Nootropic#Miscellaneous

The term nootropic is derived {{ety|grc|{{wikt-lang|grc|νόος}} (nóos)|mind||{{wikt-lang|grc|τροπή}} (tropḗ)|turning}}.{{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 }}{{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}}

The first documented use of "nootropic" in reference to substances purported to increase cognitive functions was by Corneliu E. Giurgea in 1972.{{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 }} 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.

Giurgea stated that nootropic drugs should have the following characteristics:

1. They should enhance learning and memory.
2. They should enhance the resistance of learned behaviors or memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).
3. They should protect the brain against various physical or chemical injuries.
4. They should increase the efficacy of the tonic cortical control mechanisms.
5. They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess few adverse effects 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.

Nootropics include both prescription drugs and dietary supplements marketed to enhance brain function, but while FDA-approved drugs have proven benefits and oversight, many dietary supplements lack evidence, may contain unapproved or hidden drugs, and pose safety and regulatory risks.

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.{{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}} In 2019, the US FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplement products.{{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}}{{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 |access-date=May 11, 2019 |publisher=US Food and Drug Administration}}{{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}}{{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}} The FDA and FTC stated that some nootropic products had not been 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.

In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing.{{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}}{{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}} In 2019, the FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.

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.{{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}}

In 2008, stimulants, such as caffeine, were the most commonly used nootropic agent.{{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 }} 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.{{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}} Piracetam, noopept and meclofenoxate have been sold as dietary supplements.{{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 }}

The main concern with pharmaceutical drugs and dietary supplements are adverse effects, 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.{{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 }}

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.{{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 }}

{{anchor|Drugs}}

Systematic reviews 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.{{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 }}{{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 }} In particular, the classes of stimulants that demonstrate possible cognition-enhancing effects in humans have evidence in vitro as direct agonists or indirect agonists of dopamine receptor D₁ or adrenoceptor 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 }}{{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 }}{{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}} Relatively high doses of stimulants cause cognitive deficits.

• 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) in healthy people and in individuals with ADHD. 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. It also improves task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.
• Caffeine{{snd}} a meta-analysis found an increase in alertness and attentional performance.{{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 }}
• 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. 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.{{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 }} Modafinil does not improve mood or motivation in sleep-deprived or non-sleep deprived individuals.{{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 }}
• Methylphenidate{{snd}} a benzylpiperidine derivative that may improve working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency in healthy people. It also may improve task saliency and performance on tedious tasks. At above optimal doses, methylphenidate has off–target effects that decrease learning.{{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 }}
• Nicotine{{snd}} has been associated with improved alertness, attention, memory, and motor performance, according to a meta-analysis.{{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 }} 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.{{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}}

{{Main|Cholinergic}}

Some supposed nootropic substances are compounds and analogues of choline, a precursor of acetylcholine (a neurotransmitter) and phosphatidylcholine (a structural component of cell membranes).

• Alpha-GPC – L-alpha glycerylphosphorylcholine has been studied only in the context of cognitive performance alongside other substances such as caffeine.{{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 }}
• 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.{{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 }}
• 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.{{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 }}{{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 }}

{{Main|Racetam}}

Racetams, such as piracetam, oxiracetam, phenylpiracetam, and aniracetam, are often marketed as cognitive enhancers and sold over the counter.{{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 }}{{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 }} A 2019 study found that piracetam supplements sold in the United States were inaccurately labeled. 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.{{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 }} 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.{{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 }} Similar compounds, such as noopept and aloracetam, do not meet the chemical definition for being a racetam, though they are considered "racetam-like" due to their high similarityhttps://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/stembook-2018.pdf

According to the FDA,

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.{{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}}

• Centella asiatica{{snd}} A 2017 meta-analysis showed no significant improvement in cognitive function.{{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 }} Clinical efficacy and safety have not been scientifically confirmed for this herb.{{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}}
• 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.{{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 }}{{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}}
• Panax ginseng{{snd}} A 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."{{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 }}

• Folate{{snd}} no cognition-enhancing effects in middle-aged and older adults without folate deficiency.{{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 }}
• Omega-3 fatty acids: DHA and 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.{{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 }}{{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 }} Two other systematic reviews found no cognition-enhancing effects in the general population.{{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 }}
• Vitamin B₁₂{{snd}} no cognition-enhancing effects in middle-aged and older adults without B12 deficiency.
• Vitamin B₆{{snd}} no cognition-enhancing effects in middle-aged and older adults without B6 deficiency.
• Vitamin E{{snd}} no cognition-enhancing effects in middle-aged and older adults without vitamin E deficiency.

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{{Reflist}}

{{wiktionary|nootropic}}

• {{Commons category-inline|Nootropics}}

{{Major Drug Groups}}

{{Chemical classes of psychoactive drugs}}

{{Authority control}}

Category:1970s neologisms

Category:Amphetamine

Category:Methylphenidate

Category:Drug classes defined by psychological effects