Editing Nootropic

{{Short description|Compound intended to improve cognitive function}}
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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}}) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are [[chemical substance]]s which purportedly improve [[cognitive function]]s, such as [[attention]], [[memory]], [[wakefulness]], and [[self-control]].<ref name="Lexico">{{cite encyclopedia |title=Nootropic |url=https://www.oed.com/search/advanced/Meanings?scope=HistoricalThesaurus&q=nootropic|encyclopedia=Oxford English Dictionary|date=2024|accessdate=14 January 2024 |language=en}}</ref>

In the United States, nootropics can be [[over-the-counter drugs]] and commonly advertised with unproven claims of effectiveness for improving cognition. The [[Federal Trade Commission]] and [[Food and Drug Administration|FDA]] have warned manufacturers and consumers about possible [[fraud|advertising fraud]] and [[Confidence trick|marketing scams]] concerning nootropic supplements.<ref name="ftc" /><ref name="fda-fraud" /> Nootropics include both [[prescription drug]]s and [[dietary supplement]]s marketed to enhance brain function, but while [[U.S. Food and Drug Administration|FDA]]-approved drugs have proven benefits and oversight, many dietary supplements lack evidence, may contain unapproved or hidden [[drug|drugs]], and pose safety and regulatory risks.<ref name="opss">Nootropics: Drugs vs Dietary Supplements for Brain Health. Operation Supplement Safety. https://www.opss.org/article/nootropics-drugs-vs-dietary-supplements-brain-health. Accessed 2025-05-20.</ref>

==History of term==
The term ''nootropic'' is derived {{ety|grc|''{{wikt-lang|grc|νόος}}'' (nóos)|mind||''{{wikt-lang|grc|τροπή}}'' (tropḗ)|turning}}.<ref name="Lexico"/><ref name="Giurgea1972">{{cite journal | vauthors = Giurgea C | title = [Pharmacology of integrative activity of the brain. Attempt at nootropic concept in psychopharmacology] | language = fr | journal = Actualites Pharmacologiques | volume = 25 | pages = 115–156 | date = 1972 | pmid = 4541214 }}</ref><ref name="Giurgea1977">{{cite journal| vauthors = Giurgea C, Salama M |date=January 1, 1977|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>

The first documented use of "nootropic" in reference to substances purported to increase cognitive functions was by [[Corneliu E. Giurgea|{{Nobr|Corneliu E. Giurgea}}]] in 1972.<ref name="Giurgea1972"/><ref name="Giurgea1977"/><ref name="malik">{{cite journal | vauthors = Malík M, Tlustoš P | title = Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs | journal = Nutrients | volume = 14 | issue = 16 | page = 3367 | date = August 2022 | pmid = 36014874 | pmc = 9415189 | doi = 10.3390/nu14163367 | doi-access = free }}</ref> When researching a new compound, Giurgea found a spectrum of effects that did not align with any psychotropic drug category, leading to his proposal of a new category and the concept of the term nootropic.<ref name="Giurgea1977"/>

Giurgea stated that nootropic drugs should have the following characteristics:

# They should enhance [[learning]] and [[memory]].
# They should enhance the resistance of learned behaviors or memories to conditions which tend to disrupt them (e.g. [[electroconvulsive shock]], [[hypoxia (medical)|hypoxia]]).
# They should protect the brain against various physical or chemical injuries.
# They should increase the efficacy of the tonic [[cerebral cortex|cortical]] control mechanisms.
# They should lack the usual pharmacology of other [[psychotropic]] drugs (e.g. [[sedation]], motor stimulation) and possess few [[adverse effect]]s and low [[toxicity]].

