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categories: ["enhancement"]categories: ["enhancement"]tags: ["cognition", "enhancement", "pharmacology", "supplements", "evidence", "regulation"]tags: ["cognition", "enhancement", "pharmacology", "supplements", "evidence", "regulation"]summary: "Substances taken to improve cognition in healthy people, a category whose best-evidenced members produce small effects and whose best-selling members produce none."summary: "Substances taken to improve cognition in healthy people, a category whose best-evidenced members produce small effects and whose best-selling members produce none."updated: "2026-07-27"updated: "2026-10-27"humanEvidence: "Meta-analyses in healthy adults find small effects of stimulants and modafinil on laboratory tasks; no trial has shown any nootropic improves a real-world outcome, and the racetams have almost no modern human data."humanEvidence: "Meta-analyses in healthy adults find small effects of stimulants and modafinil on laboratory tasks; no trial has shown any nootropic improves a real-world outcome, and the racetams have almost no modern human data."access: "Caffeine and supplement blends are sold over the counter with no efficacy review; stimulants and modafinil are prescription-only and used off-label; racetams are bought online outside any approval."access: "Caffeine and supplement blends are sold over the counter with no efficacy review; stimulants and modafinil are prescription-only and used off-label; racetams are bought online outside any approval."reversibility: "reversible"reversibility: "reversible"lines 49–55 → 49–5534 unchanged lines not shown
## What the evidence supports## What the evidence supports **Caffeine** is the most widely used psychoactive substance in the world and the best-established agent in the category. It reliably improves alertness, vigilance and reaction time, especially under fatigue. A long-standing dispute concerns how much of the benefit in habitual users is restoration from overnight withdrawal rather than enhancement above an unmedicated baseline; the withdrawal-reversal effect is real, though evidence in non-consumers suggests it does not explain the whole effect.**Caffeine** is the most widely used psychoactive substance in the world and the best-established agent in the category. It reliably improves alertness, vigilance and reaction time, especially under fatigue. A long-standing dispute concerns how much of the benefit in habitual users is restoration from overnight withdrawal rather than enhancement above an unmedicated baseline; the withdrawal-reversal effect is real, though evidence in non-consumers suggests it does not explain the whole effect. Its separate reputation as a longevity aid rests on cohort associations discussed under [[coffee-and-aging]]. **Modafinil** is licensed for narcolepsy and shift-work sleep disorder and used off-label for wakefulness. In sleep-deprived people its effects are clear. In rested healthy volunteers, a systematic review by Battleday and Brem found consistent improvement on complex tasks involving attention, executive function and learning, and little or no effect on simple tasks or on mood.[^battleday2015] An earlier review by Repantis and colleagues had reached a more cautious conclusion, finding limited evidence for enhancement outside sleep deprivation.[^repantis2010] Both note that longer and more demanding tasks show effects that brief tests miss.**Modafinil** is licensed for narcolepsy and shift-work sleep disorder and used off-label for wakefulness. In sleep-deprived people its effects are clear. In rested healthy volunteers, a systematic review by Battleday and Brem found consistent improvement on complex tasks involving attention, executive function and learning, and little or no effect on simple tasks or on mood.[^battleday2015] An earlier review by Repantis and colleagues had reached a more cautious conclusion, finding limited evidence for enhancement outside sleep deprivation.[^repantis2010] Both note that longer and more demanding tasks show effects that brief tests miss. lines 62–68 → 62–686 unchanged lines not shown
**The racetams.** Piracetam, aniracetam, oxiracetam and phenylpiracetam are the compounds most closely associated with the word "nootropic". A Cochrane review of piracetam for dementia and cognitive impairment concluded the evidence was insufficient to support its use.[^flicker2001] Controlled data in healthy young adults are sparse, small and mostly old. The newer racetams have essentially no published human trials at all.**The racetams.** Piracetam, aniracetam, oxiracetam and phenylpiracetam are the compounds most closely associated with the word "nootropic". A Cochrane review of piracetam for dementia and cognitive impairment concluded the evidence was insufficient to support its use.