Nootropics: Research, Benefits, and Types

What Are Nootropics?

Nootropics are bioactive substances that act on the central nervous system to promote cognitive function, performance, behavior, mood, and/or sociability in healthy individuals by supporting and protecting, either directly or indirectly, the functional and structural status of the brain. 

The term nootropic is derived from the Greek words nous (mind) and trepein (turn, bend)—literally “mind-turning” or “mind-bending.” It was coined in the early 1970s by the Romanian psychologist and chemist Corneliu E. Giurgea, who pioneered nootropic research [1–3]. But nootropics had actually been used for centuries before the term was coined: caffeine is the quintessential nootropic and its use for mental stimulation dates back to ancient times. 

How Do They Work?

Nootropics promote cognitive function by supporting brain health and influencing functional and structural properties of the brain. There are several processes and pathways that nootropics may support and many mechanisms through which they may do so. Some actions have immediate and transient effects, like the stimulating action of caffeine, but other mechanisms, particularly those that support brain health, can build up with time and lead to a sustained support of brain function. 

How Nootropics Support Neurotransmitter Synthesis

Neurotransmitters are the primary communication molecules of the nervous system. It’s through their actions that we are able to focus, sustain attention, process and memorize information, and be motivated. Neurotransmitters are constantly being synthesized and recycled by the brain through metabolic pathways that involve the activity of myriad precursors, enzymes, enzyme cofactors, and many other types of molecules. 

Nootropics may support neurotransmitter synthesis by supporting the activity of all these molecules and structures. Some nootropic compounds actually are those molecules. For example, the amino acid L-tyrosine is a precursor for the synthesis of the neurotransmitter dopamine, while vitamin B6 (in its active form pyridoxal-5’-phosphate) is a cofactor required for the last step of dopamine synthesis [4]. When these processes are efficient, so is neural communication and whatever function neurotransmitters are controlling.* 

How Nootropics Support Neuronal Communication and Synaptic Plasticity

Synapses are the structures where two neurons meet and transmit information through neurotransmitters. The efficiency of neuronal communication depends on the proper activity of the synapse and all its elements. The brain has trillions of synapses connecting billions of neurons and they play the most crucial part in cognitive function.

Some nootropics target synaptic activity and support synaptic plasticity, helping them to respond and adjust.

Synapses are dynamic structures—they change in ways that either strengthen or weaken the connection between two neurons. This property is known as synaptic plasticity and it underlies a number of important cognitive processes, particularly memory and learning. Some nootropics target synaptic activity and support synaptic plasticity, helping them to respond and adjust. By doing so, nootropics support some of the most important neural mechanisms that allow you to process and retain information.* 

Supporting Healthy Cerebral Blood Flow and Metabolism

The brain requires massive amounts of cellular energy to function properly, even at rest. When you’re performing cognitively demanding tasks that require active alertness, focus, information processing, reasoning, and creativity, the brain’s energy demands skyrocket. 

When you’re performing cognitively demanding tasks that require active alertness, focus, information processing, reasoning, and creativity, the brain’s energy demands skyrocket.

To generate the cell energy it needs, the brain needs a steady and efficient supply of oxygen, glucose (the primary fuel of the brain), and other nutrients, and this requires healthy blood flow to the brain. Some nootropics promote cognition precisely by supporting a healthy cerebral blood flow and oxygen and nutrient delivery.*  

The brain also needs mitochondria to work efficiently, as these are the cellular organelles where cellular energy is produced. Compounds that support healthy brain mitochondrial function and energy metabolism can have nootropic actions because they help the brain generate the energy it needs to support cognitive performance.* 

How Nootropics Support Brain Structure

For the brain to function at its best, the structural integrity of the nervous system must be maintained. This means supporting healthy myelination, synaptic remodeling, i.e., formation of new synapses and pruning of old synapses, or supporting the activity of glial cells that provide functional and structural support and protection to neurons, for example.  

