Nootropic

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 align with Giurgea's characteristics.^[7]

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.^[4]

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.^{[2][3][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.^[2][3]

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.^[2][3]

From 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, as well as misleading marketing.^{[2][3][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, omberacetam and meclofenoxate have been sold as dietary supplements.^[17][18][19]

The main concern with pharmaceutical drugs and dietary supplements is adverse effects, including the potential for psychological dependence. Long-term safety evidence is 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.^[20]

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.^[21]

• Centella asiatica – a 2017 meta-analysis showed no significant improvement in cognitive function after consuming Centella asiatica.^[39] Clinical efficacy and safety have not been scientifically confirmed for this herb.^[40]
• Ginkgo biloba – an extract of Ginkgo biloba leaf is marketed in dietary supplement form with claims that it can enhance cognitive function in people without known cognitive problems. However, there is no established evidence to support such effects on memory or attention in healthy people.^[41][42]
• Panax ginseng – a Cochrane review found possible "improvement of some aspects of cognitive function, behavior and quality of life" after consuming Panax ginseng 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."^[43]

• Folate – no cognition-enhancing effects in middle-aged and older adults without folate deficiency have been established after the ingestion of folate.^[44]
• 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.^[45][46] Two other systematic reviews found no cognition-enhancing effects in the general population.^[44][47]
• Vitamin B₁₂ – no cognition-enhancing effects in middle-aged and older adults without B12 deficiency have been established after the ingestion of vitamin B₁₂.^[44]
• Vitamin B₆ – no cognition-enhancing effects in middle-aged and older adults without B6 deficiency have been established after the ingestion of vitamin B₆.^[44]
• Vitamin E – no cognition-enhancing effects in middle-aged and older adults without vitamin E deficiency have been established after the ingestion of vitamin E.^[44]

• Cosmetic pharmacology
• List of drugs used by militaries
• List of investigational cognition and memory disorder drugs
• Neuroenhancement
• Psychoactive drug