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The terminology used in discussing drug dependence, abuse, and addiction has long been confusing. Confusion stems from the fact that repeated use of certain prescribed medications can produce neuroplastic changes resulting in 2 distinctly abnormal states. The first is dependence, or "physical" dependence, produced when there is progressive pharmacological adaptation to the drug resulting in tolerance. In the tolerant state, repeating the same dose of drug produces a smaller effect. If the drug is abruptly stopped, a withdrawal syndrome ensues in which the adaptive responses are now unopposed by the drug. The appearance of withdrawal symptoms is the cardinal sign of "physical" dependence. Addiction, the second abnormal state produced by repeated drug use, occurs in only a minority of those who initiate drug use; addiction leads progressively to compulsive, out-of-control drug use.

Addiction can be defined fundamentally as a form of maladaptive memory. It begins with the administration of substances (e.g., cocaine) or behaviors (e.g., the thrill of gambling) that directly and intensely activate brain reward circuits. Activation of these circuits motivates normal behavior and most humans simply enjoy the experience without being compelled to repeat it. For some (~16% of those who try cocaine) the experience produces strong conditioned associations to environmental cues that signal the availability of the drug or the behavior. The individual becomes drawn into compulsive repetition of the experience focusing on the immediate pleasure despite negative long-term consequences and neglect of important social responsibilities. The distinction between dependence and addiction is important because patients with pain sometimes are deprived of adequate opioid medication simply because they have shown evidence of tolerance or they exhibit withdrawal symptoms if the analgesic medication is stopped or reduced abruptly.


Most of those who initiate drug use do not progress to become addicts. Many variables operate simultaneously to influence the likelihood that a beginning drug user will lose control and develop an addiction. These variables can be organized into 3 categories: agent (drug), host (user), and environment (Table 24–1).

Table 24–1Multiple Simultaneous Variables Affecting Onset and Continuation of Drug Abuse and Addiction

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