Compounds that support these aspects of brain health may help to maintain the integrity of the neuronal communication network and allow for neuronal messages to be conveyed efficiently, which may be reflected in cognitive performance.*

Nootropics Support Neuroprotective and Antioxidant Functions 

An additional way to support healthy brain structure and function is to promote the brain’s capacity to respond to potentially damaging molecules, i.e., to support neuroprotective functions. One type of molecules that are particularly detrimental to brain health are reactive oxygen species (ROS), which can oxidize molecules, cellular membranes, and other cellular structures to the point of loss of function [5]. 

ROS are generated as byproducts of energy metabolism. Because of the brain’s high metabolic activity, the production of ROS is also high. Although brain cells have antioxidant defenses against ROS, an imbalance between the production of ROS and the cells’ ability to inactivate them may arise, leading to oxidative stress, which is among the main causes of cognitive decline [6]. 

Antioxidant compounds that support antioxidant defenses and balanced ROS  levels can have nootropic action by promoting the brain’s ability to control ROS levels and protect itself from their detrimental effects. This is important both in the short-term, to support daily brain activity, and in the long-term, to support cognitive health and delay cognitive decline.* 

How Nighttime Nootropics Supporting Sleep and Physiology

Sleep is essential for healthy cognitive performance. Sleep is a time of rest and recovery for the brain, but for sleep to be truly restful and regenerative, a lot of upkeep needs to take place while we sleep. The brain’s high metabolic activity results in the production and accumulation of several metabolic byproducts. Sleep gives the brain a daily period of time when its activity is low enough to be able to clean up and do some maintenance. The brain also uses sleep time to organize and consolidate memories and learn. 

Compounds that support nighttime physiology can have nootropic action by contributing to the processes that ensure a restful and regenerative sleep. By helping the brain rest, clean up, organize, and recharge, these nootropics can support next-day cognitive performance.* Learn more about our research-backed nighttime nootropic, Qualia Night. 

Types of Nootropics

Nootropics can be divided into two major categories: natural and synthetic nootropics. 

Natural nootropics are dietary ingredients and other compounds available in nature such as vitamins, minerals, amino acids, herbs, mushrooms, and other dietary substances, often taken in the form of extracts. Synthetic nootropics are compounds produced through chemical synthesis in a laboratory. Some of the most popular nootropics are natural compounds. Here are some examples:

Caffeine

Caffeine is one of the most used and studied nootropic compounds. Caffeine is a central nervous system stimulant that promotes wakefulness and supports resistance to mental fatigue. Studies have shown that caffeine supports alertness, attention, reaction time, information processing, executive function, reasoning, and even creative thinking, all of which contribute to our capacity for mental work [7–14].* 

L-Theanine

L-theanine is an amino acid found in highest amounts in green and black tea. L-theanine has calming actions by promoting alpha brain waves (α-waves), which are regarded as a marker of relaxation [15,16]. It is used as a nootropic because it supports focused attention, reaction times, mental alertness, and a calm, relaxed sense of mental energy [17–22]. L-theanine is often used with caffeine in nootropic stacks, because it helps to balance the stimulating action of caffeine. Together, they support alertness, attention, mood, and cognition [23–27].*

Citicoline 

Citicoline, or CDP-choline, is a choline-containing compound that can be used to support brain choline levels. Choline is a precursor for the neurotransmitter acetylcholine, which supports attention, concentration, mental focus, and memory [28,29]. CDP-choline is also a precursor for phosphatidylcholine, a component of cell membranes needed for healthy cell function [30,31].*

Magnesium

Magnesium is an essential mineral with crucial functions in every organ in the human body. In the brain, magnesium is involved in all biochemical and metabolic pathways of cellular energy metabolism and is fundamental for neurotransmitter synthesis, synaptic transmission, neuroplasticity, and neuroprotection, all of which are essential for brain health and cognitive function [32]. Maintaining adequate brain levels of magnesium is critical for maintaining cognitive health, particularly as we age [33,34]. Clinical studies have indicated that people consuming diets rich in magnesium may have a reduced risk of cognitive decline [35,36].* 

