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'''Nootropics''' ({{IPAc-en|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 ]s, ]s, ]s, and ]s that purportedly improve mental functions such as ], ], ], ], ], 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 = January 30, 2008}}</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 |date=March 2008 |pmid=18353672 |doi=10.1016/j.phrs.2008.02.004 |url=}}</ref> The word ''nootropic'' was coined in 1972 by the ] Dr. ],<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= ("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 ] words νους ''nous'', or "mind," and τρέπειν ''trepein'' meaning "to bend/turn". Nootropics are thought to work by altering the availability of the ] supply of neurochemicals (], ], and ]), by improving the brain's ] supply, or by stimulating nerve growth. | '''Nootropics''' ({{IPAc-en|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 ]s, ]s, ]s, and ]s that purportedly improve mental functions such as ], ], ], ], ], 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 = January 30, 2008}}</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 |date=March 2008 |pmid=18353672 |doi=10.1016/j.phrs.2008.02.004 |url=}}</ref> The word ''nootropic'' was coined in 1972 by the ] Dr. ],<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= ("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 ] words νους ''nous'', or "mind," and τρέπειν ''trepein'' meaning "to bend/turn". Nootropics are thought to work by altering the availability of the ] supply of neurochemicals (], ], and ]), by improving the brain's ] supply, or by stimulating nerve growth. | ||
==Nootropics vs. cognitive enhancers== | |||
{{Expert-subject|Pharmacology|section|date=February 2010}} | |||
Cognitive enhancers are ]s, supplements, nutraceuticals, and ]s that enhance ] 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 = January 30, 2008}}</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 |date=March 2008 |pmid=18353672 |doi=10.1016/j.phrs.2008.02.004 |url=}}</ref> Nootropics are cognitive enhancers that are ] or extremely nontoxic. Nootropics (such as Modafinil) are by definition cognitive enhancers, but a cognitive enhancer is not necessarily a nootropic. | |||
'''Giurgea's nootropic criteria:''' | |||
# Enhances learning and memory. | |||
# Enhances learned behaviors under conditions which are known to disrupt them (e.g. ], ]). | |||
# Protects the brain from physical or chemical injury. | |||
# Enhances the tonic cortical/subcortical control mechanisms | |||
# Exhibits few side effects and extremely low toxicity, while lacking the pharmacology of typical psychotropic drugs (motor stimulation, sedation, etc.). | |||
Since Giurgea's original criteria were first published, there has been little agreement as to what truly constitutes a nootropic compound. The most well defined criteria to date was established by Skondia in 1979. Skondia uses a metabolic approach, taking into account the pharmacological mode of action. | |||
'''Skondia's nootropic criteria:''' | |||
I. No direct vasoactivity | |||
:A. No vasodilation | |||
:B. No vasoconstriction | |||
II. EEG activity: No change in basic rhythm | |||
:A. Quantitative EEG: Increased power spectrum (beta 2 and alpha) | |||
:B. Qualitative EEG: Decreased delta waves and cerebral suffering | |||
III. Must pass blood-brain barrier | |||
:A. Under normal conditions | |||
:B. Under pathological conditions | |||
IV. Must show metabolic activity in: | |||
:A. Animal brain metabolism | |||
::1. Molecular | |||
::2. Physiopathological | |||
:B. Human brain metabolism (clinical evaluation) | |||
::1. A-V differences | |||
:::a. Increased extraction quotients of O2 | |||
:::b. Increased extraction quotients of glucose | |||
:::c. Reduced lactate pyruvate ratio | |||
::2. Regional cerebral metabolic rates (rCMR) | |||
:::a. Increased ICMR of O2 | |||
:::b. Increased rCMR of glucose | |||
::3. Regional cerebral blood flow: Normalization | |||
V. Minimal side effects | |||
VI. Clinical trials must be conducted with several rating scales designed to objectify metabolic cerebral improvement. | |||
==Availability and prevalence== | ==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.<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 |date=December 2007 |pmid=18097378 |doi=10.1038/4501157a |url=|bibcode = 2007Natur.450.1157S }}</ref> The most commonly used class of drug is ].<ref name=Nature2008/> | 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 |date=December 2007 |pmid=18097378 |doi=10.1038/4501157a |url=|bibcode = 2007Natur.450.1157S }}</ref> The most commonly used class of drug is ].<ref name="Nature2008">{{cite journal |url=http://www.nature.com/nature/journal/v456/n7223/full/456702a.html |title=Towards responsible use of cognitive-enhancing drugs by the healthy |work=] |date=December 10, 2008 |publisher=] |issn=1476-4687 |oclc=01586310 |bibcode = 2008Natur.456..702G |accessdate=March 25, 2014 |doi=10.1038/456702a |pages=702–705 |volume=456 |issue=7223 |subscription=yes |first1=Henry |last1=Greely |first2=Barbara |last2=Sahakian |first3=John |last3=Harris |first4=Ronald C. |last4=Kessler |first5=Michael |last5=Gazzaniga |first6=Philip |last6=Campbell |first7=Martha J. |last7=Farah}}</ref> | ||
These drugs are used primarily to treat people with cognitive or motor function difficulties attributable to such disorders as ], ], ] and ]. 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=]|accessdate=November 4, 2012}}</ref> These drugs have a variety of ] applications as well, and are marketed heavily on the ]. Nevertheless, intense marketing may not correlate with ]; while scientific studies support |
These drugs are used primarily to treat people with cognitive or motor function difficulties attributable to such disorders as ], ], ] and ]. 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=]|accessdate=November 4, 2012}}</ref> These drugs have a variety of ] applications as well, and are marketed heavily on the ]. Nevertheless, intense marketing may not correlate with ]; while scientific studies support the beneficial effects of some compounds, the marketing claims by manufacturers of ] products are not formally tested. | ||
===Academic doping=== | ===Academic doping=== | ||
{{main|Academic doping}} | {{main|Academic doping}} | ||
In academia |
In academia, ] has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals.<ref name=NatureProfessor/> Stimulants such as ] and ] are used on college campuses and by younger groups.<ref name=NatureProfessor/> One survey found that 7% of students had used stimulants for a cognitive edge, and on some campuses use in the past year is as high as 25%.<ref name=Nature2008/><ref name=StudentSurvey>{{cite journal|last=McCabe|first=Sean Esteban|coauthors=Knight, John R.; Teter, Christian J.; Wechsler, Henry|title=Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey|journal=Addiction|date=January 1, 2005|volume=100|issue=1|pages=96–106|doi=10.1111/j.1360-0443.2005.00944.x|pmid=15598197|url=http://www.ncbi.nlm.nih.gov/pubmed/15598197|accessdate=August 15, 2013}}</ref> The use of prescription stimulants is especially prevalent among students attending academically competitive colleges and students who are members of a fraternity or sorority.<ref name=StudentSurvey/> | ||
Surveys suggest that |
Surveys suggest that 3–11% of American students and 0.7–4.5% of German students have used cognitive enhancers in their lifetime.<ref name="doi10.1371/journal.pone.0068821">{{cite doi|10.1371/journal.pone.0068821}}</ref><ref name="C4WDefault-10.3109/10826084.2012.751426">{{cite journal |url=http://informahealthcare.com/doi/abs/10.3109/10826084.2012.751426 |title=Cognitive Test Anxiety and Cognitive Enhancement: The Influence of Students’ Worries on Their Use of Performance-Enhancing Drugs |work=Substance Use & Misuse |volume = 48 |number = 3 |pages=220–232 |date=February 25, 2013 |publisher=Informa Healthcare New York |accessdate=April 5, 2014 |doi=10.3109/10826084.2012.751426 |first1=Sebastian |last1=Sattler |first2=Constantin |last2=Wiegel}}</ref> | ||
Several factors positively and negatively influence the use of drugs to increase cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.<ref name="doi10.1371/journal.pone.0068821"/><ref name="C4WDefault-10.3109/10826084.2012.751426"/><ref name="C4WDefault-10.1186/1747-597X-9-8">{{cite web |url=http://www.substanceabusepolicy.com/content/9/1/8 |title=Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics |date=February 1, 2014 |publisher=BioMed Central Ltd |issn=1747-597X |accessdate=April 5, 2014 |doi=10.1186/1747-597X-9-8 |issue=1 |volume=9 |page=8 |journal=Substance Abuse Treatment, Prevention, and Policy |first1=Sebastian |last1=Sattler |first2=Guido |last2=Mehlkop |first3=Peter |last3=Graeff |first4=Carsten |last4=Sauer}}</ref><ref name="PLOS ONE-10.1371/journal.pone.0071452">{{cite journal |url=http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0071452 |title=Impact of Contextual Factors and Substance Characteristics on Perspectives toward Cognitive Enhancement |date=August 5, 2013 |publisher=] |issn=1932-6203 |oclc=228234657 |accessdate=April 5, 2014 |journal=] |lccn=2006214532 |doi=10.1371/journal.pone.0071452 |issue=8 |volume=8 |page=e71452 |first1=Sebastian |last1=Sattler |first2=Cynthia |last2=Forlini |first3=Éric |last3=Racine |first4=Carsten |last4=Sauer}}</ref> | |||
==Hazards== | ==Hazards== | ||
