Nootropics (// noh-ə-TROP-iks), also referred to as smart drugs, memory enhancers, neuro enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve one or more aspects of mental function, such as working memory, motivation, and attention. The word nootropic was coined in 1972 by the Romanian Dr. Corneliu E. Giurgea, derived from the Greek words νους nous, or "mind", and τρέπειν trepein meaning to bend or turn.
Availability and prevalence
At present, there are only a few drugs which have been shown to improve some aspect of cognition in medical reviews. Many more are in different stages of development. The most commonly used class of drug is stimulants.
These drugs are used primarily to treat people with cognitive or motor function difficulties attributable to such disorders as Alzheimer's disease, Parkinson's disease, Huntington's disease and ADHD. However, more widespread use is being recommended by some researchers. Many drugs are marketed heavily on the Internet as having a variety of human enhancement applications as well. Nevertheless, intense marketing may not correlate with efficacy; while scientific studies support the beneficial effects of some compounds, the marketing claims by manufacturers of over-the-counter products are not formally tested.[by whom?]
||It has been suggested that Academic doping be merged into this section. (Discuss) Proposed since December 2014.|
In academia, modafinil has been used to increase productivity, although its long-term effects have not been assessed in healthy individuals. Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups. One survey found that 7% of students had used stimulants for a cognitive edge, and on some campuses use in the past year is as high as 25%. The use of prescription stimulants is especially prevalent among students attending academically competitive colleges and students.
Several factors positively and negatively influence the use of drugs to increase cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.
The main concern with pharmaceutical drugs is adverse effects, and these concerns apply to cognitive-enhancing drugs as well. Cognitive enhancers are often taken for the long-term when little data is available. While certain racetam compounds are suspected to have nootropic qualities, few side-effects, and a wide therapeutic window (low overdose risk), other cognitive enhancers may be associated with a high incidence of adverse effects or a narrower therapeutic window (higher overdose risk).[clarification needed] While addiction to stimulants is sometimes asserted to be a cause for concern, a very large body of research on the therapeutic use of the "more addictive" psychostimulants indicate that addiction is fairly rare in therapeutic doses.
Certain stimulants will enhance cognition in the general population, but only when used at low (therapeutic) concentrations. Relatively high doses of stimulants will result in cognitive deficits.
- Amphetamine pharmaceuticals (Adderall, dextroamphetamine, and lisdexamfetamine [a prodrug]) – TAAR1 agonists that mimic the effect of endogenous phenethylamine. Benefits in cognitive control and working memory are evident in the general population, and especially in individuals with ADHD. It also improves performance on tedious tasks that require a high degree of effort.
- Methylphenidate – a substituted phenethylamine that improves working memory and cognitive control. It also improves performance on tedious tasks that require a high degree of effort. At above optimal doses, methylphenidate has offtarget effects that can decrease learning by activating neurons not involved in the task at hand.
- Eugeroics (armodafinil and modafinil) – wakefulness promoting agents; increase alertness, particularly in sleep deprived individuals. They are clinically prescribed for narcolepsy, shift work sleep disorder, and daytime sleepiness remaining after sleep apnea treatments.
- Xanthines – most notably, caffeine – shown to increase alertness, performance, and in some studies, memory. Children and adults who consume low doses of caffeine showed increased alertness, yet a higher dose was needed to improve performance.
- Nicotine – A meta-analysis of 41 double-blind, placebo-controlled studies concluded that nicotine or smoking had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory.
- Phosphatidylserine (a phospholipid) with DHA and EPA (omega-3 fatty acids) – a review of literature and subsequent randomized controlled trial indicate concurrent supplemental use can protect and potentially improve brain function, with clinical benefits for those with ADHD and other disorders. Two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids alone (without phosphatidylserine) for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder.
- Tianeptine – enhances several metrics of cognition in animal models. It has also been shown to prevent stress-induced dendritic remodeling in various brain structures, and antagonizes alcohol's neurodegenerative effects.
- Valproate – a study has suggested that valproate may be able to enhance the cognitive ability of absolute pitch.