However, there is no globally accepted or clinical definition of a nootropic. Most compounds described as nootropic do not correspond to Giurgea's characteristics.<ref name="malik" />

==Unproven marketing claims==
Nootropics include both [[prescription drug]]s and [[dietary supplement]]s marketed to enhance brain function, but while [[U.S. Food and Drug Administration|FDA]]-approved drugs have proven benefits and oversight, many dietary supplements lack evidence, may contain unapproved or hidden [[drug|drugs]], and pose safety and regulatory risks.<ref name=opss/>

In the United States, nootropics are commonly advertised with unproven claims of effectiveness for improving cognition. Manufacturers' marketing claims for dietary supplements are usually not formally tested and verified by independent entities.<ref>{{Cite web |date=2019-02-11 |title=FTC and FDA Send Warning Letters to Companies Selling Dietary Supplements Claiming to Treat Alzheimer's Disease and Remediate or Cure Other Serious Illnesses Such as Parkinson's, Heart Disease, and Cancer |url=https://www.ftc.gov/news-events/news/press-releases/2019/02/ftc-fda-send-warning-letters-companies-selling-dietary-supplements-claiming-treat-alzheimers-disease |access-date=2025-02-06 |website=Federal Trade Commission |language=en}}</ref> In 2019, the US FDA and [[Federal Trade Commission|FTC]] [[FDA warning letter|warned]] manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplement products.<ref name="ftc">{{cite web |date=February 11, 2019 |title=FTC and FDA Send Warning Letters to Companies Selling Dietary Supplements Claiming to Treat Alzheimer's Disease and Remediate or Cure Other Serious Illnesses Such as Parkinson's, Heart Disease, and Cancer |url=https://www.ftc.gov/news-events/press-releases/2019/02/ftc-fda-send-warning-letters-companies-selling-dietary |access-date=May 11, 2019 |publisher=US Food and Drug Administration, US Federal Trade Commission}}</ref><ref name="fda-fraud">{{cite web |date=December 22, 2018 |title=Health fraud scams: Unproven Alzheimer's disease products |url=https://www.fda.gov/consumers/health-fraud-scams/unproven-alzheimers-disease-products |archive-url=https://web.archive.org/web/20190913120205/https://www.fda.gov/consumers/health-fraud-scams/unproven-alzheimers-disease-products |url-status=dead |archive-date=September 13, 2019 |access-date=May 11, 2019 |publisher=US Food and Drug Administration}}</ref><ref name="fda">{{cite web |url=https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/peak-nootropics-llc-aka-advanced-nootropics-565256-02052019 |title=FDA Warning Letter: Peak Nootropics LLC aka Advanced Nootropics | vauthors = Correll Jr WA |date=February 5, 2019 |publisher=Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration |access-date=May 11, 2019}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref><ref name="fda2">{{cite web |url=https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/tek-naturals-565026-02042019 |title=FDA Warning Letter: TEK Naturals | vauthors = Correll Jr WA |date=February 5, 2019 |publisher=Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration |access-date=May 11, 2019}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref> The FDA and FTC stated that some nootropic products had not been [[drug approval|approved]] as a prescription 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]].<ref name=ftc/><ref name=fda-fraud/>

In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing.<ref name="schultz">{{cite web | vauthors = Schultz H |date=May 17, 2018 |title=Some shady ingredients find home in nootropics category |url=https://www.nutraingredients-usa.com/Article/2018/05/17/Some-shady-ingredients-find-home-in-nootropics-category# |access-date=May 11, 2019 |publisher=NutraIngredients-USA.com, William Reed Business Media Ltd}}</ref><ref name="heid">{{cite web | vauthors = Heid M |date=January 23, 2019 |title=Nootropics, or 'Smart Drugs,' Are Gaining Popularity. But Should You Take Them? |url=https://time.com/5509993/nootropics-smart-drugs-brain/ |access-date=May 12, 2019 |publisher=Time}}</ref> In 2019, the FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.<ref name="ftc" /><ref name="fda-fraud" />

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 listed on the products, together with misleading marketing.<ref name="ftc" /><ref name="fda-fraud" /><ref name="fda" /><ref name="fda2" /><ref name="cerebral">{{cite web |url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm198452.htm |archive-url=https://wayback.archive-it.org/7993/20170112195041/https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm198452.htm |url-status=dead |archive-date=January 12, 2017 |title=FDA Warning Letter: Cerebral Health LLC | vauthors = Singleton ER |date=January 7, 2010 |publisher=Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration |access-date=May 12, 2019}}</ref><ref name="unlimited" />

