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'''Nootropics''' ({{IPAc-en|n|oʊ|.|ə|ˈ|t|r|oʊ|p|ᵻ|k|s}} {{respell|noh|ə|TROHP|iks}}, or {{IPAc-en|n|oʊ|.|ə|ˈ|t|r|ɒ|p|ᵻ|k|s}} {{respell|noh|ə|TROP|iks}}<ref name="Lexico">{{Cite encyclopedia |title=Nootropic |url=https://www.lexico.com/definition/nootropic|archive-url=https://web.archive.org/web/20200929201325/https://www.lexico.com/definition/nootropic|url-status=dead|archive-date=September 29, 2020|access-date=2021-07-03|encyclopedia=Lexico Dictionaries |language=en}}</ref>) ([[colloquial]]: '''smart drugs''' and '''cognitive enhancers''') are numerous natural or synthetic [[dietary supplement|supplements]] or [[drug]]s and other substances that are claimed to improve [[cognitive function]] or to promote [[Relaxation (psychology)|relaxation]],<ref>{{Cite journal |last1=Ostrovskaia |first1=R U |last2=Trofimov |first2=S S |date=1984-02-01 |title=[Nootropic properties of gamma-aminobutyric acid derivatives] |url=https://europepmc.org/article/med/6538101 |journal=Biulleten' Eksperimental'noi Biologii I Meditsiny |volume=97 |issue=2 |pages=170–172 |issn=0365-9615 |pmid=6538101}}</ref> particularly boosting mood,<ref name="Tireki* 1057–1059">{{cite journal | last=Tireki | first=Suzan | title=Herbal nootropics: Crocus Sativus, Ginkgo Biloba and Melissa Officinalis | journal=Open Access Journal of Biomedical Science | publisher=Journal of Biomedical Science Network LLC | volume=4 | issue=2 | date=2 July 2021 | issn=2690-487X | doi=10.38125/oajbs.000300 | doi-access=free }}</ref> [[executive functions]], [[attention]], memory, creativity, or [[motivation]] in healthy individuals.<ref name="Smart drugs">{{Cite journal |vauthors=Frati P, Kyriakou C, Del Rio A, Marinelli E, Vergallo GM, Zaami S, Busardò FP |date=January 2015 |title=Smart drugs and synthetic androgens for cognitive and physical enhancement: revolving doors of cosmetic neurology |journal=Current Neuropharmacology |volume=13 |issue=1 |pages=5–11 |doi=10.2174/1570159X13666141210221750 |pmc=4462043 |pmid=26074739}}</ref>
'''Nootropics''' ({{IPAc-en|n|oʊ|.|ə|ˈ|t|r|oʊ|p|ᵻ|k|s}} {{respell|noh|ə|TROHP|iks}} or {{IPAc-en|n|oʊ|.|ə|ˈ|t|r|ɒ|p|ᵻ|k|s}} {{respell|noh|ə|TROP|iks}}<ref name="Lexico">{{Cite encyclopedia |title=Nootropic |url=https://www.lexico.com/definition/nootropic|archive-url=https://web.archive.org/web/20200929201325/https://www.lexico.com/definition/nootropic|url-status=dead|archive-date=September 29, 2020|access-date=2021-07-03|encyclopedia=Lexico Dictionaries |language=en}}</ref>) ([[colloquial]]: '''smart drugs''' and '''cognitive enhancers''') are numerous natural, semi-synthetic and synthetic [[molecules]] that promote [[neuroprotection]] and improve [[cognitive functions]] ([[executive functions]], [[attention]], [[memory]], [[creativity]]...) in both "[[neurotypical]]" and "[[neuroatypical]]" individuals.


