Nootropics run from coffee to drugs the FDA never approved

Key takeaways

• In a Harvard-led study published in 2020, 10 brain supplements contained five drugs not approved in the U.S., and one product held four of them.
• Caffeine is the brain booster most people already use, and the FDA says about 400 mg a day is generally not linked with harm in most adults.
• A review of 48 studies found prescription stimulants gave healthy people only small to modest gains in thinking skills.
• The FDA says phenibut, picamilon, sulbutiamine and tianeptine don’t qualify as dietary ingredients, and yearly tianeptine poison center cases rose from 4 in 2013 to about 350 in 2024.
• A ginkgo trial of more than 3,000 older adults found no drop in dementia, while early creatine trials hint at small memory gains.

For a study published in 2020, a team led by Pieter Cohen of Harvard Medical School went looking in the “brain health” aisle. They searched an NIH label database and a second supplement database for products that listed compounds similar to piracetam, a drug prescribed in parts of Europe¹⁹.

Testing the 10 products that turned up, the team identified five drugs that have no U.S. approval¹. Several products mixed two or more, one combined four, and some of the drugs were missing from the label entirely¹.

Doses were unpredictable, too. Omberacetam is usually prescribed at 10 mg, yet a single recommended serving of some products delivered as much as 40 mg¹.

“The effects of consuming untested combinations of unapproved drugs at unpredictable dosages are simply unknown,” Cohen said¹.

That’s the nootropic market in miniature. The word now covers your morning coffee, prescription pills, herbal extracts and foreign drugs packaged as supplements.

They don’t belong in one bucket. This guide sorts them by what the research shows and what each one risks.

The word “nootropic” was born in a drug lab

The term comes from a scientist named C. Giurgea. In 1972, he published a French-language paper proposing a “nootropic concept” in psychopharmacology, the study of drugs that act on the mind².

His paper was about drugs aimed at what he called the brain’s integrative activity, its higher mental functions². The idea came out of drug research, not herbal tradition.

That history matters today. Some products sold as brain supplements still borrow from that drug-research shelf, listing synthetic compounds under chemical names most shoppers won’t recognize¹⁹.

Coffee is the brain booster you already use, and dose is the whole story

Caffeine is a stimulant you probably already use. The FDA says about 400 mg a day, roughly two to three 12-ounce cups of coffee, is generally not linked with negative effects in most adults³.

Amounts vary widely. A 12-ounce cup of brewed coffee has about 113 to 247 mg, and a 16-ounce energy drink can have 54 to 328 mg³. People also differ a lot in how sensitive they are and how fast they clear caffeine³.

Does it help you think? In a small pilot trial published in 2021 in the journal Psychopharmacology, healthy men took caffeine, one of two prescription stimulants, or a placebo, a dummy pill. Caffeine improved sustained attention, the ability to stay focused on a dull task⁵.

The authors called the benefits from all three drugs small and limited to certain skills⁵.

Some “focus” products pair caffeine with L-theanine, an amino acid found in tea. A 2014 review in Nutrition Reviews pooled 11 placebo-controlled trials of tea compounds⁴. The caffeine and L-theanine combination had moderate effects on alertness and on accuracy when switching between tasks, mostly in the first two hours after a dose⁴.

There’s a twist: the effects tracked the caffeine dose more closely than the L-theanine dose⁴. One of the review’s four authors listed an affiliation with the drug company GlaxoSmithKline⁴.

Too much caffeine can cause a racing heart, high blood pressure, anxiety, jitters, insomnia and an upset stomach³. Pure or highly concentrated caffeine is the real hazard. The FDA says about 1,200 mg, less than half a teaspoon of the pure product, can cause toxic effects such as seizures if swallowed quickly³.

Prescription stimulants help healthy brains less than people expect

Some students and young adults use pills meant for ADHD or sleep disorders without a medical need⁸. The ones most often studied in healthy people are methylphenidate (Ritalin), amphetamine salts (Adderall) and modafinil (Provigil), a drug that promotes wakefulness⁶⁷.

A 2010 review in the journal Pharmacological Research pooled randomized trials of methylphenidate and modafinil in healthy people⁶. Methylphenidate improved memory, with no consistent evidence of other gains, while modafinil helped attention in people who were well rested⁶.

In sleep-deprived people, modafinil kept them more awake and helped memory and executive function, the mental skills used for planning and self-control⁶. But repeated doses didn’t stop the decline over longer sleep loss, and may have made people overconfident⁶. The authors concluded that expectations exceed what the drugs do⁶.

A 2015 meta-analysis in the Journal of Cognitive Neuroscience pooled 48 studies with 1,409 healthy people⁷. A meta-analysis combines many studies to get a clearer answer. Methylphenidate and amphetamine gave small gains in inhibitory control, the ability to stop an automatic response, and in short-term memory⁷.

Gains for working memory, which holds information while you use it, were small and shaky⁷. The authors found signs of publication bias, meaning positive results were more likely to be published⁷. They suggested healthy users may take stimulants more for energy and drive than for brainpower⁷.

The risks are real. In 2023, the FDA required an updated boxed warning, its most prominent label warning, about misuse, addiction and overdose for all prescription stimulants⁸.

The FDA’s review found that 56% to 80% of people who use stimulants without a medical reason get them from friends or family⁸. Pills bought from illegal sellers may be fake and can contain fentanyl or methamphetamine⁸. The agency’s advice: never share your stimulant⁸.

Some brain “supplements” are foreign prescription drugs

Piracetam is prescribed in parts of Europe for dementia and other memory problems, though a review of the research found little evidence that it works⁹. In 2004, the FDA turned down a company’s bid to sell it in the U.S. as a dietary supplement, citing doubts about the evidence of safety⁹.

It’s still sold online. In a research letter published in JAMA Internal Medicine in November 2019, Cohen’s team tested five U.S. products marketed with piracetam⁹.

According to the trade publication ISHN’s report on the letter, four contained the drug and the fifth had none that could be detected⁹. Recommended daily doses ranged from 831 mg to 11,283 mg, more than a 13-fold spread⁹.

At medical doses, piracetam can cause anxiety, agitation, depression and weight gain⁹.

The FDA keeps a public directory of supplement ingredients and other substances it has taken action on. As of May 2026, it lists phenibut, picamilon, sulbutiamine and tianeptine among substances that don’t meet the legal definition of a dietary ingredient¹⁰. The same group includes DMAA and DMHA¹⁰.

That legal status doesn’t stop online sellers. It does mean no regulator checked the dose, the purity or how the drug mixes with your medicines before it reached you¹.

Phenibut and tianeptine show up in poison center calls

Phenibut began as a Russian anxiety medicine in the 1960s¹¹. The FDA has never approved it, yet online stores sell it as a supplement¹¹.

A CDC report published in September 2020 counted 1,320 phenibut cases reported to U.S. poison centers from 2009 to 2019, most of them called in from hospitals and other health care settings¹¹. Roughly 3 in 10 patients were agitated, and a similar share were drowsy. About 1 in 5 had a racing heart, about as many were confused, and 80 people fell into a coma¹¹.

Effects that were life-threatening or disabling showed up in 12.6% of cases, and three people died¹¹. Reports climbed sharply over the decade, especially after 2015, when poison centers began using “phenibut” as a search term; before that, cases were mostly filed under another name, “phenygam”¹¹.

Some countries prescribe tianeptine for depression, but in the U.S. it has no approved medical use, according to the FDA¹³. Online sellers still promise sharper thinking and relief from anxiety, pain and more, claims the agency calls unproven¹³.

In May 2025, the FDA reported that yearly tianeptine cases at U.S. poison centers rose from 4 in 2013 to about 350 in 2024, based on national poison center data¹³. Some American users described daily amounts anywhere from 1.3 to 250 times what doctors abroad typically recommend¹³. Reported harms run from a pounding heart and high blood pressure to confusion, breathing that slows or stops, coma and death¹³.

Heavy use and withdrawal can look like opioid poisoning and opioid withdrawal¹³. In an earlier CDC study of 218 tianeptine calls, phenibut was the substance most often taken with it¹². Cases that involved other substances were more likely to have major outcomes¹².

When to get help. If someone is very drowsy, confused or breathing slowly after taking one of these products, call 911. For other poisoning questions, call Poison Help at 1-800-222-1222¹³. For help stopping, find treatment at findtreatment.gov or call 1-800-662-4357¹³. Report side effects to FDA MedWatch online, or call 1-800-332-1088 to get a paper form¹³.

