamined2d3.html |title=( Stablon, Coaxil ) and the dopamine D(2) and D(3) receptors |publisher=Tianeptine |date= |accessdate=2010-08-13}}</ref> but this effect is modest and almost certainly indirect.<ref name=mp09/>
   
 
===Anti-depression, adaptogenic (antistress), and mood stabilization===
 
===Anti-depression, adaptogenic (antistress), and mood stabilization===
{{Unreferencedsection|date=January 2008}}
+
[[stress (biological)|Stress]] (specifically elevated levels of circulating corticosteroids) has been associated with the cognitive deficits seen in human aging.<ref>{{Cite journal|author=Lupien S, Lecours AR, Lussier I, Schwartz G, Nair NP, Meaney MJ |title=Basal cortisol levels and cognitive deficits in human aging. |journal=J Neurosci. |volume=14 |issue=5pt1 |pages=2893–903 |year=1994 |month=May |pmid=8182446}}</ref> Depression and [[Depression (mood)|depressed mood]] negatively affect cognitive performance.{{Citation needed|date=February 2011}} It is reasoned that counteracting and preventing depression and [[stress management|stress]] may be an effective nootropic strategy.{{Citation needed|date=February 2011}} The term [[adaptogen]] applies to most herbal anti-stress claims.{{Citation needed|date=February 2011}}
[[Clinical depression|Depression]] and [[Depression (mood)|depressed mood]] negatively affect cognitive performance. Feelings of sadness, guilt, helplessness, hopelessness, [[anxiety]], and fear caused by depression detract from productive thought, while apathy (which is also induced by depression) is the lack of motivation and driving moods (like curiosity, interest, determination, etc.) Other symptoms include disturbed sleep patterns, mental fatigue and loss of energy, trouble concentrating or making decisions, and a generalized slowing and obtunding of cognition, including memory. Obviously, removing these effects improves intelligence and mental performance, and therefore, counteracting and preventing depression are effective nootropic strategies. There is a high correlation between depression and a reduction or depletion of neurotransmitters (dopamine, acetylcholine, and serotonin) in the brain, therefore it is no surprise that increasing the brain's supply of neurotransmitters alleviates (or at least reduces the symptoms of) most depressions. Stress is another major factor in neurotransmitter depletion, being both a cause and effect of it (creating a vicious downward spiral), therefore [[stress management]] and anti-stress substances are also very useful nootropic strategies.
 
   
All of the "nergics" listed above have been found to increase stress tolerance and alleviate depression (by replenishing or increasing the brain's supply of specific neurotransmitters){{Fact|date=September 2007}}, especially when used in precursor/co-factor combinations{{Fact|date=September 2007}}.
+
The substances below may not have been mentioned earlier on the page:
  +
* [[Beta blockers]]&mdash;evidence from controlled trials spanning 25 years supports the claim that beta-blockers are effective for reducing anxiety, likely through peripheral blockade of beta-receptors; most data comes from studies of generalized anxiety and acute stress.<ref>{{Cite journal|author=Tyrer P |title=Anxiolytics not acting at the benzodiazepine receptor: beta blockers. |journal=Prog Neuropsychopharmacol Biol Psychiatry |volume=16 |issue=1 |pages=17–26 |year=1992 |month=January |pmid=1348368}}</ref>
  +
* [[Lemon Balm]]&mdash;displays adaptogen properties; in rats it has been shown to possess [[GABA transaminase inhibitor]] activity<ref>{{Cite journal|author=Awad, R.; Levac, D.; Cybulska, P.; Merali, Z.; Trudeau, V.L.; Arnason, J.T. |title=Effects of traditionally used anxiolytic botanicals on enzymes of the γ-aminobutyric acid (GABA) system |journal=Can J Physiol Pharmacol. |volume=85 |issue=9 |pages=933–42 |year=2007 |month=September |pmid=18066140 |doi=10.1139/Y07-083}}</ref> and in homogenates of human cerebral cortical cell membranes possesses activity at [[acetylcholine receptors]].<ref>{{Cite journal|author=Wake G, Court J, Pickering A, Lewis R, Wilkins R, Perry E |title=CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory |journal=J Ethnopharmacol. |volume=69 |issue=2 |pages=105–14 |year=2000 |month=February |pmid=10687867 |doi=10.1016/S0378-8741(99)00113-0}}</ref> In a randomized, double-blind, placebo-controlled study of 18 healthy volunteers, 600&nbsp;mg of 'Melissa officinalis' extract attenuated volunteers' response to a laboratory-induced stress test 1 hour after administration; 300&nbsp;mg significantly improved speed of mathematical processing 1 hour after administration.<ref>{{Cite journal|author=Kennedy DO, Little W, Scholey AB |title=Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm) |journal=Psychosom Med. |volume=66 |issue=4 |pages=607–13 |year=2004 |month=Jul-Aug |pmid=15272110 |doi=10.1097/01.psy.0000132877.72833.71}}</ref>
  +
* [[Passion Flower]]&mdash;possible [[MAOI]] and neurotransmitter reuptake activity {{Citation needed|date=February 2011}}
  +
* [[Rhodiola Rosea]]&mdash;adaptogen; possible MAOI activity<ref>Panossian A., Wikman G."Evidence based efficacy of adaptogens in fatigue" [[Planta Medica]] 2009 75:9</ref>
  +
* [[St John's Wort]]&mdash;herbal supplement approved (in Europe) to treat mild depression. Method of action is unproven but exhibits effects similar to both MAOIs and SSRIs. {{Citation needed|date=February 2011}} There is evidence that it may decrease the effectiveness of methylphenidate treatment.<ref>{{cite pmid|17254717}}</ref>
  +
* [[Ginseng]] (including [[Siberian ginseng]])&mdash;adaptogenic effects shown{{Citation needed|date=February 2011}}
  +
* [[Sutherlandia frutescens]]&mdash;possible anti-inflammatory, reducing pain from those illnesses {{Citation needed|date=February 2011}}
  +
* [[Kava]]&mdash;anxiolytic herb{{Citation needed|date=February 2011}}
  +
* [[Tea]]&mdash;contains many different adaptogens{{Citation needed|date=February 2011}}
  +
* [[Theanine]]&mdash;GABAergic activity producing relaxation, also increases brain serotonin and dopamine levels{{Citation needed|date=February 2011}}
  +
* [[Grape seed extract]]&mdash;has shown some efficacy in reducing bodily stress{{Citation needed|date=February 2011}}
  +
* [[Adafenoxate]]&mdash;possible anxiolytic effect{{Citation needed|date=February 2011}}
  +
* [[Phenibut]] GABA receptor agonist excerting anxiolytic effects
  +
* [[Picamilon]] GABA prodrug which excerts anxiolytic effects by releasing GABA and niacin in the CNS.
  +
* [[Valerian (herb)|Valerian]]&mdash;possible anxiolytic effect through agonism at [[GABA-A]] receptors{{Citation needed|date=February 2011}}
  +
* [[Butea frondosa]]&mdash;possible anxiolytic effect<ref name="Soman et al. 2004">{{Cite journal|author=Soman I, Mengi SA, Kasture SB |title=Effect of leaves of ''Butea frondosa'' on stress, anxiety, and cognition in rats |journal=Pharmacol. Biochem. Behav. |volume=79 |issue=1 |pages=11–6 |year=2004 |month=September |pmid=15388278 |doi=10.1016/j.pbb.2004.05.022}}</ref>
  +
* [[Gotu Kola]]&mdash;adaptogen and anxiolytic {{Citation needed|date=February 2011}}
  +
* [[Foti]]&mdash;adaptogen; possible MAOI activity {{Citation needed|date=February 2011}}
  +
* [[Panax ginseng]]&mdash;Multiple randomized, placebo-controlled studies in healthy volunteers have been performed, results include increases in accuracy of memory, speed in performing attention tasks and improvement in performing difficult mental arithmetic tasks, as well as reduction in fatigue and improvement in mood.<ref>{{Cite journal|author=Kennedy DO, Wightman EL |title=Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. |journal=Adv Nutr. |volume=2 |issue=1 |pages=32–50 |year=2011 |month=Jan |pmid=22211188 |doi=10.3945/an.110.000117}}</ref>
  +
* Many Chinese herbs such as [[Polygala tenuifolia]], [[Acorus gramineus]] and [[Huperzia serrata]].<ref>{{Cite journal
  +
| last1 = Jesky | first1 = R.
  +
| last2 = Hailong | first2 = C.
  +
| doi = 10.1002/ptr.3388
  +
| title = Are Herbal Compounds the Next Frontier for Alleviating Learning and Memory Impairments? An Integrative Look at Memory, Dementia and the Promising Therapeutics of Traditional Chinese Medicines
  +
| journal = Phytotherapy Research
  +
| volume = 25
  +
| issue = 8
  +
| pages = 1105–1118
  +
| year = 2011
  +
| month = August
  +
| pmid = 21305632
  +
}}</ref>
  +
* [[Bacopa monnieri]]<ref>{{Cite journal
  +
| last1 = Morgan | first1 = A.
  +
| last2 = Stevens | first2 = J.
  +
| doi = 10.1089/acm.2009.0342
  +
| title = DoesBacopa monnieriImprove Memory Performance in Older Persons? Results of a Randomized, Placebo-Controlled, Double-Blind Trial
  +
| journal = The Journal of Alternative and Complementary Medicine
  +
| volume = 16
  +
| issue = 7
  +
| pages = 753–759
  +
| year = 2010
  +
| month = July
  +
| pmid = 20590480
  +
}}</ref>
  +
* [[Tulsi]] ([[Ocimum sanctum]], sweet holy basil)<ref>{{Cite journal
  +
| last1 = Mondal | first1 = Shankar
  +
| last2 = Mirdha | first2 = Bijay R.
  +
| last3 = Mahapatra | first3 = Sushil C.
  +
| title = The science behind sacredness of ''Tulsi'' (''Ocimum sanctum'' Linn.)
  +
| journal = Indian journal of physiology and pharmacology
  +
| volume = 53
  +
| issue = 4
  +
| pages = 291–306
  +
| year = 2009
  +
| month = October–December
  +
| pmid = 20509321
  +
| url = http://www.ijpp.com/vol53_4/291-306.pdf
  +
}}</ref>
   