They are often found in the form of [[dietary supplements]], [[nutraceuticals]] and [[energy drinks]]. Some nootropic molecules can also be found as prescription and non-prescription [[pharmaceutical drugs]] in diverse countries.
The use of cognition-enhancing supplements by healthy individuals in the absence of a [[medical indication]] spans various controversial issues, including the [[Medical ethics|ethics]] and fairness of their use, concerns over [[adverse effect]]s, and the [[drug diversion|diversion]] of [[prescription drug]]s for non-medical uses.<ref name="Smart drugs" /><ref name="Cognition-enhancing drug culture">{{Cite journal |vauthors=Albertson TE, Chenoweth JA, Colby DK, Sutter ME |date=February 2016 |title=The Changing Drug Culture: Use and Misuse of Cognition-Enhancing Drugs |journal=FP Essentials |volume=441 |pages=25–29 |pmid=26881770}}</ref> Nonetheless, the international sales of cognitive- or mood-enhancing supplements have continued to grow over time and in 2012 reached {{currency|1|US}}0.69 billion.<ref name=":1">{{Cite web |date=2022-07-05 |title=Nootropics Market Share, Size, Trends, Industry Analysis Report, By Form (Capsules/Tablets, Powder, Drinks, Others); By Distribution Channel (Offline, Online), By Regions; Segment Forecast, 2022–2030 |url=https://www.polarismarketresearch.com/industry-analysis/nootropics-market |access-date=2022-08-17 |website=Polaris Market Research |language=en |type=Market Research Report}}</ref> With sales supported by global health trends, the market is expected to reach [[US$]]33.85 billion by the year 2030, at a [[CAGR]] of 14.8%.<ref name=":1" />

They are often found in supplement form as [[nutraceutical]]s,<ref name="Tireki* 1057–1059"/> or as [[Functional beverage|functional]] food or drinks.<ref>{{Cite web |last=Dingwall |first=Kate |title=Where Is The Functional Beverage Category Headed? |url=https://www.forbes.com/sites/katedingwall/2021/12/31/where-is-the-functional-beverage-category-headed/ |access-date=2022-08-11 |website=Forbes |language=en |date=December 31, 2021}}</ref><ref>{{Cite news |date=2022-07-26 |title=The growing thirst for mood-boosting drinks |work=Financial Times |url=https://www.ft.com/content/bcf78a49-5111-4240-9058-81e344030265 |archive-url=https://ghostarchive.org/archive/20221211/https://www.ft.com/content/bcf78a49-5111-4240-9058-81e344030265 |archive-date=December 11, 2022 |url-access=subscription |url-status=live |first=Sara |last=Semic |access-date=2022-08-11}}</ref> Some companies use nootropics in [[beer]] as an [[Alcohol (drug)|alcohol]] replacement.<ref>{{Cite web |date=2022-01-27 |title=Drink and be merry – but without the hangover |url=https://www.kentonline.co.uk/canterbury/news/drink-be-merry-but-without-the-hangover-261351/ |access-date=2022-08-11 |website=Kent Online |language=en}}</ref>