Ginkgo and creatine: one big trial said no, and one young field says maybe

Ginkgo is a fixture of the memory aisle, and it got a big test. The Ginkgo Evaluation of Memory study followed more than 3,000 people aged 75 and older for a median of six years¹⁴.

People were randomly assigned to take ginkgo or a placebo. The two groups developed dementia, including Alzheimer’s disease, at similar rates¹⁴. The National Center for Complementary and Integrative Health (NCCIH) notes that ginkgo may raise bleeding risk in people taking blood thinners such as warfarin¹⁴. It may also be unsafe in pregnancy¹⁴.

Creatine, best known as a muscle supplement, is a newer story. A 2024 review in Frontiers in Nutrition pooled 16 randomized trials with 492 adults and found a small gain in memory¹⁵. People also finished attention and processing-speed tasks faster, but there was no clear effect on overall thinking or planning skills¹⁵.

The reviewers rated the memory evidence as moderate in certainty and the other findings as lower¹⁵. The trials were small, the authors called for larger ones, and the journal later posted a correction to the paper¹⁵.

Memory products built on newer ingredients deserve the same questions. Our article on company-funded research walks through one well-known example, Prevagen.

What the evidence says, product by product

This table uses four levels: strong evidence, promising but early, not enough evidence, and evidence says no (or unsafe).

Claim	Evidence level	What the research shows
Caffeine sharpens thinking skills in healthy adults	Promising but early	Small gains in sustained attention in a pilot trial of healthy men5
Caffeine plus L-theanine boosts short-term alertness	Promising but early	Moderate gains in alertness and task switching in 11 trials, tracking the caffeine dose most4
Prescription stimulants give healthy people only small thinking gains	Strong evidence	48 studies show small gains in some skills, with signs of publication bias; boxed warning for misuse and addiction78
Modafinil sharpens thinking in healthy people	Promising but early	Better attention when rested and alertness when sleep-deprived; possible overconfidence6
Creatine improves memory	Promising but early	Small memory gain across 16 small trials15
Ginkgo prevents dementia	Evidence says no	No difference in dementia rates over a median of six years14
Piracetam and other racetams sharpen memory	Not enough evidence	Little evidence it works; FDA rejected it as a supplement in 2004; doses in U.S. products varied more than 13-fold9
Phenibut is safe to take as a supplement	Evidence says no, or unsafe	1,320 poison center cases and three deaths in 2009 to 201911
Tianeptine is safe to take as a supplement	Evidence says no, or unsafe	About 350 poison center cases in 2024; opioid-like withdrawal13

Before you buy a brain booster: a seven-point check

Many people come to nootropics for good reasons. They want to stay sharp, avoid more prescriptions and take charge of their own health. Those are natural-health values, and they point toward a careful approach.

A traditional herb or food has a history of human use. A synthetic drug relabeled as a supplement has none of that history in your kitchen, and none of the testing a pharmacy drug gets. Treat it with more caution, not less.

Use this check before you buy or take any brain product:

1. Read every ingredient name. Compare it against the box above. Chemical names ending in “-acetam,” or the words phenibut or tianeptine, mean stop.
2. Total your caffeine. Add coffee, tea, soda, energy drinks and any “focus” capsules. Stay near or below 400 mg a day, and less if you’re pregnant or sensitive³.
3. Skip pure or highly concentrated caffeine. Bulk packages can hold thousands of servings, and a toxic amount fits in less than half a teaspoon³.
4. Pass on drugs dressed as supplements. If an ingredient is on the FDA’s list of substances that aren’t dietary ingredients, no one has vouched for its dose or purity¹¹⁰.
5. Never borrow a stimulant. Ask a clinician instead, and tell them why you want it⁸.
6. List your medicines first. Bring the bottle to a pharmacist, especially if you take a blood thinner¹⁴ or any prescription for mood, sleep or seizures.
7. Watch how you feel. Stop and get help for drowsiness, confusion, a racing heart or trouble stopping a product¹¹¹³.

The basics come first. If poor sleep, stress, depression or a medical problem is dulling your focus, a pill won’t fix the cause. A clinician can help you sort that out.