[^flicker2001] Controlled data in healthy young adults are sparse, small and mostly old. The newer racetams have essentially no published human trials at all. **Herbal and supplement agents.** Ginkgo biloba was tested in a large, long randomised prevention trial and did not reduce the incidence of dementia.[^dekosky2008] Bacopa monnieri, Rhodiola, lion's mane and citicoline have small trials with mixed results and heterogeneous preparations. Effects reported in this literature are rarely distinguishable from expectancy, and the placebo response for a subjectively assessed cognitive outcome is large.**Herbal and supplement agents.** Ginkgo biloba was tested in a large, long randomised prevention trial and did not reduce the incidence of dementia.[^dekosky2008] Bacopa monnieri, Rhodiola, lion's mane and citicoline have small trials with mixed results and heterogeneous preparations. Effects reported in this literature are rarely distinguishable from expectancy, and the placebo response for a subjectively assessed cognitive outcome is large. [[magnesium-l-threonate|Magnesium L-threonate]], sold for memory and sleep after a 2010 rat study reported raised brain magnesium and better learning, illustrates the pattern: every placebo-controlled trial of its effects on cognition or sleep has been funded by a company selling the ingredient, and the largest of the compound alone, in 100 adults aged 18 to 45, found a small advantage on one cognitive composite after six weeks and none on Raven's matrices.[^lopresti2025] **Proprietary blends.** Products combining a dozen ingredients at undisclosed doses cannot be evaluated. Where they have been analysed chemically, results have been poor: Cohen and colleagues found several unapproved drugs, including omberacetam, phenibut, vinpocetine, picamilon and aniracetam, present in commercially sold cognitive-enhancement supplements, sometimes at doses above those used pharmaceutically.[^cohen2020] Phenibut in particular carries dependence and withdrawal risk that consumers buying a "focus" supplement have no reason to expect.**Proprietary blends.** Products combining a dozen ingredients at undisclosed doses cannot be evaluated. Where they have been analysed chemically, results have been poor: Cohen and colleagues found several unapproved drugs, including omberacetam, phenibut, vinpocetine, picamilon and aniracetam, present in commercially sold cognitive-enhancement supplements, sometimes at doses above those used pharmaceutically.[^cohen2020] Phenibut in particular carries dependence and withdrawal risk that consumers buying a "focus" supplement have no reason to expect. lines 109–112 → 109–11340 unchanged lines not shown
[^flicker2001]: `paper` Flicker, L. and Grimley Evans, J. "Piracetam for dementia or cognitive impairment." *Cochrane Database of Systematic Reviews*, 2001. {The trials pooled were in patients with dementia or cognitive impairment; the review says nothing about piracetam in healthy adults, who are most of the market.}[^flicker2001]: `paper` Flicker, L. and Grimley Evans, J. "Piracetam for dementia or cognitive impairment." *Cochrane Database of Systematic Reviews*, 2001. {The trials pooled were in patients with dementia or cognitive impairment; the review says nothing about piracetam in healthy adults, who are most of the market.}[^dekosky2008]: `paper` DeKosky, S. T. et al. "Ginkgo biloba for prevention of dementia: a randomized controlled trial." *JAMA*, 2008. {A long prevention trial in older adults with dementia incidence as the endpoint; it did not test short-term cognitive performance in healthy younger users.}[^dekosky2008]: `paper` DeKosky, S. T. et al. "Ginkgo biloba for prevention of dementia: a randomized controlled trial." *JAMA*, 2008. {A long prevention trial in older adults with dementia incidence as the endpoint; it did not test short-term cognitive performance in healthy younger users.}[^cohen2020]: `paper` Cohen, P. A. et al. "Five unapproved drugs found in cognitive enhancement supplements." *Neurology: Clinical Practice*, 2020. {A chemical analysis of products bought off the shelf, not a study in people; it establishes what was in the bottles tested, not what the ingredients do.}[^cohen2020]: `paper` Cohen, P. A. et al. "Five unapproved drugs found in cognitive enhancement supplements." *Neurology: Clinical Practice*, 2020. {A chemical analysis of products bought off the shelf, not a study in people; it establishes what was in the bottles tested, not what the ingredients do.}[^lopresti2025]: `paper` Lopresti, A.L. and Smith, S.J. "The effects of magnesium L-threonate (Magtein) on cognitive performance and sleep quality in adults: a randomised, double-blind, placebo-controlled trial." *Frontiers in Nutrition*, 2025 (published online January 2026). {Funded by Threotech, which supplied the product; participants were adults under 46 with self-reported poor sleep, not older adults.} removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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