==History and definition==
==History and definition==
{{Expand section|date=November 2019|with=historical accounts of nootropic or nootropic-like substances and uses}}
{{Expand section|date=November 2019|with=historical accounts of nootropic or nootropic-like substances and uses}}
{{wikt|nootropic}}
{{wikt|nootropic}}
The term ''nootropic'' is derived {{ety|grc|''{{wikt-lang|grc|νόος}}'' (nóos)|mind||''{{wikt-lang|grc|τροπή}}'' (tropḗ)|turning}}.<ref name="Lexico"/><ref name="Giurgea1977">{{Cite journal|last1=Giurgea|first1=Corneliu|last2=Salama|first2=M. | name-list-style = vanc |date=1977-01-01|title=Nootropic drugs|journal=Progress in Neuro-Psychopharmacology |volume=1 |issue=3 |pages=235–247 |doi=10.1016/0364-7722(77)90046-7 |quote=The term "nootropic" (noos = mind; tropein = towards) was proposed by us (Giurgea, 1972,1973) to designate psychotropic drugs}}</ref><ref name="Giurgea1972">{{cite journal | vauthors = Giurgea C | title = [Pharmacology of integrative activity of the brain. Attempt at nootropic concept in psychopharmacology] | journal = Actualites Pharmacologiques | volume = 25 | pages = 115–156 | date = 1972 | pmid = 4541214 | language = fr }}</ref> It was first introduced<ref>{{cite web |last1=Khan |first1=Manzoor |title=Nootropics {{!}} Smart Drugs {{!}} Brain Boosters {{!}} Are They Clinically Proven? |url=https://www.drugsbanks.com/nootropics-smart-drugs/ |website=Drugsbank|date=May 15, 2022 }}</ref> by Corneliu Giurgea in 1972 to describe a new classification of molecules that acted selectively towards the brain's higher-level integrative activity. In order for a product to qualify as a true nootropic, it must fulfill Giurgea's five criteria for the category.
The term ''nootropic'' is derived {{ety|grc|''{{wikt-lang|grc|νόος}}'' (nóos)|mind||''{{wikt-lang|grc|τροπή}}'' (tropḗ)|turning}}.<ref name="Lexico"/><ref name="Giurgea1977">{{Cite journal|last1=Giurgea|first1=Corneliu|last2=Salama|first2=M. | name-list-style = vanc |date=1977-01-01|title=Nootropic drugs|journal=Progress in Neuro-Psychopharmacology |volume=1 |issue=3 |pages=235–247 |doi=10.1016/0364-7722(77)90046-7 |quote=The term "nootropic" (noos = mind; tropein = towards) was proposed by us (Giurgea, 1972,1973) to designate psychotropic drugs}}</ref><ref name="Giurgea1972">{{cite journal | vauthors = Giurgea C | title = [Pharmacology of integrative activity of the brain. Attempt at nootropic concept in psychopharmacology] | journal = Actualites Pharmacologiques | volume = 25 | pages = 115–156 | date = 1972 | pmid = 4541214 | language = fr }}</ref>


⚫
It was first introduced by [[Corneliu Giurgea]] in 1972 to describe a new classification of molecules that acted selectively towards the [[central nervous system]]'s higher-level integrative activity. In order for a molecule to qualify as a true nootropic, it must fulfill Giurgea's five criteria for the category.<ref>{{cite journal |last1=Giurgea |first1=Corneliu E. |title=The nootropic concept and its prospective implications |journal=Drug Development Research |date=1982 |volume=2 |issue=5 |pages=441–446 |doi=10.1002/ddr.430020505 |s2cid=145059666 |quote=The nootropic concept emerged about 10 years ago essentially from the unusual pharmacology of piracetam, which later on was confirmed and extended to human pharmacoclinics and therapeutics. A nootropic drug is characterized by a direct functional activation of the higher integrative brain mechanisms that enhances cortical vigilance, a telencephalic functional selectivity, and a particular efficiency in restoring deficient higher nervous activity.}}</ref>
# It should aid with improvement in working memory and learning.

# Supports brain function under hypoxic conditions or after electroconvulsive therapy.
# It should enhance [[learning]] and [[memory]].
# Protection of the brain from physical or chemical toxicity.
# It should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. [[electroconvulsive shock]], [[hypoxia]]...).
# Natural cognitive functions are enhanced.
# It should promote [[neuroprotection]] against various physical or chemical injuries (e.g. [[free radicals]], [[neurotoxins]], [[scopolamine]], strong [[psychostimulants]]...).
⚫
# It requires to be non-toxic to humans, without depression or stimulation of the brain.<ref>{{cite journal |last1=Giurgea |first1=Corneliu E. |title=The nootropic concept and its prospective implications |journal=Drug Development Research |date=1982 |volume=2 |issue=5 |pages=441–446 |doi=10.1002/ddr.430020505 |s2cid=145059666 |quote=The nootropic concept emerged about 10 years ago essentially from the unusual pharmacology of piracetam, which later on was confirmed and extended to human pharmacoclinics and therapeutics. A nootropic drug is characterized by a direct functional activation of the higher integrative brain mechanisms that enhances cortical vigilance, a telencephalic functional selectivity, and a particular efficiency in restoring deficient higher nervous activity.}}</ref>
# It should increase the efficacy of the [[cortico-basal ganglia-thalamo-cortical loop]] mechanisms.
# It should lack the usual pharmacology of other psychotropic molecules like strong dopaminergic stimulation ([[amphetamines]], [[phenidates]]...), opioidergic stimulation ([[tianeptine]], [[kratom]]...) or sedation ([[benzodiazepines]], [[calcium channel blockers]], [[phenibut]]...), thus not provoking [[addiction]] or strong [[drug tolerance]] leading to addiction through [[homeostasis]]. At most, it should possess very few temporary side effects and extremely low toxicity.


