Nootropics (/noʊ.əˈtroʊpɪks/ noh-ə-TROHP-iks or /noʊ.əˈtrɒpɪks/ noh-ə-TROP-iks[1]) (colloquial: brain supplements, smart drugs and cognitive enhancers) are numerous natural, semi-synthetic and synthetic molecules that improve cognitive functions (such as executive functions, attention, memory, creativity).
They are often found in the form of dietary supplements, nutraceuticals and energy drinks.[2] Some nootropic molecules can also be found as prescription and non-prescription pharmaceutical drugs in diverse countries.
The term nootropic is derived from Ancient Greek νόος (nóos) 'mind', and τροπή (tropḗ) 'turning'.[1][3][4]
Nootropics are often 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.[5] The US Food and Drug Administration (FDA) and Federal Trade Commission (FTC) warned manufacturers and consumers in 2019 about possible advertising fraud and marketing scams concerning nootropic supplement products.[6][7][8][9] The FDA and FTC stated that some nootropic products had not been approved as a 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.[6][7]
In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing.[10][11] In 2019, the FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.[6][7]
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.[6][7][8][9][12][13]
In 2008, the most commonly used class of drug was stimulants, such as caffeine.[14] 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.[15] More recently piracetam, noopept and meclofenoxate have been sold as dietary supplements.[16][2][17]
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.[18]
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.[19]
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See also: Yerkes–Dodson law |
Systematic reviews and meta-analyses of clinical human research using low doses of certain central nervous system stimulants found that these drugs enhance cognition in healthy people.[20][21][22] 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.[20][21][23][24] Relatively high doses of stimulants cause cognitive deficits.[23][24]
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Main article: Amino acid-based formula |
A 2016 review reported that theanine may increase alpha waves in the brain. Alpha waves may contribute to a relaxed yet alert mental state.[30] A 2014 systematic review and meta-analysis found that concurrent caffeine and L-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching. These effects were most pronounced during the first hour post-dose.[25]
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Main article: Racetams |
Racetams, such as piracetam, oxiracetam, phenylpiracetam, and aniracetam, are often marketed as cognitive enhancers and sold over the counter.[2][31] A 2019 study found that piracetam supplements sold in the United States were inaccurately labeled.[31] Racetams are often referred to as nootropics, but this property is not well established.[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.[13]
Some of the most widely used nootropic substances are the cholinergics. These are typically compounds and analogues of choline. Choline is an essential nutrient needed for the synthesis of acetylcholine (a neurotransmitter), and phosphatidylcholine (a structural component of brain cell membranes).
The cognitive enhancing effects of pramipexole, guanfacine, clonidine, and fexofenadine have been tested, but no significant cognition-enhancing effects in healthy individuals were found.[40]
Psychedelic microdosing is the novel practice of using sub-threshold doses (microdoses) of psychedelic drugs in an attempt to improve mood and cognition.[43] The efficacy of this has not been verified.[44][45] In a study examining the qualitative reports of 278 microdosers the researchers found that there were mixed results among users.[46] While some users reported positive effects such as improved mood and cognition, others paradoxically reported negative effects such as physiological discomfort and anxiety.[46] In one of the only double-blind, randomized studies to date, those given microdoses of LSD did not perform better than those given the placebo on cognitive tasks.[47]
A 2015 review found that use of omega-3 fatty acids, B vitamins, and vitamin E as nootropics was ineffective on cognitive function in normal middle-aged and older people.[58]
