Most drugs affect the brain's "reward circuit" by flooding it with the chemical messenger dopamine. This reward system controls the body's ability to feel pleasure and motivates a person to repeat behaviors needed to thrive, such as eating and spending time with loved ones. This over stimulation of the reward circuit causes the intensely pleasurable "high" that can lead people to take a drug again and again.
As a person continues to use drugs, the brain adjusts to the excess dopamine by making less of it and/or reducing the ability of cells in the reward circuit to respond to it. This reduces the high that the person feels compared to the high they felt when first taking the drug—an effect known as tolerance. They might take more of the drug, trying to achieve the same dopamine high. It can also cause them to get less pleasure from other things they once enjoyed, like food or social activities.
Long-term use also causes changes in other brain chemical systems and circuits as well, affecting functions that include: