Nootropics, sometimes called “smart drugs,” are substances that are claimed to improve cognitive function. Nootropics are becoming an increasingly popular way to boost mental performance, and there is a wide variety of different substances that fall into this category.
This comprehensive list will outline all of the most important nootropics, including their key benefits and side effects. If you’re looking to give your mind an extra edge, then read on!
3-oxypyridine is a synthetic compound that was developed in Russia for cognitive enhancement and protection. It’s also known by the names of its derivatives, which include emoxypine, Mexidol, or Mexifin. It may have nootropic benefits for:
It may also have a positive holistic effect on diabetes and heart health. 3-oxypyridine was first synthesized by the Russian Academy Of Medical Science. It is prescribed for various conditions in Russia, but is not approved for treatment in the US. However, you can purchase it as a supplement. It is structurally very similar to Vitamin B6. This similarity may be the source of some of oxypyridine’s therapeutic value. This nootropic appears to work by increasing neurotransmitters (like serotonin, dopamine, and norepinephrine), inhibiting free radicals, increasing antioxidant activity, and increasing the binding ability of membranes. It may also improve cerebral blood flow.1T.A.Voronina. <a href=”https://pdfs.semanticscholar.org/43a6/5be5a59e71eceacade6a888123635d0a1e44.pdf”
5-HTP (5-Hydroxytryptophan) is a naturally occurring amino acid that may have a nootropic effect when taken as a supplement. Many people use it for:
- Treating depression
- Reducing anxiety
- Improving sleep and fighting insomnia
- Addiction recovery
What Is 5-HTP?
5-HTP is a naturally occurring extract found in the seeds of the African plant Griffonia simplicifolia and is the immediate precursor to serotonin. Serotonin is one of the major neurotransmitters associated with mood, motivation, sleep and other major functions. Supplementing with 5-HTP has been shown to raise serotonin levels in many clinical settings.2Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan, Pharmacol Ther. 2006 3UDENFRIEND S, WEISSBACH H, BOGDANSKI DF. Increase in tissue serotonin following administration of its precursor 5-hydroxytryptophan, J Biol Chem. 1957 4Trachte GJ, Uncini T, Hinz M. Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human population, Neuropsychiatr Dis Treat. 2009 You usually synthesize serotonin from tryptophan, which is an amino acid typically found in poultry, dairy, and some vegetables. However, if you aren’t getting enough tryptophan, or your body is not converting it efficiently, you may end up with a serotonin deficiency that could lead to a number of issues. 5-HTP is one of the most popular over the counter supplements, although actual evidence that it is effective is very mixed. As you will see, simply trying to manipulate one neurotransmitter system (serotonin) may not be the most effective way to treat the disorders it is often used for.
Acetyl-L-carnitine (ALCAR) is an amino acid that is naturally produced in the body.
ALCAR supplements are often taken as a cognitive enhancer and memory booster.
Some studies have shown that ALCAR can help improve cognitive function in people with Alzheimer’s disease and age-related cognitive decline.5Carlo Ori, Ulderico Freo, Gilberto Pizzolato, Mauro Dam Effects of acetyl-l-carnitine on regional cerebral glucose metabolism in awake rats Department of Anesthesiology, University of Padova, Padova, Italy; Department of Neurology, University of Padova, Padova, Italy. 2002
It is thought to work by increasing levels of acetylcholine, a neurotransmitter that is important for memory and learning.6Gustavo C. Ferreira and Mary C. McKennaL-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201. 2017
ALCAR has also been shown to protect neurons from damage caused by inflammation.7T. Lau, B. Bigio, D. Zelli, BS. McEwen, and C. NascaStress-induced structural plasticity of medial amygdala stellate neurons and rapid prevention by a candidate antidepressant Laboratory of Neuroendocrinology, The Rockefeller University, New York; 10065, USA.; The Rockefeller University, Center for Clinical & Translational Science, New York, USA. 2017 while also regulating the release of glutamate.8
In addition to its cognitive benefits, ALCAR has also been shown to have anti-aging effects, including reducing wrinkles and improving skin elasticity.
It is also an antioxidant, which means it helps protect cells from damage caused by free radicals.
Adrafinil is a powerful eugeroic, or wakefulness-promoting drug, that has a wide variety of cognitive benefits.
These benefits include improved alertness, vigilance, and wakefulness; increased focus and concentration; and enhanced memory and recall. Adrafinil also has anti-anxiety and antidepressant effects.
The exact mechanism of action of adrafinil is not known, but it is thought to work by increasing levels of norepinephrine and dopamine in the brain. Norepinephrine is a neurotransmitter that plays a role in wakefulness, attention, and learning.9Müller U, et al. Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers Neuropharmacology. 2013
Dopamine is a neurotransmitter that plays a role in mood, motivation, and reward-seeking behavior. Adrafinil is structurally similar to piracetam, another eugeroic that is used to treat cognitive impairment and dementia. Adrafinil is metabolized in the liver to modafinil, which is a more potent wakefulness-promoting drug.10Salteu B, Grunberger J, Linzmayer L, Stohr H. Pharmaco-EEG, psychometric and plasma level studies with two novel alpha-adrenergic stimulants CRL 40476 and 40028 (Adrafinil), New Trends Exp Clin Psychiatry 1986
Modafinil has many of the same cognitive benefits as adrafinil, but it is also associated with some side effects, such as headaches and nausea. Adrafinil is not associated with these side effects.11Guglietta A, et al. Drug Treatment Of Sleep Disorders Milestones In Drug Therapy. 2014
Adrafinil supplements are available without a prescription and can be purchased online or in health food stores.
Adrafinil dosages range from 200 mg to 600 mg per day. The recommended dose of adrafinil is 300 mg per day, taken in two or three divided doses. Adrafinil should be taken with food to avoid gastrointestinal upset.
Alpha GPC (α-Glycerophosphocholine) is a popular nootropic supplement that can improve memory and learning, boost mood and energy, and prevent cognitive decline. Alpha GPC is a choline source synthesized from sunflower or soy. Choline is an essential nutrient that can also be found in food, particularly eggs. It’s required for many basic processes inside cells, and it is critical for proper brain development. Alpha GPC happens to be a more bioavailable form of choline that can easily cross the blood-brain barrier. 12Zeisel SH. Choline: needed for normal development of memory, J Am Coll Nutr. 2000 13Zeisel SH. Choline and human nutrition Annu Rev Nutr. 1994 Once absorbed by the body, Alpha GPC increases a critical neurotransmitter called acetylcholine (ACh). Acetylcholine is one of the most abundant neurotransmitters in the central nervous system. It is heavily involved in learning, memory, and emotions. Maintaining proper ACh levels can optimize cognitive function.14Acetylcholine – Wikipedia 15Kawamura T1, Okubo T, Sato K, Fujita S, Goto K, Hamaoka T, Iemitsu M.Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults. Nutrition. 2012 Alpha GPC is a common part of nootropic stacks and is often paired with racetams (oxiracetam, aniracetam, etc..). This is because racetams can deplete choline stores. Stacking with a choline source like Alpha GPC can prevent this from happening and synergize the nootropic effects of both substances.
Ampakines are a class of nootropic drugs that modulate the brain’s AMPA receptors and may have a positive effect on:16Zheng Y, et al. Effects of the putative cognitive-enhancing ampakine, CX717, on attention and object recognition memory, Curr Alzheimer Res. 2011
- Memory and learning
Ampakines may prove to be a novel new treatment for various conditions such as Alzheimer’s, Parkinson’s, treatment-resistant depression, ADHD, schizophrenia, and others.
The Strongest Nootropics?
One of the most interesting things about ampakines is their potency. These nootropics are up to 1000x more powerful than piracetam, the original nootropic supplement. Despite their strength, ampakines do not seem to have the same side-effects of traditional stimulants, such as amphetamines. There are several ampakines currently in development and undergoing clinical trials that may hit the market soon. Ampakines can increase the size and duration of excitatory synaptic responses and induce the expression of neurotrophic factors as well.17Arai A, et al. A centrally active drug that modulates AMPA receptor gated currents, Brain Res. 1994 18Gary Lynch, et al. Ampakines and the threefold path to cognitive enhancement, Trends In Neuroscience. 2006 This indicates that ampakines can have a large effect on increasing certain kinds of brain activity and improving brain plasticity.
There are a few commercial examples available or currently in development:
These compounds all share similar mechanisms of action as ampakines, but their individual effects may vary somewhat.
Aniracetam is a cognitive enhancer that has been shown to improve memory and cognitive function. Aniracetam primarily acts on AMPA and NMDA receptors in the brain by releasing the neurotransmitter acetylcholine (ACh), increasing glutamate sensitivity.19Zhao X, et al. Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons Mol Pharmacol. 2001
Aniracetam may also increase levels of the neurotransmitter serotonin.20Shirane M, Nakamura K. Aniracetam enhances cortical dopamine and serotonin release via cholinergic and glutamatergic mechanisms in SHRSP Brain Res. 2001
Serotonin is a neurotransmitter that plays a role in mood, appetite, and sleep. It is thought that aniracetam’s effects on serotonin may contribute to its cognitive-enhancing effects.
Aniracetam is structurally similar to piracetam, another cognitive enhancer. However, aniracetam is more potent than piracetam and has a shorter half-life.
Aniracetam is not approved for use in the United States but is available in other countries as a dietary supplement.
Armodafinil (sold under the brand name NuVigil) is a wakefulness-promoting drug prescribed to treat narcolepsy, sleep apnea, and shift work disorder.21Mona Darwish, Mary Kirby, Edward T Hellriegel, Philmore Robertson Jr. Armodafinil and Modafinil Have Substantially Different Pharmacokinetic Profiles Despite Having the Same Terminal Half-Lives: Analysis of Data From Three Randomized, Single-Dose, Pharmacokinetic Studies, Clin Drug Investig. 2009 However, it is often used off-label for its nootropic effects on:
- Cognitive enhancement
Armodafinil is chemically similar to its more famous -afinil cousins, modafinil and adrafinil. In many respects, they have many of the same effects on the brain when taken as supplements. But there are some differences. Brand name Modafinil is composed of both the right-handed and left-handed modafinil isomers. The right-handed isomer is quicker acting and more powerful, while the left-handed isomer is slower-release and long-lasting. Armodafinil gets its name because it is ONLY the right-handed isomer of modafinil. This means that it metabolizes slightly differently and may give it more of a kick. Some nootropics users claim that armodafinil can feel stronger and interfere with sleep more than modafinil.
Ashwagandha is an “adaptogen,” a natural substance that helps the body adapt to stress and promote overall well-being. Ashwagandha is one of the most popular herbs in Ayurvedic medicine. It has been used for centuries as a general tonic to increase energy, stamina, and vitality. Ashwagandha is also commonly used to help alleviate anxiety and stress.
There are several ways that ashwaganda supplements can benefit your health. One of the primary ways is by reducing cortisol levels. Cortisol is a hormone that’s released in response to stress. When cortisol levels are chronically high, it can lead to a host of problems including weight gain, trouble sleeping, and decreased immunity.
Ashwagandha has also been shown to boost brain function. One study found that ashwagandha improved memory and reaction time in young adults. Another study found that it improved working memory and task performance in people with mild cognitive impairment.
If you’re looking for a natural way to improve your health, consider adding ashwaganda supplements to your diet. Ashwagandha is safe for most people when taken as directed. However, if you’re pregnant or breastfeeding, it’s best to avoid ashwagandha supplements.
Bacopa monnieri is an herb that has been used in traditional Indian medicine (Ayurveda) for centuries. Bacopa monnieri supplements are becoming increasingly popular as people look for ways to improve their cognitive function and memory. Bacopa Monnieri is a tropical plant that grows in marshy areas. The leaves of the plant are used to make Bacopa Monnieri supplements. The active ingredient in Bacopa Monnieri is called bacosides. These bacosides are thought to help repair damaged neurons and improve communication between neurons. This action is thought to improve cognitive function and memory. Bacopa Monnieri supplements are generally well tolerated, but some people may experience stomach upset, dry mouth, or diarrhea. Bacopa Monnieri supplements should not be taken if you are pregnant or breastfeeding.
Brain Derived Neurotrophic Factor (BDNF) is a protein in the human brain that supports the growth and maintenance of neurons. It is considered a neurotrophin, capable of generating new brain cells through a process known as neurogenesis. It is a critical factor for optimizing memory, learning, and overall cognition. Without BDNF, your brain would not be able to create new neural pathways or heal itself. Because of this, BDNF affects nearly every aspect of mental function in some way.22Brain-derived neurotrophic factor, Wikipedia. 2019 BDNF is very important for brain health and function, but it cannot be taken directly. However, you may be able to increase BDNF indirectly by taking certain nootropic supplements such as:
It’s also important to realize that you can encourage BDNF levels through regular exercise, proper sleep, meditation, and getting enough sun exposure. In fact, these are probably the best ways to holistically encourage this important growth factor. BDNF levels naturally decline as you age, which can lead to neurological degeneration. It is important to maintain proper levels of this protein to ensure your brain can regenerate and stay healthy.23Kirk I. Erickson, et al. Brain-Derived Neurotrophic Factor Is Associated with Age-Related Decline in Hippocampal Volume, J Neurosci. 2010
Boron is an essential trace mineral that plays an important role in a number of biological processes. Humans, as well as animals and plants, require boron to grow. There is evidence that it may also have nootropic benefits for:
- Brain Fog
- Cognitive enhancement
- Memory and learning
Low levels of boron are related to poor immune function, increased risk of mortality, osteoporosis, and cognitive deterioration. Research continues to show the importance of maintaining proper levels of the often-overlooked nutrient. Fortunately, you can make sure you are consuming enough of this key micronutrient by taking it in the form of a boron citrate supplement. There are physical benefits as well as mental. In trials, animals and humans that supplemented with boron had improved bone density, embryonic development, wound healing, and cancer resistance. It may also increase testosterone and libido in males.24Khaliq H, Juming Z, Ke-Mei P. The Physiological Role of Boron on Health, Biol Trace Elem Res. 2018 25Abdelnour SA, et al. The vital roles of boron in animal health and production: A comprehensive review, J Trace Elem Med Biol. 2018
Boron’s history as a nutrient and preservative is a bit controversial. In the 1870s, scientists discovered that Boron could be used as a food preservative as boric acid and borax. For the next 50 years, borates were used to preserve many perishable foods.26Wiley H. Influence of food preservatives and artificial colors on digestion and health. I. Boric acid and borax, Bureau Of Chemistry, USDA. 1904 However, a few decades later, high concentrations of boron were shown to cause health issues in humans. Despite limited evidence, boron was pulled as a food additive in most countries. As late as 1960, the WHO listed borates as a banned preservative.27Joint FAO/WHO Expert Committee on Food Additives. Evaluation of the toxicity of a number of antimicrobials and antioxidants : sixth report of the Joint FAO/WHO Expert Committee on Food Additives, WHO. 1961 Luckily, in the 1970s scientists began studying the use of boron in animals. They found that while too much boron can be toxic, too little can also be dangerous. Boron started to come back in favor with nutritionists.28Hunt CD. Dietary boron modified the effects of magnesium and molybdenum on mineral metabolism in the cholecalciferol-deficient chick, Biol Trace Elem Res. 1989 Now the accepted wisdom is that proper boron intake is necessary, and it only poses a problem if you supplement in exceptionally large amounts.
What Foods Contain Boron?
- Leafy greens
- Non-citrus fruits
- Dried beans
Celastrus Paniculatus, also known as intellect tree, is a climbing shrub that is native to India. The plant has been used in traditional Ayurvedic medicine for centuries and is prized for its nootropic effects. In recent years, Celastrus Paniculatus supplements have become popular among students and professionals seeking to boost their cognitive performance.
While the exact mechanism of action is not fully understood, it is believed that the plant helps to increase cerebral blood flow and protect neurons from damage.
Additionally, Celastrus Paniculatus is thought to improve communication between the left and right hemisphere of the brain and that the plant’s active compounds play a role in modulating neurotransmitter levels in the brain. As a result, this unique supplement may help to improve memory, focus, and creativity. If you are looking for a natural way to enhance your cognitive function, Celastrus Paniculatus is worth considering.
Centrophenoxine (sold as Lucidril, Centrophenoxin, Cerutil, Helfergin, or meclofenoxate) is a nootropic used as a prescription drug in some European countries well as Japan.
Centrophenoxine acts as an antioxidant, stimulates glucose uptake, oxygen consumption, and increases energy metabolism in the brain.30Zs-Nagy I. A survey of the available data on a new nootropic drug, BCE-001, Ann N Y Acad Sci. 1994
It is a combination of DMAE (dimethylethanolamine) and pCPA (parachlorphenoxyacetic acid). These two individual nootropic compounds have a synergistic effect.
Because of this, it may have nootropic benefits for:
- Memory and learning31Nandy K. Centrophenoxine: effects on aging mammalian brain J Am Geriatr Soc. 1978
- Anti-aging32Ohtani R, Kawashima S. Reduction of lipofuscin by centrophenoxine and chlorpromazine in the neurons of rat cerebral hemisphere in primary culture Exp Gerontol. 1983
- Cerebral blood flow33Gustafson L, et al. Effects of piracetam on regional cerebral blood flow and mental functions in patients with organic dementia Psychopharmacology (Berl). 1978
- Neuroprotection34FOSSATI P, et al. Centrophenoxine in the resuscitation of cranium-injured patients Lille Med. 1962
The Chaga mushroom (Inonotus obliquus) is a fungus that is commonly found on trees in Eastern and Northern Europe.
Traditional folk medicine in these regions has used this mushroom to treat various conditions for centuries (if not millennia).
Recently, holistic health practitioners and nootropics enthusiasts have started paying more attention to this strange-looking fungus.
According to research, Chaga may possess a variety of health and nootropic benefits for the brain and body, including:
- Reducing inflammation
- Boosting the immune system
- Stress relief
- Lowering blood pressure
Chaga contains more antioxidants than almost any other food. It has an extremely high ORAC value, which is the scale used to measure antioxidant levels.35Alaska Chaga What Is The ORAC Value Of Chaga Mushroom?, AlaskaChaga.com. 2018
It is also believed to have adaptogenic qualities, which can help the body adapt to stress.
Citicoline (sometimes called CDP-choline) is a naturally occurring choline source in the body. It is taken as a nootropic supplement for:
- Improved cognition
- Mental function
- Energy and focus
Citicholine is an endogenous nucleotide found in every cell. It is a necessary component of the cell membrane phosphatidylcholine, which is a major component of all neurons.36Fernández-Murray JP1, McMaster CR. Glycerophosphocholine catabolism as a new route for choline formation for phosphatidylcholine synthesis by the Kennedy pathway, J Biol Chem. 2005 This nootropic is an excellent source of choline, which is a precursor of acetylcholine (ACh). ACh is an extremely important neurotransmitter that is necessary for learning, memory, and overall cognitive function. Low ACh levels can cause problems with memory and other mental functions, eventually leading to cognitive degeneration. Citicoline has emerged as a treatment for patients with chronic cerebrovascular disorders or memory problems.37Mario Fioravanti and Ann E Buckley. Citicoline (Cognizin) in the treatment of cognitive impairment, Clin Interv Aging. 2006 Citicoline is often combined with a member of the racetam family (piracetam, aniracetam, oxiracetam, etc…) for a performance-enhancing nootropic “stack”. This is one of the most popular uses of citicoline in the nootropics community.
Cordyceps refers to a genus of 400+ parasitic mushrooms that grow on insect larvae, digesting them, and growing long sprouts that can be harvested. Despite the somewhat disgusting origins of these fungi, they may actually have some powerful nootropic and health benefits. And don’t worry, actually harvesting cordyceps from larvae is prohibitively expensive; most supplements use lab-grown fungus, no bug larvae involved. Two species of cordyceps in particular, Cordyceps sinensis and Cordyceps militaris, have been used for centuries in Chinese and Tibetan medicine. The reported health benefits include:
- Improved athletic performance
- Increased mood and memory
- Higher libido
- Anti-aging effects
- Lower inflammation
Folk healers have been using this fungus for an extremely wide variety of ailments. Among the Sikkim in northern India, cordyceps is prescribed for practically “all illnesses.” And now modern medicine is starting to confirm what these cultures have practiced for ages. According to one review of cordyceps, “many studies… support C. Sinensis having diverse biological activities and pharmacological potential.”38Ashok Kumar Panda, et al. Traditional uses and medicinal potential of Cordyceps sinensis of Sikkim, J Ayurveda Integr Med. 2011 It is worth noting that actual wild-harvested cordyceps are still prohibitively expensive. Unless you are extraordinarily wealthy you are unlikely to get your hands on “the real deal.” Most of the supplements sold as cordyceps are actually lab-grown strains that are then made into an extract called CS-4. It is unclear how effective CS-4 is in relation to naturally occurring cordyceps. However, most of the studies listed in this article make use of CS-4, so it is clear that there is still a therapeutic benefit to this extract.
DLPA (DL-phenylalinine) is a more bioavailable form of the essential amino acid phenylalanine. Phenylalanine is one of the 9 essential amino acids, meaning it is not made in the body and must be obtained from outside sources.39Phenylalanine Wikipedia Many people take DLPA as a nootropic supplement for:
- Mental Sharpness
- Pain Relief
There are plenty of reports that DLPA can improve cognition and general feelings of wellbeing, and there is some clinical evidence that backs up these claims. DLPA is made from combining D-phenylalanine and L-phenylalanine. D- and L-phenylalanine are isomers, meaning they are mirror images of one another. L-phenylalanine is found naturally, while D-phenylalanine must be synthesized in a laboratory. DLPA, then, is both of these isomers combined into one substance. It provides the best of both worlds. Phenylalanine is a precursor for tyrosine, dopamine, norepinephrine, and epinephrine, and the skin pigment melanin. By affecting these systems, DLPA can have various nootropic and health effects.
DMAE (dimethylaminoethanol) is a naturally occurring amine in the human brain. Researchers believe it can modulate choline and possibly the neurotransmitter acetylcholine.40PEPEU G, FREEDMAN DX, GIARMAN NJ. Biochemical and pharmacological studies of dimethylaminoethanol (deanol), J Pharmacol Exp Ther. 1960 It’s effects on the cholinergic system may mean it has nootropic benefits for:
In theory, DMAE could be used to enhance learning and memory, as would most cholinergic substances. However, there is not a lot of research to back this claim up. Despite this, many nootropics enthusiasts claim to have good results with this supplement.
DMAE As An Ingredient
DMAE has been used as an ingredient in cognitive- and mood-enhancing products for years, as well as skincare products.412-DIMETHYLAMINOETHANOL, Toxnet. 2019 It occurs naturally in some seafood, particularly anchovies. DMAE bitartrate is the predominant form of DMAE on the market.
GABA is the main neurotransmitter of the central nervous system in humans and other mammals responsible for inhibition.
This means that it is responsible for regulating relaxation, sleep, and overall mood.
Think of GABA as the “brakes” of your brain.
It also plays a vital role in modulating synaptic transmission, promoting neuronal development, and preventing depression.43Ngo DH, Vo TS. An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid, Molecules. 2019
Many people take GABA as a nootropic for:
- Addiction recovery
GABA may also have some positive effects on physical issues like blood pressure, diabetes, and cancer.
You can purchase GABA as a supplement, however, it is unclear whether or not it can actually cross the blood-brain barrier and have an effect.
As you will see, it may be more useful to take a synthetic derivative to boost your GABA levels, rather than simply taking GABA itself.
Ginkgo Biloba is a powerful nootropic herb used for:
- Cognitive Function
Gingko is also a treatment for dementia, peripheral vascular disease, cerebral ischemia, and Reynaud’s Syndrome. Ginkgo biloba extract comes from the leaves of the Ginkgo biloba tree. This is the only surviving member of the ancient Ginkoales plant group. According to fossil dating, this species has been around for more than 200 million years.44Field BH, Vadnal R. Ginkgo biloba and Memory: An Overview, Nutr Neurosci. 1998 The Ginkgo achieved its remarkable longevity due to nearly complete resistance to pests, diseases and environmental assaults. Almost nothing can kill this plant.45Major RT. The ginkgo, the most ancient living tree. The resistance of Ginkgo biloba L. to pests accounts in part for the longevity of this species, Science. 1967 One specimen of this tree even grew from ground zero of the 1945 atomic bomb dropped on Hiroshima. It re-sprouted after it was obliterated in the nuclear explosion.46Hibaku Trees of Hiroshima, Arnoldia Arboretum Ginko Biloba is a powerful natural medicine. The first reported use of Ginkgo in China stretches back to 14th-century herbal manuscripts, although it was almost certainly used even earlier than that.47Hoon Huh, John Staba. The Botany and Chemistry of Ginkgo biloba L,</a Journal of Herbs, Spices & Medicinal Plants, 1992 Ginkgo Biloba has recently caught on in the West as a nootropic supplement.
The amino acid glutamate is the major excitatory neurotransmitter in the nervous system. It is one of the most common chemical messengers that nerve cells use to communicate in the brain.48Orrego F, Villanueva S.The chemical nature of the main central excitatory transmitter: a critical appraisal based upon release studies and synaptic vesicle localization, Neuroscience. 1993
In fact, it accounts for over 90% of the total synaptic connections, and is involved in every major excitatory process.49<ahref=”https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)” target=”_blank”Glutamate (neurotransmitter), Wikipedia. 2019
So, from the chemistry point of view, the human nervous system can largely be thought of as a glutamate transmission machine.