The main concern with ]s is ]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/> While certain ] compounds are suspected to have nootropic qualities, few side-effects, and a wide ] (low overdose risk),<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> other cognitive enhancers may be associated with a high incidence of adverse effects or a narrower therapeutic window (higher overdose risk). While addiction to stimulants is sometimes asserted to be a cause for concern,<ref name="pmid23164208">{{cite journal | author = Noble KA | title = Brain gain: adolescent use of stimulants for achievement | journal = J. Perianesth. Nurs. | volume = 27 | issue = 6 | pages = 415–9 |date=December 2012 | pmid = 23164208 | doi = 10.1016/j.jopan.2012.09.001 | url = }}</ref> a very large body of research on the therapeutic use of the "more addictive" psychostimulants indicate that addiction is fairly rare in therapeutic doses.<ref name="EncycOfPsychopharm">{{Cite book | author = Stolerman IP | editor = Stolerman IP | title = Encyclopedia of Psychopharmacology | year = 2010 | publisher = Springer | location = Berlin; London | isbn = 9783540686989 | page = 78}}</ref><ref name="Westfall">{{cite book | editor = Brunton LL, Chabner BA, Knollmann BC | title = Goodman & Gilman's Pharmacological Basis of Therapeutics | year = 2010 | publisher = McGraw-Hill | location = New York | isbn = 9780071624428 | author = Westfall DP, Westfall TC | section = Miscellaneous Sympathomimetic Agonists | sectionurl = http://www.accessmedicine.com/content.aspx?aID=16661601 | edition = 12th }}</ref><ref name="FDA Abuse & OD">{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | page = 11 | work = United States Food and Drug Administration |date=December 2013 | accessdate = December 30, 2013 }}</ref> | |||
The main concern with ]s is ]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/> | |||
In the United States, ] or dietary supplements do not require safety or efficacy approval before being sold.<ref>{{Cite journal|author=Goldman P |title=Herbal medicines today and the roots of modern pharmacology |journal=Annals of Internal Medicine |volume=135 |issue=8 Pt 1 |pages=594–600 |year=2001 |pmid=11601931 |doi=10.7326/0003-4819-135-8_Part_1-200110160-00010}}</ref> | |||
==Drugs== | ==Drugs== | ||
===Racetams=== | |||
The word ''nootropic'' was coined upon discovery of the effects of ], 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> Studies of the ] have revealed that these structurally similar compounds often act via different mechanisms. Notable drugs include ], ], and ]. Their mechanisms of action are not fully understood. Piracetam and aniracetam are known to act as ]s of ]s and appear to modulate ] 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 ] show affinity for muscarinic receptors, only ] shows it at the nanomolar range. Racetams have been called "pharmacologically safe" drugs.<ref name=BetterBrain/> | |||
===Vitamins and supplements=== | ===Vitamins and supplements=== | ||
* ]& |
* ] – may influence cognitive function through an effect on ] and ] 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> A 2008 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 |date=August 2008 |pmid=18721399 |doi=10.1111/j.1365-277X.2008.00887.x |url=}}</ref> | ||
* ] (a ]) with ] and ] (]s) – concurrent supplemental use can protect and potentially improve brain function.<ref name="Review1">{{cite journal | author = Kidd PM | title = Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids | journal = Altern Med Rev | volume = 12 | issue = 3 | pages = 207–27 |date=September 2007 | pmid = 18072818 | doi = | url = }}</ref><ref name="RCT1">{{cite journal | author = Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman A | title = The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension | journal = Eur. Psychiatry | volume = 27 | issue = 5 | pages = 335–42 |date=July 2012 | pmid = 21807480 | doi = 10.1016/j.eurpsy.2011.05.004 | url = }}</ref> DHA and EPA are compounds that support brain function and ], especially during brain development.<ref>{{cite journal | author= Sheila M. Innis | title= Dietary (n-3) fatty acids and brain development | journal= The journal of nutrition | volume=137 | issue=4 |date=April 2007}}</ref> A ] and a more recent ] on supplemental phosphatidylserine with DHA and EPA indicate that there are clinical benefits for those with ADHD,<ref name="Review1" /><ref name="RCT1" /> in addition to a range of other clinical applications.<ref name="Review1" /> However, ] reviews on the use of supplemental omega-3 fatty acids alone (''without'' phosphatidylserine) indicate that there is limited evidence of treatment benefits for individuals with ADHD<ref name="Cochrane ADHD">{{cite journal | author = Gillies D, Sinn JKh, Lad SS, Leach MJ, Ross MJ | title = Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents | journal = Cochrane Database Syst Rev | volume = 7 | issue = | pages = CD007986 | year = 2012 | pmid = 22786509 | doi = 10.1002/14651858.CD007986.pub2 | url = }}</ref> or other learning disorders.<ref name="Cochrane LD">{{cite journal | author = Tan ML, Ho JJ, Teh KH | title = Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders | journal = Cochrane Database Syst Rev | volume = 12 | issue = | pages = CD009398 | year = 2012 | pmid = 23235675 | doi = 10.1002/14651858.CD009398.pub2 | url = }}</ref> A Norwegian study demonstrated a ''potential'' link between Omega-3 consumption during pregnancy and child intelligence test scores.<ref>''Pediatrics''. 2003 Jan;111(1) e39–44</ref><ref name="Chillot">Prevention Chillot yr.2004 vol.56 iss.1 pg. 122–129</ref> | |||
* ]— Higher concurrent ] intake was related to better cognitive performance.<ref name="AmJourClinNut-1608716">{{cite journal |url=http://ajcn.nutrition.org/content/94/6/1584.full |title=The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort |date=December 1, 2011 |publisher=] |issn=1938–3207 |oclc=01480127 |accessdate=March 24, 2014 |journal=] |lccn=56032466 |doi=10.3945/ajcn.110.008938 |issue=6 |volume=94 |pages=1584–1591 |first1=Coreyann |last1=Poly |first2=Joseph M |last2=Massaro |first3=Sudha |last3=Seshadri |first4=Philip A |last4=Wolf |first5=Eunyoung |last5=Cho |first6=Elizabeth |last6=Krall |first7=Paul F |last7=Jacques |first8=Rhoda |last8=Au |archiveurl=//web.archive.org/web/20140324144311/http://ajcn.nutrition.org/content/94/6/1584.full |archivedate=March 24, 2014 |deadurl=no}}</ref> It improves long-term memory in animal models.<ref name="C4Wauto-1685762">{{cite web |url=http://timesofindia.indiatimes.com/life-style/health-fitness/diet/Eating-beef-liver-improves-long-term-memory/articleshow/21035424.cms?referral=PM |title=Eating beef liver improves long-term memory - The Times of India |work=timesofindia.indiatimes.com |date=July 25, 2013 |accessdate=March 24, 2014 |author=<!--Staff writer(s); no by-line.--> |archiveurl=//web.archive.org/web/20140324144701/http://timesofindia.indiatimes.com/life-style/health-fitness/diet/Eating-beef-liver-improves-long-term-memory/articleshow/21035424.cms?referral=PM |archivedate=March 24, 2014 |deadurl=no}}</ref> | |||
* ] – 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 50 nmol/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 |date=Aug 2009 |pmid=19377013 |url= |doi=10.1093/gerona/glp032 |pmc=2981461}}</ref> Vitamin D has also been shown to be necessary in the production of ].<ref>{{cite web | author=Thomas H. J. Burne, PhD | title= vitamin d and the brain |date=May 2013 | website= http://chemistry.beloit.edu/Ordman/nutrition/aln13/1305lpi.htm}}</ref> | |||
* ] have been linked to the maintenance of brain function. Omega-3's provide ], important in the function and growth of nervous tissue. It is especially important during brain development.<ref>{{cite journal | author= Sheila M. Innis | title= Dietary (n-3) fatty acids and brain development | journal= the journal of nutrition | volume=137 | issue=4 |date=April 2007}}</ref> A study preformed 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 Chillot yr.2004 vol.56 iss.1 pg. 122–129</ref> A cross-sectional population-based study of 1,613 subjects found an association between ] intake and decreased risk for impairment of cognitive function & cognitive speed.<ref name="PubMed-14745067">{{cite journal |url=http://www.ncbi.nlm.nih.gov/pubmed/14745067 |title=Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. |date=January 2, 2004 |publisher=] |accessdate=March 24, 2014 |issue=2 |volume=62 |pmid=14745067 |pages=275–80 |journal=Neurology |first1=S |last1=Kalmijn |first2=Mp |last2=van Boxtel |first3=Ocké |last3=M |first4=Wm |last4=Verschuren |first5=D |last5=Kromhout |first6=Lj |last6=Launer}}</ref> Another study showed that boys with lower levels of Omega-3 had more behavior issues, including ].<ref name="AmJourClinNut-2564006">{{cite journal |url=http://ajcn.nutrition.org/content/71/1/327S.full |title=Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder |date=January 1, 2000 |publisher=] |issn=1938–3207 |oclc=01480127 |accessdate=March 24, 2014 |journal=] |lccn=56032466 |issue=1 |volume=71 |pages=327S–330S |first1=John R |last1=Burgess |first2=Laura |last2=Stevens |first3=Wen |last3=Zhang |first4=Louise |last4=Peck |archiveurl=//web.archive.org/web/20140324145318/http://ajcn.nutrition.org/content/71/1/327S.full |archivedate=March 24, 2014 |deadurl=no}}</ref> | |||
