Nootropic

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Nootropics (Template:IPAc-en Template:Respell or Template:IPAc-en Template:Respell) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self-control.<ref name="Lexico">Template:Cite encyclopedia</ref>

In the United States, nootropics can be over-the-counter drugs and commonly advertised with unproven claims of effectiveness for improving cognition. The Federal Trade Commission and FDA have warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.<ref name="ftc" /><ref name="fda-fraud" /> Nootropics include both prescription drugs and dietary supplements marketed to enhance brain function, but while FDA-approved drugs have proven benefits and oversight, many dietary supplements lack evidence, may contain unapproved or hidden drugs, and pose safety and regulatory risks.<ref name="opss">Nootropics: Drugs vs Dietary Supplements for Brain Health. Operation Supplement Safety. https://www.opss.org/article/nootropics-drugs-vs-dietary-supplements-brain-health. Accessed 2025-05-20.</ref>

History of termEdit

The term nootropic is derived Template:Ety.<ref name="Lexico"/><ref name="Giurgea1972">Template:Cite journal</ref><ref name="Giurgea1977">Template:Cite journal</ref>

The first documented use of "nootropic" in reference to substances purported to increase cognitive functions was by [[Corneliu E. Giurgea|Template:Nobr]] in 1972.<ref name="Giurgea1972"/><ref name="Giurgea1977"/><ref name="malik">Template:Cite journal</ref> 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.<ref name="Giurgea1977"/>

Giurgea stated that nootropic drugs should have the following characteristics:

They should enhance learning and memory.
They should enhance the resistance of learned behaviors or memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).
They should protect the brain against various physical or chemical injuries.
They should increase the efficacy of the tonic cortical control mechanisms.
They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess few adverse effects and low toxicity.

However, there is no globally accepted or clinical definition of a nootropic. Most compounds described as nootropic do not correspond to Giurgea's characteristics.<ref name="malik" />

Unproven marketing claimsEdit

Nootropics include both prescription drugs and dietary supplements marketed to enhance brain function, but while FDA-approved drugs have proven benefits and oversight, many dietary supplements lack evidence, may contain unapproved or hidden drugs, and pose safety and regulatory risks.<ref name=opss/>

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2019, the US FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplement products.<ref name="ftc">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="fda-fraud">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="fda">{{#invoke:citation/CS1|citation |CitationClass=web }}Template:Dead link Template:Cbignore</ref><ref name="fda2">{{#invoke:citation/CS1|citation |CitationClass=web }}Template:Dead link Template:Cbignore</ref> The FDA and FTC stated that some nootropic products had not been approved as 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 the Federal Food, Drug, and Cosmetic Act.<ref name=ftc/><ref name=fda-fraud/>

In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing.<ref name="schultz">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="heid">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2019, the FDA and FTC warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.<ref name="ftc" /><ref name="fda-fraud" />

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.<ref name="ftc" /><ref name="fda-fraud" /><ref name="fda" /><ref name="fda2" /><ref name="cerebral">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="unlimited" />

Availability and prevalenceEdit

In 2008, stimulants, such as caffeine, were the most commonly used nootropic agent.<ref name="Nature2008">Template:Cite journal</ref> 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.<ref name="ama">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Piracetam, noopept and meclofenoxate have been sold as dietary supplements.<ref name="NeuroClin"/><ref name="JAMAIM"/><ref>Template:Cite journal</ref>

Adverse effectsEdit

The main concern with pharmaceutical drugs and dietary supplements are adverse effects, including the potential for psychological dependence. 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.<ref name="Racetam efficacy review 2010">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

TypesEdit

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Central nervous system stimulants Template:AnchorEdit

Systematic reviews and meta-analyses of clinical research using low doses of certain central nervous system stimulants found that these drugs may enhance cognition in healthy people.<ref name="Unambiguous PFC D1 A2" /><ref name="Cognitive and motivational effects">Template:Cite journal</ref><ref name="Systematic 2014 – Amph, MPH, Modafinil">Template:Cite journal</ref> In particular, the classes of stimulants that demonstrate possible cognition-enhancing effects in humans have evidence in vitro as direct agonists or indirect agonists of dopamine receptor D₁ or adrenoceptor A₂.<ref name="Unambiguous PFC D1 A2">Template:Cite journal</ref><ref name="Cognitive and motivational effects" /><ref name="Continuum">Template:Cite journal</ref><ref name="NHMH_3e-Higher Cognitive Function">Template:Cite book</ref> Relatively high doses of stimulants cause cognitive deficits.<ref name="Continuum" /><ref name="NHMH_3e-Higher Cognitive Function" />

