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Nootropic

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

Nootropics (/noʊ.əˈtroʊpɪks/ noh-ə-TROHP-iks or /noʊ.əˈtrɒpɪks/ noh-ə-TROP-iks[1]; but not /njuːˈtroʊpɪks/ new-TROHP-iks or /njuːˈtrɒpɪks/ new-TROP-iks[1], which are common mispronunciations), colloquially brain supplements, smart drugs and cognitive enhancers, are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.

While commonly in the form of dietary supplements, nutraceuticals or energy drinks,[2] some nootropic compounds are prescription and non-prescription drugs in various countries.

In the United States, the Federal Trade Commission and FDA have warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.[3][4]

History of term

The term nootropic is derived from Ancient Greek νόος (nóos) 'mind' and τροπή (tropḗ) 'turning'.[1][5][6]

The first documented use of "nootropic" in reference to substances purported to increase cognitive functions was by Corneliu E. Giurgea in 1972.[5][6][7] 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.[6]

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.[7]

Unproven marketing claims

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.[8] In 2019, the US FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplement products.[3][4][9][10] 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.[3][4]

In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing.[11][12] In 2019, the FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.[3][4]

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.[3][4][9][10][13][14]

Availability and prevalence

In 2008, stimulants, such as caffeine, were the most commonly used nootropic agent.[15] 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.[16] Piracetam, noopept and meclofenoxate have been sold as dietary supplements.[2][17][18]

Adverse effects

The main concern with pharmaceutical drugs and dietary supplements are adverse effects. 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.[19]

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.[20]

Types

Central nervous system stimulants

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.[21][22][23] 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.[21][22][24][25] Relatively high doses of stimulants cause cognitive deficits.[24][25]

  • Amphetamine – 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.[21][22][23][25] 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.[23] It also improves task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.[22][24][25]
  • Caffeine – a meta-analysis found an increase in alertness and attentional performance.[26][24]
  • Eugeroics (armodafinil and modafinil) – 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.[23] 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.[27] Modafinil does not improve mood or motivation in sleep-deprived or non-sleep deprived individuals.[28]
  • Methylphenidate – a benzylpiperidine derivative that may improve working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency in healthy people.[21][23] It also may improve task saliency and performance on tedious tasks.[25] At above optimal doses, methylphenidate has off–target effects that decrease learning.[29]
  • Nicotine – has been associated with improved alertness, attention, memory, and motor performance, according to a meta-analysis.[30] 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.[31]

Racetams

Main article: Racetam

Racetams, such as piracetam, oxiracetam, phenylpiracetam, and aniracetam, are often marketed as cognitive enhancers and sold over the counter.[2][17] A 2019 study found that piracetam supplements sold in the United States were inaccurately labeled.[17] 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.[32] 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.[33]

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.[14]

Cholinergics

Main article: 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.[34]
  • 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.[35]
  • 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.[36][37]

Herbs

  • Centella asiatica – A 2017 meta-analysis showed no significant improvement in cognitive function.[38] Clinical efficacy and safety have not been scientifically confirmed for this herb.[39]
  • 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.[40][41]
  • Panax ginseng – 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."[42]

Nutrients and dietary supplements

  • Folate – no cognition-enhancing effects in middle-aged and older adults without folate deficiency.[43]
  • 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.[44][45] Two other systematic reviews found no cognition-enhancing effects in the general population.[43][46]
  • Vitamin B12 – no cognition-enhancing effects in middle-aged and older adults without B12 deficiency.[43]
  • Vitamin B6 – no cognition-enhancing effects in middle-aged and older adults without B6 deficiency.[43]
  • Vitamin E – no cognition-enhancing effects in middle-aged and older adults without vitamin E deficiency.[43]

