Jump to content

Nootropic: Difference between revisions

From Wikipedia, the free encyclopedia
Content deleted Content added
SmackBot (talk | contribs)
m Date the maintenance tags or general fixes
Line 20: Line 20:
=====Piracetam=====
=====Piracetam=====
{{Main|Piracetam}}
{{Main|Piracetam}}
[[Piracetam]] (Nootropil) is a [[prescription drug]] in Europe. The original<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 ''(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=McDaniel2002/> nootropic drug. It is a cholinergic agent synergistic with [[DMAE]], [[Centrophenoxine]], [[choline]], [[Alpha-GPC]] and [[Hydergine]]. It increases brain cell metabolism and energy levels,<ref name=Gabryel&Trzeciak1994>{{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=McDaniel2002/> and speeds up interhemispheric flow of information (left-right brain hemisphere communication). It 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 | doi = 10.1111/j.1749-6632.1985.tb37604.x | pmid = 3860093}}</ref> improves concentration, and enhances memory. Protects neurons from hypoxia,<ref name=McDaniel2002/> and stimulates growth of acetylcholine receptors.{{fact|July 2008}} May also cause nerves to regenerate.{{fact|July 2008}} 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 | doi = 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 | doi = 10.1002/(SICI)1099-1077(1998110)13:2 <S108::AID-HUP55>3.0.CO;2-R | doi_brokendate = 2008-06-21}}</ref> It is not regulated in the US.{{Fact|date=June 2008}} It is a [[pyrrolidone]] derivative.
[[Piracetam]] (Nootropil) is a [[prescription drug]] in Europe. The original<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 ''(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=McDaniel2002/> nootropic drug. It is a cholinergic agent synergistic with [[DMAE]], [[Centrophenoxine]], [[choline]], [[Alpha-GPC]] and [[Hydergine]]. It increases brain cell metabolism and energy levels,<ref name=Gabryel&Trzeciak1994>{{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=McDaniel2002/> and speeds up interhemispheric flow of information (left-right brain hemisphere communication). It 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 | doi = 10.1111/j.1749-6632.1985.tb37604.x | pmid = 3860093}}</ref> improves concentration, and enhances memory. Protects neurons from hypoxia,<ref name=McDaniel2002/> and stimulates growth of acetylcholine receptors.{{Fact|date=July 2008}} May also cause nerves to regenerate.{{Fact|date=July 2008}} 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 | doi = 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 | doi = 10.1002/(SICI)1099-1077(1998110)13:2 <S108::AID-HUP55>3.0.CO;2-R | doi_brokendate = 2008-06-21}}</ref> It is not regulated in the US.{{Fact|date=June 2008}} It is a [[pyrrolidone]] derivative.


