Nootropics: Benefits and Safety

Trang Tran, PharmD, is a pharmacist and a health and wellness writer/blogger.

Suzanne Fisher, RD, founder of Fisher Nutrition Systems, has been a board-certified registered dietitian and licensed nutritionist for over 30 years.

Getty Images / Akaradech Pramoonsin

The Food and Drug Administration (FDA) determined that piracetam cannot be sold as a dietary supplement. However, due to limited enforcement, piracetam supplements remain available for sale.

The FDA also does not consider vinpocetine (synthetic derivative of vincamine) to be a supplement. However, it is still marketed as such.

Nootropics are substances that boost brain and cognitive performance. They are derived from plants or can also be synthetic (artificial).

Supplements known as nootropics include herbs, stimulants, antioxidants, amino acids, and other supplements with cognitive-enhancing effects. Vitamin B12 fits into this category as it enhances cognitive performance by ensuring proper brain metabolic function.

Nootropics enhance cognitive health by improving the following functions:

This article discusses the potential uses of nootropics, side effects, and safety concerns.

Dietary supplements are not regulated the way drugs are in the United States, meaning the FDA does not approve them for safety and effectiveness before products are marketed. When possible, choose a supplement tested by a trusted third party, such as the U.S. Pharmacopeia (USP), ConsumerLab.com, or NSF.org. However, even if supplements are third-party tested, they are not necessarily safe for all or effective in general. Therefore, talking to your healthcare provider about any supplements you plan to take and asking about potential interactions with other supplements or medications is essential.

The following nootropics have been shown to enhance cognition.

An analysis of a group of studies looked at using 300 milligrams (mg) of bacopa (Bacopa monnieri) for at least 12 weeks in healthy adults. It showed a decrease in choice reaction time and an improvement in attention speed. However, the effect of Bacopa on memory remains to be seen due to conflicting results.

It would be helpful for larger trials to compare Bacopa with an approved nootropic prescription drug, such as Aricept (donepezil).

Bacopa has been shown to improve cognitive function in healthy adults, children, and adolescents. A systematic review of research in children (4 to 18 years of age) showed improvements in cognition and behavior.

It also improved attention shortfalls in young people with the neurodevelopmental disorder attention deficit hyperactivity disorder (ADHD).

Low-to-moderate doses (around 100 to 275 mg) of caffeine before and/or during exercise improved attention, energy, and mood in studies of adult athletes. However, in some of the studies, caffeine was taken with carbohydrates. This may have changed caffeine's effects.

One review looked at the effect of short-term caffeine consumption in individuals with sleep deprivation. It revealed caffeine improved cognitive performance and appears to counteract the effects of sleep loss.

Another review found that using caffeine before a mentally tiresome task helped counteract mental fatigue.

However, another group of studies examining the effect of caffeine on mental fatigue in healthy participants aged 18 to 45 found that caffeine did not affect some cognitive tests.

It's essential to get adequate sleep whenever possible. Replacing rest with caffeine intake is not advised.

Studies have used citicoline (CDP-choline) with acetylcholinesterase inhibitors (ACHEIs), such as Aricept (donepezil).

This combination improved cognitive performance among people with Alzheimer's disease vs. ACHEIs alone.

Further study is needed.

A review of ginkgo (Ginkgo biloba) studies revealed that it significantly benefited research participants with cognitive impairment. However, ginkgo did not improve cognitive function in healthy subjects.

Further research is needed to clarify the cognitive effect of ginkgo in healthy individuals.

Huperzine A has been studied for its effects on several cognitive issues. A review of studies looked at data from 1,823 participants with Alzheimer's disease between 50 and 85 years old.

The huperzine A dosage was 0.2 to 0.8 mg daily, with an average daily dose of about 0.37 mg.

The studies lasted eight to 36 weeks, with an average duration of 14.7 weeks.

Huperzine A showed beneficial effects for Alzheimer's disease, improving cognitive function, compared with placebo (no treatment), psychotherapy, and conventional medicine. However, the quality of the included studies was not the best.

A different systematic review, from 2016, showed that using huperzine A with antipsychotics improved cognitive function in people with schizophrenia.

Higher-quality studies are needed.

A review of a group of studies found that L-theanine in combination with caffeine improved cognitive tasks such as enhancing attention.

Further research is needed to determine the minimum period necessary to take L-theanine to provide long-term effects.

Racetams are technically a drug class used to treat seizures or as nootropics. They are made synthetically (in a lab).

Racetams typically used as nootropics include the following:

The FDA has prohibited the sale of piracetam as a dietary supplement. However, piracetam supplements remain available in the marketplace at high doses.

