Addictive disease disorders are characterized by the chronic use of a drug (such as heroin, cocaine, or amphetamines), alcohol, or similar substance. These disorders usually result in (1) the development of tolerance for the substance, with the need for increasing amounts to achieve the desired effect; (2) physical dependence, characterized by a sequence of well-defined signs and physiological symptoms, such as the withdrawal or abstinence syndrome on cessation of use of the substance; and (3) compulsive drug-seeking behavior, with chronic, regular, or intermittent use, despite possible harm to self or others. Since the early 1960s, research has been increasing in the biology of addictive diseases, and emphasis has shifted from only psychological, sociological, and epidemiological studies to investigations of the metabolic, neurobiological, and molecular bases of addiction.