Glutamate is regulated by the GABA system, which acts as an inhibitory counterbalance.
Not having enough GABA to mediate the excitatory qualities of glutamate can cause significant problems. Unchecked, glutamate can build up in the brain and become neurotoxic, damaging neurons.
In this way, you can think of glutamate as the gas pedal of the brain, and GABA as the brakes.
Maintaining proper levels of glutamate and GABA is critical for a healthy brain and mental function.
Gotu Kola (Centella asiatica) is a powerful medicinal herb that is widely used in traditional eastern medicine. It is used for:
- Raising mood and fighting depression/anxiety
- Improving sleep
- Skincare and wound healing
It is a perennial plant native to the wetlands of Asia and is not to be confused with the kola nut.
It has been used in Indian Ayurvedic medicine for thousands of years, and in China, it is considered one of the “miracle elixirs of life”.
The famous Chinese herbalist Li Ching Yuen claimed that Gotu kola helped him live an incredibly long life (197 or 256 years old, depending on which records you believe)
While you might not quite see those results yourself, it is evident that Gotu kola does have some very useful therapeutic properties.
And you don’t have to take the work of ancient traditions, either. Research has started to back up these claims. 51Howes MJ, Houghton PJ. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function, Pharmacol Biochem Behav. 2003
Gotu kola has recently started gaining attention in the West for its anti-anxiety and nootropic effects.
It’s also used for treating a variety of skin conditions, as well as illnesses like fever, and gastrointestinal problems.52Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica, Phytomedicine. 2000 53Howes MJ, Houghton PJ. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function, Pharmacol Biochem Behav. 2003
Green tea extract is a popular dietary supplement, and for good reason. Green tea extract is rich in antioxidants, which have been shown to offer numerous health benefits. These include reducing inflammation, boosting brain function, and protecting against heart disease and cancer. Green tea extract supplements are typically made from the dried leaves of the Camellia sinensis plant. The leaves are then ground into a powder and concentrated into an extract. This process preserves most of the beneficial compounds in green tea, including polyphenols like epigallocatechin-gallate (EGCG). When it comes to cognitive benefits, green tea extract has been shown to improve memory and reaction time. One study showed that participants who took green tea extract performed better on a memory test than those who didn’t. Another study found that green tea extract can help improve reaction time in people with attention deficit hyperactivity disorder (ADHD). The mechanism of action behind these cognitive benefits is not fully understood, but it is thought that the EGCG in green tea extract helps to protect the brain from damage and improve blood flow to the brain. So, if you’re looking for a natural way to boost your brain power, green tea extract could be worth trying. Just be sure to talk to your doctor first, as green tea supplements can interact with some medications.
Hordenine (N,N-Dimethyltyramine, Anhaline, peyocactine) is an all-natural extract from the Anhalonium fissuratum cactus plant that may have some nootropic benefits. It is used for:
- Attention and alertness
- Antibiotic and antimicrobial properties
- Skin protection
Hordenine is naturally found in barley, and may be present in low levels in beer.54Jay D. Mann, Carol E. Steinhart, S. Harvey Mudd. Alkaloids and Plant Metabolism V. THE DISTRIBUTION AND FORMATION OF TYRAMINE METHYLPHERASE DURING GERMINATION OF BARLEY, The Journal Of Biological Chemistry. 1963
Huperzine A is a supplement that has been used for centuries in traditional Chinese medicine. It is derived from the Chinese club moss plant and has a variety of benefits. Huperzine A works by inhibiting the breakdown of acetylcholine, which is a neurotransmitter that plays a role in memory and learning. This can lead to improved cognitive function and memory. Huperzine A is also an antioxidant and has anti-inflammatory properties. It has been shown to be effective in treating Alzheimer’s disease, dementia, and age-related cognitive decline. Huperzine A is available in capsules or tablets. It is important to start with a low dose and gradually increase the dose as tolerated. Huperzine A is generally well-tolerated, but side effects can include nausea, vomiting, diarrhea, and dizziness. If you experience any of these side effects, stop taking Huperzine A and consult your healthcare provider.
Glutamine is the most abundant and versatile amino acid in the body. This makes it one of the most fundamentally essential factors in protein synthesis, metabolism, glutamate production, and many other functions. Glutamine is the precursor of glutamate (Glu) and γ-aminobutyric acid (GABA), which are the main excitatory and inhibitory neurotransmitters, respectively, within the brain. This means that glutamine plays a huge role in the function and regulation of mental processes.55Walls AB, et al. The glutamine-glutamate/GABA cycle: function, regional differences in glutamate and GABA production and effects of interference with GABA metabolism, Neurochem Res. 2015 Among the 20 amino acids detailed in the human genetic code, glutamine has the most varied uses.56Curi R, et al. Molecular mechanisms of glutamine action, J Cell Physiol. 2005 And as the most abundant amino acid, glutamine concentration is 10- to 100-fold more than any other.57Labow BI, Souba WW, Abcouwer SF. Mechanisms governing the expression of the enzymes of glutamine metabolism–glutaminase and glutamine synthetase, J Nutr. 2001 Researchers estimate that endogenous glutamine production is between 40 to 80 g/day in the average human.58Newsholme EA, Parry-Billings M. Properties of glutamine release from muscle and its importance for the immune system, JPEN J Parenter Enteral Nutr. 1990 Bodybuilders and athletes have been using glutamine for years as a performance enhancer. But glutamine may also be taken as a nootropic supplement for:
- Memory and learning
- Concentration and focus
- Stress relief
High-quality research on L-glutamine’s specific nootropic effects tend to be scarce in this respect, but there is some evidence that it could be a worthwhile addition to your nootropic stack.
L-ornithine is a common amino acid that naturally occurs in the liver. It can be taken as a nootropic supplement for:59Morris SM Jr. Regulation of enzymes of the urea cycle and arginine metabolism, Annu Rev Nutr. 2002
- Stress and anxiety
- Physical performance
L-ornithine is a non-essential amino acid. Although you can get L-ornithine from some foods, the amount is usually small. Since ancient times, corbicula, a clam rich in this compound, has been eaten for liver health. This nootropic is generally considered useful for lowering anxiety and increasing energy holistically, especially under stressful situations. Some users also report brighter moods and more energy. It may be a useful supplement for athletes as well. L-ornithine works primarily by modulating the GABA system, lowering stress hormones, buffering ammonia toxicity, and disposing of excess nitrogen.
L-theanine (r-glutamylethylamide) is a unique type of amino acid that has been proven to:
It is prized for its ability to modulate brain waves and neurotransmitters in a way that promotes a relaxed but clear-headed state. It is by far one of the most popular and widely used nootropic supplements out there, especially when paired with caffeine. This nootropic compound also has several benefits for the body as well, including lower blood pressure, This compound naturally occurs in the leaves of the species Camellia sinensis AKA the tea plant.
L-theanine and Caffeine
L-theanine is what gives brewed tea, particularly green tea, it’s calming effects. Because tea contains this chemical, it is far less likely to cause the jitters than coffee (which does not have l-theanine). You may have noticed that drinking tea is far less “speedy” than coffee, despite similar caffeine levels. L-theanine acts as a counterweight to caffeine, calming the mind and body as the caffeine stimulates it. This action has a synergistic effect, creating an energized focus free from the anxious energy associated with too much caffeine. In fact, l-theanine plus caffeine is considered to be the simplest, but most effective, entry-level nootropic stack out there. If green tea is not your thing, you can purchase l-theanine as a bulk supplement for cheap. Many people take it before their morning coffee to balance out their morning caffeine rush and sustain their energy and mood.
