Use of cocaine, like other drugs of abuse, induces long-term changes in the brain. Animal studies show that cocaine exposure can cause significant neuroadaptations in neurons that release the excitatory neurotransmitter glutamate.^9,10 Animals chronically exposed to cocaine demonstrate profound changes in glutamate neurotransmission—including how much is released and the level of receptor proteins—in the reward pathway, particularly the nucleus accumbens. The glutamate system may be an opportune target for anti-addiction medication development, with the goal of reversing the cocaine-induced neuroadaptations that contribute to the drive to use the drug. Although addiction researchers have focused on adaptations in the brain’s reward system, drugs also affect the brain pathways that respond to stress. Stress can contribute to cocaine relapse, and cocaine use disorders frequently co-occur with stress-related disorders.