Every addiction starts with gratification of some kind. Drugs of abuse work on different neurotransmitter systems in the brain, but they all act directly or indirectly on the brain's reward (mesolimbic) system and on the amygdala, flooding the reward circuit with dopamine and other neurotransmitters. Dopamine, which is associated with emotion, cognition, and feeling of pleasure, rewards natural behaviors, but drugs release 2 to 10 times the amount of dopamine that natural rewards do. Overstimulation of this system produces the euphoric feelings sought by drug users. Repeatedly activating the brain's reward system with supranatural stimuli results in reinforcement and addiction.

However, the brain adjusts to these overwhelming surges of dopamine and other neurotransmitters by producing less of the neurotransmitters, or by reducing the number of receptors that can receive and transmit signals. Drug abusers' ability to experience pleasure without the drug is reduced, and they begin to feel lifeless and depressed. Now they need to take the drug just to bring their dopamine function up to normal, and must take larger and larger quantities of the drug to experience a high. This is known as developing a tolerance.

Using brain imaging studies, scientists have found that food affects the brain's dopamine systems in much the same way as drugs and alcohol. Comparing brain images of methamphetamine users with obese people, scientists found both groups had significantly fewer dopamine receptors than nonaddicted people, an indication of addiction. Moreover, the higher the body mass index, the fewer dopamine receptors were present. This could help to explain why it is so difficult for obese people to lose weight and keep it off: greater amounts of food are necessary for them to obtain gratification.

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