== Availability and prevalence ==
In 2008, stimulants, such as caffeine, were the most commonly used nootropic agent.<ref name="Nature2008">{{cite journal | vauthors = Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, Farah MJ | title = Towards responsible use of cognitive-enhancing drugs by the healthy | journal = Nature | volume = 456 | issue = 7223 | pages = 702–705 | date = December 2008 | pmid = 19060880 | doi = 10.1038/456702a | s2cid = 3598099 | bibcode = 2008Natur.456..702G | oclc = 01586310 | url = https://pure.manchester.ac.uk/ws/files/28322116/POST-PEER-REVIEW-PUBLISHERS.PDF }}</ref> 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.<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=May 12, 2019 |date=June 14, 2016}}</ref> [[Piracetam]], [[N-Phenylacetyl-L-prolylglycine ethyl ester|noopept]] and [[meclofenoxate]] have been sold as dietary supplements.<ref name="NeuroClin"/><ref name="JAMAIM"/><ref>{{cite journal | vauthors = Cohen PA, Avula B, Khan I | title = The unapproved drug centrophenoxine (meclofenoxate) in cognitive enhancement dietary supplements | journal = Clinical Toxicology | volume = 60 | issue = 10 | pages = 1156–1158 | date = October 2022 | pmid = 35959800 | doi = 10.1080/15563650.2022.2109485 | s2cid = 251516603 }}</ref>

==Adverse effects==
The main concern with [[pharmaceutical drug]]s and dietary supplements are [[adverse effect]]s, including the potential for [[psychological dependence]]. Long-term safety evidence is typically unavailable for many nootropic compounds. [[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 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 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>