=====Aniracetam=====
=====Aniracetam=====
Line 33: Line 33:
** [[Citicoline]] - less expensive and similar in effect to Alpha GPC. Appears effective in rats.<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=548494 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=548494]</ref><ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1908237 Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice.]</ref>
** [[Citicoline]] - less expensive and similar in effect to Alpha GPC. Appears effective in rats.<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=548494 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=548494]</ref><ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1908237 Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice.]</ref>
** [[Choline|Choline bitartrate]] - precursor of acetylcholine, anti-depressant.
** [[Choline|Choline bitartrate]] - precursor of acetylcholine, anti-depressant.
** [[Choline|Choline citrate]] - precursor of the neurotransmitter acetylcholine, anti-depressant.{{fact|July 2008}}
** [[Choline|Choline citrate]] - precursor of the neurotransmitter acetylcholine, anti-depressant.{{Fact|date=July 2008}}
* [[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.
* [[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).
* [[Galantamine]] - acetylcholinesterase inhibitor made from chemical synthesis or extract from plants such as Red Spider Lily (Lycoris radiata).
Line 61: Line 61:
* [[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 has been tested as a treatment for Alzheimer's disease.<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1189014 Selegiline in the treatment of Alzheimer's disease: a long-term randomized placebo-controlled trial. Czech and Slovak Senile Dementia of Alzheimer Type Study Group.</ref> 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 | doi = 10.1016/S0006-2952(00)00282-3 }}</ref>
* [[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 has been tested as a treatment for Alzheimer's disease.<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1189014 Selegiline in the treatment of Alzheimer's disease: a long-term randomized placebo-controlled trial. Czech and Slovak Senile Dementia of Alzheimer Type Study Group.</ref> 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 | doi = 10.1016/S0006-2952(00)00282-3 }}</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.
* [[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.
* [[Yohimbe]] - Bark. Aphrodisiac. Boosts dopamine levels,{{fact|July 2008}} though how it does this is not yet understood. Supplements are likely to have no yohimbe in them.<ref>[http://www.modernmedicine.com/modernmedicine/article/articleDetail.jsp?id=112017 An evidence-based approach to dietary supplements for ED (Part 2 of 2)]</ref> 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.
* [[Yohimbe]] - Bark. Aphrodisiac. Boosts dopamine levels,{{Fact|date=July 2008}} though how it does this is not yet understood. Supplements are likely to have no yohimbe in them.<ref>[http://www.modernmedicine.com/modernmedicine/article/articleDetail.jsp?id=112017 An evidence-based approach to dietary supplements for ED (Part 2 of 2)]</ref> 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.
* [[Theanine]] - Found in tea. Increases serotonin and dopamine levels in the brain. Increases alpha-wave based alert relaxation.
* [[Theanine]] - Found in tea. Increases serotonin and dopamine levels in the brain. Increases alpha-wave based alert relaxation.
<!--If there's no cite for "contraindicated for", consider removing the last line -- wikipedia isn't a venue for health advice-->
<!--If there's no cite for "contraindicated for", consider removing the last line -- wikipedia isn't a venue for health advice-->
Line 197: Line 197:
* MDL 26,479<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1907590 MDL 26,479: a potential cognition enhancer with benzodiazepine inverse agonist-like properties.]</ref>
* MDL 26,479<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1907590 MDL 26,479: a potential cognition enhancer with benzodiazepine inverse agonist-like properties.]</ref>
* [[Propentofylline]]
* [[Propentofylline]]



====Contentious or possibly unsafe nootropics====
====Contentious or possibly unsafe nootropics====

Revision as of 06:25, 13 July 2008

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).[1] This article covers all substances, including drugs, nutrients, and herbs, that have purported cognitive enhancing effects.

The word nootropic was coined in 1964 by the Romanian Dr. Corneliu E. Giurgea, derived from the 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.

Availability

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. 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.

Therapy or enhancement

Some argue that nootropics may theoretically be used for human enhancement, boosting mental function in otherwise normal healthy people. However, there is much controversy over the legitimacy (efficacy) and ethics of such applications. This may contribute to the lack of research on such effects.

Examples

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.

Replenishing and increasing neurotransmitters

As the brain ages, its ability to produce and maintain youthful levels of neurotransmitters declines.[2] 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.[citation needed] Furthermore, there are declines in immune and endocrine functioning. [3] Certain nootropics enhance immune and endocrine functioning.

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.).[citation needed] 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.[citation needed] Cholinergic nootropics include acetylcholine precursors and cofactors, and acetylcholinesterase inhibitors:

Piracetam

Piracetam (Nootropil) is a prescription drug in Europe. The original[4] and most commonly taken[5][4] nootropic drug. It is a cholinergic agent synergistic with DMAE, Centrophenoxine, choline, Alpha-GPC and Hydergine. It increases brain cell metabolism and energy levels,[6][4] and speeds up interhemispheric flow of information (left-right brain hemisphere communication). It increases alertness,[7] improves concentration, and enhances memory. Protects neurons from hypoxia,[4] and stimulates growth of acetylcholine receptors.[citation needed] May also cause nerves to regenerate.[citation needed] Piracetam markedly decreases the formation of neuronal lipofuscin.[8] It improves posture in elderly people.[9] It is not regulated in the US.[citation needed] It is a pyrrolidone derivative.

Aniracetam

Aniracetam is a pyrrolidone derivative drug, analogous of piracetam, and considered more potent[citation needed]. Like piracetam, aniracetam protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.[10] Also like piracetam, aniracetam may enhance memory in aging adults by increasing levels of brain biogenic monoamines, which are beneficial to learning and memory.[2] Both racetams have possible therapeutic use in treating fetal alcohol syndrome.[11] Aniracetam increases vigilance[7]. Aniracetam has shown to positively potentiate AMPA receptors.

