Literature Review: Caffeine as Mental Stimulant and Nootropic

Supplementation, even with the most familiar substances, can be a murky issue. The biochemistry is often not fully understood; the potential for dependence or withdrawal symptoms not studied. Even if the drug in question has been deemed safe and effective at producing some desirable effect, whether enhanced working memory or increased alertness, there then follows the questions surrounding effective and optimal dosage, interactions with other OTC and prescription drugs (and perhaps food?) and controlling for adverse side effects.

what is caffeine?

Caffeine is a xanthine (purine base) alkaloid, which functions as a central nervous system stimulant when ingested. In North America, it is estimated that over 90% of people ingest caffeine – in the form of teas, coffees, chocolate or supplements – every day. Habituation to the effects of caffeine is a well-known, often lamented, side effect of regular use. Peak blood concentration occurs approximately one hour after ingestion. The elimination rate of the compound by the body can vary quite significantly between individuals, depending on age, pregnancy, use of other medications, and liver functioning.

Caffeine can cross the blood-brain barrier, and there it functions as an antagonist of adenosine receptors. By counteracting adenosine  (it competitively inhibits adenine), caffeine reduces blood flow in the brain. It is believed that adenosine is responsible for feelings of sleepiness.

Research questions

  1. What are the physiological and cognitive effects of taking caffeine?
  2. What are the potential adverse side effects of taking caffeine? How can these be controlled?
  3. Is there a serious risk of dependence and addiction for habitual caffeine users? Is there really such a thing as “Caffeine Withdrawal Syndrome”? Can its effects be mitigated through OTC medicines?

Physiological and Cognitive Effects

  • Jarvis (1993) found a positive dose-response trend for reaction time, choice reaction time, incidental verbal memory and visuo-spatial reasoning; controlled for potential compounds
  • Jarvis (1993) also found that older people were more susceptible to the performance-enhancing effects of caffeine than younger people
  • Rogers et al. (2005) found that any cognitive benefits from taking caffeine were simply due to reversing withdrawal; suggests that there is little benefit to caffeine consumption
  • Lieberman et al. (2002) describes the results of a very interesting study with Navy SEALS. Subjects were given either 100 mg, 200 mg, 300 mg, or a placebo after 72 hours of sleep deprivation and continuous exposure to other stressors (environmental and operational stress) and were tested 1 h and 8 h following dosing. Found that caffeine mitigated many of the adverse effects from exposure to multiple stressors. Significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness. Fine motor control (as measured by a marksmanship test) was not adversely affected by caffeine.
  • Lieberman et al. (2002) found that highest effects were found 1 h after administration, but significant effects persisted for 8 h.
  • Lieberman et al. (2002) also reports that 200 mg seemed to be the optimal dose.
  • Smith (2002) states that the beneficial effects of caffeine most obvious in low-arousal situations.

Adverse Effects & Caffeine Withdrawal Syndrome

  • Smith (2002) reports that caffeine consumption, especially near bedtime, can produce feelings of anxiety and may impair sleep
  • Hewlett and Smith (2007) found that there was no effect of overnight caffeine withdrawal on mood or performance
  • Smith (2002) reports that caffeine withdrawal increases negative affect (ie, negative mood or feelings), but that this may reflect expectancy effects; unlikely that this can account for the positive mood effects produced by caffeine when given to non-consumers or to volunteers who have not had caffeine withdrawn
  • Smith (2002) reports that the mechanism of action is that caffeine blocks the effects of the naturally occurring neuromodulator adenosine; result is a net increase in CNS activity because the inhibitory action of adenosine is blocked.
  • Ozsungur et al. (2008) asserts that abrupt cessation of caffeine often results in severe withdrawal symptoms among habitual caffeine consumers. He lists: fatigue and headache (decreased energy/activeness, decreased alertness, drowsiness, confusion, difficulty concentrating), dysphoric mood (confusion, depression, anxiety, nervousness, irritability), and flu-like somatic symptoms (nausea/vomiting/upset stomach, flu-like symptoms, muscle pain, stiffness).
  • Juliano and Griffiths (2004) agree with Ozsungur et al (2008) and further suggest that there is sufficient characterization and evidence to warrant inclusion of caffeine withdrawal as a disorder in the DSM.
  • Some other studies mentioned in passing that taking Advil, or similar over the counter pain medication, could be useful in counteracting withdrawal headaches and muscle stiffness.

So, not particularly conclusive. I researched many more articles than the ones referenced below, but they mainly fell into one of two camps delineated below and were thus redundant. The two “camps” are as follows. One group posits that caffeine has measurable positive cognitive effects, such as increased alertness and shorter reaction times, and that withdrawal symptoms are really due to people’s expectations. The other group argues that the only cognitive benefits of caffeine consumption are reversing the negative effects due to withdrawal, and that the potentially severe withdrawal symptoms make caffeine a poor mental stimulant and ineffective nootropic.

However, I did not find any research suggesting any long-term or serious effects from caffeine consumption, so I figured I would subject it to a battery of field tests. I will experiment with different doses of caffeine (I am rather petite so the 200 mg optimal dose found by the Navy SEALS experiment might overwhelm me), different levels of arousal and sleep deprivation, and will record any negative side effects and potential withdrawal symptoms.


  • The research is not clear about whether caffeine actually produces positive cognitive effects, such as reduced reaction time and increased alertness, or if caffeine consumption merely reverses the effects of withdrawal among chronic users.
  • The research is also not clear about whether Caffeine Withdrawal Syndrome is a real phenomenon tied to physiology and drug metabolism, or if it is merely a result of people’s expectancies.
  • The potential benefits of using caffeine as a mental stimulant and nootropic in times of stress and/or sleep deprivation are high, while the potential for long-term, serious, negative effects are low.


Jarvis, Martin J. “Does Caffeine Intake Enhance Absolute Levels of Cognitive Performance?”Psychopharmacology 110 (1993): 45-52. Web.

Juliano, Laura M., and Roland R. Griffiths. “A Critical Review of Caffeine Withdrawal: Empirical Validation of Symptoms and Signs, Incidence, Severity and Associated Features.”Psychopharmacology 176 (2004): 1-29. Web.

Lieberman, Harris R., William J. Tharion, Barbara Shukitt-Hale, Karen L. Speckman, and Richard Tulley. “Effects of Caffeine, Sleep Loss, and Stress on Cognitive Performance and Mood during U.S. Navy SEAL Training.” Psychopharmacology 164 (2002): 250-61. Web.

Rogers, Peter J., Susan V. Heatherley, Robert C. Hayward, Helen E. Seers, Joanne Hill, and Marian Kane. “Effects of Caffeine and Caffeine Withdrawal on Mood and Cognitive Performance Degraded by Sleep Restriction.” Psychopharmacology 179 (2005): 742-52. Print.

Smith, A. “Effects of Caffeine on Behaviour.” Food and Chemical Toxicology 40 (2002): 1243-255. Web.

This blog is all about bringing personal development towards the scientific method, empirical evidence, and rationality.

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