- Amitriptyline – possesses marked neurotrophic effects (e.g., neurite growth) through agonist activity at two different tropomyosin receptor kinase family receptors, TrkA and TrkB, that typically bind the endogenous neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-4 (NT-4), although such effects may be overshadowed by its potent blockade of cholinergic receptors.
- Bacopa monnieri – A nutraceutical herb with "neural tonic" and memory enhancing properties shown in humans in a double-blinded RCTs.
- Panax ginseng – Multiple RCTs in healthy volunteers have indicated increases in accuracy of memory, speed in performing attention tasks and improvement in performing difficult mental arithmetic tasks, as well as reduction in fatigue and improvement in mood.
- Ginkgo biloba – Different reviews come to different conclusions. A 2009 Cochrane review found not enough evidence to make conclusions in those with dementia. Another review stated "there is consistent evidence that chronic administration improves selective attention, some executive processes and long-term memory for verbal and non-verbal material."
- Isoflavones – A double-blind, placebo-controlled study showed improvement in spatial working memory after administration of isoflavones. One RCT showed soy isoflavone supplementation improved performance on 6 of 11 cognitive tests, including visual-spatial memory and construction, verbal fluency and speeded dexterity, but worse on two tests of executive function.
The racetams are structurally similar compounds, such as pramiracetam, oxiracetam, coluracetam, and aniracetam, which are often marketed as cognitive enhancers and sold over-the-counter. Racetams are often referred to as nootropics, but this property of the drug class is not well established. The racetams have poorly understood mechanisms of action; however, piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.
- Cognitive science
- Human enhancement
- Intelligence amplification
- Life extension
- Memory and aging
- Neurobiological effects of physical exercise
- "Dorlands Medical Dictionary". Archived from the original on January 30, 2008.
- Lanni C, Lenzken SC, Pascale A, et al. (March 2008). "Cognition enhancers between treating and doping the mind". Pharmacol. Res. 57 (3): 196–213. doi:10.1016/j.phrs.2008.02.004. PMID 18353672.
- 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.
- 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.
- "nootropicTranslation". Retrieved 6 October 2014.
- Sahakian B; Morein-Zamir S (December 2007). "Professor's little helper". Nature 450 (7173): 1157–9. Bibcode:2007Natur.450.1157S. doi:10.1038/4501157a. PMID 18097378.
- 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 (. ))
- "Smart Drugs and Should We Take Them?". Dolan DNA Learning Center. Retrieved November 4, 2012.
- 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. Retrieved August 15, 2013.
- 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. doi:10.1371/journal.pone.0068821.
- 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.
- Bossaer, John. "The Use and Misuse of Prescription Stimulants as "Cognitive Enhancers" by Students at One Academic Health Sciences Center". Academic Medicine. Retrieved 6 October 2014.
Overall, 11.3% of responders admitted to misusing prescription stimulants. There was more misuse by respiratory therapy students, although this was not statistically significant (10.9% medicine, 9.7% pharmacy, 26.3% respiratory therapy; P = .087). Reasons for prescription stimulant misuse included to enhance alertness/energy (65.9%), to improve academic performance (56.7%), to experiment (18.2%), and to use recreationally/get high (4.5%).
- Sattler, Sebastian; Mehlkop, Guido; Graeff, Peter; Sauer, Carsten (February 1, 2014). "Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics". Substance Abuse Treatment, Prevention, and Policy 9 (1). BioMed Central Ltd. p. 8. doi:10.1186/1747-597X-9-8. ISSN 1747-597X. Retrieved April 5, 2014.
- Sattler, Sebastian; Forlini, Cynthia; Racine, Éric; Sauer, Carsten (August 5, 2013). "Impact of Contextual Factors and Substance Characteristics on Perspectives toward Cognitive Enhancement". PLOS ONE (PLOS) 8 (8): e71452. doi:10.1371/journal.pone.0071452. ISSN 1932-6203. LCCN 2006214532. OCLC 228234657. Retrieved April 5, 2014.