Other cholinergics
  • Acetyl-L-carnitine (ALCAR) - Amino acid. Precursor of acetylcholine (donating the acetyl portion to the acetylcholine molecule). It is synergistic with lipoic acid.[12] Inhibits lipofuscin formation.
  • Choline - precursor to acetylcholine (an essential component of the acetylcholine molecule).
  • DMAE - approved treatment for ADD/ADHD[citation needed], precursor of acetylcholine, 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. Recent Cochrane review concluded that it appears to have beneficial cognitive effects with limited side-effects, but more evidence is needed.[15]
  • Ispronicline - recently developed selective α4β2 partial agonist
  • Lecithin - contains phosphatidylcholine, precursor of acetylcholine.
  • Other pyrrolidone derivatives:
    • Etiracetam - It increases vigilance.[7]
    • Nefiracetam - Drug. Analog of piracetam, and facilitates hippocampal neurotransmission.[16]
    • 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. [17] There is evidence that the beneficial effect of racetams may result from an interaction with the central glutamatergic receptor function. [17]
  • 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 acetylcholinesterase inhibitor.

Acetylcholinesterase inhibitors

Acetylcholinesterase inhibitors function by inhibiting the cholinesterase enzyme which breaks down the neurotransmitter acetylcholine. They exist in the form of poisons and have been used as weapons, but they are also used to treat Alzheimer's patients. Donepezil, galantamine, and Huperzine A are notable among these.

Dopaminergics

Dopaminergics 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 (vitamin C and vitamin B6), and dopamine reuptake inhibitors:

  • Mucuna pruriens - Seed powder which contains high concentrations of levodopa (L-dopa),[18] a direct precursor of the neurotransmitter dopamine.
  • Tyrosine (requires Vitamin B6 and Vitamin C) - Amino acid. Precursor to dopamine, anti-depressant, sleep reducer.
  • Lazabemide - 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.[19]
  • 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.
  • 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 has been tested as a treatment for Alzheimer's disease.[20] 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.[21]
  • 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.
  • Yohimbe - Bark. Aphrodisiac. Boosts dopamine levels,[citation needed] though how it does this is not yet understood. Supplements are likely to have no yohimbe in them.[22] 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.
  • Theanine - Found in tea. Increases serotonin and dopamine levels in the brain. Increases alpha-wave based alert relaxation.

Serotonergics

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:

  • Griffonia simplicifolia a natural source of 5-HTP (an alternative in countries where 5-HTP not legal, freely available.)
  • Tryptophan (requires Vitamin B6 and Vitamin C) - Essential amino acid. Precursor to serotonin, found in high concentration in bananas and meats, also in milk, promotes relaxed poise and sound sleep. 5-HTP is a form of Tryptophan.
  • 5HT2A 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 )[citation needed]
  • SSRIs - Class of antidepressants that increase active serotonin levels, ie, in the synaptic junction, by inhibiting its reuptake. Have also been shown to promote Neurogenesis in the hippocampus.

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

Stress, depression, and depressed mood negatively affect cognitive performance. It is reasoned that counteracting and preventing depression and stress may be an effective nootropic strategy.

Below are a list of substances purported to function as nootropics, and claimed effects:

  • Ashwagandha (Withania somnifera) - Root. Also known as Indian ginseng. Adaptogen used as a tonic to normalize body processes and reduce stress and anxiety.
  • 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 gabaergics to GABAA 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.[23]
  • 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. [23]
  • Rhodiola Rosea - Herb. Adaptogen; elevates mood, alleviates depression. Promotes mental energy and stamina, reduces fatigue. Boosts dopamine. Slows breakdown of serotonin.
  • 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. [23]
  • Ginseng, Siberian (Eleutherococcus senticosus) - Root. Anti-anxiety adaptogen that normalizes physical stress and mental consequences.
  • 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.[24] 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. [19]
  • 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. Also stimulates the GABAergic system.
  • Tianeptine - Anxiolytic anti-depressant. It enhances working and reference memory in rats.[25]
  • Vasopressin - Drug. Memory hormone produced by the pituitary gland which improves both memory encoding and recall. Rapidly counters chronic apathy syndrome and drug-induced vasopressin depletion.