Questions readers ask

The bottom line

Nootropics range from coffee to drugs no U.S. agency has approved. Caffeine, alone or with L-theanine, gives a modest lift, and creatine shows early promise for memory. Prescription stimulants do less for healthy people than many expect and carry real risks.

At the far end, the FDA says phenibut and tianeptine don’t qualify as supplement ingredients, it turned down piracetam as one, and some of these drugs have sent people to emergency rooms. Read every ingredient, total your caffeine, never borrow a prescription, and talk with a clinician if focus problems persist.

Related reading

• Who paid for the study matters, even when the science is real
• What gets into supplements that isn’t on the label
• The supplement facts panel and the blend that hides your dose
• What happens when you don’t tell your doctor about supplements
• A stack of safe supplements can add up to an unsafe dose

Sources

1. American Academy of Neurology. “Study Discovers Multiple Unapproved Drugs in ‘Brain Boosting’ Supplements” (on Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I. “Five Unapproved Drugs Found in Cognitive Enhancement Supplements.” Neurology: Clinical Practice). AAN, 2020. aan.com
2. Giurgea C. “Pharmacology of Integrative Activity of the Brain. Attempt at Nootropic Concept in Psychopharmacology” (in French). Actualités Pharmacologiques, 1972. Record via Europe PMC. europepmc.org
3. U.S. Food and Drug Administration. “Spilling the Beans: How Much Caffeine Is Too Much?” FDA Consumer Update, 2024. fda.gov
4. Camfield DA, Stough C, Farrimond J, Scholey AB. “Acute Effects of Tea Constituents L-Theanine, Caffeine, and Epigallocatechin Gallate on Cognitive Function and Mood: A Systematic Review and Meta-Analysis.” Nutrition Reviews, 2014. pubmed.ncbi.nlm.nih.gov
5. Repantis D, Bovy L, Ohla K, Kühn S, Dresler M. “Cognitive Enhancement Effects of Stimulants: A Randomized Controlled Trial Testing Methylphenidate, Modafinil, and Caffeine.” Psychopharmacology, 2021. europepmc.org
6. Repantis D, Schlattmann P, Laisney O, Heuser I. “Modafinil and Methylphenidate for Neuroenhancement in Healthy Individuals: A Systematic Review.” Pharmacological Research, 2010. europepmc.org
7. Ilieva IP, Hook CJ, Farah MJ. “Prescription Stimulants’ Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-Analysis.” Journal of Cognitive Neuroscience, 2015. europepmc.org
8. U.S. Food and Drug Administration. “FDA Updating Warnings to Improve Safe Use of Prescription Stimulants Used to Treat ADHD and Other Conditions.” Drug Safety Communication, 2023. fda.gov
9. ISHN. “New Study Says Some Marketers of Brain-Boosting Supplements Are Flouting an FDA Ban” (on Cohen PA, Zakharevich I, Gerona R. “Presence of Piracetam in Cognitive Enhancement Dietary Supplements.” JAMA Internal Medicine). ISHN, 2019. ishn.com
10. U.S. Food and Drug Administration. “Information on Select Dietary Supplement Ingredients and Other Substances.” FDA, 2026. fda.gov
11. Graves JM, Dilley J, Kubsad S, Liebelt E. “Notes From the Field: Phenibut Exposures Reported to Poison Centers — United States, 2009–2019.” CDC Morbidity and Mortality Weekly Report, 2020. cdc.gov
12. El Zahran T, Schier J, Glidden E, et al. “Characteristics of Tianeptine Exposures Reported to the National Poison Data System, United States, 2000–2017.” CDC Morbidity and Mortality Weekly Report, 2018. cdc.gov
13. U.S. Food and Drug Administration. “Tianeptine Products Linked to Serious Harm, Overdoses, Death.” FDA Consumer Update, 2025. fda.gov
14. National Center for Complementary and Integrative Health. “Ginkgo.” NCCIH, 2025. nccih.nih.gov
15. Xu C, Bi S, Zhang W, Luo L. “The Effects of Creatine Supplementation on Cognitive Function in Adults: A Systematic Review and Meta-Analysis.” Frontiers in Nutrition, 2024. frontiersin.org