Below are additional nootropics which affect mood and stress:{{Fact|date=December 2007}} <!--needed for all!-->
+
===Blood flow and metabolic function===
* [[Ashwagandha|Ashwagandha (''Withania somnifera'')]] - Root. Also known as Indian ginseng. [[Adaptogen]] used as a tonic to normalize body processes and reduce stress and anxiety.
+
Brain function is dependent on many basic processes such as the usage of [[Adenosine triphosphate|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.
* [[Inositol]] - Is a B-vitamin like substance with anti-anxiety effects. It is believed to produce its anti-anxiety effects by improving the binding of [[Gamma-aminobutyric acid|gabaergics]] to [[GABA receptor|GABA<sub>A</sub> receptors]]. Inositol is a sugar, and is therefore an alternative energy source for brain and muscle tissues. It produces a sugar high without a sugar low, making it especially suited for sweetening tea (instead of sugar). It is also a membrane stabilizer which can strengthen (and therefore help protect) neurons.
 
* [[Kava-kava]] - The roots of the Kava-Kava plant contain Kavalactones which have GABAergic properties and are used to combat anxiety.<ref name="Susanne Kienzle-Horn 2002">{{cite journal | author = Susanne Kienzle-Horn| title = Herbal medicines for neurological diseases | journal = Current Opinion in Investigational Drugs | date= 2002 | volume = 3 | issue = 5 | pages = 763-767 | url = www.biomedcentral.com/content/pdf/cd-451283.pdf}}</ref>
 
* [[Lemon Balm|Lemon Balm (''Melissa officinalis'')]] - Herb. Anti-depressant.
 
* [[Passion Flower]] is used to treat depression. It is commonly combined with St. John’s Wort and Valerian, which work synergistically to reestablish the patients emotional balance without causing tachyphylaxia, hangovers, or addiction. <ref name="Susanne Kienzle-Horn 2002">{{cite journal | author = Susanne Kienzle-Horn| title = Herbal medicines for neurological diseases | journal = Current Opinion in Investigational Drugs | date= 2002 | volume = 3 | issue = 5 | pages = 763-767 | url = www.biomedcentral.com/content/pdf/cd-451283.pdf}}</ref>
 
* [[Rhodiola Rosea]] - Herb. Adaptogen; elevates mood, alleviates depression. Promotes mental energy and stamina, reduces fatigue.
 
* [[St John's Wort]] - Herb. The active components: hypericin and hyperforin, are clinically indicated to be effective in cases of mild to moderate depression, on par with synthetic drugs. However, St John's Wort is not suitable for the treatment of severe depression or suicidal tendencies. Side effects include gastrointestinal complaints and allergic reactions such as pruritus and phototoxicity. <ref name="Susanne Kienzle-Horn 2002">{{cite journal | author = Susanne Kienzle-Horn| title = Herbal medicines for neurological diseases | journal = Current Opinion in Investigational Drugs | date= 2002 | volume = 3 | issue = 5 | pages = 763-767 | url = www.biomedcentral.com/content/pdf/cd-451283.pdf}}</ref>
 
* [[Siberian ginseng|Ginseng, Siberian]] (''[[Eleutherococcus senticosus]]'') - Root. Anti-anxiety adaptogen that normalizes physical stress and mental consequences.
 
* [[Selegiline|Selegiline (Deprenyl)]] - Along with Piracetam and Meclofenoxate, Deprenyl decreases the amount of lipofuscin pigment and ceroid pigment accumulations in the brain by improving cellular recycling activities.<ref name="Riga & Riga 1995">{{cite journal | author = Riga, D. and Riga, S. | title = Brain lipofuscinolysis and ceroidolysis--to be or not to be. | journal = Gerontology ''(Institute of Neurology and Psychiatry, Bucharest, Romania)' | volume = 41 | issue = S2 | pages = 271–81 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8821338&dopt=Abstract | date= 1995 }}</ref> Therefore, these nootropics may slow age-related diseases in the brain. Selegiline, an MAO-B inhibitor, is used as an antioxidant for the treatment of Alzheimer’s disease. <ref name="R. Preston Mason, Edwin G. Olmstead Jr., and Robert F. Jacob">{{cite journal | author = R. Preston Mason, Edwin G. Olmstead Jr., and Robert F. Jacob | title = Antioxidant Activity of the Monoamine Oxidase B Inhibitor Lazabemide | journal = Biochemical Pharmacology | date= 2000 | volume = 60 | issue = | pages = 709-716| url = http://dx.doi.org/doi:10.1016/S0006-2952(00)00374-9 }}</ref>
 
* ''[[Sutherlandia frutescens]]'' - Herb. Adaptogen, blood detoxifier.
 
* [[Tea]] - Herb. Contains [[theophylline]] and theanine. Increases alpha-wave based alert relaxation (relieves stress).
 
* [[Theanine]] - Amino acid. Found in tea. Increases serotonin and dopamine levels in the brain. Increases alpha-wave based alert relaxation.
 
* [[Tianeptine]] - Anxiolytic anti-depressant. It enhances working and reference memory in rats.<ref>[http://www.tianeptine.com/profile.html Tianeptine ( Stablon, Coaxil ) : an unusual antidepressant<!-- Bot generated title -->]</ref>
 
* [[Vasopressin]] - Drug. [[Vasopressin#Actions within the brain|Memory hormone]] produced by the [[pituitary gland]] which improves both memory encoding and recall. Rapidly counters chronic apathy syndrome and drug-induced vasopressin depletion.
 
* [[Vitamin B3|Nicotinic acid (vitamin B3)]] - Essential nutrient. Mild enhancer of concentration and memory. [[Vasodilation|Vasodilator]] - Mood stabilizer, with a powerful anti-anxiety effect &mdash; perhaps the best and most immediate stress reliever available (note that other forms of vitamin B do not have this effect). Side effects: gastric upset (which is easily prevented and relieved with antacids), reduced blood pressure and flushing of the skin (caused by vasodilation), and itchy sensation in the skin caused by histamine release.
 