Higher doses of racetams carry an increased risk of side effects among consumers of cognitive enhancement supplements.

One review focused on piracetam's effects on post-stroke patients experiencing aphasia (a loss of the ability to understand speech), piracetam improved only short-term written language performance in people who had had a stroke.

A review suggested tyrosine can help people doing demanding work in harsh environmental conditions.

Tyrosine prevented or reversed the cognitive performance decreases in participants that these situations created. The review also suggested tyrosine increased working memory, information processing, and mood.

Researchers found that tyrosine also improved convergent thinking (the ability to give a correct answer to a question). They also suggested tyrosine's effects on working memory and information processing speed may be similar to those of methylphenidate, a medication used for ADHD.

ADHD has been associated with deficiencies in neurotransmission (transferring information between neurons), specifically involving the neurotransmitters dopamine and norepinephrine. Researchers believe L-tyrosine provides the building blocks to make dopamine and norepinephrine.

Further study is needed to confirm whether tyrosine supplementation is equivalent to methylphenidate.

The FDA does not consider vinpocetine to be a supplement. However, it is still marketed as such.

One study found that vinpocetine increased blood flow in the brain and improved cognitive ability in people with stroke.

Another study, showed no significant cognitive effects of vinpocetine in healthy volunteers or people with epilepsy.

Future studies exploring higher doses of vinpocetine are needed to determine if such doses can effectively enhance human cognition.

Supplement use should be individualized and vetted by a healthcare professional, such as a registered dietitian, pharmacist, or healthcare provider. No supplement is intended to treat, cure, or prevent disease.

Your provider may recommend you take nootropics for specific reasons.

However, consuming a nootropic supplement, such as bacopa, caffeine, citicoline (CDP-Choline), ginkgo, huperzine A, L-theanine, racetams, and vinpocetine, may have potential side effects.

These side effects may be mild or severe.

Bacopa monnieri

Side effects of B. monnieri commonly reported in clinical trials include the following:

Caffeine

Taking too much caffeine can cause the following side effects:

Citicoline (CDP-Choline)

Mild side effects of CDP-choline include the following:

Ginkgo Biloba

Side effects of ginkgo may include the following:

Huperzine A

Huperzine A is associated with some of the following cholinergic side effects:

Tyrosine

One clinical trial reported that tyrosine had no side effects.

However, tyrosine is a building block for norepinephrine and dopamine.

Theoretically, it may cause symptoms associated with norepinephrine and dopamine.

Racetams

Potential side effects of piracetam include the following:

Vinpocetine

Mild side effects such as dizziness and diarrhea were reported in one study. Moderate allergic dermatitis was also reported.

The following is a list of severe side effects:

If you experience severe side effects, seek medical help immediately.

Avoid nootropics if you have a known allergy to them or their components (ingredients or parts).

Ask your pharmacist, registered dietitian, or healthcare provider for more information regarding allergies to nootropics, and if medications you take may interact with nootropics.

Keep the following precautions in mind when using the following nootropic supplements.

You may need to limit or avoid caffeine if you:

Ginkgo may increase the risk of bleeding and seizures.

It is unknown whether it is safe to use ginkgo while breastfeeding.

However, ginkgo may be unsafe during pregnancy due to the risk of early labor or excessive bleeding during delivery.

Raw or roasted ginkgo seeds and unprocessed ginkgo leaves can be toxic.

Huperzine A may lower heart rate.

L-theanine should be avoided if you have a green tea allergy. Avoid theanine supplements if you're pregnant or breastfeeding, as there's not enough information about their safety.

Do not take vinpocetine if you are of childbearing age or are pregnant. Vinpocetine may cause harm to your fetus.

If you have low blood pressure and a history of heart problems or stroke, consult your healthcare provider before using vinpocetine.

This is not an exhaustive list. Please speak with your pharmacist, registered dietitian nutritionist, or healthcare provider for more information about possible interactions.

Bacopa may interact with the following medications:

Ginkgo may increase bleeding risk. It may interact with blood thinners, such as Jantoven (warfarin) and aspirin. It may also interact with NSAIDs.

Huperzine A should not be used with acetylcholinesterase inhibitors.

Acetylcholinesterase inhibitors include Aricept (donepezil), Razadyne (galantamine), and Exelon (rivastigmine). Huperzine A works in the same way as acetylcholinesterase inhibitors.

Taking huperzine A with such medication may increase the risk of side effects.

L-theanine relaxes the mind. It may increase drowsiness risk when taken with medications or supplements that cause drowsiness.

Speak with your healthcare provider if you are taking central nervous system (CNS) depressant medications such as Ativan (lorazepam), Valium (diazepam), or Ambien (zolpidem).