Vasodilator - Mood stabilizer, with a powerful anti-anxiety effect — 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. [26]

Brain function and improved oxygen supply

  • Chromium- stabilises blood sugar levels promoting concentration.
  • Coenzyme q-10 syn. Ubiquinone - increases oxygen transport through the mitochondria of the cells.
  • Creatine - increases brain energy levels via ATP production.
  • Inositol - B vitamin which synergizes with other nootropics
  • Lipoic acid - synergistic with Acetyl-L-carnitine.
  • 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 radicals created in the very processes it is involved in.
  • 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. [4]
  • Prazosin - Alpha-blocking blood pressure medication also prescribed as an anti-PTSD medication, appears to block the increase of steroid hormones known as glucocorticoids, Oregon Health & Science University and Portland Veterans Affairs Medical Center researchers have found. Elevated levels of glucocorticoids are associated with atrophy in nerve branches where impulses are transmitted, and even nerve cell death, in the hippocampus.

Mental agility, concentration, stamina, and focus

  • Adrafinil (Olmifon) - Drug.
  • Caffeine - Drug. Improves concentration, idea production, but hinders memory encoding. Large amounts produce 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.[7] 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.
  • Phenibut -
  • Theophylline -
  • Amphetamine - aids in concentration, focus and stamina. Prescribed for ADD/ADHD
  • Carphedon (Phenotropil) -

Purported memory enhancement and learning improvement

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:

  • Bacopa monniera (Brahmi) - Herb. Elevates curiosity, enhances memory and concentration.Cite error: The <ref> tag has too many names (see the help page). Brahmi also protects against amnesia inducing chemicals such as scopolamine or loss of memory due to electro convulsive shocks.[27] Improves protein synthesis in brain cell repair and new dendritic growth. It is a traditional ayurvedic medicine.
  • Brahmi rasayana - improved learning and memory in mice.[28]
  • Rosemary - Herb. Rosemary has a very old, albeit unverified, reputation for improving memory.
  • Vasopressin - Hormone, prescription drug.
  • Dextroamphetamine- Adderall, Dexedrine.[29]
  • Nicotine - Improves working memory and learning[30]
  • Sage - a study of young adults found that Salvia lavandulaefolia improves word recall;[31] a randomized trial has found that Salvia officinalis improves symptoms in Alzheimer's patients[32]

Nerve growth stimulation and brain cell protection

  • 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.[7]
  • 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.

Recreational drugs with purported nootropic effects

  • Amphetamine-type stimulants (such as Adderall, Dexedrine, Desoxyn, etc.) are Schedule II controlled substances in the United States, and 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 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.[33][34] These also heighten alertness, mental focus, vigilance, stamina, and sex drive. They tend to be habit-forming, and exhibit 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.
  • LSD - Schedule I / 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.[35] Also produces hallucinogenic and entheogenic effects at doses as low as 30–40 μg (micrograms), with the likelihood of having a bad trip increasing as dose is increased if these effects are undesired. May also cause cognitive shifts, synesthesia, and flashbacks. The drug sometimes spurs long-term or even permanent changes in a user's personality and life perspective. (For more details, see Albert Hofmann: LSD - My Problem Child.)
  • 4-methylaminorex
  • Pemoline (Cylert)
  • Psilocybin and Psilocin
  • MDPV
  • Mescaline

Dietary nootropics

Some regular food items are rich sources of substances with alleged nootropic benefits:

