Are Nootropics Safe? Side Effects and Who Should Avoid Them

Key takeaways

• FDA states that, under the Dietary Supplement Health and Education Act (DSHEA), it does not have the authority to approve dietary supplements before they are marketed.
• In a 2026 meta-analysis of 31 randomized trials of L-theanine, no serious adverse events were reported.
• A 2021 meta-analysis of seven randomized trials of cardiovascular outcomes found that marine omega-3 supplements were associated with an increased risk of atrial fibrillation.
• A 2015 analysis of Veterans Administration records reported a hazard ratio of 1.38 for a bleeding adverse event when ginkgo was taken together with warfarin.
• A 2023 review of published cases describes liver injury linked to ashwagandha, including one case that ended with liver transplantation.
• A 2022 review states that the long-term effects of nootropics on healthy individuals are still unknown.
• Ask a clinician or pharmacist before you start if you take prescription medicines, are pregnant or breastfeeding, are under 18, have a health condition or are about to have surgery.

New to the topic? What are nootropics? covers definitions, and Nootropics for beginners covers a first-month routine.

What "safe" can and cannot mean for supplements

FDA states that, under DSHEA, manufacturers and distributors of dietary supplements and dietary ingredients are responsible for evaluating the safety and labeling of their products before marketing. In its questions and answers, FDA says it is in general limited to postmarket enforcement, because there are no provisions in the law for FDA to approve dietary supplements for safety before they reach the consumer.

The National Center for Complementary and Integrative Health (NCCIH) states that companies must show FDA evidence that their prescription and over-the-counter drugs are safe and effective before the drugs are marketed. NCCIH also states that rules for manufacturing and distributing dietary supplements are less strict than those for prescription or over-the-counter drugs. The page Are nootropics FDA approved? covers the regulatory side in more detail.

FDA also states that it does not test dietary supplements before they are sold to consumers. Keep that in mind when you read the word "safe" on a label.

Nor does "safe" mean "proven over years in healthy people." A 2022 review of nootropics states that their long-term effects on healthy individuals are still unknown. The same review says the use of nootropics by healthy individuals is of great concern due to the lack of clinical evidence regarding their efficacy, safety, and social consequences, especially in long-term use. It also says nootropics tend to be well tolerated in patients with cognitive impairments, that the incidence of side effects is low, and that those that do occur are usually mild. Note who each statement is about: patients in one, healthy adults in the other.

Side effects by ingredient

The table summarizes what the cited sources report for seven ingredients. Each cell describes only the study, review or report named in it. Missing information is not evidence of safety, and a case report is a signal to check with a clinician, not a measure of how frequent something is.

Ingredients such as Lion's Mane, citicoline and Rhodiola are not in the table. Their absence is not a finding that they carry no risk.

Interactions worth knowing

Ginkgo and warfarin. A 2021 systematic review of warfarin interactions lists Ginkgo biloba among the foods and herbs for which healthcare professionals should be aware of the increased risk of bleeding. A 2015 analysis of Veterans Administration records reported a hazard ratio of 1.38 (95% CI 1.20 to 1.58) for a bleeding adverse event when ginkgo was taken concurrently with warfarin. If you take warfarin, ask your prescriber before adding ginkgo or any other supplement.

Huperzine A and acetylcholinesterase. A Cochrane review describes Huperzine A as a linearly competitive, reversible inhibitor of acetyl cholinesterase. The same review says cholinesterase inhibitors may block the degradation of acetylcholine. That describes how the compound acts. It is not a report of a drug interaction, and no source reviewed for this guide states one. If you take a prescription medicine for memory loss or Alzheimer's disease, ask a clinician before adding huperzine A.

Tyrosine and MAO inhibitors. A case report published in 2023 describes a 67-year-old woman with severe depression who was taking the MAOI transdermal selegiline and who needed parenteral nutrition (PN) that contained tyrosine. The authors write that monoamine oxidase inhibitors (MAOIs) prevent the breakdown of tyramine in the body and can cause a sudden increase in blood pressure with significant tyramine build up. They describe an interaction between tyrosine and MAOIs as a theoretical possibility, because tyrosine endogenously undergoes decarboxylation to produce tyramine. In this patient, the combined therapy was tolerated without any side effects. This is one patient receiving parenteral nutrition, a different setting from taking a tyrosine capsule by mouth, so it cannot show how likely a reaction is either way. If you take an MAOI, ask your prescriber before using a product containing L-tyrosine.