* [[Vitis vinifera]] (Grape Seed) Grape seed has antistress (adaptogenic) activity, protects against memory loss induced by scopolamine, is an antioxidant, has nootropic activities, and supports the traditional claims for the use of grape fruits and seeds in stress induced disorders. <ref name="Sreemantula et. al. 2005">{{cite journal | author = Sreemantula et. al. | title = Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model | url = http://www.biomedcentral.com/1472-6882/5/1 | journal = BMC Complementary and Alternative Medicine | date = 19 January 2005 | volume = 5 | issue = 1 | pages = }}</ref>
 
   
===Brain energy and improved oxygen supply===
+
* [[Blessed Thistle]]&mdash;increases blood circulation, improving memory {{Citation needed|date=February 2012}}
{{Unreferencedsection|date=December 2007}}
+
* [[Coenzyme q-10]]&mdash;antioxidant; increases oxygen usage by mitochondria
* [[Carnitine#Acetyl-L-carnitine|Acetyl-L-carnitine (ALCAR)]] - Amino acid. Transports fatty acids through cellular membranes and cytosol into cells' mitochondria, where the fats undergo oxidation to produce [[adenosine triphosphate|ATP]], the universal energy molecule. Synergistic with [[lipoic acid]].
+
* [[Creatine]]&mdash;protects ATP during transport
* [[Chromium]]- stabilises blood sugar levels promoting concentration.
+
* [[Lipoic acid]]&mdash;improves oxygen usage and antioxidant recycling, possibly improving memory
* [[Coenzyme q-10]] syn. Ubiquinone - increases oxygen transport through the mitochondria of the cells.
+
* [[Pyritinol]]&mdash;Drug similar to B vitamin Pyridoxine
* [[Creatine]] - increases brain energy levels via ATP production.
+
* [[Picamilon]]&mdash;GABA activity and blood flow improver
* [[Inositol]] -
+
* [[Ginkgo biloba]]&mdash;vasodilator. Acts as an [[Norepinephrine Reuptake Inhibitor|NRI]].<ref>{{Cite journal | last1 = Fehske | first1 = CJ. | last2 = Leuner | first2 = K. | last3 = Müller | first3 = WE. | title = Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment. | journal = Pharmacological Research | volume = 60 | issue = 1 | pages = 68–73 | month = Jul | year = 2009 | doi = 10.1016/j.phrs.2009.02.012 | PMID = 19427589 | ISSN = 1043-6618 }}</ref> A double-blind, placebo-controlled trial in young healthy females showed an improvement in short-term memory performance 1 hour after administration of a 600&nbsp;mg dose.<ref>{{Cite journal|author=Hindmarch I |title=[Activity of Ginkgo biloba extract on short-term memory]. |language=French |journal=Presse Med |volume=15 |issue=31 |pages=1592–94 |year=1986 |pmid=2947108}}</ref> An analysis of 29 placebo-controlled RCTs showed that "there is consistent evidence that chronic administration improves selective attention, some executive processes and long-term memory for verbal and non-verbal material."<ref>{{Cite journal|author=Kaschel R |title=Ginkgo biloba: specificity of neuropsychological improvement--a selective review in search of differential effects. |journal=Hum Psychopharmacol |volume=24 |issue=5 |pages=345–70 |year=2009 |pmid=19551805 |doi=10.1002/hup.1037}}</ref> A double-blind, placebo-controlled study in 20 young healthy volunteers showed a dose-dependent improvement in speed-of-attention following administration of 240&nbsp;mg and 360&nbsp;mg of Ginkgo extract, effects were measured 2.5h after administration and persisted at least until 6h; various other time- and dose-specific changes (some positive, some negative) in other areas were observed.<ref>{{Cite journal|author=Kennedy DO, Scholey AB, Wesnes KA |title=The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. |journal=Psychopharmacology (Berl) |volume=151 |issue=4 |pages=416–23 |year=2000 |pmid=11026748 |doi=10.1007/s002130000501}}</ref>
* [[Lipoic acid]] - synergistic with Acetyl-L-carnitine.
+
* [[Vinpocetine]]&mdash; is reported to have cerebral blood-flow enhancing<ref>{{Cite journal|author=Szilágyi G, Nagy Z, Balkay L, ''et al.'' |title=Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study |journal=Journal of the Neurological Sciences |volume=229-230 |pages=275–84 |year=2005 |pmid=15760651 |doi=10.1016/j.jns.2004.11.053}}</ref> and neuroprotective effects,<ref>{{Cite journal|author=Dézsi L, Kis-Varga I, Nagy J, Komlódi Z, Kárpáti E |title=[Neuroprotective effects of vinpocetine in vivo and in vitro. Apovincaminic acid derivatives as potential therapeutic tools in ischemic stroke] |language=Hungarian |journal=Acta Pharmaceutica Hungarica |volume=72 |issue=2 |pages=84–91 |year=2002 |pmid=12498034}}</ref> and is used as a drug in Eastern Europe for the treatment of [[cerebrovascular disorders]] and age-related memory impairment.<ref>{{Cite journal|title=Vinpocetine. Monograph |journal=Alternative Medicine Review |volume=7 |issue=3 |pages=240–3 |year=2002 |pmid=12126465 |url=http://www.thorne.com/altmedrev/.fulltext/7/3/240.pdf}}</ref> Also shown to inhibit voltage-sensitive Na+ channels&mdash;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.<ref>{{Cite journal | last1 = Trejo | first1 = F. | last2 = Nekrassov | first2 = V. | last3 = Sitges | first3 = M. | title = Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings. | journal = Brain Res | volume = 909 | issue = 1-2 | pages = 59–67 | month = Aug | year = 2001 | doi = 10.1016/S0006-8993(01)02621-X | PMID = 11478921 }}</ref> Vinpocetine may therefore induce or exacerbate depressive symptoms as an adverse effect. However, this effect tends to be reversible upon cessation of Vinpocetine administration, with full remission typically occurring within 3–4 weeks. Vinpocetine has been identified as a potent anti-inflammatory agent that might have a potential role in the treatment of [[Parkinson's disease]] and [[Alzheimer's disease]].<ref name="Jeon">{{Cite journal|last1=Jeon|first1=KI|last2=Xu|first2=X|last3=Aizawa|first3=T|last4=Lim|first4=JH|last5=Jono|first5=H|last6=Kwon|first6=DS|last7=Abe|first7=J|last8=Berk|first8=BC|last9=Li|first9=JD|title=Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism.|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=21|pages=9795–800|doi=10.1073/pnas.0914414107|year=2010|pmc=2906898|pmid=20448200}}</ref><ref name="Medina">{{Cite journal|last1=Medina|first1=AE|title=Vinpocetine as a potent antiinflammatory agent.|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=22|pages=9921–2|doi=10.1073/pnas.1005138107|year=2010|pmc=2890434|pmid=20495091}}</ref>
* [[Piracetam]] - improves alertness, blood flow, oxygen supply, and stroke recovery.
+
* [[Vincamine]]&mdash;increases blood circulation (vasodilator) and metabolism in the brain; related to vinpocetine; used in sustained release.
* [[Pyritinol]] (Enerbol) - Drug. Enhances oxygen and glucose uptake in the brain, and allows glucose to pass more easily through the blood-brain barrier. It is also a powerful anti-oxidant which scavenges [[Hydroxyl|hydroxyl radicals]] created in the very processes it is involved in.
+
* [[Nicergoline]]&mdash;an [[ergot]] derivative used to treat senile dementia and other disorders with [[blood vessel|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 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.<ref>{{cite journal | author = Fioravanti M, Flicker L | title = Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment | journal = Cochrane Database Syst Rev | volume = | issue = 4 | pages = CD003159 | year = 2001 | doi = 10.1002/14651858.CD003159 | PMID = 11687175}}</ref>
* [[Vinpocetine]] - Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. <ref name="McDaniel et al. 2002">{{cite journal | author = McDaniel, M.A., Maier, S.F., and Einstein, G.O. | title = Brain-Specific Nutrients: A Memory Cure? | journal = Psychological Science in the Public Interest ''(American Psychological Society)' | volume = 3 | issue = 1 | url = http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TB0-4B0KTYF-C&_coverDate=12%2F31%2F2003&_alid=448998985&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5128&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=f99a155c658f3be9a94cc485fbf37262| date = 2002}}</ref>
 
   
===Mental agility, concentration, stamina, and focus===
+
===Experimental histamine antagonists===
{{Refimprovesect|date=January 2008}}
+
The '''H<sub>3</sub>-receptor''' decreases neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin. Thus, '''H<sub>3</sub>-receptor-antagonists''' increases cognition and wakefulness.
* [[Adrafinil]] (Olmifon) - Drug.
 
