What are nootropics?

Nootropics are classified as synthetic or natural compounds that enhance mental cognitive performance – alertness, attention, cognition, executive function, memory, mental speed, reaction time, visuo-spatial skills, etc. Sometimes, they’re colloquially referred to as “smart drugs.” The word itself can be both an adjective, as in “this compound has nootropic effects,” and a noun, as in “this compound is a nootropic.”

At first, nootropics were mostly stimulants, but the definition has stretched to encompass other nutrients that are not stimulants but that make your brain function better (the L-theanine in EFS and EFS-PRO is an example). Pretty much anything your brain does can be bettered, and whatever can do that is lumped into the nootropic world.

Is caffeine a nootropic?

Short answer: YES! Calling caffeine a nootropic is a no-brainer; it’s the poster child, most prolific, and – arguably – best nootropic.

To excel at long-duration endurance exercise, you also need enhanced mental function to rapidly process and make decisions based on external and internal inputs. Endurance athletes refer to the pain cave, the box, chewing the stem, etc., as metaphors for diverting function from the brain to the body, but they are still always mentally tracking and responding to stimuli that directly impact performance. Finely honed executive function helps athletes know how to respond to changing circumstances and when to strategically dole out effort. When to push harder, let up, go with the flow, and bide their time – racing smart, if you will.  This is why we reformulated PreRace.

These crucial executive functions include being alert (visuo-spatial skills), attentive, aware (cognitive skills), responsive (reaction time and mental processing speed), and keeping racing and fueling strategies locked in (memory and recall). Caffeine is a one-size fits all way to improve all those exercise-related brain functions.

We’ll look into caffeine and mood in a later blog that will focus on attitude, feelings, willpower, and other mental intangibles that also play a big role in success or failure. Here, we’re just considering those executive functions listed above.

Think great – stimulate!

Caffeine’s effects help us think longer, faster, and harder, and it’s unsurprising that those effects have reams of evidence showing real-life benefits outside of exercise. Most of the world takes advantage of these effects by habitually using caffeine, a behavior that’s especially prevalent among endurance athletes.

So how does caffeine benefit those athletes during exercise? These effects are less studied, but they still prove positive for long-duration endurance exercise.

For example, in a crossover study of bars with 45g of carbohydrates with or without 100mg of caffeine, cyclists habituated to a daily caffeine intake of ~170mg ate one bar before exercise, one after 55 minutes of exercise, and one more after 115 minutes of exercise. The exercise was a 120-minute cycle ergometer ride at 60% VO₂ max followed by a time trial at 75% VO₂ max until exhaustion (when the athletes were no longer able to maintain 50rpm) (Hogervorst 2008).

The physical results were clear and promising: caffeine improved time to exhaustion by 354 seconds, a 27% improvement over carbohydrate bars only. Several mental tests were also conducted immediately after exercise stopped, which I’ll parse below in no particular order.

One mental test was the Stroop Color and Word test, which measures mental processing speed, alertness, and astuteness. Subjects in the caffeine bar test group showed faster response times than groups given both the carbohydrate bar without caffeine and a colored water placebo. Faster responses did not sacrifice accuracy for speed, either, which is typical for stimulated brains.

Likewise, results from the Rapid Visual Information Processing Task and Visual Search Test, which measures sustained attention and recall capacity, were better with caffeine. Results were non-significantly better for a Word Learning test, which is another measure of attention and recall.

Think big – go meta

Lumping together similar human clinical studies is one way to determine if an intervention (caffeine intake before exercise) is something repeatable, reproducible and trusted. A statistical manipulation called a meta-analysis is often used to compare apples to oranges to other fruits, so to speak.

In order to power an effective meta-analysis, the pertinent studies are scrubbed to choose the ones that are most alike. That reduces the variability of different measurement tools and other study design differences – things like caffeine dose, timing of administration, and type/duration of exercise. If those similar inputs produce a consensus output, then that’s a good sign that the results aren’t a fluke, and that similar actions will return similar results.

For a recent meta-analysis, 13 studies of caffeine’s effect on mental performance during exercise were chosen for review, and the five most alike were analyzed (Calvo 2021). Doses of caffeine ranged from 100-600mg (roughly 1-6mg/kg). Overall, caffeine improved attention performance better than a placebo.

The five most similar studies involved 18 separate trials and 988 subjects, and the meta-analysis found that attention response accuracy and speed were both improved by caffeine. Simple reaction time, which involves basic stimuli and response prompts, was not improved; however, choice reaction time, which involves multiple potential stimuli and corresponding response prompts, showed a trend for improvement. Inhibitory control accuracy and speed – essentially the ability to block unwanted stimuli out – were not improved.

Ultimately, the authors concluded that a variety of cognitive domains were improved by caffeine. The authors also felt that best results from caffeine were from endurance events instead of team sports like soccer and rugby. There were no gender differences – everyone benefited similarly. Happily, no mental functions were decreased or hampered by caffeine.

One important takeaway is that several studies administered caffeine before and during exercise. Taking caffeine before exercise showed mental function benefits, but additional doses during exercises did not show additional mental benefits. Also, smaller caffeine doses (100-300mg) showed benefits more often than higher doses (500mg or more).