Celastrus paniculatus

Celastrus paniculatus is a nootropic herb with a long history of traditional use as a brain tonic to support mental acuity, memory and intellect and to alleviate mental fatigue [37]. Because of these traditional uses, Celastrus is also known as “the intellect tree.” Celastrus supports antioxidant defenses and neuroprotective functions in the brain [38–45]. These properties, along with its ability to support neurotransmitter systems [45–48], may underlie its support of cognitive function observed in preclinical research [38,43,47–49].*

Lion’s Mane 

Lion’s Mane (Hericium erinaceus) is a mushroom that may promote brain health by supporting neuroprotective functions [50]. One of the most interesting actions of Lion’s Mane, described in preclinical studies, is the support of brain structure. Lion’s Mane supported dendrite growth and myelination, both of which contribute to the efficiency of neuronal communication [51–53]. In a clinical study, Lion’s Mane helped to maintain healthy brain structure and neural organization in older individuals [54].*

Benefits of Nootropics

As we’ve seen, there are many aspects of brain health, function, and structure that nootropics may support. Many nootropic compounds act simply by supporting the brain’s natural physiological processes and by consequently allowing the brain to properly carry out its most complex cognitive processes. 

By supporting healthy blood flow and metabolism, nootropics help the brain generate energy to sustain attention, maintain focus, and process information, while also helping to maintain mental energy and delay mental fatigue. By supporting neurotransmitter synthesis, nootropics contribute to the production of the molecules that not only transmit information but also promote executive function, motivation, and even mood and stress regulation, allowing you to perform well even in demanding or stressful situations. By supporting synaptic plasticity, nootropics may promote memory and your ability to learn. By supporting healthy brain structure, neuroprotective functions, and sleep, nootropics help to maintain brain health and a neuronal environment that allows neurons and other cells to carry out their function efficiently. And together, these mechanisms of action support the brain’s capacity to efficiently execute even the most complex cognitive tasks, such as reasoning, abstract thinking, and creativity.* 

Qualia Mind: Comprehensive and Sustained Nootropic Support 

We believe that one of the most exciting properties of nootropics is their complementarity. Selecting and combining different nootropics into nootropic stacks based on knowledge about neurophysiology and neurobiology and about the mechanisms of action of each compound allows for many different targeted interventions in the brain. Every possible mechanism of action is relevant and helpful on its own, but when we bring them together to target different aspects of brain health and function, we get a more comprehensive and sustained support of cognitive performance—a whole system upgrade.  

Learn more about nootropic stacks in our article about the science behind Qualia Mind. You may also learn more about nootropic complementarity and achieving a whole system upgrade in our article about The Science of Nootropic Stacks. 

