Drugs force the brain to destroy its own joy receivers.

When you take drugs, they release a massive flood of dopamine, the chemical that makes us feel happy. It is like turning a radio up to maximum volume. To save its speakers, the brain shuts down some of its dopamine receivers. Scientists call this downregulation. Because the brain has fewer receivers, normal life begins to feel gray and dull. The user now needs the drug just to bring their dopamine levels back up to what used to be normal. Without the drug, they feel empty and sad.