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Substance addiction is defined as a chronic relapsing disorder characterized by (1) compulsion to seek and take a substance, (2) loss of control in limiting substance intake, and (3) the emergence of a negative emotional state (e.g. dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the substance is prevented. Importantly, the occasional but limited use of addictive substances is clinically distinct from escalated substance use, loss of control over substance intake, and the emergence of chronic compulsive substance-seeking that characterizes addiction. Importantly, substance addiction (including alcohol) is a manifestation of the long-term pharmacological actions substances have on receptor mechanisms in brain networks that govern cognitive and psychological processes that have evolved for human survival.