Tyrosine is a precursor to thyroid hormones. It may change thyroid medication needs.

Do not take vinpocetine if you use the following medications:

It is essential to carefully read a supplement's ingredients list and nutrition facts panel to know which ingredients and how much of each ingredient is included. Please review this supplement label with your healthcare provider to discuss potential interactions with foods, other supplements, and medications.

Nootropics such as bacopa caffeine, CDP-choline, ginkgo, huperzine A, L-theanine, racetams, tyrosine, and vinpocetine have enhanced brain function.

However, caution should be taken. Some supplements should not be used if you have certain medical conditions or take certain medications.

Before using any nootropic supplements, please consult your healthcare provider to ensure they are appropriate for you.

Nootropics are substances that improve thinking, learning, and memory. They can be derived naturally from plants or made synthetically (human made).

Some examples of nootropics derived from plants include the following:

While more research is needed to confirm the efficacy of certain nootropics, some nootropics show promising results. For instance, caffeine has been shown to counteract the effect of sleep deprivation. Moreover, the combination of L-theanine and caffeine has been shown to enhance attention.

That said, replacing sleep with nootropics or any supplement is not recommended. Obtaining adequate, high-quality sleep is a vital part of overall health.

Nootropics should not be used if you have an allergy to such substances, are pregnant, or are breastfeeding.

Some nootropics may interact with certain prescription or nonprescription drugs. Please consult with your healthcare provider before starting a nootropic supplement.

Cohen PA, Zakharevich I, Gerona R. Presence of Piracetam in Cognitive Enhancement Dietary Supplements. JAMA Intern Med. 2020;180(3):458-459. doi:10.1001/jamainternmed.2019.5507

Food and Drug Administration. Vinpocetine in Dietary Supplements.

Lorca C, Mulet M, Arévalo-Caro C, et al. Plant-derived nootropics and human cognition: A systematic review [published online ahead of print, 2022 Jan 3]. Crit Rev Food Sci Nutr. 2022;1-25. doi:10.1080/10408398.2021.2021137

Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, Limpeanchob N, Norman Scholfield C. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-35. doi: 10.1016/j.jep.2013.11.008. Epub 2013 Nov 16. PMID: 24252493.

Kean JD, Downey LA, Stough C. A systematic review of the Ayurvedic medicinal herb Bacopa monnieri in child and adolescent populations. Complement Ther Med. 2016;29:56-62. doi:10.1016/j.ctim.2016.09.002

Lorenzo Calvo J, Fei X, Domínguez R, Pareja-Galeano H. Caffeine and Cognitive Functions in Sports: A Systematic Review and Meta-Analysis. Nutrients. 2021;13(3):868. Published 2021 Mar 6. doi:10.3390/nu13030868

Irwin C, Khalesi S, Desbrow B, McCartney D. Effects of acute caffeine consumption following sleep loss on cognitive, physical, occupational and driving performance: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2020;108:877-888. doi:10.1016/j.neubiorev.2019.12.008

Proost M, Habay J, De Wachter J, et al. How to Tackle Mental Fatigue: A Systematic Review of Potential Countermeasures and Their Underlying Mechanisms. Sports Med. 2022;52(9):2129-2158. doi:10.1007/s40279-022-01678-z

Oliver LS, Sullivan JP, Russell S, et al. Effects of Nutritional Interventions on Accuracy and Reaction Time with Relevance to Mental Fatigue in Sporting, Military, and Aerospace Populations: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2021;19(1):307. Published 2021 Dec 28. doi:10.3390/ijerph19010307

Piamonte BLC, Espiritu AI, Anlacan VMM. Effects of Citicoline as an Adjunct Treatment for Alzheimer's Disease: A Systematic Review. J Alzheimers Dis. 2020;76(2):725-732. doi:10.3233/JAD-200378

Cheng N, Bell L, Lamport DJ, Williams CM. Dietary Flavonoids and Human Cognition: A Meta-Analysis. Mol Nutr Food Res. 2022;66(21):e2100976. doi:10.1002/mnfr.202100976

Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One. 2013;8(9):e74916. Published 2013 Sep 23. doi:10.1371/journal.pone.0074916

Zheng W, Xiang YQ, Li XB, et al. Adjunctive huperzine A for cognitive deficits in schizophrenia: a systematic review and meta-analysis. Hum Psychopharmacol. 2016;31(4):286-295. doi:10.1002/hup.2537

Mancini E, Beglinger C, Drewe J, Zanchi D, Lang UE, Borgwardt S. Green tea effects on cognition, mood and human brain function: A systematic review. Phytomedicine. 2017;34:26-37. doi:10.1016/j.phymed.2017.07.008