==Types==
{{anchor|Drugs}}
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=== Central nervous system stimulants {{anchor|Xanthines|Stimulants}} ===
[[Systematic review]]s and [[meta-analyses]] of [[clinical research]] using low doses of certain [[central nervous system]] stimulants found that these drugs may enhance cognition in healthy people.<ref name="Unambiguous PFC D1 A2" /><ref name="Cognitive and motivational effects">{{cite journal | vauthors = Ilieva IP, Hook CJ, Farah MJ | title = Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis | journal = Journal of Cognitive Neuroscience | volume = 27 | issue = 6 | pages = 1069–1089 | date = June 2015 | pmid = 25591060 | doi = 10.1162/jocn_a_00776 | s2cid = 15788121 | url = https://repository.upenn.edu/neuroethics_pubs/130 | url-access = subscription }}</ref><ref name="Systematic 2014 – Amph, MPH, Modafinil">{{cite journal | vauthors = Bagot KS, Kaminer Y | title = Efficacy of stimulants for cognitive enhancement in non-attention deficit hyperactivity disorder youth: a systematic review | journal = Addiction | volume = 109 | issue = 4 | pages = 547–557 | date = April 2014 | pmid = 24749160 | pmc = 4471173 | doi = 10.1111/add.12460 }}</ref> In particular, the classes of stimulants that demonstrate possible cognition-enhancing effects in humans have evidence [[in vitro]] as [[receptor agonist|direct agonists]] or [[indirect agonist]]s of [[dopamine receptor D1|dopamine receptor D<sub>1</sub>]] or [[Alpha-2 adrenergic receptor|adrenoceptor A<sub>2</sub>]].<ref name="Unambiguous PFC D1 A2">{{cite journal | vauthors = Spencer RC, Devilbiss DM, Berridge CW | title = The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex | journal = Biological Psychiatry | volume = 77 | issue = 11 | pages = 940–950 | date = June 2015 | pmid = 25499957 | pmc = 4377121 | doi = 10.1016/j.biopsych.2014.09.013 }}</ref><ref name="Cognitive and motivational effects" /><ref name="Continuum">{{cite journal | vauthors = Wood S, Sage JR, Shuman T, Anagnostaras SG | title = Psychostimulants and cognition: a continuum of behavioral and cognitive activation | journal = Pharmacological Reviews | volume = 66 | issue = 1 | pages = 193–221 | date = January 2014 | pmid = 24344115 | pmc = 3880463 | doi = 10.1124/pr.112.007054 }}</ref><ref name="NHMH_3e-Higher Cognitive Function">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE, Holtzman DM | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2015 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071827706 | edition = 3| chapter = 14: Higher Cognitive Function and Behavioral Control}}</ref> Relatively high doses of stimulants cause cognitive deficits.<ref name="Continuum" /><ref name="NHMH_3e-Higher Cognitive Function" />
* [[Amphetamine]]{{snd}} systematic reviews and meta-analyses report that low-dose amphetamine may improve cognitive functions (e.g., [[inhibitory control]], [[episodic memory]], [[working memory]], and aspects of [[Attention#Clinical model|attention]]) in healthy people and in individuals with [[ADHD]].<ref name="Unambiguous PFC D1 A2" /><ref name="Cognitive and motivational effects" /><ref name="Systematic 2014 – Amph, MPH, Modafinil" /><ref name="NHMH_3e-Higher Cognitive Function" /> A 2014 systematic review noted that low doses of amphetamine also improve [[memory consolidation]], in turn leading to improved [[Recall (memory)|recall of information]] in non-ADHD youth.<ref name="Systematic 2014 – Amph, MPH, Modafinil" /> It also improves [[incentive salience|task saliency]] (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.<ref name="Cognitive and motivational effects" /><ref name="Continuum" /><ref name="NHMH_3e-Higher Cognitive Function" />
* [[Caffeine]]{{snd}} a meta-analysis found an increase in alertness and attentional performance.<ref name="caffeine and theanine">{{cite journal | vauthors = Camfield DA, Stough C, Farrimond J, Scholey AB | title = Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis | journal = Nutrition Reviews | volume = 72 | issue = 8 | pages = 507–522 | date = August 2014 | pmid = 24946991 | doi = 10.1111/nure.12120 | doi-access = free }}</ref><ref name="Continuum" />
* [[Eugeroics]] ([[armodafinil]] and [[modafinil]]){{snd}} are classified as "wakefulness-promoting agents"; modafinil may increase alertness, particularly in [[sleep-deprived]] individuals, and may improve reasoning and problem solving in non-ADHD youth.<ref name="Systematic 2014 – Amph, MPH, Modafinil" /> 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.<ref name="Modafinil SystRev">{{cite journal | vauthors = Battleday RM, Brem AK | title = Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review | journal = European Neuropsychopharmacology | volume = 25 | issue = 11 | pages = 1865–1881 | date = November 2015 | pmid = 26381811 | doi = 10.1016/j.euroneuro.2015.07.028 | s2cid = 23319688 }}</ref> Modafinil does not improve mood or motivation in sleep-deprived or non-sleep deprived individuals.<ref>{{cite book | vauthors = Mohamed AD | chapter = Does modafinil improve cognitive functioning in healthy individuals? | veditors = ter Meulen R, Hall W, Mohammed AD |title=Rethinking Cognitive Enhancement |date=2017 |publisher=Oxford University Press |isbn=9780198727392 |page=116 | chapter-url=https://books.google.com/books?id=aAIXDgAAQBAJ&pg=PA116 }}</ref>
* [[Methylphenidate]]{{snd}} a [[benzylpiperidine]] derivative that may improve [[working memory]], [[episodic memory]], and [[inhibitory control]], aspects of [[Attention#Clinical model|attention]], and planning latency in healthy people.<ref name="Unambiguous PFC D1 A2" /><ref name="Systematic 2014 – Amph, MPH, Modafinil" /> It also may improve task saliency and performance on tedious tasks.<ref name="NHMH_3e-Higher Cognitive Function" /> At above optimal doses, methylphenidate has off–target effects that decrease learning.<ref>{{cite journal | vauthors = Urban KR, Gao WJ | title = Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain | journal = Frontiers in Systems Neuroscience | volume = 8 | pages = 38 | date = 2014 | pmid = 24860437 | pmc = 4026746 | doi = 10.3389/fnsys.2014.00038 | doi-access = free }}</ref>
* [[Nicotine]]{{snd}} has been associated with improved alertness, attention, memory, and motor performance, according to a [[meta-analysis]].<ref>{{cite journal | vauthors = Heishman SJ, Kleykamp BA, Singleton EG | title = Meta-analysis of the acute effects of nicotine and smoking on human performance | journal = Psychopharmacology | volume = 210 | issue = 4 | pages = 453–469 | date = July 2010 | pmid = 20414766 | pmc = 3151730 | doi = 10.1007/s00213-010-1848-1 }}</ref> However, a 2020 systematic review raised concerns about potential conflicts of interest, noting industry funding in many studies and inconsistent results regarding nicotine's cognitive effects. This review found that over half of the studies published after 2010 had tobacco industry affiliations, often undisclosed.<ref name="pmid32547048">{{cite journal |last1=Pasetes |first1=Sarah V. |last2=Ling |first2=Pamela M. |last3=Apollonio |first3=Dorie E. |title=Cognitive performance effects of nicotine and industry affiliation: a systematic review |journal=Substance Abuse: Research and Treatment |date=January 2020 |volume=14 |pages=117822182092654 |doi=10.1177/1178221820926545 |pmid=32547048 |language=en |issn=1178-2218 |pmc=7271274}}</ref>