Omega-3 and atrial fibrillation. A 2021 systematic review and meta-analysis of seven randomized controlled trials of cardiovascular outcomes found that marine omega-3 supplementation was associated with an increased risk of atrial fibrillation (hazard ratio 1.25, 95% CI 1.07 to 1.46). In analyses stratified by dose, the hazard ratio was 1.49 (95% CI 1.04 to 2.15) in the trials testing more than 1 g/d and 1.12 (95% CI 1.03 to 1.22) in the trials testing 1 g/d or less. The analysis concerns marine omega-3 fatty acid supplements as a group, so do not read it as a result for DHA alone. If you have a heart rhythm condition, ask a clinician before using an omega-3 product and check the dose on the label.

Caffeine, limits and sleep. FDA says that, for most adults, 400 milligrams of caffeine a day is an amount not generally associated with negative effects. In a study with a placebo comparison, 400 mg of caffeine taken at bedtime, 3 hours before bedtime or 6 hours before bedtime each had significant effects on sleep disturbance relative to placebo. Add up caffeine from every source, including any nootropic blend. See caffeine for the ingredient page.

Liver injury reports with ashwagandha

Case reports and case series describe individual patients. They show that liver injury happened in those patients, not the number of people who take a supplement and are affected.

A 2023 paper on herb-induced liver injury (HILI) states that most patients fully recover after discontinuing herbal products, while severe hepatic traumas and fatal cases have also been reported.

The ashwagandha paper's literature review found six articles with a total of 10 cases that fulfilled the authors' predetermined criteria. The authors state that all patients recovered spontaneously after the discontinuation of ashwagandha use, that no fatalities were reported, and that only one case needed liver transplantation. They write that the main reason and mechanisms by which ashwagandha causes liver injury are unknown.

The authors also describe two new cases. The first was a 36-year-old man who used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. The second was a 30-year-old woman who developed pruritus after 45 days of using ashwagandha capsules (450 mg). The updated Roussel Uclaf Causality Assessment Method (RUCAM), with a score of seven in both cases, indicated a “probable” relationship with ashwagandha.

A 2012 randomized trial of 64 adults with a history of chronic stress, who took one capsule twice a day for 60 days, reported adverse effects that were mild in nature and comparable in both groups, and no serious adverse events. A 2024 meta-analysis of nine randomized trials says the adverse effects associated with ashwagandha are limited, and that further information is required to determine its safety with long-term administration. If you notice yellowing of the skin or eyes, dark urine or itching while taking any supplement, stop it and contact a clinician. See ashwagandha for the ingredient page.

Who should avoid nootropics or ask first

NCCIH states that if you are going to have surgery, certain dietary supplements may increase the risk of bleeding or affect your response to anesthesia.

Pregnancy and breastfeeding. NCCIH states that many dietary supplements have not been tested in pregnant women, nursing mothers, or children. For caffeine, FDA recommends talking to your health care provider about whether you need to limit caffeine consumption if you are pregnant, trying to become pregnant, or breastfeeding.

Children and teens. FDA's caffeine page says medical experts advise against energy drinks for children and teens because of the levels of sugar and caffeine, according to the American Academy of Pediatrics. The sources cited in this guide do not describe trials of the other ingredients in teenagers, so ask a pediatrician before a young person uses any nootropic.

Anxiety and panic. In the nine studies on panic attacks in a 2022 meta-analysis, 51.1% of 237 patients with panic disorder had a panic attack following caffeine, but none after placebo. The caffeine doses in those studies ranged from 400 to 750 mg. The authors add that little is known regarding doses smaller than 480 mg.

Other groups. Ask a clinician before starting if you take warfarin or another prescription medicine, take an MAOI, have a heart rhythm condition, bipolar disorder or panic disorder, or are under 18.

Are nootropics addictive?

The answer depends on which kind of product you mean. FDA states that prescription stimulants are classified as Schedule II drugs under the Controlled Substances Act and associated with serious risks, including misuse, addiction, overdose, and diversion. The DEA's schedule page describes Schedule II substances as having a high potential for abuse which may lead to severe psychological or physical dependence.

Caffeine is the one ingredient in this guide for which a source describes withdrawal. FDA states that caffeine withdrawal isn't considered dangerous but can be unpleasant. The abstracts and pages cited here for the other ingredients do not address dependence or withdrawal, so this guide cannot say whether either occurs.

