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Nootropic

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Nootropics(/noʊ.əˈtroʊpɪks/noh-ə-TROHP-iksor/noʊ.əˈtrɒpɪks/noh-ə-TROP-iks;[1]but not/njuːˈtroʊpɪks/new-TROHP-iksor/njuːˈtrɒpɪks/new-TROP-iks,[1]which are common mispronunciations[citation needed]), colloquiallybrain supplements,smart drugsandcognitive enhancers,are natural, semisynthetic or syntheticcompoundswhich purportedly improvecognitive functions,such asexecutive functions,attentionormemory.

Illustration of Coffea arabica plant and seeds
Caffeinefrom theCoffea arabicaplant is the world's most consumed nootropic.

While commonly in the form ofdietary supplements,nutraceuticalsorenergy drinks,[2]some nootropic compounds areprescriptionand non-prescription drugs in various countries.

In the United States, nootropics are commonly advertised with unproven claims of effectiveness for improving cognition. TheFederal Trade CommissionandFDAhave warned manufacturers and consumers about possibleadvertising fraudandmarketing scamsconcerning nootropic supplements.[3][4]

History of term

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The termnootropicis derived fromAncient Greekνόος(nóos)'mind' andτροπή(tropḗ)'turning'.[1][5][6]

The first documented use of "nootropic" in reference to substances purported to increase cognitive functions was byCorneliu E. Giurgeain 1972.[5][6][7]When researching a new compound, Giurgea found a spectrum of effects that did not align with any psychotropic drug category, leading to his proposal of a new category and the concept of the term nootropic.[6]

Giurgea stated that nootropic drugs should have the following characteristics:

  1. They should enhancelearningandmemory.
  2. They should enhance the resistance of learned behaviors or memories to conditions which tend to disrupt them (e.g.electroconvulsive shock,hypoxia).
  3. They should protect the brain against various physical or chemical injuries.
  4. They should increase the efficacy of the toniccorticalcontrol mechanisms.
  5. They should lack the usual pharmacology of otherpsychotropicdrugs (e.g.sedation,motor stimulation) and possess fewadverse effectsand lowtoxicity.

However, there is no globally accepted or clinical definition of a nootropic. Most compounds described as nootropic do not correspond to Giurgea's characteristics.[7]

Unproven marketing claims

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In the United States, nootropics are commonly 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.[8]In 2019, the US FDA andFTCwarnedmanufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplement products.[3][4][9][10]The FDA and FTC stated that some nootropic products had not beenapprovedas a prescription drug effective for any medical purpose, were not proven to be safe, and were illegally marketed in the United States under violation of theFederal Food, Drug, and Cosmetic Act.[3][4]

In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing.[11][12]In 2019, the FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.[3][4]

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.[3][4][9][10][13][14]

Availability and prevalence

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In 2008, stimulants, such as caffeine, were the most commonly used nootropic agent.[15]In 2016, theAmerican Medical Associationadopted 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.[16]Piracetam,noopeptandmeclofenoxatehave been sold as dietary supplements.[2][17][18]

Adverse effects

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The main concern withpharmaceutical drugsand dietary supplements areadverse 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 lowtoxicity,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 isgenerally 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 advertisehealth claimsare illegal under US law.[20]

Types

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Central nervous system stimulants

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Systematic reviewsandmeta-analysesofclinical researchusing low doses of certaincentral nervous systemstimulants found that these drugs may enhance cognition in healthy people.[21][22][23]In particular, the classes of stimulants that demonstrate possible cognition-enhancing effects in humans have evidencein vitroasdirect agonistsorindirect agonistsofdopamine receptor D1oradrenoceptor A2.[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 may improve cognitive functions (e.g.,inhibitory control,episodic memory,working memory,and aspects ofattention) in healthy people and in individuals withADHD.[21][22][23][25]A 2014 systematic review noted that low doses of amphetamine also improvememory consolidation,in turn leading to improvedrecall of informationin non-ADHD youth.[23]It also improvestask saliency(motivation to perform a task) and performance on tedious tasks that required a high degree of effort.[22][24][25]
  • Caffeine– a meta-analysis found an increase in alertness and attentional performance.[26][24]
  • Eugeroics(armodafinilandmodafinil) – are classified as "wakefulness-promoting agents"; modafinil may increase alertness, particularly insleep-deprivedindividuals, and may improve 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 enhanced executive function.[27]Modafinil does not improve mood or motivation in sleep-deprived or non-sleep deprived individuals.[28]
  • Methylphenidate– abenzylpiperidinederivative that may improveworking memory,episodic memory,andinhibitory control,aspects ofattention,and planning latency in healthy people.[21][23]It also may improve task saliency and performance on tedious tasks.[25]At above optimal doses, methylphenidate has off–target effects that decrease learning.[29]
  • Nicotine– has been associated with improved alertness, attention, memory, and motor performance, according to ameta-analysis.[30]However, a 2020 systematic review raised concerns about potential conflicts of interest, noting industry funding in many studies and inconsistent results regarding nicotine's cognitive effects. This review found that over half of the studies published after 2010 had tobacco industry affiliations, often undisclosed.[31]

Racetams

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Main article:Racetam

Racetams, such as piracetam,oxiracetam,phenylpiracetam,andaniracetam,are often marketed as cognitive enhancers and soldover the counter.[2][17]A 2019 study found that piracetam supplements sold in the United States were inaccurately labeled.[17]Racetams are often referred to as nootropics, but this property is not well established in humans, and nootropics are not consistently found in all racetams.[32]The racetams have poorly understoodmechanisms,although piracetam and aniracetam are known to act aspositive allosteric modulatorsofAMPA receptorsand appear to modulatecholinergicsystems.[33]

According to the FDA,

Piracetam is not avitamin,mineral,amino acid,herb or otherbotanical,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.[14]

Cholinergics

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Main article:Cholinergic

Some supposed nootropic substances are compounds and analogues ofcholine,aprecursorof acetylcholine (aneurotransmitter) andphosphatidylcholine(a structural component ofcell membranes).

  • Alpha-GPC– L- Alpha glycerylphosphorylcholine has been studied only in the context of cognitive performance alongside other substances such as caffeine.[34]
  • Choline bitartrate– Choline bitartrate is atartaric acidsalt containing choline (41% choline by molecular weight). One meta-analysis found choline bitartrate to be ineffective at improving any measure of cognitive performance.[35]
  • Citicoline– Compound consisting of choline andcytidine.A meta-analysis found that it may be effective for improving memory and learning in older people with mild cognitive decline, and in people recovering from a stroke.[36][37]

Herbs

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  • Centella asiatica– A 2017 meta-analysis showed no significant improvement in cognitive function.[38]Clinical efficacy and safety have not been scientifically confirmed for this herb.[39]
  • Ginkgo biloba– An extract ofGinkgo bilobaleaf is marketed indietary supplementform with claims it can enhancecognitive functionin people without known cognitive problems, although there is no high-quality evidence to support such effects on memory or attention in healthy people.[40][41]
  • Panax ginseng– ACochrane reviewfound possible "improvement of some aspects of cognitive function, behavior and quality of life", but concluded that "there is a lack of convincing evidence to show a cognitive enhancing effect ofPanax ginsengin healthy participants and no high quality evidence about its efficacy in patients with dementia. "[42]

Nutrients and dietary supplements

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See also

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References

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