* [[Caffeine]] - Drug. improves concentration, idea production, but hinders memory encoding. Also produces the jitters. Caffeine is the most widely used psychoactive substance in the world, and may be susceptible to strong levels of [[tolerance]].
 
* [[Coffee]] - Bean. Contains caffeine; brewed coffee is high in [[antioxidants]].
 
* [[Nicergoline]] - Drug. Nicergoline is an ergoloid mesylate derivative used to treat senile dementia. It has also been found to increase mental agility and enhance clarity and perception. It increases vigilance.<ref name="Saletu & Grunberger 1985"/> Increases arterial flow and use of oxygen and glucose in the brain.
 
* [[Nicotine]] - stimulus barrier (aids in concentration). Stimulus barrier rebound effect (an unpleasant side effect).
 
* [[Cocaine]] - Drug.
 
* [[Methylphenidate]] (Ritalin) - Drug
 
* [[Dextroamphetamine]] - (Adderall, Dexedrine) - Drug.
 
* [[Modafinil]] - (Provigil) - Drug.
 
* [[Piracetam]] - improves alertness, socialization, and co-operation in the brain impaired from age, dementia, and reduced blood flow.
 
* [[Phenibut]] -
 
* [[Theophylline]] -
 
* [[Amphetamine]] - aids in concentration, focus and stamina. Prescribed for [[ADHD|ADD/ADHD]]
 
* [[Carphedon]] (Phenotropil) -
 
   
===Purported memory enhancement and learning improvement===
+
* [[Ciproxifan]]&mdash;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.<ref name="pmid18305012">{{cite journal | author = Le S, Gruner JA, Mathiasen JR, Marino MJ, Schaffhauser H | title = Correlation between ''ex vivo'' receptor occupancy and wake-promoting activity of selective H<sub>3</sub> receptor antagonists | journal = J. Pharmacol. Exp. Ther. | volume = 325 | issue = 3 | pages = 902–9 | year = 2008 | month = June | pmid = 18305012 | doi = 10.1124/jpet.107.135343 | url = | issn = }}</ref>
{{Refimprovesect|date=December 2007}}
+
* [[A-349,821]]&mdash;It has nootropic effects in animal studies.<ref>{{cite journal | last1 = Esbenshade | first1 = TA | last2 = Fox | first2 = GB | last3 = Krueger | first3 = KM | last4 = Baranowski | first4 = JL | last5 = Miller | first5 = TR | last6 = Kang | first6 = CH | last7 = Denny | first7 = LI | last8 = Witte | first8 = DG | last9 = Yao | first9 = BB | title = Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist | journal = Biochemical pharmacology | volume = 68 | issue = 5 | pages = 933–45 | year = 2004 | pmid = 15294456 | doi = 10.1016/j.bcp.2004.05.048 }}</ref>
All of the "nergics" listed above are purported to improve memory (encoding and recall), As do all nootropics which improve general brain performance in categories such as the brain energy and oxygen supply, and nerve growth stimulation and protection. Other agents purported to have these specific benefits are mentioned in their own sections.
 
   
Other nootropics with specific effects on memory encoding and recall include:
+
* [[ABT-239]] - strong H3 receptor inverse agonist that is more active than ciproxifan, but its investigation into human use was dropped after it was discovered to cause [[QT prolongation]] in subjects
* ''[[Bacopa monniera]]'' (Brahmi) - Herb. Elevates curiosity, enhances memory and concentration.<ref name="Singh & Dhawan 1997">{{cite journal | author = Singh, H.K. and Dhawan, B.N. | title = Neuropsychopharmacological effects of the Ayurvedic nootropic ''Bacopa monniera'' Linn. (Brahmi) | journal = Indian Journal of Pharmacology | volume = 29 | issue = 5 | pages = 359–65| url = http://ijp-online.com/article.asp?issn=0253-7613;year=1997;volume=29;issue=5;spage=359;epage=365;aulast=Singh;type=0 | date= 1997}}</ref> Brahmi also protects against amnesia inducing chemicals such as scopolamine or loss of memory due to electro convulsive shocks.<ref name="Singh & Dhawan 1997"/> It is a traditional [[ayurvedic]] medicine.
 
* [[Piracetam]] - improves memory. Used to treat Alzheimer's, dementia, [[dyslexia]] and [[Down's syndrome]]
 
* [[Rosemary]] - Herb. Rosemary has a very old, albeit unverified, reputation for improving memory.
 
* [[Vasopressin]] - Hormone, prescription drug.
 
* [[Dextroamphetamine]]- Adderall, Dexedrine.<ref name="Dextroamphetamine">{{cite journal | author = Rapoport, J.L., Buchsbaum, M.S., Zahn, T.P., Weingartner, H., Ludlow, C., and Mikkelsen, E.J. | title = Dextroamphetamine: cognitive and behavioral effects in normal prepubertal boys | journal = Science | volume = 199 | issue = 4328 | pages = 560–3}}</ref>
 
* [[Nicotine]] - Improves working memory and learning<ref name="Nicotinic effects on cognitive function">{{cite journal | author = Edward D. Levin, F. Joseph McClernon and Amir H. Rezvani1| title = Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. | journal = Psychopharmacology | volume = 184 | issue = | pages = 523-539 | pages = http://www.springerlink.com/content/y41lg2qj24xvvh31/}}</ref>
 
   
 
===Nerve growth stimulation and brain cell protection===
 
===Nerve growth stimulation and brain cell protection===
{{Refimprovesect|date=December 2007}}
+
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.
* [[Carnitine#Acetyl-L-carnitine|Acetyl-L-carnitine (ALCAR)]] - Amino acid. Inhibits [[lipofuscin]] formation.
 
* ''[[Bacopa monnieri]]'' (Brahmi) - Herb. Improves protein synthesis in brain cell repair and new dendritic growth.
 
* [[Selegiline]] (Deprenyl) - Drug. Brain cell protectant, delays [[senescence]] of brain cells, proven to increase maximum life span in laboratory rats.
 
* [[Ergoloid mesylates]] (Hydergine) - Drug. Mimics [[nerve growth factor]] (NGF), and is a powerful anti-oxidant capable of delaying brain death in cases of heart failure and stroke by several minutes with regular use. It increases vigilance.<ref name="Saletu & Grunberger 1985"/>
 
* [[Idebenone]] - stimulates nerve growth, and has same effects as Coenzyme q-10.
 
* [[Inositol]] - Membrane stabilizer. Strengthens neurons, making them less susceptible to damage.
 
* [[Pyritinol]] (Enerbol) - Drug. Powerful anti-oxidant which scavenges hydroxyl radicals.
 
* [[Rasagiline]] (Azilect) - Drug. Treats Parkinson’s disease either as monotherapy (by itself) or in addition to levodopa therapy. Promotes increased and sustained levels of dopamine by selectively inhibiting an enzyme, monoamine oxidase-B.
 
* [[Vitamin C]] - Membrane stabilizer, involved in [[collagen]] synthesis. Vitamin C is also a co-factor in the brain's production of dopamine.
 
