Chapter 24

### INTRODUCTION

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 two distinctly abnormal states. The first is dependence, sometimes called "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. Thus, withdrawal symptoms are opposite to the original drug effects. The appearance of withdrawal symptoms is the cardinal sign of "physical" dependence. As thus defined, dependence can occur with the use of opioids, β blockers, antidepressants, benzodiazepines, and stimulants, even when these agents are used as prescribed for therapeutic purposes. The state of "physical" dependence is a normal response, easily treatable by tapering the drug dose, and is not in itself a sign of addiction.

The second abnormal state that can be produced by repeated drug use occurs in only a minority of those who initiate drug use. It leads progressively to compulsive, out-of-control drug use. Unfortunately, in 1987 the American Psychiatric Association (APA) chose to use the word "dependence" when defining the state of uncontrolled drug use more commonly known as addiction. The word "addiction" was at that time considered pejorative and thus to be avoided. The result, over the last two decades, is that confusion has developed between dependence as a normal response and dependence as addiction. The newest version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) due to be released in 2012 will correct this confusion.

This 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.

Modern neuroscience has greatly increased our understanding of the phenomenology of addiction. Using animal models as well as human brain imaging studies and clinical observations, 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. Thus, reflexive activation of reward circuits becomes involuntary and with a very rapid onset. The cues acquire strong salience that overwhelms other behaviors. 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. Of course, ...

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