What Are Nootropics? Mechanisms, Efficacy, and Safety of Cognitive Enhancers

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.

Introduction
Mechanisms of action
Categories of nootropics
    Prescription nootropics
    Natural nootropics
    Synthetic/OTC nootropics
Evidence of efficacy
Safety, tolerance, and side effects
Ethical and social considerations
Conclusions
References
Further reading

From herbal extracts to synthetic stimulants, nootropics promise sharper thinking, but at what cost? Explore how these brain-boosting agents work, what the evidence says, and why regulatory oversight and ethical debates remain front and center. 

Image Credit: Ingegneri, M., Smeriglio, E., Zebbiche, Y., Cornara, L., Visalli, L., Smeriglio, A., & Trombetta, D. (2025). The Dark Side of “Smart Drugs”: Cognitive Enhancement vs. Clinical Concerns²⁶.  

Introduction

Nootropics, which are often referred to as 'smart drugs' or 'brain boosters,' are substances designed to enhance cognitive functions, including memory, attention, executive function, creativity, and motivation. Modern nootropics can be further categorized as prescription drugs like modafinil and donepezil, natural compounds and herbal extracts including Bacopa monnieri, Ginkgo biloba, and ginseng, as well as synthetic supplements like piracetam-class racetams or blended stacks.

Mechanisms of action

Memory and attention can be improved by Bacopa monnieri and Centella asiatica, whereas racetams (piracetam) enhance acetylcholinesterase (ACh) synthesis, receptor activity, or slow breakdown. Comparatively, dopaminergic, noradrenergic, and serotonergic pathways are influenced by Panax species and agents like modafinil, which support motivation, alertness, and mood.^4,5

Glutamatergic signaling, particularly α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor modulation by piracetam‑class compounds, facilitates calcium entry and long-term potentiation (LTP), thereby strengthening synapses. Cerebral blood flow and oxygenation can be improved with vasodilatory agents like vinpocetine and Ginkgo biloba, which enhance microcirculation and nutrient delivery to improve both metabolic and mitochondrial function.^1,6

Withania somnifera and Ginkgo decrease oxidative stress, inflammation, and amyloid protein-related injuries. These actions promote neuroplasticity, synaptic growth, and cellular resilience, thereby improving cognitive performance and potentially mitigating cognitive decline resulting from disease and aging.^2,7

Categories of nootropics

Nootropics can be further categorized as prescription medications, natural compounds, and synthetic or over-the-counter (OTC) agents, each differing in mechanism, evidence base, and regulation.^1,8

Prescription nootropics

Clinically approved nootopic drugs include modafinil, which is currently used to treat narcolepsy and cognitive fatigue. Additionally, amphetamine salts like Adderall are prescribed for the treatment of attention-deficit hyperactivity disorder (ADHD) to enhance attention through dopaminergic and noradrenergic pathways.

Donepezil, an acetylcholinesterase inhibitor for Alzheimer’s disease, also supports cholinergic signaling. Other investigational agents target glutamatergic and nicotinic receptors or inhibit phosphodiesterase (PDE) enzymes for the management of ADHD, narcolepsy, dementia, and related cognitive impairments.^4,7,8

Natural nootropics

Herbal nootropic agents like Bacopa monnieri, Ginkgo biloba, Panax ginseng, and Centella asiatica enhance cholinergic activity, cerebral blood flow, and neuroprotection while reducing oxidative stress. Common combinations include Bacopa with Centella to improve attention, as well as Ginkgo with Ginseng to enhance memory and attentional speed. Caffeine and L-theanine blends are also widely marketed for their ability to provide quick alertness and mood enhancement.^1,6,8

Synthetic/OTC nootropics

Synthetic compounds can include racetams like piracetam and aniracetam, as well as noopept, all of which modulate cholinergic and glutamatergic systems to modulate synaptic plasticity and neuroprotection. Importantly, the regulation of these agents varies widely, and clinical evidence is mixed.^5,7