Lion’s Mane (scientific name Hericium erinaceus, also known as “yamabushitake”) is a medicinal mushroom with clinically proven nootropic powers. It is used for:
Lion’s Mane is one of the most powerful (possibly THE most powerful) natural supplements for boosting what is known as Nerve Growth Factor (NGF). NGF promotes nerve growth and regeneration, helping your brain rejuvenate itself and make new connections. This is a critical process needed for memory formation, mental ability, and overall brain health. Lion’s mane is a unique member of the fungus kingdom, possessing qualities that no other species has (that we know of). It contains the nootropic compounds hericenone and erinacines, both of which are only found in this particular mushroom. Lion’s Mane belongs to the “tooth fungus” group and is native to Asia, North America, and Europe. It has a distinct and unusual appearance, looking almost like a wizard’s beard. It typically grows during the late summer and fall. Many cultures have been using this fungus for thousands of years for it’s medicinal and brain-boosting powers. Lion’s Mane is extremely prized in Chinese traditional medicine, and Chinese monks have been known to use lion’s mane to help focus their minds during long meditation sessions. It is also considered a culinary delicacy, with a mild flavor reminiscent of lobster or crab. READ MORE: The Complete Guide To Nootropic Mushrooms
Lion’s Mane and Neural Regeneration
Nerve regeneration is a critical part of keeping your mind sharp, especially as you get older. Unfortunately, as we age, our NGF naturally starts to drop. As neurons become less and less able to repair themselves and grow new connections, your cognition starts to suffer. You can’t process information as quickly, it becomes more difficult to learn new things, and memories start slipping away. Severe lack of NGF is even associated with diseases like Alzheimer’s, Parkinson’s, and dementia. It is absolutely critical to make sure your brain maintains it’s plasticity. But Lion’s Mane is not simply for older people looking to fend off cognitive decline. Healthy young people may also derive nootropic benefits from taking this mushroom, meaning lion’s mane could be a cornerstone of your brain-optimizing nootropic stack.
Lithium is a mineral that may have some uses as a nootropic and mental health treatment. Its first recorded medical use was in 1871 for the treatment of mania. Most people associate lithium as a treatment for bipolar disorder. However, it can also have benefits for:
- Treating bipolar disorder
- Fighting depression
- Cognitive enhancement
Lithium is a trace element that your body needs in small amounts for proper health. Your body does not make this mineral on its own, you must get it from outside sources. It’s so critical that lithium deficiency is associated with increased rates of suicides, homicides, and arrest rates for drug use and other crimes.60Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality., J Am Coll Nutr. 2002 61Huber RS, et al. Relationship between altitude and lithium in groundwater in the United States of America: results of a 1992-2003 study, Geospat Health. 2014 62Schrauzer GN, Shrestha KP. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions, Biol Trace Elem Res. 1990 In general, diets rich in grains and vegetables provide a lot of lithium. However, due to variations in soil concentrations of lithium, the amount of can be different depending on the source of the foods. Tap water and beverages may also contain trace amounts of lithium. 63Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality, J Am Coll Nutr. 2002 According to current research, microdosing with lithium could provide many cognitive and neuroprotective benefits for the average person.
Is Lithium Orotate The Same As Lithium?
The short answer is yes. Lithium orotate is a more bioavailable form of lithium that should have essentially the same effects. It’s important to note that much of this review of the nootropic lithium orotate is based on research done on the pharmacological research done on the prescribed drug lithium in the form of lithium carbonate. This is due to the limited available research done on lithium orotate specifically. However, much of what is understood about lithium can be applied to lithium orotate. The difference between these 2 types of lithium is their forms and constituents. Lithium orotate is lithium bound to the parent compound orotic acid.64Pubchem. Lithium orotate, Pubchem. Orotic acid is found in milk and dairy products and is required for the regulation of genes that are important in the development of cells, tissues and organisms.65M Löffler, E A Carrey , E Zameitat. Orotate (Orotic Acid): An Essential and Versatile Molecule , Nucleosides Nucleotides Nucleic Acids. 2016 Evidence shows the benefit of lithium orotate vs lithium carbonate is that you need less lithium from the orotate form vs the prescription carbonate form to achieve desired results. The theory is that when the lithium-ion is combined with the orotate molecule, it acts as a targeted delivery system and transports the lithium-ion efficiently through the cell membrane to its various sites of action within the cell. Compare this with lithium carbonate where you need high doses to ‘force’ lithium into the body’s cells and lithium orotate can be a great over-the-counter option for optimizing the mood.66H A Nieper. The Clinical Applications of Lithium Orotate. A Two Years Study, Agressologie. 1973
Maitake Mushroom is a popular medicinal mushroom. It has been used in Asia for centuries and is now gaining popularity in the West. Maitake Mushroom supplements are said to offer a host of health benefits, including cognitive support. Maitake Mushroom is an edible mushroom that belongs to the genus Grifola. The most well-known species is Grifola frondosa, which is also known as ‘maitake’ in Japanese or ‘hen of the woods’ in English. Maitake mushrooms grow in clusters at the base of trees, typically oak trees. They have a brownish-gray color and a meaty texture. Maitake Mushroom supplements are typically made from the dried fruiting body of the mushroom. The active compounds in Maitake Mushroom are thought to be polysaccharides, particularly beta-glucans. These molecules are believed to offer several health benefits, including cognitive support. One study that looked at the effects of Maitake Mushroom on cognitive function found that participants who took a daily supplement containing Maitake Mushroom extract for 16 weeks showed significant improvements in memory and attention compared to those who did not take the supplement. Another study found that Maitake Mushroom supplements may help to improve mood and reduce stress levels. Stress is known to have negative effects on cognitive function, so this is an important finding. Maitake Mushroom supplements are generally considered safe, with the most common side effect being mild gastrointestinal upset.
Memantine is a synthetic compound that may have some nootropic benefits, including:
- Improving Symptoms of Alzheimer’s and Dementia
- Treating ADHD
- Lowering Anxiety
- Improving Memory
- Treating Addiction/Withdrawal
It was first synthesized in the 1960’s, and it works by blocking NMDA receptors in the brain. This is a unique method of action, and memantine is the only current drug that metabolizes this way. It is now prescribed for treating Alzheimer’s in America and elsewhere.67Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond, Nat Rev Drug Discov. 2006 68Lipton SA. Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation, Curr Drug Targets. 2007 However, recently memantine has gained a reputation as a performance-enhancing nootropic. Otherwise healthy people report seeing some cognitive benefits by taking memantine off-label. However, you should always check the laws in your country and consult with a physician before using a drug like memantine. In the United States, memantine is available by prescription only.
NAC (N-Acetyl-Cystine) is a powerful antioxidant supplement with many benefits for the body and brain. In fact, it may have the most wide-ranging positive effects of any nootropic on the market. According to research, it could potentially help with:
- Depression & mood
- Learning & memory
- Overall brain health
Hospitals around the world use it to reverse acetaminophen (Tylenol) overdose. In fact, it is so important, the World Health Organization considers it one of their “essential medicines.” Many people have started using NAC supplements for mental health issues. For some, NAC can help treat things like anxiety, OCD, or depression. Others take NAC supplements as brain-boosting nootropics. Of all the nootropics, NAC has one of the widest varieties of benefits it can confer to those who take it. There are DOZENS of positives that people report while taking this nootropic, and many of them are backed by extensive research. In fact, 300 human clinical trials have been done in the past 10 years, which is pretty incredible for a supplement. Even better, there are very few reported side effects. NAC is very well tolerated for most people. It is also inexpensive and available over the counter. NAC supplements work through the body’s glutamate system.
NALT (N-Acetyl L-Tyrosine) is a potent source of the amino acid l-tyrosine, which is a precursor to dopamine. Supplementing with NALT can boost levels of dopamine in the brain, which could have a nootropic effect on the user. Many people take NALT for:
- Stress Relief
NALT seems to be most effective at fighting the effects of fatigue and stress. People who are under difficult situations for an extended period of time usually get the most use out of this nootropic.69Jongkees BJ, et al. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands–A review, J Psychiatr Res. 2015 Some people also use NALT as a complementary treatment with ADHD medicine like Adderall and Ritalin. NALT can replenish the dopamine that these stimulants use up. Some people even use NALT as a replacement for these drugs. 70Fernstrom JD, Fernstrom MH. Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain, J Nutr. 2007
Nicotine (yes, like from tobacco) may actually have some nootropic benefits. Although there are some obvious downsides to this substance, like addiction, researchers are now starting to understand its potential benefits for the brain.
Nicotine benefits may include:
According to clinical researchers, there is now a large body of evidence that nicotine can enhance information processing and cognitive function across a number of domains, in smokers AND non-smokers. 71Levin ED, Cauley M, Rezvani AH. Improvement of attentional function with antagonism of nicotinic receptors in female rats, Eur J Pharmacol. 2013 Nicotine works by upregulating nicotinic acetylcholine receptors (nAChR) in the brain. This can promote quicker thinking, and increased focus and attention. It can also stimulate the release of other neurotransmitters like dopamine and serotonin. 72Gerald Valentine, Mehmet Sofuoglu. Cognitive Effects of Nicotine: Recent Progress, Curr Neuropharmacol. 2018 In fact, researchers are currently looking into developing new drugs from nicotine that may be used for ADHD, anxiety, Alzheimers, and other conditions in the future. 73Marty Graham. Researchers Light Up for Nicotine, the Wonder Drug, Wired. 200774Pharmacol Ther. 2013. Nicotinic acetylcholine receptors: from basic science to therapeutics, Hurst R, Rollema H, Bertrand D
Noopept (n-phenylacetyl-l-prolylglycine ethyl ester) is a synthetic nootropic that has a proven effect on:
Noopept has a very mild stimulatory effect but also acts as an anxiolytic and neuroprotectant as well. It is used mainly for: In the nootropics community, noopept is considered one of the most effective supplements out there for overall cognition. It acts powerfully on a broad spectrum of mental processes with almost no downsides, making it one of the most popular and highly recommended nootropics of all time. It doesn’t hurt that noopept is also extremely cheap, with a year’s supply costing only a few bucks.