   
===Recreational drugs with purported nootropic effects===
+
* [[Idebenone]]&mdash;antioxidant {{Citation needed|date=February 2011}}
{{seealso|Controlled substances act|Misuse of Drugs Act 1971}}
+
* [[Melatonin]]&mdash;antioxidant {{Citation needed|date=February 2011}}
* [[Amphetamine]]-type stimulants (such as Adderall, Dexedrine, [[Desoxyn]], ''etc.'') are [[Controlled Substances Act#Schedule II drugs|Schedule II controlled substances]] in the United States, and [[Misuse of Drugs Act 1971#Class B drugs|Class B drugs]] in the United Kingdom, with comparable legal controls in effect in most countries throughout the world. They are prescribed for [[attention-deficit hyperactivity disorder|attention-deficit disorders]], [[narcolepsy]], and certain cases of [[obesity]]; and are issued to counteract fatigue and to enhance performance for pilots in the armed forces of the United States of America.<ref>D. BROWN ''et al.'', [http://navymedicine.med.navy.mil/Files/Media/directives/6410.pdf “Performance Maintenance During Continuous Flight Operations - A Guide for Flight Surgeons”]; NAVMED-P6410, 1st. Ed., January 1, 2000; (US) Naval Strike and Air Warfare Center; pp. 4, 10–18, 38, 55.</ref><ref>CHOATE ''et al.'', [http://www.globalsecurity.org/org/news/2006/060926-usaf-amphetamines.htm "Amphetamine's prescribed use defended by Air Force, M.D."]; [[Abilene Reporter News]], September 26, 2006. (republished by GlobalSecurity.Org at "http://www.globalsecurity.org/org/news/2006/060926-usaf-amphetamines.htm", accessed February 27, 2008)</ref> These also heighten alertness, mental focus, vigilance, stamina, and sex drive. They tend to be habit-forming, and exhibit [[Amphetamine#Effects of use|side effects]] with prolonged or heavy use. Personal importation of amphetamine-class drugs is prohibited in many countries, and their use for recreation or for performance enhancement without a medical prescription is likewise illegal in most countries.
+
* [[Glutathione]]&mdash;chief [[antioxidant]] {{Citation needed|date=February 2011}}
* [[Cannabis (drug)|Cannabis]] is reported to heighten the ability of the senses, as well as heighten alpha wave activity in the brain associated with creativity.
+
* [[Acetylcarnitine]] (Acetyl-[[L-Carnitine]] [[Arginate]] or [[Hydrochloride]]) {{Citation needed|date=February 2011}}
* [[LSD]] - [[Controlled substances act#Schedule I drug|Schedule I]] / [[Misuse of Drugs Act 1971#Class A drugs|Class A]] drug. At higher doses, the impact of the senses on one's mind are expanded to such an overwhelming degree that what is being sensed seems qualitatively different. Many [[psychedelic drugs]] are known to produce this overwhelming effect on the mind. [[Aldous Huxley]] called this state of mind "[[Mind at Large]]". Activity in the [[Raphe Nuclei]] and [[Locus ceruleus]] increases dramatically following administration of LSD to produce extremely heightened creativity in many users. This effect on the creative process is a phenomenon that may be due to ascending traffic in the reticular activation system, which can result in stimulus overload. The longest single research project with LSD, at Spring Grove Hospital, Maryland, showed an average 10% increase in linear IQ alone.<ref>Bacon, et al., [http://www.cem.msu.edu/~cem181h/projects/96/lsd/drug.html "The Effect of LSD on the Human Brain"], [[1996]]. Accessed [[October 16]], [[2007]]</ref> Also produces [[Psychedelics, dissociatives and deliriants|hallucinogenic]] and [[entheogen]]ic effects at doses as low as 30–40 μg (micrograms), with the likelihood of having a [[Psychedelic crisis|''bad trip'']] increasing as dose is increased if these effects are undesired. May also cause [[cognitive shift]]s, [[synesthesia]], and [[LSD#flashbacks|flashbacks]]. The drug sometimes spurs long-term or even permanent changes in a user's personality and life perspective. (''For more details, see [http://www.maps.org/books/mpc/index.html Albert Hofmann: LSD - My Problem Child]''.)
+
* [[Inositol]]&mdash;implicated in memory function, deficit linked to some [[psychiatric illness]]es&mdash;has been shown particularly efficacious in [[OCD]] patients
* [[U4EA|4-methylaminorex]]
+
* [[Anticonvulsant]]s&mdash;inhibit seizure related brain malfunction if a person has seizures {{Citation needed|date=February 2011}}
* [[Pemoline]]
+
* [[Phosphatidylserine]]&mdash;possible membrane stabilizer {{Citation needed|date=February 2011}}
* [[Psilocybin]] and [[Psilocin]]
+
* [[Lion's Mane Mushroom]]&mdash;Stimulated [[myelination]] in an ''in vitro'' experiment<ref name="pmid12675022">{{Cite journal|author=Kolotushkina EV, Moldavan MG, Voronin KY, Skibo GG |title=The influence of Hericium erinaceus extract on myelination process in vitro |journal=Fiziol Zh |volume=49 |issue=1 |pages=38–45 |year=2003 |pmid=12675022 |doi= |url=}}</ref> and stimulated [[nerve growth factor]] in an ''in vitro'' experiment with human [[astrocytoma]] cells.<ref name="pmid18758067">{{Cite journal|author=Mori K, Obara Y, Hirota M, ''et al.'' |title=Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells |journal=Biol. Pharm. Bull. |volume=31 |issue=9 |pages=1727–32 |year=2008 |month=September |pmid=18758067 |doi= 10.1248/bpb.31.1727|url=}}</ref> Also improved cognitive ability, in a double-blind, parallel-group, placebo-controlled trial.<ref name="pmid18844328">{{Cite journal|author=Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T |title=Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial |journal=Phytotherapy Research |volume=23 |issue=3 |pages=367–72 |year=2009 |month=March |pmid=18844328 |doi=10.1002/ptr.2634}}</ref>
* [[MDPV]]
+
* [[SAM-e]] (S-Adenosyl methionine)&mdash;crucial for cellular regeneration (fuels [[DNA methylation]]<ref>[http://www.biopsychiatry.com/article/sameart.htm The Way SAMe Works]</ref>), also involved with the biosynthesis of dopamine & serotonin<ref>{{Cite journal
* [[Mescaline]]
+
| last1 = Mischoulon | first1 = D.
  +
| last2 = Fava | first2 = M.
  +
| title = Role of S-adenosyl-L-methionine in the treatment of depression: A review of the evidence
  +
| journal = The American journal of clinical nutrition
  +
| volume = 76
  +
| issue = 5
  +
| pages = 1158S–1161S
  +
| year = 2002
  +
| month = November
  +
| pmid = 12420702
  +
| url = http://www.ajcn.org/content/76/5/1158S.full.pdf
  +
}}</ref>
  +
* [[Acetylcysteine]] ([[L-cysteine]])&mdash;precursor to antioxidant [[glutathione]]<ref>{{Cite web |url=http://www.acetylcysteine.org/glutathione.htm |title=glutathione |quote=In short words: N-acetylcysteine (NAC) is precursor of glutathione (GSH).}}</ref>
  +
* [[Uncaria tomentosa]] (Cat's Claw)&mdash;in an ''in vitro'' experiment with rats, it inhibited formation of brain [[beta amyloid]] deposits,<ref>{{Cite journal |url=http://www.jfponline.com/Pages.asp?AID=518#8 |volume=1 |issue=6 |month=June |year=2002 |title=Medications for dementia: New drugs, mechanisms are coming for Alzheimer's disease |journal=The Journal of Family Practice |quote=PTI-00703 is a beta-amyloid inhibitor derived from the cat's claw, a woody vine found in the Peruvian rain forest. It is being tested in patients with mild-to-moderate AD [Alzheimer's disease].}}, which cites:
  +
:{{Cite news |title=OSHU Researchers Investigate Substance Derived From Amazon Rainforest Plant as Possible treatment For Alzheimer's Disease |date=March 2, 2000 |publisher=Oregon Health & Science University |url=http://www.ohsu.edu/news/archive/2000/030200rainforest.html |quote=Researchers at OHSU are interested in a particular extract, derived from the bark of the vine, called PTI-00703. It has been shown to stop the formation of, and break up beta-amyloid deposits in both a test tube and animal models.}}</ref> which have been connected to Alzheimer's disease.{{Citation needed|date=November 2011}}
  +
* ([[Dopamine]] enhancers)&mdash;dopamine is an antioxidant that can enhance dendrite extension{{Citation needed|date=February 2011}}
  +
* ([[Cannabidiol]] and [[Δ9-tetrahydrocannabinol]])&mdash;Cannabidiol (nonpsychoactive) and Δ9-tetrahydrocannabinol (psychotropic) antioxidant.<ref>{{Cite journal
  +
| doi = 10.1073/pnas.95.14.8268
  +
| last1 = Hampson | first1 = A. J.
  +
| last2 = Grimaldi | first2 = M.
  +
| last3 = Axelrod | first3 = J.
  +
| last4 = Wink | first4 = D.
  +
| title = Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants
  +
| journal = Proceedings of the National Academy of Sciences of the United States of America
  +
| volume = 95
  +
| issue = 14
  +
| pages = 8268–8273
  +
| year = 1998
  +
| pmid = 9653176
  +
| pmc = 20965
  +
| quote = The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate.
  +
|bibcode = 1998PNAS...95.8268H }}</ref>
   