===Cholinergics===
{{Main|Cholinergic}}
Some supposed nootropic substances are compounds and analogues of [[choline]], a [[precursor (chemistry)|precursor]] of acetylcholine (a [[neurotransmitter]]) and [[phosphatidylcholine]] (a structural component of [[cell membrane]]s).
* [[Alpha-GPC]] – L-alpha glycerylphosphorylcholine has been studied only in the context of cognitive performance alongside other substances such as caffeine.<ref>{{cite journal| vauthors = Parker AG, Byars A, Purpura M, Jäger R |date=September 21, 2015|title=The effects of alpha-glycerylphosphorylcholine, caffeine or placebo on markers of mood, cognitive function, power, speed, and agility|journal=Journal of the International Society of Sports Nutrition|volume=12|issue=Suppl 1|pages=P41|doi=10.1186/1550-2783-12-S1-P41|issn=1550-2783|pmc=4595381 |doi-access=free }}</ref>
* [[Choline bitartrate]] – Choline bitartrate is a [[tartaric acid]] salt containing choline (41% choline by molecular weight). One meta-analysis found choline bitartrate to be ineffective at improving any measure of cognitive performance.<ref>{{cite journal | vauthors = Lippelt DP, van der Kint S, van Herk K, Naber M | title = No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults | journal = PLOS ONE | volume = 11 | issue = 6 | pages = e0157714 | date = June 24, 2016 | pmid = 27341028 | pmc = 4920398 | doi = 10.1371/journal.pone.0157714 | doi-access = free | bibcode = 2016PLoSO..1157714L }}</ref>
* [[Citicoline]] – Compound consisting of choline and [[cytidine]]. A meta-analysis found that it may be effective for improving memory and learning in older people with mild cognitive decline, and in people recovering from a stroke.<ref>{{cite journal | vauthors = Fioravanti M, Buckley AE | title = Citicoline (Cognizin) in the treatment of cognitive impairment | journal = Clinical Interventions in Aging | volume = 1 | issue = 3 | pages = 247–251 | date = September 2006 | pmid = 18046877 | pmc = 2695184 | doi = 10.2147/ciia.2006.1.3.247 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Franco-Maside A, Caamaño J, Gómez MJ, Cacabelos R | title = Brain mapping activity and mental performance after chronic treatment with CDP-choline in Alzheimer's disease | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 16 | issue = 8 | pages = 597–607 | date = October 1994 | pmid = 7760585 }}</ref>

