Drugs of abuse act on the brain’s neurotransmitters, the chemical messengers that coordinate interactions between neurons (brain cells). Because of the direct effect of substances of abuse on neurotransmitters, there is often a dramatic change in neurotransmitter function. For example, in response to foreign chemicals that mimic the activity of neurotransmitters, the neurons may decrease production of their own neurotransmitters. Receptor sites may die off. This change of the actual structure of the neurons contributes to the addictive process. When the brain makes less neurotransmitter or is less able to process it, craving sets in. Drug tolerance, the need for more and more of the same drug to achieve the same psychological effect, is also related to the changes in the neuron’s structure. Moreover, changes to the neurons can lead to a reduction in brain volume, in other words, brain shrinkage. This is associated with cognitive, emotional, and physiological deterioration.