See also

References

  1. ^ a b c "Nootropic". Oxford English Dictionary. 2024. Retrieved January 14, 2024.
  2. ^ a b c Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I (June 2021). "Five Unapproved Drugs Found in Cognitive Enhancement Supplements". Neurology. Clinical Practice. 11 (3): e303–e307. doi:10.1212/CPJ.0000000000000960. PMC 8382366. PMID 34484905.
  3. ^ a b c d e "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". US Food and Drug Administration, US Federal Trade Commission. February 11, 2019. Retrieved May 11, 2019.
  4. ^ a b c d e "Health fraud scams: Unproven Alzheimer's disease products". US Food and Drug Administration. December 22, 2018. Retrieved May 11, 2019.
  5. ^ a b Giurgea C (1972). "[Pharmacology of integrative activity of the brain. Attempt at nootropic concept in psychopharmacology]". Actualites Pharmacologiques (in French). 25: 115–156. PMID 4541214.
  6. ^ a b c Giurgea C, Salama M (January 1, 1977). "Nootropic drugs". Progress in Neuro-Psychopharmacology. 1 (3): 235–247. doi:10.1016/0364-7722(77)90046-7. The term "nootropic" (noos = mind; tropein = towards) was proposed by us (Giurgea, 1972,1973) to designate psychotropic drugs
  7. ^ a b Malík M, Tlustoš P (August 2022). "Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs". Nutrients. 14 (16): 3367. doi:10.3390/nu14163367. PMC 9415189. PMID 36014874.
  8. ^ "Dietary Supplements: What You Need to Know". US Food and Drug Administration. Retrieved February 14, 2015.
  9. ^ a b Correll Jr WA (February 5, 2019). "FDA Warning Letter: Peak Nootropics LLC aka Advanced Nootropics". Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved May 11, 2019.
  10. ^ a b Correll Jr WA (February 5, 2019). "FDA Warning Letter: TEK Naturals". Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved May 11, 2019.
  11. ^ Schultz H (May 17, 2018). "Some shady ingredients find home in nootropics category". NutraIngredients-USA.com, William Reed Business Media Ltd. Retrieved May 11, 2019.
  12. ^ Heid M (January 23, 2019). "Nootropics, or 'Smart Drugs,' Are Gaining Popularity. But Should You Take Them?". Time. Retrieved May 12, 2019.
  13. ^ Singleton ER (January 7, 2010). "FDA Warning Letter: Cerebral Health LLC". Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Archived from the original on January 12, 2017. Retrieved May 12, 2019.
  14. ^ a b John Gridley (August 30, 2010). "FDA Warning Letter: Unlimited Nutrition". Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Archived from the original on January 12, 2017. Retrieved April 5, 2016.
  15. ^ Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, Farah MJ (December 2008). "Towards responsible use of cognitive-enhancing drugs by the healthy" (PDF). Nature. 456 (7223): 702–705. Bibcode:2008Natur.456..702G. doi:10.1038/456702a. OCLC 01586310. PMID 19060880. S2CID 3598099.
  16. ^ "AMA confronts the rise of nootropics". American Medical Association. June 14, 2016. Retrieved May 12, 2019.
  17. ^ a b c Cohen PA, Zakharevich I, Gerona R (March 2020). "Presence of Piracetam in Cognitive Enhancement Dietary Supplements". JAMA Internal Medicine. 180 (3): 458–459. doi:10.1001/jamainternmed.2019.5507. PMC 6902196. PMID 31764936.
  18. ^ Cohen PA, Avula B, Khan I (October 2022). "The unapproved drug centrophenoxine (meclofenoxate) in cognitive enhancement dietary supplements". Clinical Toxicology. 60 (10): 1156–1158. doi:10.1080/15563650.2022.2109485. PMID 35959800. S2CID 251516603.
  19. ^ Malykh AG, Sadaie MR (February 2010). "Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders". Drugs. 70 (3): 287–312. doi:10.2165/11319230-000000000-00000. PMID 20166767. S2CID 12176745.
  20. ^ Goldman P (October 2001). "Herbal medicines today and the roots of modern pharmacology". Annals of Internal Medicine. 135 (8 Pt 1): 594–600. doi:10.7326/0003-4819-135-8_Part_1-200110160-00010. PMID 11601931. S2CID 35766876.
  21. ^ a b c d Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex". Biological Psychiatry. 77 (11): 940–950. doi:10.1016/j.biopsych.2014.09.013. PMC 4377121. PMID 25499957.
  22. ^ a b c d Ilieva IP, Hook CJ, Farah MJ (June 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". Journal of Cognitive Neuroscience. 27 (6): 1069–1089. doi:10.1162/jocn_a_00776. PMID 25591060. S2CID 15788121.
  23. ^ a b c d e Bagot KS, Kaminer Y (April 2014). "Efficacy of stimulants for cognitive enhancement in non-attention deficit hyperactivity disorder youth: a systematic review". Addiction. 109 (4): 547–557. doi:10.1111/add.12460. PMC 4471173. PMID 24749160.
  24. ^ a b c d Wood S, Sage JR, Shuman T, Anagnostaras SG (January 2014). "Psychostimulants and cognition: a continuum of behavioral and cognitive activation". Pharmacological Reviews. 66 (1): 193–221. doi:10.1124/pr.112.007054. PMC 3880463. PMID 24344115.
  25. ^ a b c d e Malenka RC, Nestler EJ, Hyman SE, Holtzman DM (2015). "14: Higher Cognitive Function and Behavioral Control". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (3 ed.). New York: McGraw-Hill Medical. ISBN 9780071827706.