Contamination, mislabeling and unapproved drugs

FDA states that products that claim to help with health issues are not reviewed by the FDA and could be contaminated with dangerous hidden ingredients. FDA says its health fraud product database covers only a small fraction of the contaminated and/or fraudulent products on the market, and that if a product is not on the list, that does not mean it is safe. NCCIH states that some products marketed as dietary supplements—promoted mainly for weight loss, sexual enhancement, and bodybuilding—may contain prescription drugs not allowed in dietary supplements or other ingredients not listed on the label. Those NCCIH examples concern weight loss, sexual enhancement and bodybuilding products, not nootropics specifically.

FDA enforcement examples. In a February 2019 warning letter, FDA states that a company took orders on its website for products including adrafinil, aniracetam, Bacopa monnieri, L-Dopa and L-Theanine. The letter states that new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from the FDA. A 2023 Department of Justice press release states that an Arizona company and its CEO pleaded guilty to the introduction of misbranded drugs into interstate commerce. The press release states that FDA has not approved drugs containing tianeptine, adrafinil, phenibut, and racetams for use in the United States.

The Department of Defense's prohibited dietary supplement ingredients database says it is provided to help Service Members know what to avoid when considering dietary supplement products. It states that Service Members are prohibited from using any substance identified in the database as ingredients in dietary supplements. Its stated scope is Service Members. It is a lookup aid, not a ruling on whether a product is safe for you.

This guide does not assess private testing seals, because no source reviewed for it describes what such seals verify.

Prescription "smart drugs" used without a prescription

A 2025 narrative overview describes the typically healthy “smart drugs” user as ingesting a range of drugs/molecules to achieve improved mental performance. Its summary says health risks from using them, especially without a prescription, are a concern.

The overview says stimulant ingestion may be associated with a significant rise in body temperature and death, and that fatalities are particularly associated with seizures and coma. The overview states that individuals without cognitive impairment who take sustained high doses of cognitive enhancers are more likely to experience negative effects, including sleep disturbances, mood instability, anxiety, reward-system dysfunctions/addiction behaviors, and other psychopathological symptoms. It adds that the risk-benefit ratio in healthy populations might be unfavorable, particularly with long-term or non-medically supervised use.

How to report a problem

FDA states that it does not approve dietary supplements before they are sold to the public, and that it is therefore particularly important for consumers, healthcare professionals, and industry members to report health-related reactions or illnesses (also known as adverse events) to FDA.

FDA says that if you think a dietary supplement may have caused you or someone you know to have a serious reaction or illness, you should immediately stop using the product and fill out a safety report through the Safety Reporting Portal. FDA asks reporters to supply as much information as they can, and says that complete reports are the most helpful, but even pieces of information can help FDA identify potentially dangerous products. In its questions and answers, FDA says the first thing you should do if you think you have suffered a harmful effect or illness from a dietary supplement is contact or see your health care provider immediately. Keep the product label or container, and write down the product name, the dose and the date your symptoms began before you file a report.

Common questions

Is it safe to take nootropics every day? A 2022 review states that the long-term effects of nootropics on healthy individuals are still unknown. The same review says that, because of the incomplete clinical evidence on effectiveness, safety, and social consequences in the case of long-term use, they cannot be recommended to healthy individuals who do not suffer from any cognitive dysfunction. A 2024 ashwagandha meta-analysis says further information is required to determine its safety with long-term administration. Make that decision with a clinician, one ingredient at a time; Nootropics for beginners shows how.

Are natural nootropics safer? NCCIH states that many dietary supplements (and some prescription drugs) come from natural sources, but “natural” does not always mean “safe.” Ginkgo with warfarin and the ashwagandha liver reports, covered above, are plant-derived examples with specific cautions. See also natural vs synthetic nootropics.

Can teens take nootropics? NCCIH states that if you are considering giving a child a dietary supplement, many dietary supplements have not been tested in children. The caffeine findings for children and teens are in the section on who should ask first. Talk to a pediatrician before a teenager uses any nootropic.

Do nootropics damage the brain long term? The sources cited in this guide do not answer this directly. The 2022 review says the long-term effects of nootropics on healthy individuals are still unknown. The 2025 overview says smart drugs' use can be associated with paradoxical short- and long-term cognitive decline and addictive behavior. The 2025 statement is about "smart drugs" as a group, not a single supplement. Missing evidence of harm is different from evidence of safety. For the basics, see What are nootropics?.