===Dietary Nootropics===
+
===Direct hormones===
Some regular food items are rich sources of substances with alleged nootropic benefits:
+
These are hormones that have activity not necessarily attributable to another specific chemical interaction, but have shown effectiveness. Only specific nootropic effects are stated.
* [[Nuts]], in particular [[walnuts]], are rich sources of [[alpha-linolenic acid]] (ALA), a type of [[omega-3 fatty acid]]. A mixture of walnuts served with [[dried fruit]] pieces is known in some regions as [[student food]] (orig. German: ''Studentenfutter'') and is popularly recommended as a snack for students.
+
* [[Oily fish]], such as [[salmon]] or fresh [[tuna]] (not tuna canned in oil) are also good sources of [[omega-3 fatty acid]]s such as [[eicosapentaenoic acid]] and [[docosahexaenoic acid]], whose lack in diet has been associated with increased risk of mental illnesses such as depression, anxiety, aggressive behavior, schizophrenia, or hyper-activity in children (see [[omega-3 fatty acids]] article)
+
* [[Vasopressin]]&mdash;memory hormone that improves both memory encoding and recall. Desmopressin (1-desamino-8-D-arginine vasopressin, DDAVP) was given to 17 children with attention & learning disorders daily for 10 days in a placebo-controlled, randomized, double-blind study; memory & learning were improved compared with placebo; the same study failed to find similar benefits after administration of a single dose.<ref>{{cite journal |author=Hamburger-Bar R, Eisenberg J, Belmaker RH |title=Animal and clinical studies of vasopressin effects on learning and memory. |journal=Isr J Med Sci. |volume=23 |issue=1-2 |pages=12–8 |year=1987 |month=Jan-Feb |pmid=2952619}}</ref>
  +
* [[Pregnenolone]]&mdash;increases neurogenesis
  +
* [[Orexin]]&mdash;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]]&mdash;precursor to [[estrogen]] and [[testosterone]]
  +
  +
===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) ''&mdash; Shown to possess adaptogenic properties and enhance memory and concentration.<ref name=SD1997>{{Cite journal| author = Singh, H.K. and Dhawan, B.N. | title = Neuropsychopharmacological effects of the Ayurvedic nootropic ''Bacopa monniera'' Linn. (Brahmi) | journal = Indian Journal of Pharmacology | volume = 29 | issue = 5 | pages = 359–65| url = http://ijp-online.com/article.asp?issn=0253-7613;year=1997;volume=29;issue=5;spage=359;epage=365;aulast=Singh;type=0 | date=1 September 1997}}</ref> Folk use in Ayurvedic medicine purports "enhancement of curiosity"; Brahmi rasayana has been shown to improve learning and memory in mice<ref>{{Cite journal|author=Joshi H, Parle M |title=''Brahmi rasayana'' improves learning and memory in mice |journal=Evid Based Complement Alternat Med |volume=3 |issue=1 |pages=79–85 |year=2006 |month=March |pmid=16550227 |pmc=1375237 |doi=10.1093/ecam/nek014 |url=http://ecam.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16550227}}</ref>
  +
* ''[[Clitoria ternatea]] (Shankhpushpi) ''&mdash; In traditional Ayurvedic medicine, it has been used for centuries as a memory enhancer, nootropic, antistress, anxiolytic, antidepressant, anticonvulsant, tranquilizing and sedative agent.
  +
* [[Fipexide]]&mdash;drug for [[Dementia]]
  +
* [[Gerovital H3]]&mdash;famous alleged [[anti-aging]] mixture, most effects disproven but some mind enhancement shown
  +
* [[Sulbutiamine]]&mdash;fat soluble vitamin B<sub>1</sub> derivative&mdash;caused mice to perform better on operant conditioning tests<ref name='Micheau'>{{cite journal|title=Chronic administration of sulbutiamine improves long term memory formation in mice: possible cholinergic mediation|journal=Pharmacol Biochem Behav|year=1985|author=Micheau J, Durkin TP, Destrade C, Rolland Y, Jaffard R|volume=23|issue=2|pages=195&ndash;8|pmid=4059305|doi=10.1016/0091-3057(85)90555-6 }}</ref> and object recognition tests<ref name="Bizot">{{cite journal | author=Bizot JC, Herpin A, Pothion S, Pirot S, Trovero F, Ollat H | title=Chronic treatment with sulbutiamine improves memory in an object recognition task and reduces some amnesic effects of dizocilpine in a spatial delayed-non-match-to-sample task | journal=Prog Neuropsychopharmacol Biol Psychiatry | year=2005 | pages=928&ndash;35 | volume=29 | issue=6 | pmid=15951087 | doi=10.1016/j.pnpbp.2005.04.035}}</ref>
  +
* [[Royal Jelly]]&mdash;Increases brain cell growth and diversity, only demonstrated [[in-vitro]], improbable [[in-vivo]] (it has been reported to stimulate the growth of [[glial cells]]<ref>{{Cite journal
  +
| last1 = Hashimoto | first1 = M.
  +
| last2 = Kanda | first2 = M.
  +
| last3 = Ikeno | first3 = K.
  +
| last4 = Hayashi | first4 = Y.
  +
| last5 = Nakamura | first5 = T.
  +
| last6 = Ogawa | first6 = Y.
  +
| last7 = Fukumitsu | first7 = H.
  +
| last8 = Nomoto | first8 = H.
  +
| last9 = Furukawa | first9 = S.
  +
| title = Oral administration of royal jelly facilitates mRNA expression of glial cell line-derived neurotrophic factor and neurofilament H in the hippocampus of the adult mouse brain
  +
| journal = Bioscience, Biotechnology, and Biochemistry
  +
| volume = 69
  +
| issue = 4
  +
| pages = 800–805
  +
| year = 2005
  +
| month = April
  +
| pmid = 15849420
  +
| url = http://journals2005.pasteur.ac.ir/BBB/69%284%29/800-805.pdf
  +
}}</ref> and [[neural stem cells]] in the [[brain]].<ref>{{Cite journal
  +
| last1 = Hattori | first1 = N.
  +
| last2 = Nomoto | first2 = H.
  +
| last3 = Fukumitsu | first3 = H.
  +
| last4 = Mishima | first4 = S.
  +
| last5 = Furukawa | first5 = S.
  +
| title = Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro
  +
| journal = Biomedical research (Tokyo, Japan)
  +
| volume = 28
  +
| issue = 5
  +
| pages = 261–266
  +
| year = 2007
  +
| month = October
  +
| pmid = 18000339
  +
}}</ref>)
  +
* [[Curcumin]]&mdash;significant in-vitro activity, but in-vivo activity limited by low [[bioavailability]] unless accompanied by ingestion of piperine
  +
  +
===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 causation]].
  +
  +
Examples of adaptogens are plants like the ayurvedic "[[Holy Basil]]" or "Tulsi" which is commonly found in nootropic supplements like excelerol.<ref name="SD1997"/>
   
 
===Other nootropics===
 
===Other nootropics===
{{Refimprovesect|date=December 2007}}
+
Other substances sometimes classified as nootropics include [[mexidol]], [[hydergine]],<ref name=BetterBrain/> [[noopept]], [[selank]], [[semax]] and [[bifemelane]].
<!--The following list contains nootropics and possible nootropics that haven't been relevancy-checked (are they all nootropics?), category checked, or which don't have a description yet. Before adding them to the article proper, make sure they are nootropics, and find out what kind of nootropics they are (to know what sections to place them in).-->
 
* [[Adafenoxate]] - Has an anti-anxiety effect for rats<ref name="Petkov et al. 1987">{{cite journal | author = Petkov, V.D., Getova, D., and Mosharrof, A.H. | title = A study of nootropic drugs for anti-anxiety action. | journal = Acta Physiol. Pharmacol. Bulg. ''(Institute of Physiology, Bulgarian Academy of Sciences, Sofia)' | date= 1987 | volume = 13 | issue = 4 | pages = 25–30 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2896427&dopt=Citation}}</ref> and possibly the same for humans.
 
* ''[[Butea frondosa]]'' - "The plant ''Butea frondosa'' has been indicated in the Indian system of medicine as a plant augmenting memory and as a rejuvenator. ... ''B. frondosa'' possesses anti-stress and weak nootropic activity."<ref name="Soman et al. 2004">{{cite journal | author = Soman, I., Mengi, S.A., and Kasture, S.B. | title = Effect of leaves of ''Butea frondosa'' on stress, anxiety, and cognition in rats. | journal = Pharmacology, Biochemistry & Behavior ''(C.U. Shah College of Pharmacy, SNDT University Santacruz, Mumbai, Maharashtra, India)' | date Sep. 2004 | volume = 79 | issue = 1 | pages = 11–6 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15388278&dopt=Citation | date= 2004}}</ref>
 
* [[BMY 21502]] - Injured animals treated with BMY-21502 at one week post-injury showed significant improvement in post-injury learning ability compared to injured animals treated with vehicle. Paradoxically, in uninjured control animals BMY-21502 treatment appeared to worsen learning scores. The results of this study indicate that BMY-21502 may be useful for attenuating the dysfunction in learning ability that occurs following traumatic brain injury.
 