  26. ^ Camfield DA, Stough C, Farrimond J, Scholey AB (August 2014). "Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis". Nutrition Reviews. 72 (8): 507–522. doi:10.1111/nure.12120. PMID 24946991.
  27. ^ Battleday RM, Brem AK (November 2015). "Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review". European Neuropsychopharmacology. 25 (11): 1865–1881. doi:10.1016/j.euroneuro.2015.07.028. PMID 26381811. S2CID 23319688.
  28. ^ Mohamed AD (2017). "Does modafinil improve cognitive functioning in healthy individuals?". In ter Meulen R, Hall W, Mohammed AD (eds.). Rethinking Cognitive Enhancement. Oxford University Press. p. 116. ISBN 9780198727392.
  29. ^ Urban KR, Gao WJ (2014). "Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain". Frontiers in Systems Neuroscience. 8: 38. doi:10.3389/fnsys.2014.00038. PMC 4026746. PMID 24860437.
  30. ^ Heishman SJ, Kleykamp BA, Singleton EG (July 2010). "Meta-analysis of the acute effects of nicotine and smoking on human performance". Psychopharmacology. 210 (4): 453–469. doi:10.1007/s00213-010-1848-1. PMC 3151730. PMID 20414766.
  31. ^ Pasetes SV, Ling PM, Apollonio DE (January 2020). "Cognitive performance effects of nicotine and industry affiliation: a systematic review". Substance Abuse: Research and Treatment. 14: 117822182092654. doi:10.1177/1178221820926545. ISSN 1178-2218. PMC 7271274. PMID 32547048.
  32. ^ Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2 ed.). New York: McGraw-Hill Medical. p. 454. ISBN 9780071481274.
  33. ^ Gualtieri F, Manetti D, Romanelli MN, Ghelardini C (2002). "Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs". Current Pharmaceutical Design. 8 (2): 125–138. doi:10.2174/1381612023396582. PMID 11812254.
  34. ^ Parker AG, Byars A, Purpura M, Jäger R (September 21, 2015). "The effects of alpha-glycerylphosphorylcholine, caffeine or placebo on markers of mood, cognitive function, power, speed, and agility". Journal of the International Society of Sports Nutrition. 12 (Suppl 1): P41. doi:10.1186/1550-2783-12-S1-P41. ISSN 1550-2783. PMC 4595381.
  35. ^ Lippelt DP, van der Kint S, van Herk K, Naber M (June 24, 2016). "No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults". PLOS ONE. 11 (6): e0157714. Bibcode:2016PLoSO..1157714L. doi:10.1371/journal.pone.0157714. PMC 4920398. PMID 27341028.
  36. ^ Fioravanti M, Buckley AE (September 2006). "Citicoline (Cognizin) in the treatment of cognitive impairment". Clinical Interventions in Aging. 1 (3): 247–251. doi:10.2147/ciia.2006.1.3.247. PMC 2695184. PMID 18046877.
  37. ^ Franco-Maside A, Caamaño J, Gómez MJ, Cacabelos R (October 1994). "Brain mapping activity and mental performance after chronic treatment with CDP-choline in Alzheimer's disease". Methods and Findings in Experimental and Clinical Pharmacology. 16 (8): 597–607. PMID 7760585.
  38. ^ Puttarak P, Dilokthornsakul P, Saokaew S, Dhippayom T, Kongkaew C, Sruamsiri R, Chuthaputti A, Chaiyakunapruk N (September 2017). "Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis". Scientific Reports. 7 (1): 10646. Bibcode:2017NatSR...710646P. doi:10.1038/s41598-017-09823-9. PMC 5587720. PMID 28878245.
  39. ^ "Gotu kola". Drugs.com. January 23, 2023. Retrieved September 21, 2023.
  40. ^ Laws KR, Sweetnam H, Kondel TK (November 2012). "Is Ginkgo biloba a cognitive enhancer in healthy individuals? A meta-analysis". Human Psychopharmacology. 27 (6): 527–533. doi:10.1002/hup.2259. PMID 23001963. S2CID 6307491.
  41. ^ "Ginkgo". National Center for Complementary and Integrative Health, US National Institutes of Health. September 2016. Retrieved July 9, 2018.
  42. ^ Geng J, Dong J, Ni H, Lee MS, Wu T, Jiang K, Wang G, Zhou AL, Malouf R (December 2010). "Ginseng for cognition". The Cochrane Database of Systematic Reviews (12): CD007769. doi:10.1002/14651858.CD007769.pub2. PMID 21154383.
  43. ^ a b c d e Forbes SC, Holroyd-Leduc JM, Poulin MJ, Hogan DB (December 2015). "Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials". Canadian Geriatrics Journal. 18 (4): 231–245. doi:10.5770/cgj.18.189. PMC 4696451. PMID 26740832.
  44. ^ Gillies D, Leach MJ, Perez Algorta G (April 2023). "Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents". The Cochrane Database of Systematic Reviews. 2023 (4): CD007986. doi:10.1002/14651858.CD007986.pub3. PMC 10103546. PMID 37058600.{{cite journal}}: CS1 maint: PMC embargo expired (link)
  45. ^ Tan ML, Ho JJ, Teh KH (December 2012). Tan ML (ed.). "Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders". The Cochrane Database of Systematic Reviews. 12: CD009398. doi:10.1002/14651858.CD009398.pub2. PMID 23235675.
  46. ^ Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P (July 2015). "Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis". Journal of Psychopharmacology. 29 (7): 753–763. doi:10.1177/0269881115587958. PMID 26040902. S2CID 358375.
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