- Malik R, Sangwan A, Saihgal R, Jindal DP, Piplani P (2007). "Towards better brain management: nootropics". Curr. Med. Chem. 14 (2): 123–31. doi:10.2174/092986707779313408. PMID 17266573.
- Noble KA (December 2012). "Brain gain: adolescent use of stimulants for achievement". J. Perianesth. Nurs. 27 (6): 415–9. doi:10.1016/j.jopan.2012.09.001. PMID 23164208.
- Stolerman IP (2010). Stolerman IP, ed. Encyclopedia of Psychopharmacology. Berlin; London: Springer. p. 78. ISBN 9783540686989.
- Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 121–123. ISBN 9781441913968.
- Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge". CNS Drugs 25 (7): 539–554. doi:10.2165/11589380-000000000-00000. PMID 21699268.
- 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.
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 318. ISBN 9780071481274.
Mild dopaminergic stimulation of the prefrontal cortex enhances working memory. ...
Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in in normal subjects and those with ADHD. Positron emission tomography (PET) demonstrates that methylphenidate decreases regional cerebral blood flow in the doroslateral prefrontal cortex and posterior parietal cortex while improving performance of a spacial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. ... [It] is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control ... stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors.
- Wood S, Sage JR, Shuman T, Anagnostaras SG (January 2014). "Psychostimulants and cognition: a continuum of behavioral and cognitive activation". Pharmacol. Rev. 66 (1): 193–221. doi:10.1124/pr.112.007054. PMID 24344115.
- Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
- Bidwell LC, McClernon FJ, Kollins SH (August 2011). "Cognitive enhancers for the treatment of ADHD". Pharmacol. Biochem. Behav. 99 (2): 262–274. doi:10.1016/j.pbb.2011.05.002. PMC 3353150. PMID 21596055.
- 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. PMID 24860437.
- Mereu M, Bonci A, Newman AH, Tanda G (October 2013). "The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders". Psychopharmacology (Berl.) 229 (3): 415–34. doi:10.1007/s00213-013-3232-4. PMID 23934211.
- "Modafinil". MedlinePlus. Retrieved 19 August 2014.
- Rogers, P. (2007). "Caffeine, mood and mental performance in everyday life". Psychology Today 32 (1): 84–89. doi:10.1111/j.1467-3010.2007.00607.x.
- Kiefer, I. (2007). "Brain Food". Scientific American Mind 18 (5): 58–63. doi:10.1038/scientificamericanmind1007-58. Retrieved November 1, 2009.
- Heishman SJ, Kleykamp BA, Singleton EG (June 2010). "Meta-analysis of the acute effects of nicotine and smoking on human performance". Psychopharmacology (Berl). 210 (4): 453–69. doi:10.1007/s00213-010-1848-1. PMC 3151730. PMID 20414766. Retrieved March 23, 2012.
- Kidd PM (September 2007). "Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids". Altern Med Rev 12 (3): 207–27. PMID 18072818.
- Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman A (July 2012). "The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension". Eur. Psychiatry 27 (5): 335–42. doi:10.1016/j.eurpsy.2011.05.004. PMID 21807480.
- 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.
- 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.
- McEwen BS, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, Fuchs E (March 2010). "The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation". Mol. Psychiatry 15 (3): 237–49. doi:10.1038/mp.2009.80. PMC 2902200. PMID 19704408.
Cognitive deficits, such as an impairment of attention, memory and problem solving, have often been reported in patients with depressive disorders (69). Cognitive deficits and memory impairments in patients with depression may arise via disruption of the hypothalamic-pituitary adrenal (HPA) axis through hippocampal volume loss and changes in the amygdala. The magnitude of the hippocampal shrinkage reported in certain experimental conditions may partly underlie some of cognitive deficits that accompany major depression. Conversely, any prevention or restoration of these morphological changes in the hippocampus should be parallel to procognitive/promnesiant effects. Accordingly, tianeptine has particularly favorable effects on cognitive functions and the positive effect of tianeptine may be mediated through its upregulation of neurogenesis, but of course, the impact of neurogenesis on cognitive functions remains a matter of controversial debate.
