Nootropic
Nootropics (.
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, the
History of term
The term nootropic is derived from
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:
- 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. 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.[7]
Unproven marketing claims
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.
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
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]
Adverse effects
The main concern with
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]
Types
Central nervous system stimulants
- Caffeine – a meta-analysis found an increase in alertness and attentional performance.[26][24]
- sleep-deprived individuals, 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 – a benzylpiperidine derivative that may improve working memory, episodic memory, and inhibitory control, aspects of attention, 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 a meta-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
Racetams, such as piracetam,
According to the FDA,
Piracetam is not a
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.[14]
Cholinergics
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.[34]
- 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.[35]
- 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.[36][37]
Herbs
- 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]
- 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]
Nutrients and dietary supplements
- middle-aged and older adults without folate deficiency.[43]
- Omega-3 fatty acids: 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]
See also
- List of drugs used by militaries
- Neuroenhancement
- Psychoactive drug
References
- ^ a b c "Nootropic". Oxford English Dictionary. 2024. Retrieved January 14, 2024.
- ^ PMID 34484905.
- ^ a b c d e "FTC and FDA Send Warning Letters to Companies Selling Dietary Supplements Claiming to Treat Alzheimer's Disease and Remediate or Cure Other Serious Illnesses Such as Parkinson's, Heart Disease, and Cancer". US Food and Drug Administration, US Federal Trade Commission. February 11, 2019. Retrieved May 11, 2019.
- ^ a b c d e "Health fraud scams: Unproven Alzheimer's disease products". US Food and Drug Administration. December 22, 2018. Retrieved May 11, 2019.
- ^ PMID 4541214.
- ^ .
The term "nootropic" (noos = mind; tropein = towards) was proposed by us (Giurgea, 1972,1973) to designate psychotropic drugs
- ^ PMID 36014874.
- ^ "Dietary Supplements: What You Need to Know". US Food and Drug Administration. Retrieved February 14, 2015.
- ^ a b Correll Jr WA (February 5, 2019). "FDA Warning Letter: Peak Nootropics LLC aka Advanced Nootropics". Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved May 11, 2019.
- ^ a b Correll Jr WA (February 5, 2019). "FDA Warning Letter: TEK Naturals". Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved May 11, 2019.
- ^ Schultz H (May 17, 2018). "Some shady ingredients find home in nootropics category". NutraIngredients-USA.com, William Reed Business Media Ltd. Retrieved May 11, 2019.
- ^ Heid M (January 23, 2019). "Nootropics, or 'Smart Drugs,' Are Gaining Popularity. But Should You Take Them?". Time. Retrieved May 12, 2019.
- ^ Singleton ER (January 7, 2010). "FDA Warning Letter: Cerebral Health LLC". Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Archived from the original on January 12, 2017. Retrieved May 12, 2019.
- ^ a b John Gridley (August 30, 2010). "FDA Warning Letter: Unlimited Nutrition". Office of Compliance, Center for Food Safety and Applied Nutrition, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Archived from the original on January 12, 2017. Retrieved April 5, 2016.
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- ^ "AMA confronts the rise of nootropics". American Medical Association. June 14, 2016. Retrieved May 12, 2019.
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- ^ "Gotu kola". Drugs.com. January 23, 2023. Retrieved September 21, 2023.
- S2CID 6307491.
- ^ "Ginkgo". National Center for Complementary and Integrative Health, US National Institutes of Health. September 2016. Retrieved July 9, 2018.
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- ^ PMID 26740832.
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External links
- Media related to Nootropics at Wikimedia Commons