Other nootropics

  • Adafenoxate - Has an anti-anxiety effect for rats[36] and possibly the same for humans.
  • Moderate use of alcohol - Moderate drinking has been associated with better cognitive ability than both abstention and heavy drinking.[37][38][39][40][41]
  • 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."[42]
  • 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) - A lysergic acid amide derivative, is a potent dopamine receptor agonist on D2 receptors. Maybe carcinogenic.
  • Celastrus paniculatus - Oil made from the seeds of this shrub are used in Ayurvedice medicine to increase memory and facilitate learning. It allegedly induces a feeling of well-being and has reported aphrodisiac effects.
  • Cerebrolysin - A neuroprotective nootropic agent, might affect Alzheimer's disease pathology. Currently in clinical trials [citation needed]
  • Clausenamide - Facilitated learning and memory acquisition in step down and step through tests and increased thickness of cerebral cortex and synapse density significantly in the dentate cells over pyramidel cells in hippocampal region in mice.
  • Coluracetam - It may also have potential use in prevention and treatment of ischemic retinopathy and retinal and optic nerve injury [citation needed]
  • Desmopressin (DDAVP) - Analog of vasopressin, a neuropeptide responsible for memory.
  • DHEA - Hormone created by the adrenal glands; Precursor to Estrogen and Testosterone
  • Dostinex - (see Cabergoline above)
  • Fasoracetam - A nootropic drug of the racetam family.
  • Essential Fatty Acids- Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the best known. EPA in particular, has an anti-depressant function and is positively indicated in trials with autism and learning difficulties [citation needed]
  • Fipexide (Vigilor) - It protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.[10]
  • Gerovital H3 - Romanian anti-aging formula containing procaine hydrochloride, but which breaks down into PABA and DMAE.
  • Gotu Kola - Herb and root.
  • Meclofenoxate - Has an anti-anxiety effect for rats[36] and possibly the same for humans. Like Fipexide, it protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.[10] Like many racetams, it may treat fetal alcohol syndrome.[11]
  • Milacemide - A glycine prodrug which is both an inhibitor and a substrate for monoamine oxidase-type B (MAO-B) and also an inhibitor of MAO-type A (MAO-A).
  • Nimodipine - A dihydropyridine calcium channel blocker originally developed for the treatment of high blood pressure.
  • Ondansetron (Zofran) - A serotonin 5-HT3 receptor antagonist used mainly as an antiemetic to treat nausea and vomiting following chemotherapy.
  • Phenytoin (Dilantin) - A neuroleptic and anti-seizure medication advocated by Jack Dreyfus for a variety of psychological conditions.
  • Phosphatidylserine- In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. [4]
  • Picamilon or Pikamilone - Compound of Niacin and GABA. It can pass the blood-brain barrier and increase amount of GABA in the brain.[citation needed]
  • Pregnenolone - Hormone; Precursor to DHEA;
  • Pyroglutamate - An amino acid shown to improve learning.
  • 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[citation needed]
  • Somatotropin - Growth hormone, a polypeptide containing 191 amino acids, produced by the anterior pituitary, the front section of the pituitary gland. It acts by stimulating the release of another hormone called somatomedin by the liver, thereby causing growth.
  • Sulbutiamine (Arcalion) - Drug - derivative of thiamine (vitamin B1) that can cross the blood-brain barrier and work as anti-fatigue and cognitive support agent.[citation needed]
  • Sunifiram
  • Turmeric - has possible benefits in Alzheimer's disease, cancer and liver disorders. Turmeric, under the name Avea, is becoming popular to treat depression.
  • Unifiram
  • Xanthinol Nicotinate (Complamin) - A drug that has been shown to stimulate memory and concentration, by improving blood flow to the brain.
  • MDL 26,479[43]
  • Propentofylline

Contentious or possibly unsafe nootropics

  • Royal Jelly - Produced by bees for the Queen. Can cause fatal allergic reactions in rare cases [citation needed]
  • Ginkgo biloba - Patients with dementia treated with Ginkgo showed significant improvement of symptoms like memory loss, concentration difficulties, fatigue, anxiety and depressive mood. [23] As a vasodilator, it should not be taken with aspirin, for doing so could increase the risk of bleeding.[44] Ginkgo is widely used in Europe to treat subjective tinnitus, although there is as yet no hard evidence supporting this assertion. [44] 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.[45]
  • Arecoline

See also

Brain and neurology

Thought and thinking (what nootropics are used for)