* ]s—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 |date=October 2008 |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 ], ] & ].<ref name="PubMed-9071926">{{cite journal |url=http://www.ncbi.nlm.nih.gov/pubmed/19480732 |title=Soya isoflavone supplementation enhances spatial working memory in men. |date=Nov 2009 |publisher=] |accessdate=March 24, 2014 |doi=10.1017/S0007114509990201 |issue=9 |volume=102 |pmid=19480732 |pages=1348–54 |journal=Br J Nutr |first1=Aa |last1=Thorp |first2=N |last2=Sinn |first3=Jd |last3=Buckley |first4=Am |last4=Coates |first5=Pr |last5=Howe}}</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 |date=January 2009 |pmid=19054783 |pmc=2720778 |doi=10.1093/ageing/afn227}}</ref> | |||
* ]—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.<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 |date=Aug 2009 |pmid=19377013 |url= |doi=10.1093/gerona/glp032 |pmc=2981461}}</ref> Vitamin D has also been shown to be necessary in the production of ] <ref>{{cite web | author=Thomas H. J. Burne, PhD | title= vitamin d and the brain |date=May 2013 | website= http://chemistry.beloit.edu/Ordman/nutrition/aln13/1305lpi.htm}}</ref> | |||
*]— has been shown to help reduce brain injury and also reduce the amount of ] in the body. High levels of Cortisol have been linked to ].<ref>{{cite web | author= Roc Ordman | title=AGE meeting June, 2012 |date=June 2012 | website=http://chemistry.beloit.edu/Ordman/nutrition/aldo/1206AGE.htm | |||
}}</ref>{{Medical citation needed|date=February 2014}} | |||
*]—protects neurons from injury caused by ].<ref>{{cite web | author= Roc Ordman | title=VITAMIN C MAY REDUCE STROKE (COMA and TRAUMATIC BRAIN INJURY) DAMAGE |date=October 2009 | website= http://chemistry.beloit.edu/Ordman/nutrition/stroke.htm}}</ref>{{Medical citation needed|date=February 2014}} | |||
* 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 ] and ] which is commonly call 'Goat weed'.<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 |date=September 2007 |pmid=17720341 |doi=10.1016/j.jep.2007.07.016 |url=}}</ref> | |||
===Stimulants=== | ===Stimulants=== | ||
] are often seen as ''smart drugs,'' but may be more accurately termed ''productivity enhancers.'' These typically improve concentration and a few areas of cognitive performance, but only while the drug is still in the blood at therapeutic concentrations. |
] are often seen as ''smart drugs,'' but may be more accurately termed ''productivity enhancers.'' These typically improve concentration and a few areas of cognitive performance, but only while the drug is still in the blood at therapeutic concentrations. | ||
* Anti-ADHD agents | |||
* ]s | |||
** ] pharmaceuticals (], ], and ] ]]) – ] agonists that mimic the effect of endogenous ].<ref name="Miller">{{cite journal | author = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = J. Neurochem. | volume = 116 | issue = 2 | pages = 164–176 |date=January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref> Benefits in ] and ] are evident in the general population, and especially in individuals with ADHD.<ref name="Malenka_2009">{{cite book| author = Malenka RC, Nestler EJ, Hyman SE | editor = Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | page = 318 | edition = 2nd | chapter = Chapter 13: Higher Cognitive Function and Behavioral Control | quote=Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in in normal subjects and those with ADHD. Positron emission tomography (PET) demonstrates that methylphenidate decreases regional cerebral blood flow in the doroslateral prefrontal cortex and posterior parietal cortex while improving performance of a spacial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. ... is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control ... stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors.}}</ref><ref name="cognition enhancers">{{cite journal | author = Bidwell LC, McClernon FJ, Kollins SH | title = Cognitive enhancers for the treatment of ADHD | journal = Pharmacol. Biochem. Behav. | volume = 99 | issue = 2 | pages = 262–274 |date=August 2011 | pmid = 21596055 | pmc = 3353150 | doi = 10.1016/j.pbb.2011.05.002 }}</ref> | |||
** ] (], ])—] agonist and consequently a ] | |||
** ] – a ] that improves working memory and cognitive control.<ref name="Malenka_2009" /><ref name="cognition enhancers" /> | |||
** ] (Vyvanse)—dextroamphetamine ] | |||
* ] – wakefulness promoting agents; increase alertness, particularly in ] individuals<ref name="Mod" /> | |||
* ]s | |||
** ]<ref name="Mod">{{cite journal | author = Mereu M, Bonci A, Newman AH, Tanda G | title = The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders | journal = Psychopharmacology (Berl.) | volume = 229 | issue = 3 | pages = 415–34 |date=October 2013 | pmid = 23934211 | doi = 10.1007/s00213-013-3232-4 | url = }}</ref> | |||
** ]—Non addictive stimulant. Once used in the treatment of ADHD and Burnout, but later discontinued. | |||
** ]<ref name="Mod" /> | |||
** ]—]; uncompetitive ]; clinically used in the treatment of ADHD | |||
* ] A meta-analysis of 41 ], ]-controlled studies concluded that ] or smoking had 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=] |volume=210 |issue=4 |pages=453–69 |date=June 2010 |accessdate=March 23, 2012 |pmid=20414766 |pmc=3151730 |doi=10.1007/s00213-010-1848-1}}</ref> | |||
** ]—Norepinephrine reuptake inhibitor; approved in Europe for ] but may also be used off-label to treat ADHD | |||
*] – most notably, ] – 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 = November 1, 2009| 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 = November 1, 2009 | doi = 10.1038/scientificamericanmind1007-58 | |||
** ]—endogenous ] found in significant concentrations in the ];agonist at ]s | |||
* ]s | |||
** ]—] and ] at muscarinic receptors M<sub>1-4</sub><ref>{{cite journal|last=Ghelardini|first=C|coauthors=Galeotti, N; Lelli, C; Bartolini, A|title=M1 receptor activation is a requirement for arecoline analgesia|journal=Farmaco (Societa chimica italiana : 1989)|date=2001 May-Jul|volume=56|issue=5–7|pages=383–5|pmid=11482763}}</ref><ref>{{cite journal|last=Yang|first=YR|coauthors=Chang, KC; Chen, CL; Chiu, TH|title=Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor|journal=The Chinese journal of physiology|date=March 31, 2000|volume=43|issue=1|pages=23–8|pmid=10857465}}</ref><ref>{{cite journal|last=Xie|first=DP|coauthors=Chen, LB; Liu, CY; Zhang, CL; Liu, KJ; Wang, PS|title=Arecoline excites the colonic smooth muscle motility via M3 receptor in rabbits|journal=The Chinese journal of physiology|date=June 30, 2004|volume=47|issue=2|pages=89–94|pmid=15481791}}</ref> | |||
** ] A meta-analysis of 41 ], ]-controlled studies concluded that ] or smoking had ] 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=] |volume=210 |issue=4 |pages=453–69 |date=June 2010 |accessdate=March 23, 2012 |pmid=20414766 |pmc=3151730 |doi=10.1007/s00213-010-1848-1}}</ref> | |||
* ] ("Wakefulness Enhancers")—unproven primary mechanisms but proven efficacy as a Nootropic | |||
** ] | |||
** ] | |||
** ] | |||
** ] | |||
** ]—Shown to be more effective than modafinil at producing wakefulness while being less addictive. | |||
* ]s—reduces ] perception via ] antagonism. | |||
** ]—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 = November 1, 2009| 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 = November 1, 2009 | doi = 10.1038/scientificamericanmind1007-58 | |||
}}</ref> | |||
** ] | |||
** ] | |||
** ]. | |||
===Concentration and memory enhancement=== | |||
The nootropics in this section are purported or shown to enhance concentration or the recollection and formation of memories. | |||
====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 ]: | |||
* Precursors | |||
** ]—precursor of acetylcholine and ] | |||
** ]—precursor of acetylcholine;{{Medial citation needed|Date=February 2014}} appears promising in treating ADHD, though results are inconclusive<ref>{{cite journal|last=Knobel|first=M|title=Approach to a combined pharmacologic therapy of childhood hyperkinesis|journal=Behavioral neuropsychiatry|date=1974 Apr-1975 Mar|volume=6|issue=1–12|pages=87–90|pmid=4619768}}</ref> | |||
** ]—probable precursor of acetylcholine, approved for ] and ] | |||
** ] | |||
* Cofactors | |||
** ]—amino acid that functions in acetylcholine production by donating the acetyl portion to the acetylcholine molecule | |||
** ]—cofactor in the conversion of choline into acetylcholine | |||
* ] inhibitors | |||
** ]—also allosterically modulates certain ] to facilitate acetylcholine release<ref>{{cite journal|last=Woodruff-Pak|first=DS|coauthors=Vogel RW, 3rd; Wenk, GL|title=Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning|journal=Proceedings of the National Academy of Sciences of the United States of America|date=February 13, 2001|volume=98|issue=4|pages=2089–94|pmid=11172080}}</ref> | |||
** ] (Neiromidin) is a reversible cholinesterase inhibitor used in memory disorders of different origins. | |||
** '']'' (Red Spider Lily)—natural source for ] | |||
** ]—also shown to act as an ] and appears to increase ] 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> | |||
** ] | |||
** ] | |||
** ] | |||
** '']'' | |||
** ] Due to its AChE-inhibiting properties, Cannabis appears to increase ] levels and therefore 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> ] and ] found in cannabis. Neuroprotectant, possible Alzheimer's prevention and possible ] 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=] |volume=115 |issue=11 |pages=3104–16 |date=November 1, 2005 |doi=10.1172/JCI25509 |pmc=1253627 |accessdate=March 2, 2011 |pmid=16224541}}</ref> ] is a constituent with neuroprotective properties. Possible neurotoxic effects of a notable constituent, ], have been documented<ref>{{cite journal|last=Rocchetti|first=M|coauthors=Crescini, A; Borgwardt, S; Caverzasi, E; Politi, P; Atakan, Z; Fusar-Poli, P|title=Is cannabis neurotoxic for the healthy brain? A meta-analytical review of structural brain alterations in non-psychotic users|journal=Psychiatry and clinical neurosciences|date=November 2013|volume=67|issue=7|pages=483–92|pmid=24118193}}</ref> | |||
* ] inhibitors and enhancers | |||