* [[Cabergoline]] (Dostinex) -
 
* ''[[Celastrus panicaltus]]'' - Herb.
 
* [[Cerebrolysin]] - A neuroprotective nootropic agent, might affect Alzheimer's disease pathology. Currently in clinical trials {{Fact|date=December 2007}}
 
* [[Clausenamide]]
 
* [[Coluracetam]] - It may also have potential use in prevention and treatment of ischemic retinopathy and retinal and optic nerve injury {{Fact|date=December 2007}}
 
* [[Desmopressin]] (DDAVP) - Analog of [[vasopressin]]
 
* [[DHEA]] - Hormone created by the adrenal glands; Precursor to Estrogen and Testosterone
 
* [[Dostinex]] -
 
* [[Fasoracetam]] -
 
* [[Fatty acids|Essential Fatty Acids]]- [[Eicosapentaenoic acid]] (EPA) and [[docosahexaenoic acid]] (DPA) are the best known. EPA in particular, has an anti-depressant function and is positively indicated in trials with autism and learning difficulties {{Fact|date=December 2007}}
 
* [[Fipexide]] (Vigilor) - It protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.<ref name="Genkova-Papasova & Lazarova-Bakurova 1988"/>
 
* [[Gerovital H3]] -
 
* ''[[Ginkgo biloba]]'' - Ginkgo (Ginkgo biloba), a root, is used to treat a variety of problems, including chronic cerebrovascular insufficiency, tinnitus, vertigo and peripheral arterial disease. Patients with dementia treated with ginkgo showed significant improvement of symptoms like memory loss, concentration difficulties, fatigue, anxiety and depressive mood. <ref name="Susanne Kienzle-Horn 2002">{{cite journal | author = Susanne Kienzle-Horn| title = Herbal medicines for neurological diseases | journal = Current Opinion in Investigational Drugs | date= 2002 | volume = 3 | issue = 5 | pages = 763-767 | url = www.biomedcentral.com/content/pdf/cd-451283.pdf}}</ref> However, because Ginkgo is a vasodilator, it ought not be taken with Aspirin, for doing so could increase the risk of bleeding. <ref name="Paul F Smith & Cynthia L Darlington">{{cite journal | author = Paul F Smith & Cynthia L Darlington Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand | title = Drug treatments for subjective tinnitus: Serendipitous discovery versus rational drug design | journal = Current Opinion in Investigational Drugs | date= 2005 | volume = 6 | issue = 7 | pages = 712-716 | url = http://www.biomedcentral.com/1472-4472/id/cd-608223/abstract/ }}</ref> Ginkgo is widely used in Europe to treat subjective tinnitus, however, there is as yet no hard evidence supporting this assertion. <ref name="Paul F Smith & Cynthia L Darlington">{{cite journal | author = Paul F Smith & Cynthia L Darlington Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand | title = Drug treatments for subjective tinnitus: Serendipitous discovery versus rational drug design | journal = Current Opinion in Investigational Drugs | date= 2005 | volume = 6 | issue = 7 | pages = 712-716 | url = http://www.biomedcentral.com/1472-4472/id/cd-608223/abstract/ }}</ref> Ginkgolides are extracts from the leaves of the tree. They produce a beneficial effect for Alzheimer’s disease, and for amyloid-B, the toxic prion protein, which suggests they could be relevant to treating those diseases. <ref name="Clive Bate, Mario Salmona, and Alun Williams">{{cite journal | author = Clive Bate, Mario Salmona, and Alun Williams | title = Ginkgolide B inhibits the neurotoxicity of prions or amyloid-B<sub>I-42</sub>| journal = Journal of Neuroinflammation | date= 11 May 2004| volume = 1 | issue = 4 | pages = | url = http://www.jneuroinflammation.com/content/1/1/4 }}</ref>
 
* [[Gotu Kola]] - Herb and root.
 
* [[Meclofenoxate]] - Has an anti-anxiety effect for rats<ref name="Petkov et al. 1987"/> and possibly the same for humans. Like Fipexide, it protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.<ref name="Genkova-Papasova & Lazarova-Bakurova 1988"/> Like many racetams, it may treat fetal alcohol syndrome.<ref name="Vaglenova & Petkov 2001"/>
 
* [[Milacemide]] - Drug.
 
* [[Nimodipine]] -
 
* [[Ondansetron]] -
 
* [[Phenytoin]] (Dilantin) -
 
* [[Phosphatidylserine]]- In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. <ref name="McDaniel et al. 2002">{{cite journal | author = McDaniel, M.A., Maier, S.F., and Einstein, G.O. | title = Brain-Specific Nutrients: A Memory Cure? | journal = Psychological Science in the Public Interest ''(American Psychological Society)' | volume = 3 | issue = 1 | url = http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TB0-4B0KTYF-C&_coverDate=12%2F31%2F2003&_alid=448998985&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5128&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=f99a155c658f3be9a94cc485fbf37262| date = 2002}}</ref>
 
* [[Picamilon]] or Pikamilone - Compound of [[Niacin]] and [[GABA]]. It can pass the [[blood-brain barrier]] and increase amount of GABA in the brain.{{Fact|date=December 2007}}
 
* [[Pregnenolone]] - Hormone; Precursor to DHEA;
 
* [[Pyroglutamate]] -
 
* [[Royal Jelly]] - Produced by bees for the Queen. Can cause fatal allergic reactions in rare cases {{Fact|date=December 2007}}
 
* [[Sapunifiram]]
 
* [[Semax]] - A neuropeptide (stimulator of the nervous system) developed from a short fragment of ACTH, Pro8-Gly9-Pro10 ACTH(4-10). Claims of significant increase in salvation of neurons are made{{Fact|date=December 2007}}
 
* [[Somatotropin]] -
 
* [[Sulbutiamine]] (Arcalion) - Drug - derivative of thiamine (vitamin B1) that can cross the [[blood-brain barrier]] and work as anti-fatigue and cognitive support agent.{{Fact|date=December 2007}}
 
* [[Sunifiram]]
 
* [[Turmeric]] - has possible benefits in [[Alzheimer's disease]], [[cancer]] and [[Liver#Diseases of the liver|liver disorders]]. Turmeric, under the name Avea, is becoming popular to treat [[depression]].
 
* [[Unifiram]]
 
* [[Xanthinol]] -
 
   
 
==See also==
 
==See also==
  +
* [[Cognitive science]]
  +
* [[Eidetic memory]]
  +
* [[Human enhancement]]
  +
* [[Long-term potentiation]]
  +
* [[Memory and aging]]
  +
* [[Psychedelics in problem-solving experiment]]
  +
 
===Brain and neurology===
 
===Brain and neurology===
 
{| style="background-color: transparent; width: {{{width|100%}}}"
 
{| style="background-color: transparent; width: {{{width|100%}}}"
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==References==
 
==References==
 
{{reflist|2}}
 
{{reflist|2}}
  +
* {{Cite journal|author=Greely H, Sahakian B, Harris J, ''et al.'' |title=Towards responsible use of cognitive-enhancing drugs by the healthy |journal=Nature |volume=456 |issue=7223 |pages=702–5 |year=2008 |month=December |pmid=19060880 |doi=10.1038/456702a |url=http://www.nature.com/nature/journal/vaop/ncurrent/full/456702a.html }}
  +
{{Psychostimulants, agents used for ADHD and nootropics}}
   
 
==External links==
 
==External links==
 
* [http://www.circuitblue.com/psypharm/ Society for the Advancement of Cosmetic Pharmacotherapy]
 
* [http://www.circuitblue.com/psypharm/ Society for the Advancement of Cosmetic Pharmacotherapy]
* [http://www.businessweek.com/@@*TTz0oUQYsI6ogEA/magazine/content/03_35/b3847001_mz001.htm Business Week Online - "I Can't Remember"] [[September 1]], [[2003]]
 
 
* [http://science.slashdot.org/article.pl?sid=04/12/20/2352239&tid=191&tid=14 Slashdot Cognitive Enhancement Drugs]
 
* [http://science.slashdot.org/article.pl?sid=04/12/20/2352239&tid=191&tid=14 Slashdot Cognitive Enhancement Drugs]
 
* [http://www.nootropic.com/ HedWeb]
 
* [http://www.nootropic.com/ HedWeb]
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* [http://cerebralhealth.com/neuroscienceresearch.php List of Neurobiology Links Relevant to Nootropics]
 
* [http://cerebralhealth.com/neuroscienceresearch.php List of Neurobiology Links Relevant to Nootropics]
   
{{Psychostimulants, agents used for ADHD and nootropics}}
 
   
  +
[[Category:Drugs]]
 
[[Category:Nootropics|Nootropics]]
 
[[Category:Nootropics|Nootropics]]
   

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Nootropics (11px /n.əˈtrɒpɨks/ Template:Respell), 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

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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 are by definition cognitive enhancers, but a cognitive enhancer is not necessarily a nootropic.

