Drug tolerance is increased resistance to the drug’s effects after continued drug use. Larger doses are needed in order to produce initial drug effects. There are two types of tolerance: metabolic and cellular.
Metabolic (Dispositional) Tolerance happens after repeated administrations of a drug over time. After a person takes a drug over and over, a drug may facilitate the process that produce the drug’s enzyme breakdown in the liver. For example, the speed of the body’s ability to get rid of alcohol increases over an extended period of time if alcohol is taken over and over again over an extended period of time. When the liver breaks down the drug faster than it had at first, a smaller amount of the drug is left available for absorption into the bloodstream, therefore a decrease in the “high”. In the case of alcohol, the alcoholic feels less of the alcohol’s effect and compensates by increasing the amount of alcohol consumed.
In Cellular (pharmacodynamic) Tolerance, the synaptic receptors actually change after repeated administration of the drug. The prolonged effects of the drug transform the cells. Cell receptors that have been overstimulated by a drug compensates by cutting back or reducing receptor sites for the neurotransmitters that a particular drug effects. It is a pruning effect. The Brain will actually cut off the receptor sites for a neurotransmitter like dopamine if there is an overstimulation/supply of it. With less receptor sites for the neurotransmitter, the neurotransmitter has nowhere to go and the person needs more and more of the drug to get “high” as he or she did originally. In fact, it is thought that the drug addict NEVER is able to regain the initial high they once received from the drug and that drug addiction is a drawn out process of chasing after a “high” that will biologically never be achieved again.
The Tolerance Aspect of addiction is a fascinating phenomenon. The brain and the person actually begin to war against each other in a sense. The brain and body does what it can to reduce the effects of overstimulation, while the person seeks the overstimulation. Once the war is begun within a person, it is extremely difficult to stop and addiction develops. This is where psychological dependence comes into play. Despite the body’s attempts at regulating the effects of a drug a person will continue the attempts to deregulate it. The problem is time. The brain responds to overstimulation of a neurotransmitter by reducing the ability of that neurotransmitter to do it’s job, but after the drug wears off, the brain is left starving for that neurotransmitter, so a person begins seeking (on a biological and psychological level) to modulate neurotransmitter levels. The brain begins to war against itself. The only thing that can repair the brain’s former ability to regulate neurotransmitters is TIME. The problem is of course that people who are predisposed to alcoholism and drug addiction seem to have a TIME problem. They are notoriously impatient. So they seek to speed up the process and control their own neurotransmitter levels, but this exacerbates the problem and the decent into chronic addiction begins.