** ]— Increases high affinity choline uptake<ref>http://www.smarternootropics.com/coluracetam/</ref> | |||
** ]— Increases high affinity choline uptake | |||
** ]— Increases high affinity choline uptake<ref name=Spignoli /> | |||
** ]— Increases high affinity choline uptake<ref name=Spignoli>{{cite journal|last=Spignoli|first=G|coauthors=Pedata, F; Giovannelli, L; Banfi, S; Moroni, F; Pepeu, G|title=Effect of oxiracetam and piracetam on central cholinergic mechanisms and active-avoidance acquisition|journal=Clinical neuropharmacology|year=1986|volume=9 Suppl 3|pages=S39–47|pmid=3594455}}</ref> | |||
** ]— Increases high affinity choline uptake<ref>{{cite journal|last=Shih|first=YH|coauthors=Pugsley, TA|title=The effects of various cognition-enhancing drugs on in vitro rat hippocampal synaptosomal sodium dependent high affinity choline uptake|journal=Life sciences|date=June 3, 1985|volume=36|issue=22|pages=2145–52|pmid=2987637}}</ref> | |||
** ]— Increases high affinity choline uptake<ref>{{cite journal|last=Micheau|first=J|coauthors=Durkin, TP; Destrade, C; Rolland, Y; Jaffard, R|title=Chronic administration of sulbutiamine improves long term memory formation in mice: possible cholinergic mediation|journal=Pharmacology, biochemistry, and behavior|date=August 1985|volume=23|issue=2|pages=195–8|pmid=4059305}}</ref> | |||
** ] | |||
* Agonists | |||
** ] | |||
** ] | |||
** ] | |||
** ] | |||
** ] | |||
** ] | |||
** ] | |||
** ] | |||
** ] | |||
====GABA blockers==== | |||
The ] ] receptor site has recently displayed memory improvements when ]. | |||
*]—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 GABA inverse agonism.{{Medial citation needed|Date=February 2014}} | |||
*]—α5 partial inverse agonist | |||
*] has a direct effect on the GABA-B receptor-channel complex.<ref>http://pantogam.ru/preparaty/pantogam-tabletki-instrukcija</ref> | |||
====Glutamate modulators==== | |||
{{See also|AMPAkine}} | |||
Ligands and modulators of the ], an ], are being researched for a myriad of conditions, from Alzheimer's to ]. Although there are many AMPAkines being researched, those mentioned here show signs of entering the market in the near future. Other notable drugs with AMPA-modulating activity include ] and ]. | |||
* ]—pending FDA approval for memory-impairing illnesses and ADHD | |||
* ]—believed to improve memory by significantly enhancing ] but used only in animals; incredibly potent | |||
* ]—under development for Parkinson's but showing increase in ], specifically in areas of memory and higher cognitive skills | |||
====cAMP==== | |||
] is a ] that may improve certain aspects of memory if increased. Common research tools for this purpose include ], which prevents cAMP catabolism, and forskolin, a stimulator of adenylate cyclase. | |||
* ]—stimulates ]<ref>{{cite journal|last=Miyazaki|first=K|coauthors=Goldman, ME; Kebabian, JW|title=Forskolin stimulates adenylate cyclase activity, adenosine 3',5'-monophosphate production and peptide release from the intermediate lobe of the rat pituitary gland|journal=Endocrinology|date=March 1984|volume=114|issue=3|pages=761–6|pmid=6321138}}</ref> | |||
* ]—nonselective phosphodiesterase inhibitor with some ] | |||
* ]—PDE4 inhibitor, shows alertness enhancement, long term memory improvement and neuroprotection | |||
* ]—PDE4-inhibitor with possible serotonergic activity | |||
====Other==== | |||
] receptors are concentrated heavily in the ] and the ], 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> | |||
* ] is an α<sub>2A</sub> receptor agonist, FDA approved the treatment of ADHD.<ref> 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=June 24, 2007 |work=Medical News Today}}</ref> Guanfacine has been found 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 name="Springer-5206966">{{cite journal |url=http://link.springer.com/article/10.1007%2Fs00213-005-0078-4 |title=Lack of effects of guanfacine on executive and memory functions in healthy male volunteers |date=October 1, 2005 |publisher=Springer-Verlag |issn=0033-3158 |accessdate=March 24, 2014 |doi=10.1007/s00213-005-0078-4 |issue=2 |volume=182 |pages=205–213 |journal=Psychopharmacology |first1=Ulrich |last1=MüLler |first2=Luke |last2=Clark |first3=Minh L. |last3=Lam |first4=Rebecca M. |last4=Moore |first5=C. Louise |last5=Murphy |first6=Nicola K. |last6=Richmond |first7=Ranbir S. |last7=Sandhu |first8=Ingrid A. |last8=Wilkins |first9=David K. |last9=Menon |first10=Barbara J. |last10=Sahakian |first11=Trevor W. |last11=Robbins}}</ref> | |||
* ] is a potent ] drug that significantly increases ] with a currently unknown ] involving ] and ] activation.<ref>{{cite journal|coauthors=Nikolaus R. Hansl, Beverley T. Mead|title=PRL-8-53: Enhanced learning and subsequent retention in humans as a result of low oral doses of new psychotropic agent|journal=Psychopharmacology|year=1978|volume=56|issue=3|pages=249–253|doi=10.1007/BF00432846|pmid=418433|last1=Hansl|first1=NR}}</ref><ref>{{Cite pmid|4824605}}</ref> | |||
===Serotonergics=== | |||
] is a neurotransmitter with various effects on mood and possible effects on ]. ]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 ]: | |||
* Precursors | |||
** ]—precursor (intermediate between ] and serotonin) | |||
** ]—essential amino acid precursor; multiple neurotoxic metabolites<ref>{{cite journal|last=Smith|first=AJ|coauthors=Stone, TW; Smith, RA|title=Neurotoxicity of tryptophan metabolites|journal=Biochemical Society transactions|date=November 2007|volume=35|issue=Pt 5|pages=1287–9|pmid=17956331}}</ref> | |||
* Cofactors | |||
** ] (or PLP, pyridoxal-5'-phosphate, P5P, active form of ])—plays role in conversion of ] into serotonin (via the enzyme ]).<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 |date = Juy-August 2004 | 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 |date=Mar 1988 | doi = 10.1016/0091-3057(88)90020-2 | pmid = 3362950 }}</ref> | |||
* ] | |||
** ]s—class of antidepressants that increase active serotonin levels by inhibiting reuptake, also shown to promote Neurogenesis in the hippocampus | |||
** '']''—active constituent ] shown to act as an ]<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 |date=Oct 2008 | doi = 10.1016/j.jep.2008.08.010 | pmid = 18775771 }}</ref> and ]. (Half-life unknown) | |||
** '']''—inhibits reuptake of serotonin (as well as Norepinephrine, Dopamine, GABA and Glutamate) via activation of ] | |||
* ] | |||
** ]<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 |date=Jun 2006 | doi = 10.1016/j.bbrc.2006.03.190 | pmid = 16631124 }}</ref> | |||
** ]<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 |date=Jul 2005 | doi = 10.1016/j.ejphar.2005.06.002 | pmid = 15987635 }}</ref> | |||
** ]<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 |date=Jan 2010 | doi = 10.1016/j.bmcl.2009.11.106 | pmid = 19969454 }}</ref> | |||
** ]<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 |date=Mar 2010 | doi = 10.1016/j.fct.2009.12.019 | pmid = 20036304 }}</ref> One of the major constituents of harmal, harmaline, has demonstrated acetylcholinesterase inhibition. | |||
** '']''<ref name="Diermen2009"/> | |||
* 5-HT<sub>2A</sub> receptor agonists | |||
** ]—it has been reported that some these compounds causes nootropic, stimulant, or anti-anxiety effects at low doses. 2C-D, 2C-I, and 2C-C are examples. However, at hallucinogenic doses, these chemical compounds may be unpredictable. Research on these chemicals is sparse; they require further investigation. | |||
* Other | |||
** ]—atypical antidepressant with anxiolytic properties; a hypothesized mechanism of action revolves around modulation of ] and AMPA receptors, based on tianeptine's effect of promoting stress-associated impaired ];<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 increases the extracellular concentration of ] in the ]<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 |date=March 1992 |pmid=1630590 |doi=10.1016/0028-3908(92)90171-K}}</ref> and modulates the ] and ] 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=August 13, 2010}}</ref> but this effect is modest and almost certainly indirect.<ref name=mp09/> | |||
===Dopaminergics=== | |||
* Metabolic precursors—raise levels{{Medical citation needed|date=February 2014}} | |||
