Nootropic

Nootropics (/noʊ.əˈtroʊpɪks/ noh-ə-TROHP-iks or /noʊ.əˈtrɒpɪks/ noh-ə-TROP-iks;^[1] but not /njuːˈtroʊpɪks/ new-TROHP-iks or /njuːˈtrɒpɪks/ new-TROP-iks,^[1] which are common mispronunciations^{[citation needed]}), colloquially brain supplements, smart drugs and cognitive enhancers, are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.

Caffeine from the Coffea arabica plant is the world's most consumed nootropic.

While commonly in the form of dietary supplements, nutraceuticals or energy drinks,^[2] some nootropic compounds are prescription and non-prescription drugs in various countries.

In the United States, nootropics are 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.^[3][4]

The term nootropic is derived from Ancient Greek νόος (nóos) 'mind' and τροπή (tropḗ) 'turning'.^[1][5][6]

The first documented use of "nootropic" in reference to substances purported to increase cognitive functions was by Corneliu E. Giurgea in 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 enhance learning and memory.
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 tonic cortical control mechanisms.
5. 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.^[7]

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 and FTC warned manufacturers 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 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.^[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]}

In 2008, stimulants, such as caffeine, were the most commonly used nootropic agent.^[15] 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.^[16] Piracetam, noopept and meclofenoxate have been sold as dietary supplements.^[2][17][18]

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.^[19]

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.^[20]

• 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 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.^[40][41]
• Panax ginseng – 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."^[42]

• Folate – no cognition-enhancing effects in middle-aged and older adults without folate deficiency.^[43]
• Omega-3 fatty acids: DHA and EPA – 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.^[44][45] Two other systematic reviews found no cognition-enhancing effects in the general population.^[43][46]
• Vitamin B₁₂ – no cognition-enhancing effects in middle-aged and older adults without B12 deficiency.^[43]
• Vitamin B₆ – no cognition-enhancing effects in middle-aged and older adults without B6 deficiency.^[43]
• Vitamin E – no cognition-enhancing effects in middle-aged and older adults without vitamin E deficiency.^[43]

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• Neuroenhancement
• Psychoactive drug