==Marketing claims==
==Marketing claims==
Line 50: Line 50:


In 2016, the [[American Medical Association]] adopted a policy to discourage [[prescription drug|prescriptions]] of nootropics for healthy people, on the basis that the cognitive effects appear to be highly variable among individuals, are dose-dependent, and limited or modest at best.<ref name="ama">{{cite web |title=AMA confronts the rise of nootropics |url=https://www.ama-assn.org/press-center/press-releases/ama-confronts-rise-nootropics |publisher=American Medical Association |access-date=12 May 2019 |date=14 June 2016}}</ref>
In 2016, the [[American Medical Association]] adopted a policy to discourage [[prescription drug|prescriptions]] of nootropics for healthy people, on the basis that the cognitive effects appear to be highly variable among individuals, are dose-dependent, and limited or modest at best.<ref name="ama">{{cite web |title=AMA confronts the rise of nootropics |url=https://www.ama-assn.org/press-center/press-releases/ama-confronts-rise-nootropics |publisher=American Medical Association |access-date=12 May 2019 |date=14 June 2016}}</ref>

===Use by students===
The use of prescription stimulants is especially prevalent among students.<ref name=StudentSurvey>{{cite journal | vauthors = McCabe SE, Knight JR, Teter CJ, Wechsler H | title = Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey | journal = Addiction | volume = 100 | issue = 1 | pages = 96–106 | date = January 2005 | pmid = 15598197 | doi = 10.1111/j.1360-0443.2005.00944.x | hdl = 2027.42/74786 | hdl-access = free }}</ref> Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetimes.<ref name="doi10.1371/journal.pone.0068821">{{cite journal | vauthors = Sattler S, Sauer C, Mehlkop G, Graeff P | title = The rationale for consuming cognitive enhancement drugs in university students and teachers | journal = PLOS ONE | volume = 8 | issue = 7 | pages = e68821 | year = 2013 | pmid = 23874778 | pmc = 3714277 | doi = 10.1371/journal.pone.0068821 | bibcode = 2013PLoSO...868821S | doi-access = free }}</ref><ref name="C4WDefault-10.3109/10826084.2012.751426">{{cite journal | vauthors = Sattler S, Wiegel C | title = Cognitive test anxiety and cognitive enhancement: the influence of students' worries on their use of performance-enhancing drugs | journal = Substance Use & Misuse | volume = 48 | issue = 3 | pages = 220–232 | date = February 2013 | pmid = 23302063 | doi = 10.3109/10826084.2012.751426 | s2cid = 34698382 }}</ref><ref>{{cite journal | vauthors = Bossaer JB, Gray JA, Miller SE, Enck G, Gaddipati VC, Enck RE | title = The use and misuse of prescription stimulants as "cognitive enhancers" by students at one academic health sciences center | journal = Academic Medicine | volume = 88 | issue = 7 | pages = 967–971 | date = July 2013 | pmid = 23702522 | doi = 10.1097/ACM.0b013e318294fc7b | doi-access = free }}</ref> Stimulants such as [[dimethylamylamine]] and [[methylphenidate]] are used on college campuses and by younger groups.<ref name=NatureProfessor>{{cite journal | vauthors = Sahakian B, Morein-Zamir S | title = Professor's little helper | journal = Nature | volume = 450 | issue = 7173 | pages = 1157–1159 | date = December 2007 | pmid = 18097378 | doi = 10.1038/4501157a | bibcode = 2007Natur.450.1157S | s2cid = 2051062 | author1-link = Barbara Sahakian }}</ref> Based upon studies of self-reported illicit stimulant use, {{nowrap|5–35%}} of college students use [[drug diversion|diverted]] [[Attention deficit hyperactivity disorder|ADHD]] stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs.<ref name="pmid16999660">{{cite journal | vauthors = Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ | title = Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration | journal = Pharmacotherapy | volume = 26 | issue = 10 | pages = 1501–1510 | date = October 2006 | pmid = 16999660 | pmc = 1794223 | doi = 10.1592/phco.26.10.1501 }}</ref><ref name="Diversion prevalence 1">{{cite journal | vauthors = Weyandt LL, Oster DR, Marraccini ME, Gudmundsdottir BG, Munro BA, Zavras BM, Kuhar B | title = Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants | journal = Psychology Research and Behavior Management | volume = 7 | pages = 223–249 | date = September 2014 | pmid = 25228824 | pmc = 4164338 | doi = 10.2147/PRBM.S47013 }}</ref><ref name="Diversion prevalence 2">{{cite journal | vauthors = Clemow DB, Walker DJ | title = The potential for misuse and abuse of medications in ADHD: a review | journal = Postgraduate Medicine | volume = 126 | issue = 5 | pages = 64–81 | date = September 2014 | pmid = 25295651 | doi = 10.3810/pgm.2014.09.2801 | s2cid = 207580823 }}</ref> Several factors positively and negatively influence an individual's willingness to use a drug for the purpose of enhancing 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 journal | vauthors = Sattler S, Mehlkop G, Graeff P, Sauer C | 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 | journal = Substance Abuse Treatment, Prevention, and Policy | volume = 9 | issue = 1 | pages = 8 | date = February 2014 | pmid = 24484640 | pmc = 3928621 | doi = 10.1186/1747-597X-9-8 }}</ref><ref name="PLOS ONE-10.1371/journal.pone.0071452">{{cite journal | vauthors = Sattler S, Forlini C, Racine E, Sauer C | title = Impact of contextual factors and substance characteristics on perspectives toward cognitive enhancement | journal = PLOS ONE | volume = 8 | issue = 8 | pages = e71452 | date = August 5, 2013 | pmid = 23940757 | pmc = 3733969 | doi = 10.1371/journal.pone.0071452 | lccn = 2006214532 | bibcode = 2013PLoSO...871452S | oclc = 228234657 | doi-access = free }}</ref>


==Side effects==
==Side effects==
The main concern with [[pharmaceutical drug]]s is [[adverse effect]]s, which also apply to nootropics with undefined effect. Long-term safety evidence is typically unavailable for nootropics.<ref name=NatureProfessor/> [[Racetam]]s, [[piracetam]] and other compounds that are structurally related to piracetam, have few serious adverse effects and low [[toxicity]], but there is little evidence that they enhance cognition in people having no cognitive impairments.<ref name="Racetam efficacy review 2010">{{cite journal | vauthors = Malykh AG, Sadaie MR | title = Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders | journal = Drugs | volume = 70 | issue = 3 | pages = 287–312 | date = February 2010 | pmid = 20166767 | doi = 10.2165/11319230-000000000-00000 | s2cid = 12176745 }}</ref>
The main concern with [[pharmaceutical drug]]s is [[adverse effect]]s, which also apply to nootropics with undefined effect. Long-term safety evidence is typically unavailable for nootropics. [[Racetams]], [[piracetam]] and other compounds that are structurally related to piracetam, have few serious adverse effects and low [[toxicity]], but there is little evidence that they enhance cognition in people having no cognitive impairments.<ref name="Racetam efficacy review 2010">{{cite journal | vauthors = Malykh AG, Sadaie MR | title = Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders | journal = Drugs | volume = 70 | issue = 3 | pages = 287–312 | date = February 2010 | pmid = 20166767 | doi = 10.2165/11319230-000000000-00000 | s2cid = 12176745 }}</ref>


