Nootropic

Nootropic

Nootropics ( )—also called 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. Specific effects can include improvements to working memory, motivation, or attention.[1][2] The word nootropic was coined in 1972 by a Romanian psychologist and chemist, Corneliu E. Giurgea,[3][4] from the Greek words νους nous, or "mind", and τρέπειν trepein meaning to bend or turn.[5]

Contents

  • Availability and prevalence 1
    • Academic use 1.1
  • Side effects 2
  • Drugs 3
    • Stimulants 3.1
    • Miscellaneous 3.2
    • Nutraceuticals 3.3
    • Racetams 3.4
  • See also 4
  • References 5
  • External links 6

Availability and prevalence

There are only a few drugs that are known to improve some aspect of cognition. Many more are in different stages of development.[6] The most commonly used class of drug is stimulants, such as caffeine.[7]

These drugs are purportedly used primarily to treat cognitive or motor function difficulties attributable to disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and ADHD. Some researchers, however, report more widespread use despite concern for further research.[8] Nevertheless, intense marketing may not correlate with efficacy. While scientific studies support the beneficial effects of some compounds, manufacturer's marketing claims for dietary supplements are usually not formally tested and verified by independent entities.[9]

Academic use

In academia, nootropics have been used to increase productivity, despite their long-term effects lacking conclusive research in healthy individuals.[6] The use of prescription stimulants is especially prevalent among students attending academically competitive colleges.[10] Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetime.[11][12][13] Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups.[6] Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for performance enhancement rather than as recreational drugs.[14][15][16]

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.[11][12][17][18]

Side effects

The main concern with pharmaceutical drugs is adverse effects, and these concerns apply to cognitive-enhancing drugs as well. Long-term safety data is typically unavailable for some types of nootropics[6] (e.g., many non-pharmaceutical cognitive enhancers, newly developed pharmaceuticals and pharmaceuticals with short-term therapeutic use). Racetams—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 individuals without cognitive impairments.[19][20] While addiction to stimulants is sometimes identified as a cause for concern,[21] a very large body of research on the therapeutic use of the "more addictive" psychostimulants indicate that addiction is fairly rare in therapeutic doses.[22][23][24] On their safety profile, a systematic review from June 2015 asserted, "Evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers."[25]

In the United States, unapproved drugs or dietary supplements do not require efficacy approval before being sold.[26]

Drugs

Stimulants

Hebbian version of the Yerkes–Dodson law

In 2015, systematic medical reviews and meta-analyses of clinical research in humans established consensus that certain stimulants, only when used at low (therapeutic) concentrations, unambiguously enhance cognition in the general population;[25][27][28][29] 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 receptors in the prefrontal cortex.[25][27][29] Relatively high doses of stimulants cause cognitive deficits.[29][30]

Miscellaneous

  • Phosphatidylserine (a phospholipid) with DHA and EPA (omega-3 fatty acids) – 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.[39][40]
  • Tianeptine – enhances several metrics of cognition in animal models.[41] It has also been shown to prevent stress-induced dendritic remodeling in various brain structures, and antagonizes alcohol's neurodegenerative effects.[41]
  • L-theanine – see the Xanthines entry above.[37]
  • Valproate – a study has suggested that valproate may be able to enhance the cognitive ability of absolute pitch.[42]

Nutraceuticals

  • Bacopa monnieri – A nutraceutical herb with "neural tonic" and memory enhancing properties shown in humans in a double-blinded RCTs.[43][44]
  • 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.[45]
  • Salvia officinalis Although some evidence is suggestive of cognition benefits, the study quality is so poor that no conclusions can be drawn from it.[46]
  • Ginkgo biloba – Different reviews come to different conclusions. A 2009 Cochrane review found not enough evidence to make conclusions in those with dementia.[47] 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."[48]
  • Isoflavones – A double-blind, placebo-controlled study showed improvement in spatial working memory after administration of isoflavones.[49] 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.[50]

Racetams

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.[51] 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.[52]

See also

References

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  9. ^ "Dietary Supplements: What You Need to Know". US Food and Drug Administration. Retrieved February 14, 2015. 
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  11. ^ a b 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.  
  12. ^ a b 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.  
  13. ^ Bossaer, John. "The Use and Misuse of Prescription Stimulants as "Cognitive Enhancers" by Students at One Academic Health Sciences Center". Academic Medicine. Retrieved October 6, 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%). 
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  27. ^ a b c d e f Ilieva IP, Hook CJ, Farah MJ (January 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". J. Cogn. Neurosci.: 1–21. PMID 25591060. doi:10.1162/jocn_a_00776. The present meta-analysis was conducted to estimate the magnitude of the effects of methylphenidate and amphetamine on cognitive functions central to academic and occupational functioning, including inhibitory control, working memory, short-term episodic memory, and delayed episodic memory. In addition, we examined the evidence for publication bias. Forty-eight studies (total of 1,409 participants) were included in the analyses. We found evidence for small but significant stimulant enhancement effects on inhibitory control and short-term episodic memory. Small effects on working memory reached significance, based on one of our two analytical approaches. Effects on delayed episodic memory were medium in size. However, because the effects on long-term and working memory were qualified by evidence for publication bias, we conclude that the effect of amphetamine and methylphenidate on the examined facets of healthy cognition is probably modest overall. In some situations, a small advantage may be valuable, although it is also possible that healthy users resort to stimulants to enhance their energy and motivation more than their cognition. ... Earlier research has failed to distinguish whether stimulants’ effects are small or whether they are nonexistent (Ilieva et al., 2013; Smith & Farah, 2011). The present findings supported generally small effects of amphetamine and methylphenidate on executive function and memory. Specifically, in a set of experiments limited to high-quality designs, we found significant enhancement of several cognitive abilities. ...

    The results of this meta-analysis cannot address the important issues of individual differences in stimulant effects or the role of motivational enhancement in helping perform academic or occupational tasks. However, they do confirm the reality of cognitive enhancing effects for normal healthy adults in general, while also indicating that these effects are modest in size.
     
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  30. ^ a b c d 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 . 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.
     
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  39. ^ 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.  
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  41. ^ a b 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. PMC 2902200. PMID 19704408. doi:10.1038/mp.2009.80. 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)...
     
  42. ^ 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).  
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  49. ^ Thorp, Aa; Sinn, N; Buckley, Jd; Coates, Am; Howe, Pr (November 2009). "Soya isoflavone supplementation enhances spatial working memory in men.". Br J Nutr ( 
  50. ^ 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.  
  51. ^ 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.  
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External links

Medical journal articles

  • Whose well-being? Common conceptions and misconceptions in the enhancement debate – PMID 25191232 (Frontiers in Systems Neuroscience, August 2014)
  • Towards responsible use of cognitive-enhancing drugs by the healthy – PMID 19060880 (Nature, December 2008)

News articles

  • "A Pandora's box full of smart drugs" by Ann Robinson (The Guardian, February 23, 2010)
  • "Brain Gain: The underground world of 'neuro-enhancing' drugs" by Margaret Talbot (The New Yorker, April 27, 2009)