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

References

[1]C. Giurgea, Actual. Pharmacol. 25 (1972) 115–156.
[2]C. Giurgea, M. Salama, Prog. Neuropsychopharmacol. 1 (1977) 235–247.
[3]C. Giurgea, Cond. Reflex 8 (1973) 108–115.
[4]M.E. Gnegy, in: S.T. Brady, G.J. Siegel, R.W. Albers, D.L. Price (Eds.), Basic Neurochemistry (Eighth Edition), Academic Press, New York, 2012, pp. 283–299.
[5]M. Schieber, N.S. Chandel, Curr. Biol. 24 (2014) R453–62.
[6]I. Hajjar, S.S. Hayek, F.C. Goldstein, G. Martin, D.P. Jones, A. Quyyumi, J. Neuroinflammation 15 (2018) 17.
[7]T.M. McLellan, J.A. Caldwell, H.R. Lieberman, Neurosci. Biobehav. Rev. 71 (2016) 294–312.
[8]A. Smith, Food Chem. Toxicol. 40 (2002) 1243–1255.
[9]S.J.L. Einöther, T. Giesbrecht, Psychopharmacology 225 (2013) 251–274.
[10]J. Lanini, J.C.F. Galduróz, S. Pompéia, Hum. Psychopharmacol. 31 (2016) 29–43.
[11]A. Nehlig, J. Alzheimers. Dis. 20 Suppl 1 (2010) S85–94.
[12]C.H.S. Ruxton, Nutr. Bull. 33 (2008) 15–25.
[13]K. Soar, E. Chapman, N. Lavan, A.S. Jansari, J.J.D. Turner, Appetite 105 (2016) 156–163.
[14]M.J. Jarvis, Psychopharmacology 110 (1993) 45–52.
[15]L.R. Juneja, D.-C. Chu, T. Okubo, Y. Nagato, H. Yokogoshi, Trends Food Sci. Technol. 10 (1999) 199–204.
[16]C.H. Song, J.H. Jung, J.S. Oh, K.S. Kim, Korean Journal of Nutrition 36 (2003) 918–923.
[17]A. Higashiyama, H.H. Htay, M. Ozeki, L.R. Juneja, M.P. Kapoor, J. Funct. Foods 3 (2011) 171–178.
[18]S.-K. Park, I.-C. Jung, W.K. Lee, Y.S. Lee, H.K. Park, H.J. Go, K. Kim, N.K. Lim, J.T. Hong, S.Y. Ly, S.S. Rho, J. Med. Food 14 (2011) 334–343.
[19]S. Hidese, S. Ogawa, M. Ota, I. Ishida, Z. Yasukawa, M. Ozeki, H. Kunugi, Nutrients 11 (2019).|
[20]M. Gomez-Ramirez, B.A. Higgins, J.A. Rycroft, G.N. Owen, J. Mahoney, M. Shpaner, J.J. Foxe, Clin. Neuropharmacol. 30 (2007) 25–38.
[21]A.C. Nobre, A. Rao, G.N. Owen, Asia Pac. J. Clin. Nutr. 17 Suppl 1 (2008) 167–168.
[22]D.J. White, S. de Klerk, W. Woods, S. Gondalia, C. Noonan, A.B. Scholey, Nutrients 8 (2016).
[23]C.F. Haskell, D.O. Kennedy, A.L. Milne, K.A. Wesnes, A.B. Scholey, Biol. Psychol. 77 (2008) 113–122.
[24]S.J.L. Einöther, V.E.G. Martens, J.A. Rycroft, E.A. De Bruin, Appetite 54 (2010) 406–409.
[25]T. Giesbrecht, J.A. Rycroft, M.J. Rowson, E.A. De Bruin, Nutr. Neurosci. 13 (2010) 283–290.
[26]G.N. Owen, H. Parnell, E.A. De Bruin, J.A. Rycroft, Nutr. Neurosci. 11 (2008) 193–198.
[27]C.N. Kahathuduwa, T.L. Dassanayake, A.M.T. Amarakoon, V.S. Weerasinghe, Nutr. Neurosci. 20 (2017) 369–377.
[28]G.B. Weiss, Life Sci. 56 (1995) 637–660.