===Racetams===
{{Main|Racetam}}
Racetams, such as piracetam, [[oxiracetam]], [[phenylpiracetam]], and [[aniracetam]], are often marketed as cognitive enhancers and sold [[over the counter]].<ref name="NeuroClin">{{cite journal | vauthors = Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I | title = Five Unapproved Drugs Found in Cognitive Enhancement Supplements | journal = Neurology. Clinical Practice | volume = 11 | issue = 3 | pages = e303–e307 | date = June 2021 | pmid = 34484905 | pmc = 8382366 | doi = 10.1212/CPJ.0000000000000960 }}</ref><ref name="JAMAIM">{{cite journal | vauthors = Cohen PA, Zakharevich I, Gerona R | title = Presence of Piracetam in Cognitive Enhancement Dietary Supplements | journal = JAMA Internal Medicine | volume = 180 | issue = 3 | pages = 458–459 | date = March 2020 | pmid = 31764936 | pmc = 6902196 | doi = 10.1001/jamainternmed.2019.5507 }}</ref> A 2019 study found that piracetam supplements sold in the United States were inaccurately labeled.<ref name="JAMAIM"/> Racetams are often referred to as nootropics, but this property is not well established in humans, and nootropics are not consistently found in all racetams.<ref name="NHM">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=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 = 2 }}</ref> The racetams have poorly understood [[mechanism of action|mechanisms]], although piracetam and aniracetam are known to act as [[positive allosteric modulator]]s of [[AMPA receptor]]s and appear to modulate [[acetylcholine|cholinergic]] systems.<ref>{{cite journal | vauthors = 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 = Current Pharmaceutical Design | volume = 8 | issue = 2 | pages = 125–138 | year = 2002 | pmid = 11812254 | doi = 10.2174/1381612023396582 }}</ref> Similar compounds, such as [[N-Phenylacetyl-L-prolylglycine ethyl ester|noopept]] and [[aloracetam]], do not meet the chemical definition for being a racetam, though they are considered "racetam-like" due to their high similarity.<ref name="WHO-INN-Stembook2018">[https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/stembook-2018.pdf The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances.] Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1).</ref>

According to the FDA,

<blockquote>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.<ref name="unlimited">{{cite web|url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm225605.htm|archive-url=https://wayback.archive-it.org/7993/20170112004501/https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm225605.htm|url-status=dead|archive-date=12 January 2017|title=FDA Warning Letter: Unlimited Nutrition|author=John Gridley|date=30 August 2010|publisher=Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration |access-date=5 April 2016}}</ref></blockquote>

==Herbs==
* ''[[Centella asiatica]]''{{snd}} A 2017 meta-analysis showed no significant improvement in  cognitive function.<ref name="pmid28878245">{{cite journal | vauthors = Puttarak P, Dilokthornsakul P, Saokaew S, Dhippayom T, Kongkaew C, Sruamsiri R, Chuthaputti A, Chaiyakunapruk N | title = Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 10646 | date = September 2017 | pmid = 28878245 | pmc = 5587720 | doi = 10.1038/s41598-017-09823-9 | bibcode = 2017NatSR...710646P }}</ref> Clinical efficacy and safety have not been scientifically confirmed for this herb.<ref name="drugs">{{cite web|title=Gotu kola|url=https://www.drugs.com/npp/gotu-kola.html|publisher=Drugs.com|access-date=21 September 2023|date=23 January 2023}}</ref>
* ''[[Ginkgo biloba]]''{{snd}} 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.<ref>{{cite journal | vauthors = Laws KR, Sweetnam H, Kondel TK | title = Is Ginkgo biloba a cognitive enhancer in healthy individuals? A meta-analysis | journal = Human Psychopharmacology | volume = 27 | issue = 6 | pages = 527–533 | date = November 2012 | pmid = 23001963 | doi = 10.1002/hup.2259 | s2cid = 6307491 }}</ref><ref name="nccih">{{cite web|url=http://nccih.nih.gov/health/ginkgo/ataglance.htm|date=September 2016|title=Ginkgo|publisher=National Center for Complementary and Integrative Health, US National Institutes of Health|access-date=July 9, 2018}}</ref>
* ''[[Panax ginseng]]''{{snd}} A [[Cochrane Collaboration|Cochrane review]] found possible "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."<ref>{{cite journal | vauthors = Geng J, Dong J, Ni H, Lee MS, Wu T, Jiang K, Wang G, Zhou AL, Malouf R | title = Ginseng for cognition | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD007769 | date = December 2010 | pmid = 21154383 | doi = 10.1002/14651858.CD007769.pub2 }}</ref>

