Nootropic

Nootropics (/noʊ.əˈtrɒpɪks/ noh-ə-TROP-iks) (colloquial: smart drugs and cognitive enhancers) are drugs, supplements, and other substances that may improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals.[1] While many substances are purported to improve cognition, research is at a preliminary stage as of 2018, and the effects of the majority of these agents are not fully determined.

The use of cognition-enhancing drugs by healthy individuals in the absence of a medical indication spans numerous controversial issues, including the ethics and fairness of their use, concerns over adverse effects, and the diversion of prescription drugs for nonmedical uses, among others.[1][2] Nonetheless, the international sales of cognition-enhancing supplements exceeded US$1 billion in 2015 when global demand for these compounds grew.[3]

The word nootropic was coined in 1972 by a Romanian psychologist and chemist, Corneliu E. Giurgea,[4][5] from the Greek words νοῦς (nous), or "mind", and τρέπειν (trepein), meaning to bend or turn.[6]

Availability and prevalence

In 2008, the most commonly used class of drug was stimulants, such as caffeine.[7] Manufacturer's marketing claims for dietary supplements are usually not formally tested and verified by independent entities.[8]

Use by students

The use of prescription stimulants is especially prevalent among students.[9] Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetime.[10][11][12] Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups.[13] Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily intended for performance enhancement rather than as recreational drugs.[14][15][16] 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.[10][11][17][18]

Side effects

The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effects. Long-term safety evidence is typically unavailable for nootropics.[13] 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]

Drugs

Central nervous system stimulants

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 enhanced cognition in healthy people.[21][22][23] 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.[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 improved 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 improved memory consolidation, in turn leading to improved recall of information in non-ADHD youth.[23] It also improved task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.[22][24][25]
  • Methylphenidate – a benzylpiperidine that had cognitive effects (e.g., working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency) in healthy people.[21][22][23] It also may improve task saliency and performance on tedious tasks.[25] At above optimal doses, methylphenidate had off–target effects that decreased learning.[26]
  • Eugeroics (armodafinil and modafinil) – are classified as "wakefulness promoting" agents; modafinil increased alertness, particularly in sleep deprived individuals, and was noted to facilitate 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 appeared to enhance executive function.[27] Modafinil does not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals.[28]
  • Caffeine – a meta-analysis found an increase in alertness and attentional performance.[29][24]
  • Nicotine – a meta-analysis of 41 clinical studies concluded that nicotine or smoking caused small improvements in fine motor abilities, alerting and orienting attention, and episodic and working memory.[30]

Racetams

Racetams, such as piracetam, oxiracetam, and aniracetam, which are often marketed as cognitive enhancers and sold over-the-counter. Racetams are often referred to as nootropics, but this property is not well established.[31] 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.[32]

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 man 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."[33]

Miscellaneous

Dietary supplements

  • Panax ginseng – A review by the Cochrane Collaboration 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."[36] According to the National Center for Complementary and Integrative Health, "[a]lthough Asian ginseng has been widely studied for a variety of uses, research results to date do not conclusively support health claims associated with the herb."[37]
  • 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.[38][39]
  • Salvia officinalis (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.[40][41] The thujone present in Salvia extracts may be neurotoxic.[41]

Null findings in systematic reviews

  • 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.[42][43] Two other systematic reviews noted no cognition-enhancing effects in the general population or middle-aged and older adults.[44][45]
  • Folate – no cognition-enhancing effects in middle-aged and older adults.[45]
  • Vitamin B6 – no cognition-enhancing effects in middle-aged and older adults.[45]
  • Vitamin B12 – no cognition-enhancing effects in middle-aged and older adults.[45]
  • Vitamin E – no cognition-enhancing effects in middle-aged and older adults.[45]
  • Pramipexole – no significant cognition-enhancing effects in healthy individuals.[35]
  • Guanfacine – no significant cognition-enhancing effects in healthy individuals.[35]
  • Clonidine – no significant cognition-enhancing effects in healthy individuals.[35]
  • Fexofenadine – no significant cognition-enhancing effects in healthy individuals.[35]

