Cocaine

Whatever the route of administration, within thirty to sixty minutes, the process of biotransformation and excretion cut in half cocaine’s concentration in the blood-which is one of the reasons its effects are of relatively short duration. However, even before this decline, cocaine’s effects are diminished through other "protective mechanisms". The most important is the rapid distribution of the drug from the bloodstream to the rest of the body, including to sites with no cocaine receptors. Thus, the same activity that delivers cocaine rapidly to active sites in the brain and heart also removes it form these sites, thereby reducing the drug’s effects. At the same time, cocaine’s effects are also diminished through homeostatic mechanisms that reduce neurotransmitter activity at receptor sites- the same mechanisms that operate when factors other than drugs cause an increase in neurotransmitter activity. It it this diminishing of effects-prior even to the decline in the drug’s concentration in the blood-that cocaine users experience as "acute tolerance". That is, to maintain a stable effect over time, users must follow each dose of the drug with a larger subsequent dose. However, acute tolerance also can be viewed as a preexisting protective mechanism because it diminishes cocaine’s potentially harmful effects on the cardiovascular and central nervous system.

Source: Crack in America
Edited by Craig Reinarman and Harry G. Levine