The Most Popular Nootropic
In fact, it may currently be THE most popular nootropic worldwide. In our opinion, if you were to boil down the entire array of nootropics into one single “prototypical nootropic” it would probably look a lot like noopept. Noopept is considered an ampakine, similar to the racetam class of nootropics, but it is much more potent than any known racetam. Compared to piracetam, noopept is actually 1000x stronger, with effective doses starting at just 10mg. It works in a similar way as racetams, by modulating acetylcholine production and AMPA receptor function. Noopept was first synthesized in the ’90s by a Russian pharmaceutical company.
Is Noopept Legal In The US?
There are currently no restrictions for buying noopept in the United States. It is a prescription drug in some countries but is sold as an over the counter supplement in the US and others. Noopept can boost nerve growth factor, neuroplasticity, brain wave activity, and downregulate glutamate production and inflammation, which helps protect the brain. Users report lower anxiety levels, increased focus, and quicker recall when using this nootropic.
Does Noopept Get You High?
No, unlike stimulants such as Adderall, noopept will not get you high. However, you may feel a mild lift after using it. Unlike other nootropics, which can sometimes take weeks of daily use until their effects become apparent, noopept kicks in about 10 minutes after ingestion. Also unlike more subtle nootropics, noopept has a bit more”oomph” behind it. While not exactly as strong as drinking a coffee, it’s usually pretty apparent when it starts working. Most noopept users experience a moderate “lifted” feeling when it hits, with heightened senses, but without overstimulation or anxiety. It’s become popular for students and professionals around the world, with many people using it as a substitute for “harder” smart drugs, such as amphetamines. If you are new to the nootropics world, noopept should be one of the first options to consider trying.
Oat straw supplements are a popular herbal remedy made from the dried stems and leaves of the oat plant. They have been used for centuries to treat a variety of ailments, including anxiety, insomnia, and fatigue. There is some scientific evidence to support the use of oat straw supplements for cognitive enhancement. One study found that oat straw supplementation improved attention span and reaction time in healthy adults. The mechanism of action for the cognitive benefits of oat straw supplements is not fully understood, but it is thought to be related to the high levels of flavonoids present in the oats. Flavonoids are a type of phytonutrient that has been shown to have neuroprotective effects. If you are looking for a safe and effective way to improve your cognitive function, oat straw supplements may be worth considering.
Oxiracetam (4-Hydroxy-2-oxopyrrolidine-N-acetamide) is a synthetic nootropic in the ampakine family of supplements. It is a derivative of the original racetam, piracetam. It was first synthesized in the 1970s. Oxiracetam is considerably stronger than its predecessor and has more nootropic benefits. These include:
- Processing speed
This nootropic is one of the most popular choices among the biohacker community. It is also famous for its mild stimulatory effect. Some describe oxiracetam as a subtler form of Adderall without the nasty side effects. Oxiracetam works by modulating AMPA receptors, regulating glutamate levels, and increasing neurotransmitter release in the brain. Oxiracetam is safe and well-tolerated, with a low side-effects profile.
Phenibut (β-phenyl-γ-aminobutyric acid) is a synthetic nootropic supplement used for:
- Better mood
- Better sleep
Phenibut has a pretty interesting history. The former USSR developed it as an anti-anxiety medication for cosmonauts during spacewalks. They needed something that would ease their nerves as they floated in the void of space. However, they still needed their thinking clear and their motors skills intact so they could perform complicated mechanical work. So, in the early 60’s, researchers in St. Petersburg first synthesized phenibut.
Is Phenibut Legal In The US?
Doctors still prescribe phenibut as a treatment for anxiety, insomnia, depression, PTSD, and alcoholism in Russia and other eastern European countries. However, it is mostly unscheduled in the rest of the world, including the US. This means you can buy it legally, without a prescription, from online vendors. However, just because it is legal does not mean it is without risks. As you will see, it is critical to approach phenibut cautiously. When phenibut kicks in, most users find that it makes them feel focused, free of stress, and more sociable. It typically takes about half an hour to start feeling the initial effects, but it takes about 5-6 hours before it starts to peak. The effects can linger in the body as long as 24-48 hours, with some users reporting a “halo” effect the next day. We do not advise taking phenibut more than once or twice a week, max.
Phenylpiracetam (AKA phenotropil or phenotropyl) is a phenyl derivative of piracetam. Piracetam was the original racetam nootropic, and phenylpiracetam is a newer version that acts quicker and has higher bioavailability. It is more potent and has a broader range of use. Nootropics users take phenylpiracetam for:
- Improved Cognition
- Memory and Learning
- Energy and Physical Performance
Many users report strong stimulatory effects from this substance. In fact, phenylpiracetam is so powerful that it is actually banned by the World Anti-Doping Organization as a performance enhancing drug.75WADA Prohibited List, uasada.com. 2017 Some users use it as a substitute for heavier pharmaceutical stimulants like Adderall. Phenylpiracetam can provide some of the energy, focus, and motivation, but without the edginess, loss of appetite, or dreaded “Adderall crash.” Phenylpiracetam modulates acetylcholine (ACh), dopamine, GABA, and NMDA receptors in the brain. All of these neurotransmitters are heavily involved in learning, memory, focus, attention, and overall mental function. It seems that this nootropic up-regulates the number of available receptors, making them more responsive.76Yu. Yu. Firstova D. A. AbaimovI. G. KapitsaT. A. Voronina G. I. Kovalev. The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task, Neurochemical Journal June 2011 It also seems to be effective as a neuroprotectant. It can be used to treat a range of central nervous system disorders. It is effective against epilepsy and can help people recover from strokes or cognitive impairment.77Malykh AG, Sadaie MR. Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders, Drugs. 2010
Phosphatidylcholine is a phospholipid that forms a critical part of the membrane in each cell in your body. It makes up about 30% of the lipids in your cells, making it one of the most abundant compounds in your nervous system. This makes it a very important substance that can affect many different aspects of cognition and physical health. It can be great choice as an overall holistic nootropic for many people. 78James Meschino. Choline and Phosphatidylcholine (Lecithin), Natural Health Products Compendium 79Nature Publishing Group. Phosphatidylcholine, Lipidomics Gateway 2009 In fact, the futurist and inventor Ray Kurzweil claims to get PC injections every week to maintain his youth. 80Gary Wolf. Ray Kurzweil Pulls Out All the Stops (and Pills) to Survive to the Singularity, Wired. 2000 Although you might not want to go quite that far, supplementing with phosphatidylcholine can help with:
- Memory and learning
- Forming neural connections
- Physical performance
PC is present is some food, like eggs and beef. Most supplemental choline is in the form of lecithin, which usually contains 10-20 percent Phosphatidylcholine. However, more concentrated forms of phosphatidylcholine are now available, which are generally labeled as Phosphatidylcholine (not lecithin). This can have a more pronounced benefit for users because phosphatidylcholine can raise blood concentrations of choline 12x higher than other choline sources.81Hirsch MJ, Growdon JH, Wurtman RJ. Relations between dietary choline or lecithin intake, serum choline levels, and various metabolic indices, Metabolism. 1978 This supplement works as a nootropic by increasing flow of acetylcholine (ACh). This is a critical neurotransmitter involved in memory, learning, and overall cognition. PC is also a necessary building block in cell membranes, so keeping proper levels can ensure that your body has enough to repair damaged cells and grow new ones. This can have a profound effect on brain health and mental function. 82Wang L, et al. Dietary uridine-5′-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats, J Mol Neurosci. 2005
Phosphatidylserine (which we’ll shorten to “PS” for this article) is a naturally occurring phospholipid that permeates your brain. In fact, it is present in every single one of your cells throughout your entire body. In particular, it is highly concentrated in brain cells. Its ubiquity in the brain makes it one of the most important factors in many vital functions, including neuroplasticity, nerve growth, brain cell health, and efficient cross-brain communication. Supplementing with PS has been linked to improvements in:
- Attention span
- Overall cognitive health.