In the United States, [[dietary supplement]]s may be marketed if the manufacturer can show that the supplement is [[generally recognized as safe]], and if the manufacturer does not make any claims about using the supplement to treat or prevent any disease or condition; supplements that contain [[drugs]] or advertise [[health claim]]s are illegal under US law.<ref>{{cite journal | vauthors = 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 | date = October 2001 | pmid = 11601931 | doi = 10.7326/0003-4819-135-8_Part_1-200110160-00010 | s2cid = 35766876 }}</ref>
In the United States, [[dietary supplement]]s may be marketed if the manufacturer can show that the supplement is [[generally recognized as safe]], and if the manufacturer does not make any claims about using the supplement to treat or prevent any disease or condition; supplements that contain [[drugs]] or advertise [[health claim]]s are illegal under US law.<ref>{{cite journal | vauthors = 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 | date = October 2001 | pmid = 11601931 | doi = 10.7326/0003-4819-135-8_Part_1-200110160-00010 | s2cid = 35766876 }}</ref>

Revision as of 15:56, 5 February 2023

Illustration of Coffea arabica plant and seeds
Caffeine is the world's most consumed nootropic, from the Coffea arabica plant.

Nootropics (/noʊ.əˈtroʊpɪks/ noh-ə-TROHP-iks or /noʊ.əˈtrɒpɪks/ noh-ə-TROP-iks[1]) (colloquial: smart drugs and cognitive enhancers) are numerous natural, semi-synthetic and synthetic molecules that promote neuroprotection and improve cognitive functions (executive functions, attention, memory, creativity...) in both "neurotypical" and "neuroatypical" individuals.

They are often found in the form of dietary supplements, nutraceuticals and energy drinks. Some nootropic molecules can also be found as prescription and non-prescription pharmaceutical drugs in diverse countries.

History and definition

Look up nootropic in Wiktionary, the free dictionary.

The term nootropic is derived from Ancient Greek νόος (nóos) 'mind', and τροπή (tropḗ) 'turning'.[1][2][3]

It was first introduced by Corneliu Giurgea in 1972 to describe a new classification of molecules that acted selectively towards the central nervous system's higher-level integrative activity. In order for a molecule to qualify as a true nootropic, it must fulfill Giurgea's five criteria for the category.[4]

  1. It should enhance learning and memory.
  2. It should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia...).
  3. It should promote neuroprotection against various physical or chemical injuries (e.g. free radicals, neurotoxins, scopolamine, strong psychostimulants...).
  4. It should increase the efficacy of the cortico-basal ganglia-thalamo-cortical loop mechanisms.
  5. It should lack the usual pharmacology of other psychotropic molecules like strong dopaminergic stimulation (amphetamines, phenidates...), opioidergic stimulation (tianeptine, kratom...) or sedation (benzodiazepines, calcium channel blockers, phenibut...), thus not provoking addiction or strong drug tolerance leading to addiction through homeostasis. At most, it should possess very few temporary side effects and extremely low toxicity.

Marketing claims

Nootropics are often advertised with unproven claims of effectiveness at improving cognition. The FDA and FTC warned manufacturers and consumers in 2019 about possible advertising fraud and marketing scams concerning nootropic supplement products.[5][6][7][8] The FDA and FTC stated that some nootropic products had not been approved as a drug effective for any medical purpose, were not proven to be safe, and were illegally marketed in the United States under violation of the Federal Food, Drug, and Cosmetic Act.[5][6]

In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing.[9][10] In 2019, the US Food and Drug Administration (FDA) and Federal Trade Commission (FTC) warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.[5][6]

Over the years 2010 to 2019, the FDA warned numerous supplement manufacturers about the illegal status of their products as unapproved drugs with no proven safety or efficacy at the doses recommended, together with misleading marketing.[5][6][7][8][11][12]