[29]S.K. Fisher, S. Wonnacott, in: S.T. Brady, G.J. Siegel, R.W. Albers, D.L. Price (Eds.), Basic Neurochemistry (Eighth Edition), Academic Press, New York, 2012, pp. 258–282.
[30]J. Agut, E. Font, A. Sacristán, J.A. Ortiz, Arzneimittelforschung 33 (1983) 1048–1050.
[31]P. Galletti, M. De Rosa, M.G. Cotticelli, A. Morana, R. Vaccaro, V. Zappia, J. Neurol. Sci. 103 Suppl (1991) S19–25.
[32]J.A.M. Maier, L. Locatelli, G. Fedele, A. Cazzaniga, A. Mazur, Int. J. Mol. Sci. 24 (2022).
[33]M. Barbagallo, L.J. Dominguez, Curr. Pharm. Des. 16 (2010) 832–839.
[34]M. Barbagallo, N. Veronese, L.J. Dominguez, Nutrients 13 (2021).
[35]N. Cherbuin, R. Kumar, P.S. Sachdev, K.J. Anstey, Front. Aging Neurosci. 6 (2014) 4.
[36]M. Ozawa, T. Ninomiya, T. Ohara, Y. Hirakawa, Y. Doi, J. Hata, K. Uchida, T. Shirota, T. Kitazono, Y. Kiyohara, J. Am. Geriatr. Soc. 60 (2012) 1515–1520.
[37]N. Arora, S.P. Rai, Int. J. Pharma Bio Sci. 3 (2012) 290–303.
[38]M.H.V. Kumar, Y.K. Gupta, Phytomedicine 9 (2002) 302–311.
[39]J. Malik, M. Karan, R. Dogra, Pharm. Biol. 55 (2017) 980–990.
[40]M. Chakrabarty, P. Bhat, S. Kumari, A. D’Souza, K.L. Bairy, A. Chaturvedi, A. Natarajan, M.K.G. Rao, S. Kamath, J. Pharmacol. Pharmacother. 3 (2012) 161–171.
[41]P.B. Godkar, R.K. Gordon, A. Ravindran, B.P. Doctor, Phytomedicine 13 (2006) 29–36.
[42]P. Godkar, R.K. Gordon, A. Ravindran, B.P. Doctor, Fitoterapia 74 (2003) 658–669.
[43]V. Bhagya, T. Christofer, B.S. Shankaranarayana Rao, Indian J. Pharmacol. 48 (2016) 687–693.|
[44]M. Gattu, K.L. Boss, A.V. Terry Jr, J.J. Buccafusco, Pharmacol. Biochem. Behav. 57 (1997) 793–799.
[45]P.B. Godkar, R.K. Gordon, A. Ravindran, B.P. Doctor, J. Ethnopharmacol. 93 (2004) 213–219.
[46]R. Valecha, D. Dhingra, Basic Clin Neurosci 7 (2016) 49–56.
[47]K. Nalini, K.S. Karanth, A. Rao, A.R. Aroor, J. Ethnopharmacol. 47 (1995) 101–108.
[48]M. Bhanumathy, M.S. Harish, H.N. Shivaprasad, G. Sushma, Pharm. Biol. 48 (2010) 324–327.
[49]S.B. Raut, R.R. Parekar, K.S. Jadhav, P.A. Marathe, N.N. Rege, Anc. Sci. Life 34 (2015) 130–133.
[50]I.-C. Li, L.-Y. Lee, T.-T. Tzeng, W.-P. Chen, Y.-P. Chen, Y.-J. Shiao, C.-C. Chen, Behav. Neurol. 2018 (2018) 5802634.
[51]P.-L. Lai, M. Naidu, V. Sabaratnam, K.-H. Wong, R.P. David, U.R. Kuppusamy, N. Abdullah, S.N.A. Malek, Int. J. Med. Mushrooms 15 (2013) 539–554.
[52]S. Samberkar, S. Gandhi, M. Naidu, K.-H. Wong, J. Raman, V. Sabaratnam, Int. J. Med. Mushrooms 17 (2015) 1047–1054.
[53]E.V. Kolotushkina, M.G. Moldavan, K.Y. Voronin, G.G. Skibo, Fiziol. Zh. 49 (2003) 38–45.
[54]I.-C. Li, H.-H. Chang, C.-H. Lin, W.-P. Chen, T.-H. Lu, L.-Y. Lee, Y.-W. Chen, Y.-P. Chen, C.-C. Chen, D.P.-C. Lin, Front. Aging Neurosci. 12 (2020) 155.