Analysis of the behavior of cocaine in the human brain with Positron Emission Tomography reveals that it is not only its affinity for the dopamine transporter that gives it its unique properties but also its fast pharmacokinetics. Its very fast uptake and clearance from the brain contrast with that of methylphenidate, another drug that inhibits the DA transporter. Methylephenidate clears from the brain at a much slower rate and is less addictive than cocaine. We postulate that periodic and frequent stimulation of the dopaminergic system secondary to chronic use of cocaine favors activation of a circuit that involves the orbitofrontal cortex, cingulate gyrus, thalamus and striatum. This circuit is abnormal in cocaine abusers and we postulate that is activation by cocaine perpetuates the compulsive administration of the drug and is perceived by the cocaine abuser as a intense desire resulting in the loss of control over the drive to take more cocaine.