Amphetamine Template:Snd systematic reviews and meta-analyses report that low-dose amphetamine may improve cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people and in individuals with ADHD.<ref name="Unambiguous PFC D1 A2" /><ref name="Cognitive and motivational effects" /><ref name="Systematic 2014 – Amph, MPH, Modafinil" /><ref name="NHMH_3e-Higher Cognitive Function" /> A 2014 systematic review noted that low doses of amphetamine also improve memory consolidation, in turn leading to improved recall of information in non-ADHD youth.<ref name="Systematic 2014 – Amph, MPH, Modafinil" /> It also improves task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.<ref name="Cognitive and motivational effects" /><ref name="Continuum" /><ref name="NHMH_3e-Higher Cognitive Function" />
Caffeine Template:Snd a meta-analysis found an increase in alertness and attentional performance.<ref name="caffeine and theanine">Template:Cite journal</ref><ref name="Continuum" />
Eugeroics (armodafinil and modafinil)Template:Snd are classified as "wakefulness-promoting agents"; modafinil may increase alertness, particularly in sleep-deprived individuals, and may improve reasoning and problem solving in non-ADHD youth.<ref name="Systematic 2014 – Amph, MPH, Modafinil" /> 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.<ref name="Modafinil SystRev">Template:Cite journal</ref> Modafinil does not improve mood or motivation in sleep-deprived or non-sleep deprived individuals.<ref>Template:Cite book</ref>
Methylphenidate Template:Snd a benzylpiperidine derivative that may improve working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency in healthy people.<ref name="Unambiguous PFC D1 A2" /><ref name="Systematic 2014 – Amph, MPH, Modafinil" /> It also may improve task saliency and performance on tedious tasks.<ref name="NHMH_3e-Higher Cognitive Function" /> At above optimal doses, methylphenidate has off–target effects that decrease learning.<ref>Template:Cite journal</ref>
Nicotine Template:Snd has been associated with improved alertness, attention, memory, and motor performance, according to a meta-analysis.<ref>Template:Cite journal</ref> 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.<ref name="pmid32547048">Template:Cite journal</ref>

CholinergicsEdit

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Some supposed nootropic substances are compounds and analogues of choline, a precursor of acetylcholine (a neurotransmitter) and phosphatidylcholine (a structural component of cell membranes).

Alpha-GPC – L-alpha glycerylphosphorylcholine has been studied only in the context of cognitive performance alongside other substances such as caffeine.<ref>Template:Cite journal</ref>
Choline bitartrate – Choline bitartrate is a tartaric acid salt containing choline (41% choline by molecular weight). One meta-analysis found choline bitartrate to be ineffective at improving any measure of cognitive performance.<ref>Template:Cite journal</ref>
Citicoline – Compound consisting of choline and cytidine. 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

RacetamsEdit

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Racetams, such as piracetam, oxiracetam, phenylpiracetam, and aniracetam, are often marketed as cognitive enhancers and sold over the counter.<ref name="NeuroClin">Template:Cite journal</ref><ref name="JAMAIM">Template:Cite journal</ref> A 2019 study found that piracetam supplements sold in the United States were inaccurately labeled.<ref name="JAMAIM"/> 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.<ref name="NHM">Template:Cite book</ref> 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.<ref>Template:Cite journal</ref> Similar compounds, such as noopept and aloracetam, do not meet the chemical definition for being a racetam, though they are considered "racetam-like" due to their high similarity.<ref name="WHO-INN-Stembook2018">The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1).</ref>

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.<ref name="unlimited">{{#invoke:citation/CS1|citation
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HerbsEdit

Centella asiaticaTemplate:Snd A 2017 meta-analysis showed no significant improvement in cognitive function.<ref name="pmid28878245">Template:Cite journal</ref> Clinical efficacy and safety have not been scientifically confirmed for this herb.<ref name="drugs">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

Ginkgo bilobaTemplate:Snd An extract of Ginkgo biloba leaf is marketed in dietary supplement form with claims it can enhance cognitive function in people without known cognitive problems, although there is no high-quality evidence to support such effects on memory or attention in healthy people.<ref>Template:Cite journal</ref><ref name="nccih">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

Panax ginsengTemplate:Snd A Cochrane review found 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 of Panax ginseng in healthy participants and no high quality evidence about its efficacy in patients with dementia."<ref>Template:Cite journal</ref>

Nutrients and dietary supplementsEdit

Folate Template:Snd no cognition-enhancing effects in middle-aged and older adults without folate deficiency.<ref name="Systematic rev – B vitamins">Template:Cite journal</ref>
Omega-3 fatty acids: DHA and EPA Template:Snd two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder.<ref>Template:Cite journal</ref><ref name="Cochrane LD">Template:Cite journal</ref> Two other systematic reviews found no cognition-enhancing effects in the general population.<ref name="Systematic rev – B vitamins" /><ref name="Systematic review: Omega-3s">Template:Cite journal</ref>
Vitamin B₁₂ Template:Snd no cognition-enhancing effects in middle-aged and older adults without B12 deficiency.<ref name="Systematic rev – B vitamins" />
Vitamin B₆ Template:Snd no cognition-enhancing effects in middle-aged and older adults without B6 deficiency.<ref name="Systematic rev – B vitamins" />
Vitamin E Template:Snd no cognition-enhancing effects in middle-aged and older adults without vitamin E deficiency.<ref name="Systematic rev – B vitamins" />