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How Does ADHD Medication Work? Stimulants are the first treatment option for ADHD. They aid in regulating the levels of two brain chemical substances (neurotransmitters) that transmit messages between neurons to improve attention and decrease hyperactivity. However, up to 20 percent of people don't respond to the most frequently prescribed stimulants, methylphenidate and amphetamine. This could be due to the body's chemistry of the person or other medications that they are taking. What