** ]—purported cognitive improvement{{citation needed|date=February 2014}} | |||
** ] (or N-Acetyl-L-Tyrosine, more bioavailable form)—purported cognitive improvement | |||
** ] (L-3,4-dihydroxyphenylalanine)—] to ]s (]); 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 |date=Dec 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. | last10 = Misu | first10 = Yoshimi | title = L-DOPA neurotoxicity is mediated by glutamate release in cultured rat striatal neurons | journal = Brain Res | volume = 771 | issue = 1 | pages = 159–62 |date=Oct 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 = ] | volume = 66 | issue = 9 | pages = 1787–95 |date=Nov 2003 | doi = 10.1016/S0006-2952(03)00421-0| pmid = 14563489 }}</ref> | |||
** ]—a ] (]) that is synthesized in the ]<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 |date=Sep 1981 | doi = 10.1126/science.6168019| pmid = 6168019 |bibcode = 1981Sci...213.1129K }}</ref> & crucial to the ] of dopamine | |||
** ] (or PLP, pyridoxal-5'-phosphate, P5P, active form of ])—cofactor for ], the enzyme that decarboxylases L-DOPA, producing dopamine. | |||
* Reuptake inhibitors—stabilize/improve levels{{Medical citation needed|date=February 2014}} | |||
** ]—mild stimulant | |||
** ]—stimulant approved for ADHD; potent ] and ] agonist<ref>{{cite journal|last=Zhang|first=CL|coauthors=Feng, ZJ; Liu, Y; Ji, XH; Peng, JY; Zhang, XH; Zhen, XC; Li, BM|title=Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action|journal=PloS one|year=2012|volume=7|issue=12|pages=e51910|pmid=23284812}}</ref> | |||
** ]—atypical antidepressant; weak ]<ref>{{cite journal|last=Stahl|first=SM|coauthors=Pradko, JF; Haight, BR; Modell, JG; Rockett, CB; Learned-Coughlin, S|title=A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor|journal=Primary care companion to the Journal of clinical psychiatry|year=2004|volume=6|issue=4|pages=159–166|pmid=15361919}}</ref> and ]<ref>{{cite journal|last=Slemmer|first=JE|coauthors=Martin, BR; Damaj, MI|title=Bupropion is a nicotinic antagonist|journal=The Journal of pharmacology and experimental therapeutics|date=October 2000|volume=295|issue=1|pages=321–7|pmid=10991997}}</ref> | |||
* ]—prevent some catabolism of dopamine and ] | |||
** ]—irreversible; amphetamine metabolites<ref>{{cite journal|last=Romberg|first=RW|coauthors=Needleman, SB; Snyder, JJ; Greedan, A|title=Methamphetamine and amphetamine derived from the metabolism of selegiline|journal=Journal of forensic sciences|date=November 1995|volume=40|issue=6|pages=1100–2|pmid=8522918}}</ref> | |||
** ]—irreversible | |||
** '']''—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 |date=Mar 2009 | doi = 10.1016/j.jep.2009.01.007 | pmid = 19168123 }}</ref> | |||
* ] | |||
** ]—agonist at D<sub>2</sub>, D<sub>3</sub>, and D<sub>4</sub> receptors | |||
** ]—agonist at D<sub>2</sub>, D<sub>3</sub>, and D<sub>4</sub> receptors | |||
** ] —] with higher affinity for the presynaptic ] than postsynaptic, facilitating dopaminergic transmission in lower doses.<ref>{{cite web|title=PRODUCT INFORMATION SOLIAN® TABLETS and SOLUTION|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf|work=Sanofi-Aventis Australia Pty Ltd|publisher=TGA eBusiness Services|accessdate=February 20, 2014}}</ref> | |||
* Others | |||
** ] (Velvet Bean)—natural source of L-DOPA | |||
** ]—purported dopaminergic activity that exhibits the criteria of a Nootropic | |||
** ] (]) (aka: ]-choline (CDP-Choline) & cytidine 5'-diphosphocholine)—studies suggest CDP-choline supplements partially prevent the loss of dopamine D<sub>2</sub> receptors in aged mice,<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 |date=November 1991 |pmid=1839138 |pmc=1908237}}</ref> and that CDP-choline supplementation ameliorates memory impairment caused by environmental conditions (in rats).<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 may have potential in the treatment of attention deficit-hyperactivity disorder.<ref>{{cite news |url=http://www.smh.com.au/articles/2008/02/24/1203788130776.html |title=Supplement naturally boosts ageing brain power |date=February 25, 2008 |work=] |accessdate=July 28, 2009}}</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 |date=November 2008 |pmid=18816480 |doi=10.1002/nbm.1281}}</ref> | |||
===Sleep=== | |||
] is known to be important in memory consolidation, mood, anxiety, appetite, and numerous other physiological processes. Drugs that improve sleep may therefore have an indirect nootropic effect. | |||
{{See also|REM sleep#Theories about the functions of REM sleep|l1=Theories about the functions of REM sleep}} | |||
* ]—antioxidant.<ref>{{cite journal|last=Hardeland|first=R|title=Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance|journal=Endocrine|date=July 2005|volume=27|issue=2|pages=119–30|pmid=16217125}}</ref><ref>{{cite journal|last=Reiter|first=RJ|coauthors=Acuña-Castroviejo, D; Tan, DX; Burkhardt, S|title=Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system|journal=Annals of the New York Academy of Sciences|date=June 2001|volume=939|pages=200–15|pmid=11462772}}</ref> Exogenous melatonin protects against ] cell loss in ovariectomized rats.<ref>{{cite journal|last=Mehraein|first=F|coauthors=Talebi, R; Jameie, B; Joghataie, MT; Madjd, Z|title=Neuroprotective effect of exogenous melatonin on dopaminergic neurons of the substantia nigra in ovariectomized rats|journal=Iranian biomedical journal|year=2011|volume=15|issue=1–2|pages=44–50|pmid=21725499}}</ref> May normalize circadian rhythms in humans<ref>{{cite journal|last=Kunz|first=D|coauthors=Mahlberg, R; Müller, C; Tilmann, A; Bes, F|title=Melatonin in patients with reduced REM sleep duration: two randomized controlled trials|journal=The Journal of clinical endocrinology and metabolism|date=January 2004|volume=89|issue=1|pages=128–34|pmid=14715839}}</ref> | |||
* ]— ] receptor agonist and ] neutral antagonist<ref>{{cite journal|last=Popoli|first=M|title=Agomelatine: innovative pharmacological approach in depression|journal=CNS drugs|year=2009|volume=23 Suppl 2|pages=27–34|pmid=19708723}}</ref> | |||
===Anti-depression, adaptogenic (anti-stress), and mood stabilization=== | |||
] (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 |date=May 1994 |pmid=8182446}}</ref> Many studies show that stress and fatigue negatively impact cognitive functioning in young adults.<ref name="PALMER, L. K. 2013">PALMER, L. K. (2013). The Relationship between Stress, Fatigue, and Cognitive Functioning. College Student Journal, 47(2), 312-325.</ref><ref name="Singh, Y 2012">Singh, Y, Ratna, A (2012). "Immediate and Long-term Effects of Meditation on Acute Stress Reactivity, Cognitive Functions, and Intelligence." Alternative Therapies in Health & Medicine 18, no. 6: 46-53.</ref> Some level of stress in the learning environment may aid the ability to focus and retain information. However, stress levels, especially high, sustained or traumatic stressors, hinder declarative memory, spatial reasoning, learning, attention and working memory. Fatigue is also a stressor that impedes attention, processing, retrieval, working memory and short term memory.<ref name="PALMER, L. K. 2013"/> The effects of stress on cognitive performance seem to be controlled by the sympatho-adrenal system and the hypothalamic-hypophysial-adrenal axis.<ref name="Singh, Y 2012"/> | |||
Depression and ] negatively affect cognitive performance and memory.<ref name="Howe, M. L. 2011">Howe, M. L., & Malone, C. (2011). Mood-congruent true and false memory: Effects of depression. Memory, 19(2), 192-201. {{DOI|10.1080/09658211.2010.544073}}</ref> Depression was found to increase false memory, especially with negative words or subjects.<ref name="Howe, M. L. 2011"/> | |||
It is reasoned that counteracting and preventing depression and ] may be an effective nootropic strategy.<ref name="PALMER, L. K. 2013"/><ref name="Singh, Y 2012"/> Proper nutrition, adequate sleep, and mechanisms for coping with stress, such as meditation, have been shown to improve learning and cognitive functioning both in the short and long term.<ref name="PALMER, L. K. 2013"/><ref name="Singh, Y 2012"/> | |||
The term ] applies to most herbal anti-stress claims.{{Citation needed|date=February 2011}} | |||
The substances below may not have been mentioned earlier on the page: | |||
* ]—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 |date=January 1992 |pmid=1348368 |doi=10.1016/0278-5846(92)90004-X}}</ref> | |||
* ]<span class="">—</span>relaxation; found in ]; increases nicotinic acetylcholine and reduces nicotinic dopamine {{Citation needed|date=February 2014}} | |||
* ]—displays adaptogen properties; in rats it has been shown to possess ] 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 |date=September 2007 |pmid=18066140 |doi=10.1139/Y07-083}}</ref> and in homogenates of human cerebral cortical cell membranes possesses activity at ].<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 |date=February 2000 |pmid=10687867 |doi=10.1016/S0378-8741(99)00113-0}}</ref> In a randomized, double-blind, placebo-controlled study of 18 healthy volunteers, 600 mg of ']' extract attenuated volunteers' response to a laboratory-induced stress test 1 hour after administration; 300 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 |date=Jul–Aug 2004 |pmid=15272110 |doi=10.1097/01.psy.0000132877.72833.71}}</ref> | |||
* ]—possible ] and neurotransmitter reuptake activity {{Citation needed|date=February 2011}} | |||
* ]—adaptogen; possible MAOI activity<ref>Panossian A., Wikman G."Evidence based efficacy of adaptogens in fatigue" '']'' 2009; 75:9</ref> | |||
* ]—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> | |||
* ] (including ])—adaptogenic effects shown{{Citation needed|date=February 2011}} | |||
* ]—possible anti-inflammatory, reducing pain from those illnesses {{Citation needed|date=February 2011}} | |||
* ]—anxiolytic herb{{Citation needed|date=February 2011}} | |||
* ]—has shown some efficacy in reducing bodily stress{{Citation needed|date=February 2011}} | |||