Evidence of efficacy

In dementia care, 240 mg/day of Ginkgo biloba (EGb-761) for at least 20 weeks alleviated neurosensory symptoms, including tinnitus and dizziness in patients ¹¹ Standardized Ginkgo biloba treatment has also been shown to improve mood, memory, learning, and working capacity in young adults reporting cognitive complaints such as headaches and attention lapses.¹⁴

A 2016 systematic review reported that 100 mg/day of Bacopa monnieri (Bm) for a duration of four to 12 weeks improved language behavior, memory, hyperactivity, and attention in children and adolescents diagnosed with ADHD.⁹ Among medical students between 19 and 22 years of age, 150 mg of Bm twice daily for six weeks improved immediate recall, working memory, and language comprehension.¹³

In a randomized, double-blinded, placebo-controlled trial, caffeine, including 50 mg delivered as coffee, improved executive function, planning, and reaction time in habitual users.¹⁶ Combining caffeine and L-theanine has also provided synergistic short-term improvements in attentional switching.¹⁷

Piracetam may confer neuroprotective and cognitive benefits in cerebrovascular, traumatic, and perioperative settings.¹⁸ Oxiracetam treatment has also been reported to improve reaction speed and attentional metrics in adults 65 years of age and older with age-associated cognitive impairment.

Most studies examining the efficacy of nootropic agents have small sample sizes, short durations, or are methodologically heterogeneous. Placebo effects, variable dosing, and limited in vivo data are preventing the widespread generalizability of these results; therefore, larger, longer, and controlled trials are indicated.^19,20

Safety, tolerance, and side effects

Most nootropics are well-tolerated when clinically supervised; however, mild headaches and insomnia have been reported. Stimulant/wakefulness agents such as modafinil and methylphenidate/amphetamine can increase the risk of anxiety, agitation, elevated heart rate, and sleep disruption. When used at high or prolonged doses, the risk of misuse or dependence increases, particularly among patients diagnosed with cardiovascular, psychiatric, or substance‑use disorders.^2,21

Multi-ingredient blends of botanicals, amino acids, and caffeine increase the risk of adverse interactions. Supra-therapeutic stimulants or overlapping cholinergic/glutamatergic effects, such as restlessness, mood changes, and poor sleep, may also occur.^2,22

Prescription drugs are typically regulated by federal entities, such as the United States Food and Drug Administration (FDA). Comparatively, unauthorized ingredients such as huperzine A and yohimbine, unapproved drugs like phenibut and emoxypine, repurposed agents including piracetam and vinpocetine, as well as research chemicals with limited toxicology data, are often sold online without oversight.^2,22

In a recent study conducted in the European Union (EU) and Australia, researchers identified 159 products with 34 nootropic-related molecules, 68% of which originated from illegal supply chains. About 50% of these products were sold as supplements but contained prescription drugs like modafinil or methylphenidate, high-dose melatonin, Russian agents like noopept and phenibut, as well as research chemicals.

These findings underscore the importance of purchasing nootropics from reputable sources, as well as strengthening current regulatory agencies to monitor the dissemination of these potentially harmful products.²³

 Image Credit: Shutterstock AI Generator / Shutterstock.com

Ethical and social considerations

Using nootropics to treat conditions for which the drug has been approved for is broadly accepted; however, treating healthy people with nooptric agents to improve their performance is ethically contested.^19,24 Normalization may create implicit coercion, as students or workers may feel pressure to artificially enhance their cognitive skills.

The misuse of prescription stimulants is reported more often in lower‑performing students, which raises fairness and integrity concerns that universities seldom address. Some view cognitive enhancement as cheating, whereas others consider it to be another performance tool, like caffeine or calculators.²⁴

Conclusions

Nootropics include prescription drugs, herbal extracts, and synthetic compounds that are used to enhance cognition. Safety concerns, including side effects, product mislabeling, and grey markets, emphasize the importance of informed and cautious use.

References

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