==Nutrients and dietary supplements==

* [[Folate]]{{snd}} no cognition-enhancing effects in [[middle-aged]] and older adults without [[folate deficiency]].<ref name="Systematic rev – B vitamins">{{cite journal | vauthors = Forbes SC, Holroyd-Leduc JM, Poulin MJ, Hogan DB | title = Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials | journal = Canadian Geriatrics Journal | volume = 18 | issue = 4 | pages = 231–245 | date = December 2015 | pmid = 26740832 | pmc = 4696451 | doi = 10.5770/cgj.18.189 }}</ref>
* [[Omega-3 fatty acids]]: [[docosahexaenoic acid|DHA]] and [[eicosapentaenoic acid|EPA]]{{snd}} 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.<ref>{{cite journal | vauthors = Gillies D, Leach MJ, Perez Algorta G | title = Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 4 | pages = CD007986 | date = April 2023 | pmid = 37058600 | pmc = 10103546 | doi = 10.1002/14651858.CD007986.pub3 }}</ref><ref name="Cochrane LD">{{cite journal | vauthors = Tan ML, Ho JJ, Teh KH | title = Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD009398 | date = December 2012 | pmid = 23235675 | doi = 10.1002/14651858.CD009398.pub2 | veditors = Tan ML }}</ref> Two other systematic reviews found no cognition-enhancing effects in the general population.<ref name="Systematic rev – B vitamins" /><ref name="Systematic review: Omega-3s">{{cite journal | vauthors = Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P | title = Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis | journal = Journal of Psychopharmacology | volume = 29 | issue = 7 | pages = 753–763 | date = July 2015 | pmid = 26040902 | doi = 10.1177/0269881115587958 | s2cid = 358375 | url = https://kclpure.kcl.ac.uk/portal/en/publications/dcd51fd9-ba02-4e7c-b84e-6b2086ae91af }}</ref>
* [[Vitamin B12|Vitamin B<sub>12</sub>]]{{snd}} no cognition-enhancing effects in middle-aged and older adults without [[B12 deficiency]].<ref name="Systematic rev – B vitamins" />
* [[Vitamin B6|Vitamin B<sub>6</sub>]]{{snd}} no cognition-enhancing effects in middle-aged and older adults without [[vitamin B6 deficiency|B6 deficiency]].<ref name="Systematic rev – B vitamins" />
* [[Vitamin E]]{{snd}} no cognition-enhancing effects in middle-aged and older adults without [[vitamin E deficiency]].<ref name="Systematic rev – B vitamins" />

== See also ==
{{Portal|Medicine|Psychology}}
* [[Cosmetic pharmacology]]
* [[List of drugs used by militaries]]
* [[Neuroenhancement]]
* [[Psychoactive drug]]

== References ==
{{Reflist}}

== External links ==
{{wiktionary|nootropic}}
* {{Commons category-inline|Nootropics}}

{{Major Drug Groups}}
{{Chemical classes of psychoactive drugs}}
{{Authority control}}

[[Category:Nootropics| ]]
[[Category:1970s neologisms]]
[[Category:Amphetamine]]
[[Category:Methylphenidate]]
[[Category:Drug classes defined by psychological effects]]