In fact, we consider PS one of THE most important nootropics currently available. It is involved in so many holistic brain processes that it would be a mistake for any nootropics enthusiast to overlook it. Don’t take our word for it either. According to a 2015 meta-analysis, 300mg of PS per day “supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and ability to communicate.” That’s straight from the researchers, not ad copy!83Glade MJ, Smith K. Phosphatidylserine and the human brain, Nutrition. 2015 PS oversees the critical task of regulating the flow of nutrients and oxygen in and out of each cell. It’s also involved in building new neurons, facilitating chemical messages across the brain, and maintaining mitochondria (which in turn powers each cell). It is absolutely necessary for healthy brains, so it should come as no surprise that it has so many positive effects when taken as a supplement. The unfortunate truth is that humans start to naturally lose PS as they age, starting in their early twenties. Cell membranes become less permeable, causing attention, memory, and mood to suffer. Your overall ability to think in general starts to decline. As such, most people should consider PS being part of their core nootropic stack. PS is naturally occurring in the brain and non-toxic. It is totally safe and has very minimal side-effects. It can be derived from animal sources, soy, or sunflower, and it is important to check the label of any product you purchase to determine which it is.
Picamilon (also known as N-nicotinoyl-GABA, pycamilon, and pikamilon), is a synthetic nootropic that may be useful for the following:
- Lowering anxiety and stress
- Improving mood
- Increasing cerebral circulation
- Improving memory and learning
- Addiction recovery
It works primarily through increasing GABA levels in the brain. Typically, GABA cannot cross the blood-brain barrier, making direct supplementation ineffective. However, picamilon gets around this by attaching a Vitamin B3 (niacin) molecule to a GABA molecule. The B3 molecule allows the GABA molecule to cross into the brain and start taking action. 84Dorofeev BF, Kholodov LE. Pikamilon pharmacokinetics in animals, Farmakol Toksikol. 1991 It was originally developed in Russia during the ’60s and is still prescribed for anxiety, attention disorders, and addiction recovery. Like Phenibut, it can promote feelings of relaxation and well-being without the drowsiness or impairment of traditional tranquilizers. 85R. P. Kruglikova-L’vova, et al. Pikamilon-a new vasoactive and nootropic preparation, Pharmaceutical Chemistry Journal. 1989
Is Picamilon Banned?
Not quite, although this supplement has caused some controversy in the US with regulatory agencies. In 2015, the FDA determined that “picamilon is a substance that does not meet the statutory definition of a dietary ingredient.” It demanded that some companies pull products “adulterated” with this product, as it is not approved for sale in the US as a human supplement. However, despite this recent controversy, picamilon is still technically legally available for purchase in the USA. Just not branded for human consumption. Please consult your local regulations to see if picamilon is legal to purchase where you live.
French maritime pine bark extract is a nootropic supplement found in the bark of the French Maritime Pine Tree (Pinus pinaster). It contains a powerful antioxidant called proanthocyanidin which has many positive benefits for neurological health.
Pine Bark Extract
Pine bark extract may have a positive effect on
- Overall cognitive function
The bark is typically made into an extract that concentrates the benefits into an easy-to-consume capsule or powder. It is often sold under the trademarked brand name “Pycnogenol.” We will use the terms pine bark extract and pycnogenol interchangeably, as they are the same thing. It is also sometimes sold under the name “Flavangenol.”
Piracetam is the worlds first synthetic nootropic, originally conceived in 1964 by the godfather of nootropics himself, Dr. Cornelieu Giurgea. It is used for:
- Attention and focus
We can credit piracetam for breaking ground in this field, and all these years later it is still considered a safe, effective memory and learning aid by researchers. It can potentially be used to enhance cognition in healthy adults, as well as people suffering from age-related degeneration and brain trauma. Piracetam was initially intended to be a treatment for motion sickness. However, after failing clinical trials in that regard, Dr. Giurgea noticed that piracetam actually improved his research subject’s scores on memory and recall tests. With a little more research he concluded that piracetam could be used as a safe and effective cognitive enhancer. We’re lucky he did, because this discovery kicked off the entire field of nootropic research. Piracetam (2-oxo-1-pyrrolidine-acetamide) belongs to the “racetam” class of cognitive enhancers. Even though it is technically a GABA derivative it does not affect the GABA receptors in the brain. It is considered an “ampakine”, meaning that it primarily modulates the AMPA and NMDA receptors in the brain. It is water-soluble, and non-toxic. It also goes by the name Nootropil, Lucetam, Biotropil, Stimulan, and Breinox in other countries. Piracetam can be considered the father of an entire family of neuro-enhancing smart drugs who all share the pyrrolidone nucleus as their base. These derivatives include phenylpiracetam, aniracetam, oxiracetam, and dozens more.
Pramiracetam (N-[2-[di(propan-2-yl) amino] ethyl]-2-(2-oxopyrrolidin-1-yl) is a central nervous system stimulant and nootropic agent belonging to the racetam family of drugs. It is a derivative of the original racetam, piracetam. It was first synthesized in the 1970s and is considered 30x more effective than the original piracetam. It was originally developed as an anti-Parkinson’s drug but has since become noticed for it’s cognitive enhancing properties. It has become popular among nootropics users for:
Pramiracetam is considered an “ampakine.” It works by stimulating the transmission of the neurotransmitter acetylcholine (ACh). It does this by modulating the AMPA and NMDA receptors in the brain. Acetylcholine is heavily tied to memory and cognition. Pramiracetam also has notable neuroprotective qualities. In fact, it may help restore brain function after stroke or traumatic injury. In many parts of the world, pramiracetam is a prescription drug. In America, it is considered an OTC supplement. It is generally a good idea to stack pramiracetam (or any racetam) with a good choline source. This is because racetams use up your body’s choline stores, so it is necessary to supplement with extra. If you don’t, you may run the risk of getting a headache. Alpha-GPC and CDP-Choline are great options for this.
Ganoderma lucidum, known as “reishi” in Japan and “lingzhi” in China, is one of the most commonly used medicinal mushrooms in the world.
It may also have some notable nootropic benefits for cognition and mental health. Reishi is considered an adaptogen, helping the body and mind find equilibrium in difficult situations.
This fungus has been used for thousands of years in Eastern medicine for a wide variety of health issues, including:
- Improved cognition
- Mood support
- Fighting cancer
- Boosting the immune system
- Anti-oxidant and anti-aging
Now, modern researchers are starting to confirm that many of the uses are clinically effective.86Sissi Wachtel-Galor, John Yuen, John A. Buswell, and Iris F. F. Benzie. Chapter 9: Ganoderma lucidum (Lingzhi or Reishi), Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. 2011
This mushroom contains several unique organic compounds that seem to give it its therapeutic value.
Reishi is one of the most commonly available medicinal mushroom on the market, and in our opinion, most people could get some benefit from regularly using it.
Rhodiola Rosea is an all-natural nootropic and adaptogenic herb that has been used for thousands of years to boost
- Athletic performance
Also known as “Golden Root” or “Arctic Root,” rhodiola grows wild in parts of Scandinavia, Eastern Europe, and Russia. It has been used in traditional medicine by the cultures of this region for a very long time, and has also been studied extensively by modern researchers. There is compelling evidence that this herb can have a powerful effect on several different cognitive and bodily functions. In fact, rhodiola may be THE most well documented herb of it’s type.
Rhodiola Rosea as an Adaptogen
As an adaptogen, it works partially by modulating the body’s response to stress, helping it adapt and “hold steady” during difficult circumstances. Rhodiola contains several different compounds that achieve this effect, including rosavin, rosarin, rosin, salidroside, and tyrosol, some of which are found exclusively in this species of plant and nowhere else. For our purposes, we will focus on the nootropic benefits of rhodiola in this article. However, it is also known to be helpful for fertility, physical endurance, erectile dysfunction, some cancers, some infectious diseases, and even scurvy. The healing properties of rhodiola rosea are powerful and varied, and certainly worth researching if you are interested in traditional medicine. In our opinion, this herb is about as close as Mother Nature comes to a “miracle cure.”87Richard P. Brown, Patricia L. Gerbarg, Zakir Ramazanov. Rhodiola rosea: A Phytomedicinal Overview, The Journal of the American Botanical Council. 2002
Rhodiola Rosea as a Nootropic
One of Rhodiola’s primary benefits is its profound effects on anxiety and overall mood. There is preliminary clinical evidence (and tons of testimonials) that this nootropic can ease the distress caused anxiety disorders and lift some people out of depression. It’s possible that for some people, rhodiola may be even more potent and involve fewer side-effects than traditional anti-depressants. In addition to improving mood, Rhodiola can increase energy, attention, and focus. Many users report a mild but noticeable stimulating effect after taking it. Rhodiola is especially useful for maintaining concentration during stressful and physically demanding activities due to its adaptogenic properties.