Health

References

  1. ^ "12577719" at Dorland's Medical Dictionary
  2. ^ a b Stancheva, S.L., Petkov, V.D., Hadjiivanova, C.I., and Petkov, V.V. (1991). "Age-related changes of the effects of a group of nootropic drugs on the content of rat brain biogenic monoamines". Gen. Pharmacol. (Department of Experimental Pharmacology, Bulgarian Academy of Sciences, Sofia)'. 22 (5): 873–7. {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)CS1 maint: multiple names: authors list (link)
  3. ^ 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 (25 August 2006). "The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones". Immunity & Ageing. 3 (9).{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ a b c d e f McDaniel, M.A., Maier, S.F., and Einstein, G.O. (2002). "Brain-Specific Nutrients: A Memory Cure?". Psychological Science in the Public Interest (American Psychological Society)'. 3 (1). {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)CS1 maint: multiple names: authors list (link)
  5. ^ Goldman, R., Klatz, R., and Berger, L. (1999). Brain fitness. New York: Doubleday.{{cite book}}: CS1 maint: multiple names: authors list (link)
  6. ^ Gabryel, B. and Trzeciak, H.I. (1994). "Nootropics: Pharmacological properties and therapeutic use". Polish Journal of Pharmacology. 46: 383–394.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ a b c d e Saletu, B. and Grunberger, J. (1985). "Memory dysfunction and vigilance: neurophysiological and psychopharmacological aspects". Annals of the New York Academy of Sciences. 444 (1): 406–27. doi:10.1111/j.1749-6632.1985.tb37604.x. PMID 3860093.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Paula-Barbosa, M.M., Brandao, F., Pinho, M.C., Andrade, J.P., Madeira, M.D., and Cadete-Leite, A. (1991-10-01). "The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study". Alcohol Clin. Exp. Res. 15 (5): 834–8. doi:10.1111/j.1530-0277.1991.tb00610.x.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Riedel, W.J., Peters, M.L., Van Boxtel, M.P.J., and O'Hanlon, J.F. (1998-12-04). "The influence of piracetam on actual driving behaviour of elderly subjects". Human Psychopharmacology: Clinical & Experimental. 13 (S2): S108–14. doi:10.1002/(SICI)1099-1077(1998110)13:2 <S108::AID-HUP55>3.0.CO;2-R. {{cite journal}}: Check |doi= value (help); Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)CS1 maint: multiple names: authors list (link)
  10. ^ a b c Genkova-Papasova, M. and Lazarova-Bakurova, M. (1988). "Influence of nootropic drugs on the memory-impairing effect of diethyldithiocarbamate and clonidine in "step down" passive avoidance in albino rats". Acta Physiol. Pharmacol. Bulg. (Institute of Physiology, Bulgarian Academy of Sciences)'. 14 (4): 36–41. {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)CS1 maint: multiple names: authors list (link)
  11. ^ a b Vaglenova, J. and Petkov, V.V. (February 2001). "Can nootropic drugs be effective against the impact of ethanol teratogenicity on cognitive performance?". European Neuropsychopharmacology. 11 (1): 33–8. doi:10.1016/S0924-977X(00)00129-2.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ 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.
  13. ^ http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=548494
  14. ^ Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice.
  15. ^ PMID 18425924
  16. ^ Nomura, T. and Nishizaki, T. (2000-07-07). "Nefiracetam facilitates hippocampal neurotransmission by a mechanism independent of the piracetam and aniracetam action". Brain Res. (Department of Physiology, Kobe University School of Medicine. Kobe, Japan)'. 870 (1–2): 157–62. {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)CS1 maint: multiple names: authors list (link)
  17. ^ a b Zdenek Hlinak and Ivan Krejci (18 July 2000). "Oxiracetam prevents the MK-801 induced amnesia for the elevated plus-maze in mice". Behavioral Brain Research. 117: 147–151. doi:10.1016/S0166-4328(00)00298-9.
  18. ^ [http://books.google.com/books?id=qDf3AO8nILoC Medical Toxicology
  19. ^ a b R. Preston Mason, Edwin G. Olmstead Jr., and Robert F. Jacob (2000). "Antioxidant Activity of the Monoamine Oxidase B Inhibitor Lazabemide". Biochemical Pharmacology. 60: 709–716. doi:10.1016/S0006-2952(00)00374-9.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1189014 Selegiline in the treatment of Alzheimer's disease: a long-term randomized placebo-controlled trial. Czech and Slovak Senile Dementia of Alzheimer Type Study Group.
  21. ^ Tiina Suuronen, Petri Kolehmainen, and Antero Salminen, Department of Neuroscience and Neurology, University of Kuopio, Finland. (2000). "Protective Effect of L-Deprenyl against Apoptosis Induced by Okadaic Adic in Cultured Neuronal Cells". Biochemical Pharmacology. 59: 1589–1595. doi:10.1016/S0006-2952(00)00282-3.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ An evidence-based approach to dietary supplements for ED (Part 2 of 2)
