The Legal Stimulants: Nicotine and Caffeine

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It is very easy to dismiss the significance of nicotine and caffeine use.  However, these drugs have a mechanism of action that makes them similar to amphetamines and cocaine.

As discussed elsewhere, the stimulant drugs act primarily by increasing dopamine in the Nucleus Accumbens, the pleasure center of the brain.  In order to do this, they cause dysfunction of the dopamine supplying nerve.  They cause either an inability to re-uptake the dopamine back into the cell or an abnormal release of dopamine out of the cell.  Both of these effects are profound but are located at the end terminals of the nerve.  The resultant increase in dopamine leads to euphoria and eventually, tolerance and withdrawal.

Nicotine works in the same cell but in a different location.  It works where the cell originates.  In that location, there are the nicotinic subtypes of acetyl-choline receptors.  When the nicotine fills these receptors, the nerve is turned on.  Unlike the illegal drugs, the nerve is working normally; it is just shooting off more frequently.   Dopamine is increased and we feel a euphoria.  Unfortunately for most smokers, there is rapid tolerance to the euphoric effect. 

The resulting  increase in dopamine in the Nucleus Accumbens synapses leads to excessive metabolism of the dopamine as well as insensitivity of the dopamine receptors.  It wil also lead  to reduced availability of dopamine because of excessive metabolism.  All this leads to reduced activity or tone of the target nerves.  This, in turn, leads to depression, cravings and behaviors to seek out more of the nicotine.  Unfortunately for the smoker, even though the euphoria is short lived, the withdrawal is more pervasive.

Caffeine has a different mechanism of action.  It does not directly affect the dopamine containing nerve or the dopamine levels in the synapse.  Rather, it works on the nerve receptors that respond to dopamine; it augments that response.  The result is a stimulant effect.

Tolerance develops because use leads to an insensitivity of the target cells to the dopamine that is normally in the synapse.  This in turns leads to withdrawal.

The most important thing to realize is that heavy caffeine usage leads to stimulant effects.  During withdrawal from various substances, patients occasionally complain of tremors, irritability, insomnia among other symptoms.  They tend to disregard their excessive use of coffee, soda,and caffeinated beverages.  But a drug is a drug is a drug.  Caffeine needs to be watched as well. 

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