These findings on mental functions jibe with over-caffeination causing anxiety that would decrease mental performance, which is also seen in non-exercising individuals and helped inform First Endurance’s approach to formulating a (spoiler alert) soon-to-be-released caffeinated Liquid Shot.

Caffeine & exercise – a nootropic summary

The lesson here for using caffeine to keep your mind sharp is to not go overboard or take it too often. There is a sweet spot of boosting brain function with caffeine during long-duration exercise – 100-300mg before exercise (less than an hour before) and lower doses (25-50 mg or caffeinated mouth rinses) two+ hours into long-duration exercise as needed.

These and other studies also buried long-debated issues with caffeine, like assumptions about habituation, which hold that if you drink coffee or caffeinated beverages every day, taking extra will not make a difference. This is untrue. Specifically designed studies have found that caffeine works for your brain function whether or not you are a regular user.

Another myth is that caffeine studies only look like they work because they prevent decreased mental performance and mood of withdrawal symptoms. Again, this question has been studied and refuted; exercise and mental effects of caffeine are not just about perception, they are real and physical. The effects in your head are due to the same mechanisms as the physical improvements – more glucose to the brain, more release of adrenalin (epinephrine, and norepinephrine), and improved circulation to feed your brain more fuel and make more neurotransmitters.

Table 1: Partial List of Nootropic Substances*


Natural Nootropics Synthetic Nootropics
Acetylcholinesterase inhibitors (Cannabis, Galantamine, Huperzine A, Rosemary, Sage) Acetams (piracetam, other whatever-acetams)
Alpha-GPC (glycerophosphocholine) Acetylcholinesterase inhibitors (Donepezil)
Amino Acids (Cysteine, L-DOPA, 5-HTP, Phenylalanine, Tryptophan, Tyrosine) Adrenergics (ADHD drugs, Atomoxetine, Reboxetine)
Antioxidants (many or any) Amphetamines
B Vitamins cAMP Inhibitors (Propentofylline, Rolipram)
Caffeine Cholinergics (Arecoline, Meclofenoxate, Nicotine)
Carnitine & Esters (Acetyl, Fumarate, Tartrate) Dopaminergics (dopamine, Ritalin, Ropinirole)
CDP-Choline (Citicoline, Cytidine DiPhosphate Choline) Eugeroics (Adrafinil, Armodafinil, Modafinil)
DMAE (DiMethylAminoEthanol) GABA Blockers (Suritozole)
Dopamine Glutamate Activators (Ampakines)
Glucose MOA-B Inhibitors (Rasagiline, Selegiline)
Herbs (Amla, Brahmi, Cinnamon, Coconut Milk (MCTs), Curcumin, Eleutherococcus, Ginger, Ginseng, Ginkgo, Gotu Kola, Green Tea, Guduchi, Guggul, Kola nuts, Licorice, Maca, Rhodiola. St. John’s Wort, Yerba Mate) Reuptake inhibitors (Amineptine, Bupropion, Coluracetam, Methylphenidate)
Iron (for repleting deficiencies) Serotonergics (SSRIs, Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline)
Omega-3 Fatty Acids (DHA, EPA) Vasopressin (also natural)
Paraxanthine Vinpocetine
Phosphatidyl Choline, Phosphatidyl Serine  
Royal Jelly  
Reuptake inhibitors (Ginsenosides)  
Synephrine (Bitter Orange extracts)  
Vincamine (from periwinkle)  

*This list is not an endorsement of nootropic effects from each substance, but just a list of what is deemed to have some sort of brain improvements under specific conditions (not just exercise). And safety is not considered in this list but is a huge factor to consider. Combinations are common but not listed here.


Anonymous. Literature review: caffeine as mental stimulant and nootropic. First, Forget What You Know, 2010 Oct28. https://firstforgetwhatyouknow.wordpress.com/2010/10/28/literature-review-caffeine/

Caldenhove S, Sambeth A, Sharma S, Woo G, Blokland A. A combination of nootropic ingredients (CAF+) is not better than caffeine in improving cognitive functions. J Cogn Enhancement. 2018;2:106-13.

Calvo JL, Fei X, Dominguez R, Pareja-Galeano H. Caffeine and cognitive functions in sports: a systematic review and meta-analysis. Nutrients. 2020 Mar6;13(3):868.

Hogervorst E, Bandelow S, Schmitt J, Jentjens R, Oliveira M, Allgrove J, Carter T, Gleeson M. Caffeine improves physical and cognitive performance during exhaustive exercise. Med Sci Sports Exerc. 2008 Oct;40(10):1841-51.

Lorca C, Mulet M, Arevalo-Caro C, Sanchez MA, Perez A, Perrino M, Bach-Faig A, Aguilar-Martinez A, Vilella E, Galart-Palau X, Serra A. Plant-derived nootropics and human cognition: A systematic review. Crit Rev Food Sci Nutr. 2022 Jan31;1-25.

Pranav J. A review on natural memory enhancers (nootropics). Unique J Engineering Adv Sci. 2013;1(1):8-18.

Zhang RC, Madan CR. How does caffeine influence memory? Drug, experimental, and demographic factors. Neurosci Biobehav Rev. 2021 Dec;131:525-38.

July 19, 2022 — Luke Bucci

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