Tianeptine prevents and reverses stress-induced glucocorticoid-mediated dendritic remodeling in CA3 pyramidal neurons in the hippocampus (40,41) and stress-induced increases in dendritic length and branching in the amygdala (50). Tianeptine blocks the dendritic remodeling caused by stress or glucocorticoids (41), blocks stress-induced impairments of spatial memory performance in radial and Y-maze (70,71) and antagonizes the deleterious effects of alcohol (72).
In a validated model of hippocampal-dependent memory impairment and synaptic plasticity changes by predator stress, acute tianeptine can prevent the deleterious effects of stress on spatial memory, an effect that does not depend on corticosterone levels (73). Tianeptine also facilitates focused attention behavior in the cat in response to its environment or towards a significant stimulus (74). It was shown to exert improving effects on learning as well as on working memory and on reference memory in rodents (72) and to exhibit vigilance-enhancing effects in rats (75) and monkeys (76)...
- Gervain Judit, Vines Bradley W., Chen Lawrence M., Seo Rubo J, Hensch Takao K., Werker Janet F, Young Allan H (2013). "Valproate reopens critical-period learning of absolute pitch". Frontiers in Systems Neuroscience 7 (00102). doi:10.3389/fnsys.2013.00102. PMC 3848041. PMID 24348349.
- Obianyo O, Ye K (October 2013). "Novel small molecule activators of the Trk family of receptor tyrosine kinases". Biochim. Biophys. Acta 1834 (10): 2213–8. doi:10.1016/j.bbapap.2012.08.021. PMC 3602283. PMID 22982231.
Amitriptyline is a TrkA and TrkB agonist ... The neurotrophic compound is also able to mimic one of the most notable actions of NGF, by inducing neurite outgrowth in PC12 cells and preventing kainic acid-induced neuronal apoptosis
- Aguiar S, Borowski T (August 2013). "Neuropharmacological review of the nootropic herb Bacopa monnieri". Rejuvenation Res 16 (4): 313–26. doi:10.1089/rej.2013.1431. PMC 3746283. PMID 23772955.
- Pase MP, Kean J, Sarris J, Neale C, Scholey AB, Stough C (July 2012). "The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials". J Altern Complement Med 18 (7): 647–52. doi:10.1089/acm.2011.0367. PMID 22747190.
- Kennedy DO, Wightman EL (January 2011). "Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function". Adv Nutr. 2 (1): 32–50. doi:10.3945/an.110.000117. PMC 3042794. PMID 22211188.
- Birks, J; Grimley Evans, J (Jan 21, 2009). "Ginkgo biloba for cognitive impairment and dementia.". The Cochrane database of systematic reviews (1): CD003120. doi:10.1002/14651858.CD003120.pub3. PMID 19160216.
- Kaschel R (2009). "Ginkgo biloba: specificity of neuropsychological improvement—a selective review in search of differential effects". Hum Psychopharmacol 24 (5): 345–70. doi:10.1002/hup.1037. PMID 19551805.
- Thorp, Aa; Sinn, N; Buckley, Jd; Coates, Am; Howe, Pr (November 2009). "Soya isoflavone supplementation enhances spatial working memory in men.". Br J Nutr (NLM) 102 (9): 1348–54. doi:10.1017/S0007114509990201. PMID 19480732. Retrieved March 24, 2014.
- Gleason CE, Carlsson CM, Barnet JH, Meade SA, Setchell KD, Atwood CS, Johnson SC, Ries ML, Asthana S (January 2009). "A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women". Age Ageing 38 (1): 86–93. doi:10.1093/ageing/afn227. PMC 2720778. PMID 19054783.
- Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY, ed. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 454. ISBN 9780071481274.
- 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". Curr. Pharm. Des. 8 (2): 125–38. doi:10.2174/1381612023396582. PMID 11812254.
- 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): 702–5. Bibcode:2008Natur.456..702G. doi:10.1038/456702a. ISSN 1476-4687. OCLC 01586310. PMID 19060880. Retrieved March 25, 2014. (subscription required (. ))