These brain scans highlight dopamine receptors, with areas of highest density shown in red. The meth abuser has severely reduced receptor levels. Other drugs, including alcohol, cocaine, and heroin, have the same effect. Images courtesy Dr. Nora Volkow, Brookhaven National Laboratory.

Drugs of abuse affect the brain much more dramatically than natural rewards, such as food and social interactions. To bring stimulation down to a more manageable level, the brain must try to adapt.

One way the brain compensates is to reduce the number of dopamine receptors at the synapse. In addition, sending neurons increase their number of dopamine transporters, more quickly clearing dopamine from the synapse. These changes make the brain less responsive to the drug, but they also decrease the brain’s response to natural rewards.

Because of these changes, after the user has "come down," they will need more of the drug next time they want to get high. This response is commonly referred to as "tolerance.”