Cognitive plants 23. Methylxanthine caffeine is one of

enhancing substance


The substances or
medications that enhance cognitive processes such as thought, perception and
memory are termed as cognitive enhancing substances 16. Bostrom and
Sandberg 17 defined cognitive enhancement as “the amplification or
extension of core capacities of the mind through improvement or augmentation of
internal or external information processing system.” Some of the cognitive
enhancing substances are the prescription stimulants and other stimulants such
as caffeine and nicotine. Stimulants have been used for a long time to improve
attention or memory and to improve productivity 17. Nowadays, these
stimulants are gaining popularity amongst students to sharpen their memory,
concentration and are often taken before examinations 18.




Stimulants are a
group of drugs that act on the central nervous system and excite body function,
behavior and cognition. These drugs tend to stimulate alertness, elevated mood,
wakefulness, increased speech and motor activity and decrease appetite. They act
either as an agonist or an antagonist. As agonists, these substances aid
physiologic activities by increasing or decreasing the effectiveness or
production of hormones or neurotransmitters. As an antagonists, they bind to
cell receptors and block the action of drug or physiological activities by
inhibiting the uptake of neurotransmitters 21.

They are also known as
psychostimulants 22. Stimulants enhance attention and memory by
increasing neuronal activation or by releasing neuromodulators which cause synaptic
changes and stimulation of cholinergic systems 17. Among the most
common stimulants are modafinil, methylphenidate, amphetamine, dexamphetamine
and caffeine.





is a naturally occurring alkaloid found in more than 60 plants 23.
Methylxanthine caffeine is one of the most widely consumed stimulants in the
world. It is a mild central nervous system stimulant, a vasodilator, and a
diuretic 22. Caffeine is present in wide range of dietary products
such as coffee, tea, coca, candy bars, soft drinks and energy drinks. In
addition, a number of prescription and over-the-counter drugs (OTCs), which are
used for headache, cold, allergy, and pain relief and alerting drugs, are often
combined with caffeine. Some examples of these drugs are as follows: No-Doz,
No-Doz Plus and Cafergot 24, 25.


Pharmacokinetics of

oral ingestion, caffeine is rapidly and almost completely absorbed from the
gastrointestinal tract and reaches peak plasma concentrations in about 30-60
mins after consumption. The volume of distribution is 0.6L/Kg and 36% is
protein bound. It passes through the blood brain barrier and all biological
membranes. It is metabolized in the liver by the cytochrome P450 (CYP) system
to dimethylxanthine stimulants theobromine and theophylline. The elimination
half-life is 4.5 hours in healthy nonsmoking adults.


Mechanism of action

A1 and A2A receptors are present in the basal ganglia. Basal ganglia are a
group of structures which help in various motor controls. As shown in Table 1,
adenosine A1 receptors are present in all brain areas whereas A2A receptors are
found more in the dopamine rich regions of the brain. There is evidence that
A2A receptors interact with the dopamine system, which is involved in reward
and arousal effects 27.


Caffeine acts as an antagonist to both types
of the receptors. The overall psychostimulant properties of caffeine in brain
are mediated by its ability to interact with neurotransmission in different
regions of the brain. It has been indicated that caffeine particularly affects
a group of projection neurons located in the striatum, which is the main
receiving area of the basal ganglia 29. Thus, caffeine blocks the
inhibitory neurotransmitter adenosine, inhibits phosphodiesterase and increases
intracellular cyclic adenosine monophosphate (cAMP) 28. At low
concentration, it blocks adenosine receptors however, at higher concentration,
it is found to inhibit phosphodiesterase and calcium mobilization 27.