Giurgea's Nootropic Criteria:

  1. Enhances learning and memory.
  2. Enhance learned behaviors under conditions which are known to disrupt them. Example: hypoxia (oxygen deficiency).
  3. Protect the brain from physical or chemical injury.
  4. Enhance the tonic cortical/subcortical control mechanisms
  5. Exhibit 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 utilizes 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

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.

In academia, modafinil has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals.[7] Stimulants such as methylphenidate 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 in the past year, and on some campuses the number is as high as 25%.[8]

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.[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.[10] In the United States, unapproved drugs or dietary supplements do not have to have safety or efficacy approval before being sold.[11]

Drugs

Racetams

The word nootropic was coined upon discovery of the effects of piracetam, developed in the 1960s.[12] Although piracetam is the most commonly taken nootropic,[12] (depending on one's definition of nootropic, which can sometimes include more popular substances such as caffeine and nicotine) 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 modulators of AMPA receptors. They also appear to modulate acetylcholinergic systems.[13] Although aniracetam and nebracetam show affinity for muscarinic receptors, only nefiracetam shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.[10]

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.[14] 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.[15] In 2008 a systematic review of trials found "little evidence of a beneficial impact" from supplements on cognitive function later in life.[16] A randomized, placebo-controlled trial in 168 70 year olds with mild cognitive impairment showed that a mix of B vitamins slowed the rate of brain atrophy; the slowing was related to a decrease in homocysteine levels.[17]
  • Omega-3—linked to the maintenance of brain function. A study done in Norway[18] demonstrated a potential link between Omega-3 consumption during pregnancy and child intelligence test scores.[19] A cross-sectional population-based study of 1,613 subjects found an association between PUFA intake and decreased risk for impairment of cognitive function & cognitive speed.[20]
  • Isoflavones—may be related to cognitive function.[21] A double-blind, placebo-controlled study showed improvement in spatial working memory after administration of an isoflavone combination containing daidzein, genistein & glycitin.[22] In a randomized, double-blind, placebo-controlled study of older, non-demented men & women, soy isoflavone supplementation improved performance on 6 of 11 cognitive tests, including visual-spatial memory and construction, verbal fluency and speeded dexterity; unexpectedly, the placebo group performed better on 2 tests of executive function.[23]
  • Vitamin D—has positive effects on cardiovascular health and may have positive effects on cognitive function separately; the active form of Vitamin D seems to be involved in brain development and in adult brain function. In particular, metabolic pathways for Vitamin D in the hippocampus and cerebellum have been found. Epidemiological data show that higher Vitamin D levels (>20 ng/mL or 50nmol/L) are associated with better cognitive function, but do not seem to be associated with better memory performance.[24]
  • A 2007 survey of online databases for herbs used in traditional herbal medicine to treat cognitive decline - without any proof of safety or efficacy - found over 150 plant species, such as Ginkgo biloba.[25]

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:

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.[8][35]

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.

  • α5IA—α5 inverse agonist. A number of α5IA analogues exist that, like α5IA, selectively and partially agonize some GABA receptor subtypes while inverse agonizing others, which may provide a nootropic effect without the associated anxiogenic effects of general GABA inverse agonism.
  • Suritozole—α5 partial inverse agonist

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.[42]

  • Guanfacine is an α2A receptor agonist, FDA approved for and frequently used to treat ADHD symptoms.[43][44] 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.[45] Another study found no effect on healthy male adult's executive functions and working memory, and small decrements on 2 tasks relating to the sedative effect of guanfacine.[46]

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 (specifically elevated levels of circulating corticosteroids) has been associated with the cognitive deficits seen in human aging.[58] 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 [citation needed]
  • 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
  • Picamilon—GABA activity and blood flow improver
  • Ginkgo biloba—vasodilator. Acts as an NRI.[70] A double-blind, placebo-controlled trial in young healthy females showed an improvement in short-term memory performance 1 hour after administration of a 600 mg dose.[71] An analysis of 29 placebo-controlled RCTs showed that "there is consistent evidence that chronic administration improves selective attention, some executive processes and long-term memory for verbal and non-verbal material."[72] A double-blind, placebo-controlled study in 20 young healthy volunteers showed a dose-dependent improvement in speed-of-attention following administration of 240 mg and 360 mg of Ginkgo extract, effects were measured 2.5h after administration and persisted at least until 6h; various other time- and dose-specific changes (some positive, some negative) in other areas were observed.[73]
  • Vinpocetine— is reported to have cerebral blood-flow enhancing[74] and neuroprotective effects,[75] and is used as a drug in Eastern Europe for the treatment of cerebrovascular disorders and age-related memory impairment.[76] 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.[77] Vinpocetine may therefore induce or exacerbate depressive symptoms as an adverse effect. However, this effect tends to be reversible upon cessation of Vinpocetine administration, with full remission typically occurring within 3–4 weeks. Vinpocetine has been identified as a potent anti-inflammatory agent that might have a potential role in the treatment of Parkinson's disease and Alzheimer's disease.[78][79]
  • Vincamine—increases blood circulation (vasodilator) and metabolism in the brain; related to vinpocetine; used in sustained release.
  • Nicergoline—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 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.[80]

Experimental histamine antagonists

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

  • Ciproxifan—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.[81]
  • A-349,821—It has nootropic effects in animal studies.[82]
  • ABT-239 - strong H3 receptor inverse agonist that is more active than ciproxifan, but its investigation into human use was dropped after it was discovered to cause QT prolongation in subjects

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. Desmopressin (1-desamino-8-D-arginine vasopressin, DDAVP) was given to 17 children with attention & learning disorders daily for 10 days in a placebo-controlled, randomized, double-blind study; memory & learning were improved compared with placebo; the same study failed to find similar benefits after administration of a single dose.[91]
  • 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:

  • Bacopa monniera (Brahmi) — Shown to possess adaptogenic properties and enhance memory and concentration.[92] Folk use in Ayurvedic medicine purports "enhancement of curiosity"; Brahmi rasayana has been shown to improve learning and memory in mice[93]
  • Clitoria ternatea (Shankhpushpi) — In traditional Ayurvedic medicine, it has been used for centuries as a memory enhancer, nootropic, antistress, anxiolytic, antidepressant, anticonvulsant, tranquilizing and sedative agent.
  • Fipexide—drug for Dementia
  • Gerovital H3—famous alleged anti-aging mixture, most effects disproven but some mind enhancement shown
  • Sulbutiamine—fat soluble vitamin B1 derivative—caused mice to perform better on operant conditioning tests[94] and object recognition tests[95]
  • Royal Jelly—Increases brain cell growth and diversity, only demonstrated in-vitro, improbable in-vivo (it has been reported to stimulate the growth of glial cells[96] and neural stem cells in the brain.[97])
  • Curcumin—significant in-vitro activity, but in-vivo activity limited by low bioavailability unless accompanied by ingestion of piperine

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 causation.

Examples of adaptogens are plants like the ayurvedic "Holy Basil" or "Tulsi" which is commonly found in nootropic supplements like excelerol.[92]

Other nootropics

Other substances sometimes classified as nootropics include mexidol, hydergine,[10] noopept, selank, semax and bifemelane.

See also

Brain and neurology

Thought and thinking (what nootropics are used for)

Health

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