See also

References

  1. 1 2 Frati P, Kyriakou C, Del Rio A, Marinelli E, Vergallo GM, Zaami S, Busardò FP (January 2015). "Smart drugs and synthetic androgens for cognitive and physical enhancement: revolving doors of cosmetic neurology". Curr Neuropharmacol. 13 (1): 5–11. doi:10.2174/1570159X13666141210221750. PMC 4462043. PMID 26074739.
  2. ↑ Albertson TE, Chenoweth JA, Colby DK, Sutter ME (2016). "The Changing Drug Culture: Use and Misuse of Cognition-Enhancing Drugs". FP Essent. 441: 25–9. PMID 26881770.
  3. ↑ Chinthapalli K (September 2015). "The billion dollar business of being smart". BMJ. 351: h4829. doi:10.1136/bmj.h4829. PMID 26370589.
  4. ↑ Gazzaniga, Michael S. (2006). The Ethical Brain: The Science of Our Moral Dilemmas (P.S.). New York, N.Y: Harper Perennial. p. 184. ISBN 0-06-088473-8.
  5. ↑ Giurgea C (1972). "[Pharmacology of integrative activity of the brain. Attempt at nootropic concept in psychopharmacology] ("Vers une pharmacologie de l'active integrative du cerveau: Tentative du concept nootrope en psychopharmacologie")". Actual Pharmacol (Paris) (in French). 25: 115–56. PMID 4541214.
  6. ↑ "nootropic | Definition of nootropic in English by Oxford Dictionaries". Oxford Dictionaries | English. Retrieved 2018-07-19.
  7. ↑ Greely, Henry; Sahakian, Barbara; Harris, John; Kessler, Ronald C.; Gazzaniga, Michael; Campbell, Philip; Farah, Martha J. (December 10, 2008). "Towards responsible use of cognitive-enhancing drugs by the healthy". Nature. Nature Publishing Group. 456 (7223): 702–705. Bibcode:2008Natur.456..702G. doi:10.1038/456702a. ISSN 1476-4687. OCLC 01586310. PMID 19060880. Retrieved March 25, 2014. (Subscription required (help)).
  8. ↑ "Dietary Supplements: What You Need to Know". US Food and Drug Administration. Retrieved February 14, 2015.
  9. ↑ McCabe, Sean Esteban; Knight, John R.; Teter, Christian J.; Wechsler, Henry (January 1, 2005). "Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey". Addiction. 100 (1): 96–106. doi:10.1111/j.1360-0443.2005.00944.x. PMID 15598197.
  10. 1 2 Sattler, S.; Sauer, C.; Mehlkop, G.; Graeff, P. (2013). "The Rationale for Consuming Cognitive Enhancement Drugs in University Students and Teachers". PLoS ONE. 8 (7): e68821. Bibcode:2013PLoSO...868821S. doi:10.1371/journal.pone.0068821. PMC 3714277. PMID 23874778.
  11. 1 2 Sattler, Sebastian; Wiegel, Constantin (February 25, 2013). "Cognitive Test Anxiety and Cognitive Enhancement: The Influence of Students' Worries on Their Use of Performance-Enhancing Drugs". Substance Use & Misuse. Informa Healthcare New York. 48 (3): 220–232. doi:10.3109/10826084.2012.751426. Retrieved April 5, 2014.
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  15. ↑ Weyandt LL, Oster DR, Marraccini ME, Gudmundsdottir BG, Munro BA, Zavras BM, Kuhar B (September 2014). "Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants". Psychol. Res. Behav. Manag. 7: 223–249. doi:10.2147/PRBM.S47013. PMC 4164338. PMID 25228824.
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  20. ↑ Goldman P (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.
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  28. ↑ Meulen, Ruud ter; Hall, Wayne; Mohammed, Ahmed (2017). Rethinking Cognitive Enhancement. Oxford University Press. p. 116. ISBN 9780198727392.
  29. 1 2 3 Camfield DA, Stough C, Farrimond J, Scholey AB (2014). "Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis". Nutr. Rev. 72 (8): 507–22. doi:10.1111/nure.12120. PMID 24946991.
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  33. ↑ "Warning Letters – Unlimited Nutrition 8/30/10". www.fda.gov. Retrieved April 5, 2016.
  34. ↑ EFSA Panel on Dietetic Products, Nutrition and Allergies; European Food Safety Authority (EFSA), Parma, Italy (2011). "Scientific Opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004) and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 9 (6): 2238. doi:10.2903/j.efsa.2011.2238.
  35. 1 2 3 4 5 6 Fond G, Micoulaud-Franchi JA, Brunel L, Macgregor A, Miot S, Lopez R, Richieri R, Abbar M, Lancon C, Repantis D (September 2015). "Innovative mechanisms of action for pharmaceutical cognitive enhancement: A systematic review". Psychiatry Res. 229 (1–2): 12–20. doi:10.1016/j.psychres.2015.07.006. PMID 26187342.
  36. ↑ Geng J, Dong J, Ni H, Lee MS, Wu T, Jiang K, Wang G, Zhou AL, Malouf R (2010). "Ginseng for cognition". Cochrane Database Syst Rev (12): CD007769. doi:10.1002/14651858.CD007769.pub2. PMID 21154383.
  37. ↑ "Asian Ginseng". National Center for Complementary and Integrative Health, US National Institutes of Health. September 2016. Retrieved 9 July 2018.
  38. ↑ Laws KR, Sweetnam H, Kondel TK (November 2012). "Is Ginkgo biloba a cognitive enhancer in healthy individuals? A meta-analysis". Hum Psychopharmacol. 27 (6): 527–33. doi:10.1002/hup.2259. PMID 23001963.
  39. ↑ "Ginkgo". National Center for Complementary and Integrative Health, US National Institutes of Health. September 2016. Retrieved 9 July 2018.
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  41. 1 2 Lopresti AL (2017). "Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects". Drugs R D. 17 (1): 53–64. doi:10.1007/s40268-016-0157-5. PMC 5318325. PMID 27888449.
  42. ↑ Gillies D; Sinn JKh; Lad SS; Leach MJ; Ross MJ (2012). "Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents". Cochrane Database Syst Rev. 7: CD007986. doi:10.1002/14651858.CD007986.pub2. PMID 22786509.
  43. ↑ Tan ML, Ho JJ, Teh KH (2012). "Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders". Cochrane Database Syst Rev. 12: CD009398. doi:10.1002/14651858.CD009398.pub2. PMID 23235675.
  44. ↑ Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P (2015). "Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis". J. Psychopharmacol. (Oxford). 29 (7): 753–63. doi:10.1177/0269881115587958. PMID 26040902.
  45. 1 2 3 4 5 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". Can Geriatr J. 18 (4): 231–45. doi:10.5770/cgj.18.189. PMC 4696451. PMID 26740832.
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