NOOTROPICS (English pronunciation: /noʊ.əˈtrɒpɪks/ noh-ə-TROP-iks ), also known as SMART DRUGS and COGNITIVE ENHANCERS, are drugs , supplements , and other substances that improve cognitive function , particularly executive functions , memory, creativity, or motivation , in healthy individuals. The use of cognition-enhancing drugs by healthy individuals in the absence of a medical indication is one of the most debated topics among neuroscientists, psychiatrists, and physicians which spans a number of issues, including the ethics and fairness of their use, concerns over adverse effects, and the diversion of prescription drugs for nonmedical uses, among others. Nonetheless, the international sales of cognition-enhancing supplements exceeded US$ 1 billion in 2015 and the global demand for these compounds is still growing rapidly.
The word nootropic was coined in 1972 by a Romanian psychologist and chemist, Corneliu E. Giurgea , from the Greek words νοῦς (nous), or "mind", and τρέπειν (trepein), meaning to bend or turn.
* 1 Availability and prevalence
* 1.1 Use by students
* 2 Side effects
* 4 Dietary supplements * 5 Null findings in systematic reviews * 6 See also * 7 References
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. The most commonly used class of drug is stimulants , such as caffeine .
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. 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.
USE BY STUDENTS
Among students, nootropics have been used to increase productivity, despite their long-term effects lacking conclusive research in healthy individuals. The use of prescription stimulants is especially prevalent among students attending academically competitive colleges. Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetime. Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups. 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.
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. Long-term safety data is typically unavailable for some types of nootropics (e.g., many non-pharmaceutical cognitive enhancers, newly developed pharmaceuticals and pharmaceuticals with short-term therapeutic use). 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 individuals without cognitive impairments. While addiction to stimulants is sometimes identified as 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. 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."
In the United States dietary supplements may be marketed if the manufacturer can show that it can manufacture the supplement safely, that the supplement is indeed generally recognized as safe , and if the manufacturer does not make any claims about the supplement's use to treat or prevent any disease or condition; supplements that contain drugs or for which treatment or prevention claims are made are illegal under US 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; 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 . Relatively high doses of stimulants cause cognitive deficits.
Main article: Racetams
Racetams, such as piracetam , oxiracetam , and aniracetam , are structurally similar compounds, 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.
According to the US Food and
* L-Theanine – A 2014 systematic review and meta-analysis found that concurrent caffeine and L-theanine use has synergistic psychoactive effects that promote alertness, attention, and task switching ; these effects are most pronounced during the first hour post-dose. However, the European Food Safety Authority reports that when L-theanine is used by itself (i.e. without caffeine) there is insufficient information to determine if positive health effects exist. * Tolcapone – a systematic review noted that it improves verbal episodic memory and episodic memory encoding . * Levodopa – a systematic review noted that it improves verbal episodic memory and episodic memory encoding. * Atomoxetine – can improve working memory and aspects of attention when used at an optimal dose.
* Bacopa monnieri – A herb sold as a dietary supplement . There is some preliminary evidence for memory-enhancing effects. * 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." According to the National Center for Complementary and Integrative Health "Although 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." According to a review published in the journal "Advances in Nutrition", 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 – An extract of Ginkgo biloba leaf (GBE) is marketed in dietary supplement form with claims it can enhance cognitive function in people without known cognitive problems. Studies have failed to find such effects on memory or attention in healthy people.
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
learning disorders conclude that there is limited evidence of
treatment benefits for either disorder. Two other systematic reviews
noted no cognition-enhancing effects in the general population or
middle-aged and older adults.
* ^ A B 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. PMC 4462043
. PMID 26074739 . doi :10.2174/1570159X13666141210221750 .
* ^ Lanni C, Lenzken SC, Pascale A, et al. (March 2008). "Cognition
enhancers between treating and doping the mind". Pharmacol. Res. 57
(3): 196–213. PMID 18353672 . doi :10.1016/j.phrs.2008.02.004 .
* ^ Albertson TE, Chenoweth JA, Colby DK, Sutter ME (2016). "The
* ^ A B C D E 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. 27: 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. * ^ 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. PMC 4471173 .
PMID 24749160 . doi :10.1111/add.12460 .
Modafinil appears to improve
reaction time (P ≤ 0.04), logical reasoning (P ≤ 0.05) and
Methylphenidate appears to improve performance in
novel tasks and attention-based tasks (P ≤ 0.05), and reduces
planning latency in more complex tasks (P ≤ 0.05).
* ^ A B C D E F 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. pp. 318, 321. 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 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 spatial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. ... 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. Beyond these general permissive effects, dopamine (acting via D1 receptors) and norepinephrine (acting at several receptors) can, at optimal levels, enhance working memory and aspects of attention. Drugs used for this purpose include, as stated above, methylphenidate, amphetamines, atomoxetine, and desipramine. * ^ Linssen AM, Sambeth A, Vuurman EF, Riedel WJ (June 2014). "Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies". Int. J. Neuropsychopharmacol. 17 (6): 961–977. PMID 24423151 . doi :10.1017/S1461145713001594 . The studies reviewed here show that single doses of MPH improve cognitive performance in the healthy population in the domains of working memory (65% of included studies) and speed of processing (48%), and to a lesser extent may also improve verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%), but does not have an effect on visual learning and memory. MPH effects are dose-dependent and the dose-response relationship differs between cognitive domains. * ^ 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. PMC 4026746 . PMID 24860437 . doi :10.3389/fnsys.2014.00038 . * ^ 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. 229 (3): 415–34. PMID 23934211 . doi :10.1007/s00213-013-3232-4 . * ^ "Modafinil". MedlinePlus. Retrieved August 19, 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 . 210 (4): 453–69. PMC 3151730 . PMID 20414766 . doi :10.1007/s00213-010-1848-1 . * ^ Sarter M (August 2015). "Behavioral-cognitive targets for cholinergic enhancement". Current Opinion in Behavioral Sciences. 4: 22–26. doi :10.1016/j.cobeha.2015.01.004 . * ^ "Nicotine: Biological activity". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 7 February 2016. Kis as follows; α2β4=9900nM , α3β2=14nM , α3β4=187nM , α4β2=1nM . Due to the heterogeneity of nACh channels we have not tagged a primary drug target for nicotine, although the α4β2 is reported to be the predominant high affinity subtype in the brain which mediates nicotine addiction . * ^ Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY, eds. 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. PMID 11812254 . doi :10.2174/1381612023396582 . * ^ "Warning Letters – Unlimited Nutri