Availability and prevalence

In 2008, the most commonly used class of drug was stimulants, such as caffeine.[13] Manufacturers' marketing claims for dietary supplements are usually not formally tested and verified by independent entities.[14]

In 2016, the American Medical Association adopted a policy to discourage prescriptions of nootropics for healthy people, on the basis that the cognitive effects appear to be highly variable among individuals, are dose-dependent, and limited or modest at best.[15]

Side effects

The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effect. Long-term safety evidence is typically unavailable for nootropics. Racetams, piracetam and other compounds that are structurally related to piracetam, have few serious adverse effects and low toxicity, but there is little evidence that they enhance cognition in people having no cognitive impairments.[16]

In the United States, dietary supplements may be marketed if the manufacturer can show that the supplement is generally recognized as safe, and if the manufacturer does not make any claims about using the supplement to treat or prevent any disease or condition; supplements that contain drugs or advertise health claims are illegal under US law.[17]

Types

Central nervous system stimulants

See also: Yerkes–Dodson law
Hebbian version of the Yerkes–Dodson law

Systematic reviews and meta-analyses of clinical human research using low doses of certain central nervous system stimulants found that these drugs enhance cognition in healthy people.[18][19][20] In particular, the classes of stimulants that demonstrate cognition-enhancing effects in humans act as direct agonists or indirect agonists of dopamine receptor D1, adrenoceptor A2, or both types of receptor in the prefrontal cortex.[18][19][21][22] Relatively high doses of stimulants cause cognitive deficits.[21][22]

  • Amphetamine – systematic reviews and meta-analyses report that low-dose amphetamine improves cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people and in individuals with ADHD.[18][19][20][22] A 2014 systematic review noted that low doses of amphetamine also improve memory consolidation, in turn leading to improved recall of information in non-ADHD youth.[20] It also improves task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.[19][21][22]
  • Methylphenidate – a benzylpiperidine derivative that improves working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency in healthy people.[18][19][20] It also may improve task saliency and performance on tedious tasks.[22] At above optimal doses, methylphenidate has off–target effects that decrease learning.[23]
  • Eugeroics (armodafinil and modafinil) – are classified as "wakefulness-promoting agents"; modafinil increases alertness, particularly in sleep-deprived individuals, and facilitates reasoning and problem solving in non-ADHD youth.[20] In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake enhanced executive function.[24] Modafinil may not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals.[25]
  • Caffeine – a meta-analysis found an increase in alertness and attentional performance.[26][21]
  • Nicotine – a meta-analysis of 41 clinical studies concluded that nicotine administration or smoking improves alerting and orienting attention and episodic and working memory and slightly improves fine motor performance.[27]

Amino acids

Main article: Amino acid-based formula

A 2016 review reported that theanine may increase alpha waves in the brain. Alpha waves may contribute to a relaxed yet alert mental state.[28] A 2014 systematic review and meta-analysis found that concurrent caffeine and L-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching. These effects were most pronounced during the first hour post-dose.[26]

Racetams

Main article: Racetams

Racetams, such as piracetam, oxiracetam, phenylpiracetam, and aniracetam, are often marketed as cognitive enhancers and sold over the counter.[29] A 2019 study found that piracetam supplements sold in the United States were inaccurately labeled.[29] Racetams are often referred to as nootropics, but this property is not well established.[30] The racetams have poorly understood mechanisms, although piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.[31]

According to the US Food and Drug Administration,

Piracetam is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by humans to supplement the diet by increasing the total dietary intake. Further, piracetam is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient. [...] Accordingly, these products are drugs, under section 201(g)(1)(C) of the Act, 21 U.S.C. § 321(g)(1)(C), because they are not foods and they are intended to affect the structure or any function of the body. Moreover, these products are new drugs as defined by section 201(p) of the Act, 21 U.S.C. § 321(p), because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling.[12]

Cholinergics

Some of the most widely used nootropic substances are the cholinergics. These are typically compounds and analogues of choline. Choline is an essential nutrient needed for the synthesis of acetylcholine (a neurotransmitter), and phosphatidylcholine (a structural component of brain cell membranes).