* ]—possible anxiolytic effect{{Citation needed|date=February 2011}} | |||
* ] GABA receptor agonist excerting anxiolytic effects | |||
* ] GABA prodrug which excerts anxiolytic effects by releasing GABA and niacin in the CNS. | |||
* ]—possible anxiolytic effect through agonism at ] receptors{{Citation needed|date=February 2011}} | |||
* ]—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 |date=September 2004 |pmid=15388278 |doi=10.1016/j.pbb.2004.05.022}}</ref> | |||
* ]—adaptogen and anxiolytic {{Citation needed|date=February 2011}} | |||
* ]—adaptogen; possible MAOI activity {{Citation needed|date=February 2011}} | |||
* ]—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 |date=Jan 2011 |pmid=22211188 |doi=10.3945/an.110.000117}}</ref> | |||
* Many Chinese herbs such as ], ] and ].<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 | |||
|date=August 2011 | |||
| pmid = 21305632 | |||
}}</ref> | |||
* ]<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 | |||
|date=July 2010 | |||
| pmid = 20590480 | |||
}}</ref> | |||
* ] (], 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 | |||
|date=October–December 2009 | |||
| pmid = 20509321 | |||
| url = http://www.ijpp.com/vol53_4/291-306.pdf | |||
}}</ref> | }}</ref> | ||
* ](]) Lifts mood and promotes a peaceful mindset. Anti-anxiety. | |||
* ] Anti-anxiety that lifts mood and increases sociability. Although it doesn't have the side effects or toxic metabolites that ethanol has, frequent use may cause dependence.{{Citation needed|date=February 2014}} | |||
===Miscellaneous=== | |||
===Blood flow and metabolic function=== | |||
* ] and ] – ]s with neuroprotective properties, especially for those with ].<ref name="Neuroprotection review">{{cite journal | author = Naoi M, Maruyama W, Inaba-Hasegawa K | title = Revelation in the neuroprotective functions of rasagiline and selegiline: the induction of distinct genes by different mechanisms | journal = Expert Rev Neurother | volume = 13 | issue = 6 | pages = 671–84 |date=June 2013 | pmid = 23739004 | doi = 10.1586/ern.13.60 | url = }}</ref> | |||
Brain function is dependent on many basic processes such as the usage of ], 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. | |||
* ] – Tianeptine prevents stress-induced dendritic remodeling in various brain structures, enhances several metrics of cognition in animal models, and antagonizes alcohol's neurodegenerative effects.<ref name="pmid19704408">{{cite journal | author = McEwen BS, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, Fuchs E | title = The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation | journal = Mol. Psychiatry | volume = 15 | issue = 3 | pages = 237–49 |date=March 2010 | pmid = 19704408 | pmc = 2902200 | doi = 10.1038/mp.2009.80 | quote = Cognitive deficits, such as an impairment of attention, memory and problem solving, have often been reported in patients with depressive disorders (69). Cognitive deficits and memory impairments in patients with depression may arise via disruption of the hypothalamic-pituitary adrenal (HPA) axis through hippocampal volume loss and changes in the amygdala. The magnitude of the hippocampal shrinkage reported in certain experimental conditions may partly underlie some of cognitive deficits that accompany major depression. Conversely, any prevention or restoration of these morphological changes in the hippocampus should be parallel to procognitive/promnesiant effects. Accordingly, tianeptine has particularly favorable effects on cognitive functions and the positive effect of tianeptine may be mediated through its upregulation of neurogenesis, but of course, the impact of neurogenesis on cognitive functions remains a matter of controversial debate.<br /><br />Tianeptine prevents and reverses stress-induced glucocorticoid-mediated dendritic remodeling in CA3 pyramidal neurons in the hippocampus (40,41) and stress-induced increases in dendritic length and branching in the amygdala (50). Tianeptine blocks the dendritic remodeling caused by stress or glucocorticoids (41), blocks stress-induced impairments of spatial memory performance in radial and Y-maze (70,71) and antagonizes the deleterious effects of alcohol (72).<br /><br />In a validated model of hippocampal-dependent memory impairment and synaptic plasticity changes by predator stress, acute tianeptine can prevent the deleterious effects of stress on spatial memory, an effect that does not depend on corticosterone levels (73). Tianeptine also facilitates focused attention behavior in the cat in response to its environment or towards a significant stimulus (74). It was shown to exert improving effects on learning as well as on working memory and on reference memory in rodents (72) and to exhibit vigilance-enhancing effects in rats (75) and monkeys (76)...}}</ref> | |||
* ] – ] | |||
===Nutraceuticals=== | |||
* ] may improve the ability of learning and memory, as the drug changes the expression of hippocampal proteins related to synaptic plasticity | |||
* ] – A neutraceutical herb with "neural tonic" and memory enhancing properties shown in humans in a double-blinded ]s.<ref name="Bacopa Review">{{cite journal |url=http://www.ncbi.nlm.nih.gov/pubmed/23772955 |title=Neuropharmacological review of the nootropic herb Bacopa monnieri. |date=Aug 2013 |accessdate=March 27, 2014 |doi=10.1089/rej.2013.1431 |issue=4 |volume=16 |pmid=23772955 |pmc=3746283 |pages=313–26 |journal=Rejuvenation Research |first1=Sebastian |last1=Aguiar |first2=Thomas |last2=Borowski}}</ref><ref name="PubMed-22747190">{{cite journal |url=http://www.ncbi.nlm.nih.gov/pubmed/22747190 |title=The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials |date=July 2012 |accessdate=March 27, 2014 |doi=10.1089/acm.2011.0367 |issue=7 |volume=18 |pmid=22747190 |pmc= |pages=647–52 |journal=The Journal of Alternative and Complementary Medicine |first1=Matthew P. |last1=Pase |first2=James |last2=Kean |first3=Jerome |last3=Sarris |first4=Chris |last4=Neale |first5=Andrew B. |last5=Scholey |first6=Con |last6=Stough}}</ref><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 |date=July 2010 | pmid = 20590480 }}</ref> | |||
* ]—increases blood circulation, improving memory {{Citation needed|date=February 2012}} | |||
* ] – Multiple RCTs in healthy volunteers have indicated 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 name="Neutraceuticals Review">{{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 |date=Jan 2011 |pmid=22211188 |doi=10.3945/an.110.000117}}</ref> | |||
* ]—antioxidant; increases oxygen usage by mitochondria | |||
* ] – A ] of 29 RCTs stated "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> | |||
* ]—protects ATP during transport | |||
* ]<ref name="Neutraceuticals Review" /> | |||
* ]—improves oxygen usage and antioxidant recycling, possibly improving memory | |||
* ]<ref name="Neutraceuticals Review" /> | |||
* ]—Drug similar to B vitamin Pyridoxine | |||
* ]<ref name="Neutraceuticals Review" /> | |||
* ]—GABA activity and blood flow improver | |||
* ]<ref name="Neutraceuticals Review" /> | |||
* ]—vasodilator. Acts as an ].<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 |date=Jul 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 mg dose.<ref>{{Cite journal|author=Hindmarch I |title=. |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 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.<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> | |||
* ]<ref name="Neutraceuticals Review" /> | |||
* ]— 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= |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 ] 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—however, through a similar mechanism to ], Vinpocetine may temporarily deplete the monoamines serotonin, dopamine and ] by inhibiting ], 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 |date=Aug 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 ] and ].<ref name="Jeon"> | |||
* ] – Anti-inflammatory, antibiotic, and neuroprotective antidepressant compound which has extremely low toxicity.<ref name="Neutraceuticals Review" /> | |||
{{cite journal |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906898/ |title=Vinpocetine inhibits NF-κB–dependent inflammation via an IKK-dependent but PDE-independent mechanism |date=May 6, 2010 |publisher=National Academy of Sciences |accessdate=March 24, 2014 |doi=10.1073/pnas.0914414107 |issue=21 |volume=107 |pmid=20448200 |pmc=2906898 |bibcode = 2010PNAS..107.9795J |pages=9795–800 |journal=Proceedings of the National Academy of Sciences of the United States of America |first1=Kye-Im |last1=Jeon |first2=Xiangbin |last2=Xu |first3=Toru |last3=Aizawa |first4=Jae Hyang |last4=Lim |first5=Hirofumi |last5=Jono |first6=Dong-Seok |last6=Kwon |first7=Jun-Ichi |last7=Abe |first8=Bradford C. |last8=Berk |first9=Jian-Dong |last9=Li |first10=Chen |last10=Yan}}</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|bibcode = 2010PNAS..107.9921M }}</ref> | |||
* ]s – A double-blind, placebo-controlled study showed improvement in spatial working memory after administration of isoflavones.<ref name="PubMed-9071926">{{cite journal |url=http://www.ncbi.nlm.nih.gov/pubmed/19480732 |title=Soya isoflavone supplementation enhances spatial working memory in men. |date=Nov 2009 |publisher=] |accessdate=March 24, 2014 |doi=10.1017/S0007114509990201 |pmid=19480732 |issue=9 |volume=102 |pages=1348–54 |journal=Br J Nutr |first1=Aa |last1=Thorp |first2=N |last2=Sinn |first3=Jd |last3=Buckley |first4=Am |last4=Coates |first5=Pr |last5=Howe}}</ref> One RCT showed soy isoflavone supplementation improved performance on 6 of 11 cognitive tests, including visual-spatial memory and construction, verbal fluency and speeded dexterity, but worse on two 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 |date=January 2009 |pmid=19054783 |pmc=2720778 |doi=10.1093/ageing/afn227}}</ref> | |||