  23. ^ a b c d Susanne Kienzle-Horn (2002). [www.biomedcentral.com/content/pdf/cd-451283.pdf "Herbal medicines for neurological diseases"] (PDF). Current Opinion in Investigational Drugs. 3 (5): 763–767. {{cite journal}}: Check |url= value (help)
  24. ^ Riga, D. and Riga, S. (1995). "Brain lipofuscinolysis and ceroidolysis--to be or not to be". Gerontology (Institute of Neurology and Psychiatry, Bucharest, Romania)'. 41 (S2): 271–81. {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)CS1 maint: multiple names: authors list (link)
  25. ^ Tianeptine ( Stablon, Coaxil ) : an unusual antidepressant
  26. ^ Sreemantula; et al. (19 January 2005). "Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model". BMC Complementary and Alternative Medicine. 5 (1): 1. doi:10.1186/1472-6882-5-1. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: unflagged free DOI (link)
  27. ^ Cite error: The named reference Singh&Dhawan1997 was invoked but never defined (see the help page).
  28. ^ [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1375237&rendertype=abstract Brahmi rasayana Improves Learning and Memory in Mice
  29. ^ Rapoport, J.L., Buchsbaum, M.S., Zahn, T.P., Weingartner, H., Ludlow, C., and Mikkelsen, E.J. (1978). "Dextroamphetamine: cognitive and behavioral effects in normal prepubertal boys". Science. 199 (4328): 560–3. doi:10.1126/science.341313. PMID 341313.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  30. ^ Edward D. Levin, F. Joseph McClernon and Amir H. Rezvani1. "Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization". Psychopharmacology. 184: http://www.springerlink.com/content/y41lg2qj24xvvh31/.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  31. ^ PMID 12895685
  32. ^ PMID 12605619
  33. ^ D. BROWN et al., “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.
  34. ^ CHOATE et al., "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)
  35. ^ Bacon, et al., "The Effect of LSD on the Human Brain", 1996. Accessed October 16, 2007
  36. ^ a b Petkov, V.D., Getova, D., and Mosharrof, A.H. (1987). "A study of nootropic drugs for anti-anxiety action". Acta Physiol. Pharmacol. Bulg. (Institute of Physiology, Bulgarian Academy of Sciences, Sofia)'. 13 (4): 25–30. {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)CS1 maint: multiple names: authors list (link)
  37. ^ Britton, A., Singh-Manoux, A., Marmot, M. Alcohol consumption and cognitive function in the Whitehall II Study. American Journal of Epidemiology,2004 Aug 1;160(3):240-7.
  38. ^ Launer LJ, Feskens EJ, Kalmijn S, Kromhout D Smoking, drinking, and thinking. The Zutphen Elderly Study American Journal of Epidemiology 1996 Feb 1;143(3):219-27
  39. ^ Galanis, DJ; Joseph C, Masaki KH, Petrovitch H, Ross GW, White L A longitudinal study of drinking and cognitive performance in elderly Japanese American men: the Honolulu-Asia Aging Study American Journal of Public Health Vol 90, Issue 8 1254-1259
  40. ^ Dufouil, Carole; Ducimetière, Pierre; Ducimetière, Pierre Sex Differences in the Association between Alcohol Consumption and Cognitive Performance American Journal of Epidemiology Vol. 146, No. 5: 405-412
  41. ^ Rodgers, B., et al. Non-linear relationships between cognitive function and alcohol consumption in young, middle-aged and older adults: The PATH Through Life Project. Addiction, 2005, 100(9), 1280-1290; Anstey, K. J., et al. Lower cognitive test scores observed in alcohol are associated with demographic, personality, and biological factors: The PATH Through Life Project. Addiction, 2005, 100(9), 1291-1301.
  42. ^ Soman, I., Mengi, S.A., and Kasture, S.B. (2004). "Effect of leaves of Butea frondosa on stress, anxiety, and cognition in rats". Pharmacology, Biochemistry & Behavior (C.U. Shah College of Pharmacy, SNDT University Santacruz, Mumbai, Maharashtra, India)'. 79 (1): 11–6. {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)CS1 maint: multiple names: authors list (link)
  43. ^ MDL 26,479: a potential cognition enhancer with benzodiazepine inverse agonist-like properties.
  44. ^ a b Paul F Smith & Cynthia L Darlington Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand (2005). "Drug treatments for subjective tinnitus: Serendipitous discovery versus rational drug design". Current Opinion in Investigational Drugs. 6 (7): 712–716.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  45. ^ Clive Bate, Mario Salmona, and Alun Williams (11 May 2004). "Ginkgolide B inhibits the neurotoxicity of prions or amyloid-BI-42". Journal of Neuroinflammation. 1 (4): 4. doi:10.1186/1742-2094-1-4.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)