  • Citicoline – Compound consisting of choline and cytidine. Several meta-analyses found that it is likely effective for improving memory and learning in older people with mild cognitive decline, as well as in people who are recovering from a stroke.[32][33][34] There is little evidence it enhances cognition in young, healthy people.
  • Choline bitartrate – Choline bitartrate is a tartaric acid salt containing choline (41% choline by molecular weight). At least one meta-analysis has found choline bitartrate to be ineffective at improving any measure of cognitive performance.[35]
  • Alpha-GPC – L-Alpha glycerylphosphorylcholine has thus far only been studied in the context of cognitive performance alongside other substances such as caffeine.[36] A more comprehensive meta-analysis is needed before any strong conclusions are made about Alpha-GPC's usefulness as a nootropic.

Miscellaneous

The cognitive enhancing effects of pramipexole, guanfacine, clonidine, and fexofenadine have been tested, but no significant cognition-enhancing effects in healthy individuals were found.[37]

Psychedelic microdosing is the novel practice of using sub-threshold doses (microdoses) of psychedelic drugs in an attempt to improve mood and cognition.[40] The efficacy of this has not been verified.[41][42] In a study examining the qualitative reports of 278 microdosers the researchers found that there were mixed results among users.[43] While some users reported positive effects such as improved mood and cognition, others paradoxically reported negative effects such as physiological discomfort and anxiety.[43] In one of the only double-blind, randomized studies to date, those given microdoses of LSD did not perform better than those given the placebo on cognitive tasks.[44]

Herbs

  • Bacopa monnieri is used in Ayurvedic traditional medicine to improve cognition.[45] In 2019, the US Food and Drug Administration (FDA) warned manufacturers of dietary supplement products containing Bacopa monnieri against making illegal and unproven claims that the herb can treat various diseases.[46][47][48]
  • Panax ginseng – A review by the Cochrane Collaboration found that the results of its analysis "suggested improvement of some aspects of cognitive function, behavior and quality of life" but concluded that "there is a lack of convincing evidence to show a cognitive enhancing effect of Panax ginseng in healthy participants and no high quality evidence about its efficacy in patients with dementia."[49]
  • Ginkgo biloba – An extract of Ginkgo biloba leaf is marketed in dietary supplement form with claims it can enhance cognitive function in people without known cognitive problems, although there is no high-quality evidence to support such effects on memory or attention in healthy people.[50][51]
  • Salvia officinalis and lavandulaefolia (sage) – Some research has suggested certain extracts of Salvia officinalis may have positive effects on human brain function, but due to significant methodological problems, no firm conclusions can be drawn.[52][53] The thujone present in Salvia extracts may be neurotoxic.[53]
  • Centella asiatica – A 2017 meta-analysis with 11 studies (5 RCTs with placebo, 6 using other herbs as a comparison group) showing no significant improvement in all cognitive function, however may have some use in improving mood and anger. Overall dosages were smaller than the typical 3 grams used traditionally.[54]

Nutrients and dietary supplements

A 2015 review found that use of omega-3 fatty acids, B vitamins, and vitamin E as nootropics was ineffective on cognitive function in normal middle-aged and older people.[55]

  • Omega-3 fatty acids: DHA and EPA – two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder.[56][57] Two other systematic reviews found no cognition-enhancing effects in the general population.[55][58]
  • Folate – no cognition-enhancing effects in middle-aged and older adults without folate deficiency.[55]
  • Vitamin B6 – no cognition-enhancing effects in middle-aged and older adults without B6 deficiency.[55]
  • Vitamin B12 – no cognition-enhancing effects in middle-aged and older adults without B12 deficiency.[55]
  • Vitamin E – no cognition-enhancing effects in middle-aged and older adults without vitamin E deficiency.[55]

See also

References

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External links

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