* ]—increases blood circulation (vasodilator) and metabolism in the brain; related to vinpocetine; used in sustained release. | |||
* ] – Stimulated ] 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 ] in an ''in vitro'' experiment with human ] 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 |date=September 2008 |pmid=18758067 |doi= 10.1248/bpb.31.1727|url=}}</ref>{{npsn|date=May 2014}} 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 |date=March 2009 |pmid=18844328 |doi=10.1002/ptr.2634}}</ref>{{npsn|date=May 2014}} | |||
* ]—an ] derivative used to treat senile dementia and other disorders with ] origins; it has been found to increase mental agility and enhance clarity and perception; it decreases ] 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> | |||
===Racetams=== | |||
===Experimental histamine antagonists=== | |||
The '''H<sub>3</sub>-receptor''' decreases neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin. Thus, '''H<sub>3</sub>-receptor-antagonists''' increases cognition, vigilance, and wakefulness. | |||
* ]—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 |date=June 2008 | pmid = 18305012 | doi = 10.1124/jpet.107.135343 | url = | issn = }}</ref> | |||
* ]—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> | |||
* ] – 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 ] 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. ] may prevent ] and cell death, therefore exerting a neuroprotective effect. | |||
* ]—antioxidant {{Citation needed|date=February 2011}} | |||
* ]—chief ] {{Citation needed|date=February 2011}} | |||
* ]—antioxidant <ref>Ohsawa, Toshiko. "Sesamol and sesaminol as antioxidants." New Food Industry (1991), 33(6), 1-5.</ref> | |||
* ] (Acetyl-] ] or ]) {{Citation needed|date=February 2011}} | |||
* ]—implicated in memory function, deficit linked to some ]es—has been shown particularly efficacious in ] patients | |||
* ]s—inhibit seizure related brain malfunction if a person has seizures {{Citation needed|date=February 2011}} | |||
* ]—possible membrane stabilizer {{Citation needed|date=February 2011}} | |||
* ]—Stimulated ] 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 ] in an ''in vitro'' experiment with human ] 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 |date=September 2008 |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 |date=March 2009 |pmid=18844328 |doi=10.1002/ptr.2634}}</ref> | |||
* ] (S-Adenosyl methionine)—crucial for cellular regeneration (fuels ]<ref></ref>), also involved with the biosynthesis of dopamine & serotonin<ref>{{Cite journal | |||
| 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 | |||
|date=November 2002 | |||
| pmid = 12420702 | |||
| url = http://www.ajcn.org/content/76/5/1158S.full.pdf | |||
}}</ref> | |||
* ] (])—precursor to antioxidant ]<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> | |||
* ] (Cat's Claw)—in an ''in vitro'' experiment with rats, it inhibited formation of brain ] deposits,<ref>{{Cite journal |url=http://www.jfponline.com/Pages.asp?AID=518#8 |volume=1 |issue=6 |date=June 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 .}}, 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 associated with Alzheimer's disease. | |||
* (] and ])—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> | |||
===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. | |||
* ]—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 |date=Jan–Feb 1987 |pmid=2952619}}</ref> | |||
* ]—increases neurogenesis{{Medical citation needed|date=February 2014}} | |||
* ] or Hypocretin—significant wakefulness promoter | |||
* ]—precursor to ] and ] | |||
===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: | |||
* '' ] (Yuan Zhi)''— A randomized, ], ]-controlled, parallel-group study of the extract of dried roots of ''Polygala tenuifolia'' in healthy adults produced memory-enhancing effects.<ref name=lee,etal>{{cite journal | author=Lee J.-Y., Kim K.Y., Shin K.Y., Won B.Y., Jung H.Y., Suh Y.H. | title=Effects of BT-11 on memory in healthy humans |journal=] |year=2009 |volume=454 |issue=2 |pages=111–114 |doi=10.1016/j.neulet.2009.03.024 |pmid=19429065}}</ref> A similar trial with elderly humans also found significant cognitive improvement.<ref name=shin,etal>{{cite journal | author = Shin K.Y., Lee J.-Y., Won B.Y., Jung H.Y., Chang K.-A., Koppula S., Suh Y.-H. |title = BT-11 is effective for enhancing cognitive functions in the elderly humans |journal=Neuroscience Letters |year=2009 |volume=465 |issue=2 |pages=157–159 |doi = 10.1016/j.neulet.2009.08.033}}</ref> | |||
* ''] (Brahmi) ''— 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=September 1, 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 |date=March 2006 |pmid=16550227 |pmc=1375237 |doi=10.1093/ecam/nek014 |url=http://ecam.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16550227}}</ref> | |||
* ''] (Shankhpushpi) ''— In traditional Ayurvedic medicine, it has been used for centuries as a memory enhancer, nootropic, antistress, anxiolytic, antidepressant, anticonvulsant, tranquilizing and sedative agent. | |||
* ]—drug for ] | |||
* ]—allegedly a mild serotonergic, nootropic, antistress, anxiolytic, and allegedly has mild to moderate memory enhancing effects. | |||
* ]—famous alleged ] mixture, most effects disproven but some mind enhancement shown | |||
* ]—fat soluble vitamin B<sub>1</sub> derivative—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=195–8|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=928–35 | volume=29 | issue=6 | pmid=15951087 | doi=10.1016/j.pnpbp.2005.04.035}}</ref> | |||
* ]—Increases brain cell growth and diversity, only demonstrated ], improbable ] (it has been reported to stimulate the growth of ]<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 | |||
|date=April 2005 | |||
| pmid = 15849420 | |||
| url = http://journals2005.pasteur.ac.ir/BBB/69%284%29/800-805.pdf | doi=10.1271/bbb.69.800 | |||
}}</ref> and ] in the ].<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 | |||
|date=October 2007 | |||
| pmid = 18000339 | |||
}}</ref>) | |||
* ]—significant in-vitro activity, but in-vivo activity limited by low ] unless accompanied by ingestion of piperine | |||
The ] are structurally similar compounds, such as ], ], ], and ], which are often marketed as cognitive enhancers and sold ]. Racetams are often referred to as nootropics, but this property of the drug class is not well established.<ref name="NHM">{{cite book | author = Malenka RC, Nestler EJ, Hyman SE | editor = Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | page = 454 | edition = 2nd }}</ref> The racetams have a poorly understood ]; however, piracetam and aniracetam are known to act as ]s of ]s and appear to modulate ] 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> | |||
===Other nootropics=== | |||
Other substances sometimes classified as nootropics include ], ], ],<ref name=BetterBrain/> ], ], ], ] and ]. | |||
==See also== | ==See also== | ||
{{multicol begin}} | |||
* ] | * ] | ||
* ] | |||
* ] | * ] | ||
{{multicol break}} | |||
* ] | |||
* ] | * ] | ||
* ] | |||
{{multicol break}} | |||
* ] | * ] | ||
* ] | * ] | ||
{{multicol end}} | |||
==References== | ==References== | ||
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==External links== | ==External links== | ||
* {{cite journal |url=http://www.nature.com/nature/journal/v456/n7223/full/456702a.html |title=Towards responsible use of cognitive-enhancing drugs by the healthy |work=] |date=December 10, 2008 |publisher=] |issn=1476-4687 |oclc=01586310 |bibcode = 2008Natur.456..702G |accessdate=March 25, 2014 |doi=10.1038/456702a |pages=702–5 |volume=456 |issue=7223 |subscription=yes |first1=Henry |last1=Greely |first2=Barbara |last2=Sahakian |first3=John |last3=Harris |first4=Ronald C. |last4=Kessler |first5=Michael |last5=Gazzaniga |first6=Philip |last6=Campbell |first7=Martha J. |last7=Farah}} | |||
* (''The Guardian'': February 23, 2010) | |||
* {{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 |date=December 2008 |pmid=19060880 |doi=10.1038/456702a |url=http://www.nature.com/nature/journal/vaop/ncurrent/full/456702a.html |bibcode = 2008Natur.456..702G }} | |||
* (''The New Yorker'': April 27, 2009) | |||
* September 1, 2003 at ] | |||
* at ] | |||
* | |||
{{Psychostimulants, agents used for ADHD and nootropics}} | {{Psychostimulants, agents used for ADHD and nootropics}} |
Revision as of 06:31, 13 July 2014
Nootropics (/noʊ.əˈtrɒpks/ noh-ə-TROP-iks), also referred to as smart drugs, memory enhancers, neuro enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that purportedly improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration. The word nootropic was coined in 1972 by the Romanian Dr. Corneliu E. Giurgea, derived from the Greek words νους nous, or "mind," and τρέπειν trepein meaning "to bend/turn". Nootropics are thought to work by altering the availability of the brain's supply of neurochemicals (neurotransmitters, enzymes, and hormones), by improving the brain's oxygen supply, or by stimulating nerve growth.