Rhodiola Rosea as a Performance Enhancer
This herb is legendary for its effects on physical abilities. Fieldworkers in Russia used it for millennia to increase their stamina as they did manual labor in the harsh elements. World-class athletes have used it to enhance their performance and recover faster. Many people claim that it helps improve their mind-body connection when exercising and playing sports. Rhodiola Rosea is also prized for it’s anti-inflammatory and neuro-regenerative qualities, which helps with overall long term brain health. Some of the compounds found in this herb fight off oxidative damage in the brain. Others are proven to help grow new neurons, which allows the brain to learn new skills and form new memories. In short, Rhodiola does a lot! It’s one of our favorite all-natural nootropics that many people can get a lot of benefit from. Read on for a more in-depth look at this adaptogen.
Saffron is a plant that has been used for centuries in traditional medicine. The active ingredient in saffron is crocin, which is responsible for its yellow color. Crocin is thought to be a powerful antioxidant and anti-inflammatory. Saffron supplements are becoming increasingly popular as people look for ways to improve their cognitive function and memory. There is some scientific evidence to support the use of saffron supplements for cognitive enhancement. One study found that crocin was able to improve memory and attention in healthy adults. Another study found that saffron supplementation improved symptoms of depression and anxiety. The mechanism of action of saffron supplements is not fully understood, but it is thought that the crocin in saffron works by increasing levels of neurotransmitters in the brain. This may help to improve communication between nerve cells and lead to improved cognitive function. If you are considering taking saffron supplements, it is important to speak with your healthcare provider first.
Sarcosine (N-methylglycine) is a precursor and derivative of the amino acid glycine. Physicians primarily prescribe sarcosine for treating schizophrenia, although it may also have some nootropic benefits for:
Sarcosine works by activating the NMDA (N-methyl-D-aspartate) receptor. Researchers believe that it achieves most of its therapeutic effects through this mechanism.88Harsing LG Jr, et al. Glycine transporter type-1 and its inhibitors, Journal or Curr Med Chem. 2006 The body produces it by turning dietary choline into glycine, or by breaking down methionine to glycine. It is a non-toxic compound that you can find in certain foods, such as meat, eggs, and vegetables. Sarcosine is also an additive in toothpaste because it can prevent cavities, and is responsible for its foaming action.
Selegiline (AKA Deprenyl) is a medication that is officially used to treat Parkinson’s Disease. However, many users also take off-label it for its nootropic effects. The main nootropic uses of selegiline are for:
- Alertness and Attention
Selegiline seems to increase the availability of dopamine and serotonin by preventing its breakdown. It also has some antioxidant and neurogenerative properties that may help it protect the brain, especially as you age. In most Western countries, including the US, selegiline is a prescription-only medication. It usually goes under the brand names Deprenyl or Emsam.
Sulbutiamine is a synthetic nootropic compound that, for many users, has a noticeable effect on
- Focus (ADHD)
It was originally developed in Japan in the 1960s for the treatment of beriberi, which was a public health problem in Japan until the 2nd World War89Lucien Bettendorff, Pierre Wins. Thiamine derivatives in excitable tissues: metabolism, deficiency and neurodegenerative diseases, Recent Res Devel. Neurochem.,2. 1999 . It’s considered one of the more potent stimulatory nootropics out there. It is one of the few that you can really feel when it “kicks in.” Many people use it as an alternative to stimulants like Adderall for short term energy boosts.
What Is Taurine?
Taurine (2-aminoethane-sulfonic acid) is an essential amino acid that is found naturally in almost every cell in your body. It is extremely abundant. In fact, it makes up about .1% of total human body weight.90Taurine, Wikipedia You can also take it as a nootropic supplement for a variety of reasons, such as:
- Increased energy
- Lowered anxiety
- Overall cellular health
Most people are familiar with taurine as an ingredient in energy drinks such as Red Bull. Taurine has a synergistic effect with caffeine, increasing energy while also taking the edge off of caffeine’s stimulation. However, you do not have to drink these (often unhealthy) beverages to get the benefit of this nootropic. Many people take taurine by itself as a supplement to avoid the excess sugar and caffeine that you usually find with these drinks. Taurine works by activating GABA and glycine receptors in the brain. This can improve memory and mood, lower anxiety, and increase energy.91Jang-Yen Wu, Howard Prentice. Role of taurine in the central nervous system, J Biomed Sci. 2010 It is also an antioxidant that can reduce excess calcium levels in the brain. This protects cells, and can help prevent diseases like strokes and Alzheimers. Taurine promotes the growth of new neurons, making it an excellent anti-aging supplement.92Stephen Schaffer, Ha Won Kim. Effects and Mechanisms of Taurine as a Therapeutic Agent, Biomol Ther (Seoul). 2018 93Gebara E. Taurine increases hippocampal neurogenesis in aging mice, Stem Cell Res. 2015
What Is Taurine Made From?
Originally taurine was extracted from bull semen and ox bile (taurus means “bull” in Latin, hence the name.) You may be relieved to find out that this is no longer the case. Taurine is now synthesized in labs, and is perfectly suitable for vegans, vegetarians, and anyone who does not want to ingest bull semen (most people).
Theacrine (1,3,7,9-tetramethyluric acid) is the predominant purine alkaloid extracted from the tea plant, Camellia kucha. According to research, it may provide a number of mental and health benefits to people who take it. You can get theacrine from drinking kucha tea, or from supplements.94Xu JK, Kurihara H, Zhao L, Yao XS. Theacrine, a special purine alkaloid with sedative and hypnotic properties from Cammelia assamica var. kucha in mice, J Asian Nat Prod Res. 2007
Structurally, it is very similar to caffeine, which is also found in the kucha plant. People use theacrine as a nootropic for:
- Increased energy
- Better sleep
- Reducing inflammation
- Improved athletic performance
Theacrine vs Caffeine
Interestingly enough, theacrine can counteract the stimulation of caffeine. Many users report that it can offer smooth, sustained energy without the jitters associated with other stimulants. 95Zheng XQ, et al. Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha), Phytochemistry. 2002 For this reason, taking theacrine and caffeine together has become a popular nootropic stack.
Uridine (Uridine Monophosphate, UMP) is a naturally occurring amino acid. It is one of the four components of DNA and RNA, and it is found in the cells of literally all life on earth. It is one of THE basic building blocks of your body. So, it should come as no surprise that it may have nootropic benefits as a supplement. These include:
- Increased mood
- Increased dopamine receptor density
- Neuroprotection and regeneration
- Overall cognitive enhancement
In fact, uridine is such a critical factor in human brain health and development that you can find some of the highest concentrations in breast milk. It is an ingredient in most infant formulas.96Sugawara M, Sato N, Nakano T, Idota T, Nakajima I. Profile of nucleotides and nucleosides of human milk, J Nutr Sci Vitaminol. 1995 97Thorell L, Sjöberg LB, Hernell O. Nucleotides in human milk: sources and metabolism by the newborn infant, Pediatr Res. 1996 You can find uridine in foods like beets, broccoli, fish, mushrooms, oats, parsley, sugar cane, tomatoes, brewer’s yeast, and beer. However, most dietary uridine is broken down by the liver and does not reach the brain. Luckily, you can supplement with uridine monophosphate, which is a highly bioavailable form of uridine that is absorbed by the brain. Uridine works by promoting neurosynthesis and synapse development. Basically, it can help the brain repair itself and forge new connections. Obviously, this could be very beneficial to many aspects of brain function. It can also regulate dopamine production (a major factor in mood), improve cellular metabolism, and lower inflammation. 98LeiWanga, Meredith A.Albrecht, Richard J.Wurtman. Dietary supplementation with uridine-5′-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat, Brain Research. 2007
Vinpocetine is a synthetic nootropic that can be used for:
- Cognitive enhancement
- Alzheimers and dementia prevention
It is an analogue of the alkaloid apovincamine, which is isolated from the leaves of Vinca minor, commonly known as the lesser periwinkle. It was discovered discovered in the late 1960s. 99Lörincz C, Szász K, Kisfaludy L. The synthesis of ethyl apovincaminate, Arzneimittelforschung. 1976 Physicians prescribe vinpocetine in the treatment of ischaemic cerebrovascular diseases and dementias of vascular type. It especially helps improve blood flow to the brain. specially helps dementia as its believed that dementia blocks blood flow to the brain. 100Valikovics A. Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions, Ideggyogy Sz. 2007