Zhang J, Wei R, Chen Z, Luo B. Piracetam for Aphasia in Post-stroke Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials. CNS Drugs. 2016;30(7):575-587. doi:10.1007/s40263-016-0348-1

Hase A, Jung SE, aan het Rot M. Behavioral and cognitive effects of tyrosine intake in healthy human adults. Pharmacol Biochem Behav. 2015;133:1-6. doi:10.1016/j.pbb.2015.03.008

He W, Wu G. Metabolism of Amino Acids in the Brain and Their Roles in Regulating Food Intake. Adv Exp Med Biol. 2020;1265:167-185. doi:10.1007/978-3-030-45328-2_10

Zhang W, Huang Y, Li Y, et al. Efficacy and Safety of Vinpocetine as Part of Treatment for Acute Cerebral Infarction: A Randomized, Open-Label, Controlled, Multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) Trial. Clin Drug Investig. 2016;36(9):697-704. doi:10.1007/s40261-016-0415-x

Meador KJ, Leeman-Markowski B, Medina AE, et al. Vinpocetine, cognition, and epilepsy. Epilepsy Behav. 2021;119:107988. doi:10.1016/j.yebeh.2021.107988

MedlinePlus. Caffeine.

Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F. Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Nutr. 2021;151(8):2153-2160. doi:10.1093/jn/nxab119

McGlade E, Agoston AM, DiMuzio J, et al. The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males. J Atten Disord. 2019;23(2):121-134. doi:10.1177/1087054715593633

National Center for Complementary and Integrative Health. Dietary Supplements and Cognitive Function, Dementia, and Alzheimer's Disease: What the Science Says

Xing SH, Zhu CX, Zhang R, An L. Huperzine a in the treatment of Alzheimer's disease and vascular dementia: a meta-analysis. Evid Based Complement Alternat Med. 2014;2014:363985. doi:10.1155/2014/363985

Israely M, Ram A, Brandeis R, Alter Z, Avraham Y, Berry EM. A Double Blind, Randomized Cross-Over Trial of Tyrosine Treatment on Cognitive Function and Psychological Parameters in Severe Hospitalized Anorexia Nervosa Patients. Isr J Psychiatry. 2017;54(3):52-58.

Food and Drug Administration. Spilling the Beans: How Much Caffeine is Too Much?

Russo V, Rago A, Russo GM, Calabrò R, Nigro G. Ginkgo biloba: an ancient tree with new arrhythmic side effects. J Postgrad Med. 2011;57(3):221. doi:10.4103/0022-3859.85214

Dassanayake TL, Kahathuduwa CN, Weerasinghe VS. L-theanine improves neurophysiological measures of attention in a dose-dependent manner: a double-blind, placebo-controlled, crossover study. Nutr Neurosci. 2022;25(4):698-708. doi:10.1080/1028415X.2020.1804098

National Center for Complementary and Integrative Health. Ginkgo.

Food and Drug Administration. Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine.

Szatmari SZ, Whitehouse PJ. Vinpocetine for cognitive impairment and dementia. Cochrane Database Syst Rev. 2003;2003(1):CD003119. doi:10.1002/14651858.CD003119

Manda VK, Avula B, Dale OR, et al. Studies on Pharmacokinetic Drug Interaction Potential of Vinpocetine. Medicines (Basel). 2015;2(2):93-105. Published 2015 Jun 5. doi:10.3390/medicines2020093

Brimson JM, Brimson S, Prasanth MI, et al. The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data. Scientific Reports. 2021;11(596). doi: 10.1038/s41598-020-80045-2

Abebe W. Review of herbal medications with the potential to cause bleeding: dental implications, and risk prediction and prevention avenues. EPMA J. 2019;10(1):51-64. Published 2019 Jan 8. doi:10.1007/s13167-018-0158-2

Damar U, Gersner R, Johnstone JT, et al. Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research. Expert Rev Neurother. 2016;16(6):671-680. doi:10.1080/14737175.2016.1175303

White DJ, de Klerk S, Woods W, et al. Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial. Nutrients. 2016;8(1):53. Published 2016 Jan 19. doi:10.3390/nu8010053

Dratman MB, Martin JV. The many faces of thyroxine. AIMS Neurosci. 2020;7(1):17-29. Published 2020 Mar 3. doi:10.3934/Neuroscience.2020002

Malík M, Tlustoš P. Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs. Nutrients. 2022;14(16):3367. Published 2022 Aug 17. doi:10.3390/nu14163367

By Trang Tran, PharmDTrang Tran, PharmD, is a pharmacist who is passionate about integrative health.