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. The most commonly used class of drug is stimulants.
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. 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 the beneficial effects of some compounds, the marketing claims by manufacturers of over-the-counter products are not formally tested.
Academic doping
Main article: Academic dopingIn academia, modafinil has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals. Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups. One survey found that 7% of students had used stimulants for a cognitive edge, and on some campuses use in the past year is as high as 25%. The use of prescription stimulants is especially prevalent among students attending academically competitive colleges and students who are members of a fraternity or sorority.
Surveys suggest that 3–11% of American students and 0.7–4.5% of German students have used cognitive enhancers in their lifetime.
Several factors positively and negatively influence the use of drugs to increase cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.
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. While certain racetam compounds are suspected to have nootropic qualities, few side-effects, and a wide therapeutic window (low overdose risk), other cognitive enhancers may be associated with a high incidence of adverse effects or a narrower therapeutic window (higher overdose risk). While addiction to stimulants is sometimes asserted to be a cause for concern, a very large body of research on the therapeutic use of the "more addictive" psychostimulants indicate that addiction is fairly rare in therapeutic doses.
In the United States, unapproved drugs or dietary supplements do not require safety or efficacy approval before being sold.
Drugs
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. A 2008 systematic review of trials found "little evidence of a beneficial impact" from supplements on cognitive function later in life.
- Phosphatidylserine (a phospholipid) with DHA and EPA (omega-3 fatty acids) – concurrent supplemental use can protect and potentially improve brain function. DHA and EPA are compounds that support brain function and neurogenesis, especially during brain development. A review of literature and a more recent randomized controlled trial on supplemental phosphatidylserine with DHA and EPA indicate that there are clinical benefits for those with ADHD, in addition to a range of other clinical applications. However, Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids alone (without phosphatidylserine) indicate that there is limited evidence of treatment benefits for individuals with ADHD or other learning disorders. A Norwegian study demonstrated a potential link between Omega-3 consumption during pregnancy and child intelligence test scores.
- 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 50 nmol/L) are associated with better cognitive function, but do not seem to be associated with better memory performance. Vitamin D has also been shown to be necessary in the production of dopamine.
Stimulants
Stimulants are often seen as smart drugs, but may be more accurately termed productivity enhancers. These typically improve concentration and a few areas of cognitive performance, but only while the drug is still in the blood at therapeutic concentrations.
- Anti-ADHD agents
- Amphetamine pharmaceuticals (Adderall, dextroamphetamine, and lisdexamfetamine ) – TAAR1 agonists that mimic the effect of endogenous phenethylamine. Benefits in cognitive control and working memory are evident in the general population, and especially in individuals with ADHD.
- Methylphenidate – a substituted phenethylamine that improves working memory and cognitive control.
- Eugeroics – wakefulness promoting agents; increase alertness, particularly in sleep deprived individuals
- Nicotine A meta-analysis of 41 double-blind, placebo-controlled studies concluded that nicotine or smoking had 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.
- Xanthines – most notably, Caffeine – shown to increase alertness, performance, and in some studies, memory. Children and adults who consume low doses of caffeine showed increase alertness, yet a higher dose was needed to improve performance.
Miscellaneous
- Selegiline and rasagiline – Monoamine oxidase B inhibitors with neuroprotective properties, especially for those with Parkinson's disease.
- Tianeptine – Tianeptine prevents stress-induced dendritic remodeling in various brain structures, enhances several metrics of cognition in animal models, and antagonizes alcohol's neurodegenerative effects.
- Bupropion – Substituted cathinone
Nutraceuticals
- Bacopa monnieri – A neutraceutical herb with "neural tonic" and memory enhancing properties shown in humans in a double-blinded RCTs.
- Panax ginseng – Multiple RCTs in healthy volunteers have indicated 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.
- Ginkgo Biloba – A meta-analysis of 29 RCTs stated "there is consistent evidence that chronic administration improves selective attention, some executive processes and long-term memory for verbal and non-verbal material."
- Melissa officinalis
- Sage
- Valerian
- Curcumin
- Epigallocatechin gallate
- St John's Wort – Anti-inflammatory, antibiotic, and neuroprotective antidepressant compound which has extremely low toxicity.
- Isoflavones – A double-blind, placebo-controlled study showed improvement in spatial working memory after administration of isoflavones. One RCT showed soy isoflavone supplementation improved performance on 6 of 11 cognitive tests, including visual-spatial memory and construction, verbal fluency and speeded dexterity, but worse on two tests of executive function.
- Lion's Mane Mushroom – Stimulated myelination in an in vitro experiment and stimulated nerve growth factor in an in vitro experiment with human astrocytoma cells. Also improved cognitive ability, in a double-blind, parallel-group, placebo-controlled trial.
Racetams
The racetams are structurally similar compounds, such as pramiracetam, oxiracetam, coluracetam, and aniracetam, which are often marketed as cognitive enhancers and sold over-the-counter. Racetams are often referred to as nootropics, but this property of the drug class is not well established. The racetams have a poorly understood mechanisms of action; however, piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.
See also
References
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Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in in normal subjects and those with ADHD. Positron emission tomography (PET) demonstrates that methylphenidate decreases regional cerebral blood flow in the doroslateral prefrontal cortex and posterior parietal cortex while improving performance of a spacial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. ... is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control ... stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors.
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Cognitive deficits, such as an impairment of attention, memory and problem solving, have often been reported in patients with depressive disorders (69). Cognitive deficits and memory impairments in patients with depression may arise via disruption of the hypothalamic-pituitary adrenal (HPA) axis through hippocampal volume loss and changes in the amygdala. The magnitude of the hippocampal shrinkage reported in certain experimental conditions may partly underlie some of cognitive deficits that accompany major depression. Conversely, any prevention or restoration of these morphological changes in the hippocampus should be parallel to procognitive/promnesiant effects. Accordingly, tianeptine has particularly favorable effects on cognitive functions and the positive effect of tianeptine may be mediated through its upregulation of neurogenesis, but of course, the impact of neurogenesis on cognitive functions remains a matter of controversial debate.
Tianeptine prevents and reverses stress-induced glucocorticoid-mediated dendritic remodeling in CA3 pyramidal neurons in the hippocampus (40,41) and stress-induced increases in dendritic length and branching in the amygdala (50). Tianeptine blocks the dendritic remodeling caused by stress or glucocorticoids (41), blocks stress-induced impairments of spatial memory performance in radial and Y-maze (70,71) and antagonizes the deleterious effects of alcohol (72).
In a validated model of hippocampal-dependent memory impairment and synaptic plasticity changes by predator stress, acute tianeptine can prevent the deleterious effects of stress on spatial memory, an effect that does not depend on corticosterone levels (73). Tianeptine also facilitates focused attention behavior in the cat in response to its environment or towards a significant stimulus (74). It was shown to exert improving effects on learning as well as on working memory and on reference memory in rodents (72) and to exhibit vigilance-enhancing effects in rats (75) and monkeys (76)...{{cite journal}}
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{{cite book}}
: CS1 maint: multiple names: authors list (link) - Gualtieri F, Manetti D, Romanelli MN, Ghelardini C (2002). "Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs". Curr. Pharm. Des. 8 (2): 125–38. doi:10.2174/1381612023396582. PMID 11812254.
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External links
- Greely, Henry; Sahakian, Barbara; Harris, John; Kessler, Ronald C.; Gazzaniga, Michael; Campbell, Philip; Farah, Martha J. (December 10, 2008). "Towards responsible use of cognitive-enhancing drugs by the healthy". Nature. 456 (7223). Nature Publishing Group: 702–5. Bibcode:2008Natur.456..702G. doi:10.1038/456702a. ISSN 1476-4687. OCLC 01586310. Retrieved March 25, 2014.
{{cite journal}}
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Psychostimulants, agents used for ADHD, and nootropics (N06B) | |||||||||
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N06BA Centrally acting sympathomimetics | |||||||||
N06BC Xanthine derivatives | |||||||||
N06BX Other psychostimulants and nootropics | |||||||||
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