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Mr V, a 47-year-old man, was recently promoted as a director of a transportation company. A routine inspection of the books shows that a large sum of money is missing. Subsequent investigation finds that Mr V has been spending more than $20,000 a month to buy cocaine; currently he consumes 2–3 g/d. He also drinks several beers each day and 5–8 shots of vodka in the evening. He spends weekend nights in clubs, where he often consumes 2–3 pills of ecstasy. He began using drugs at age 18; during parties he mostly smoked cannabis (5–6 joints per weekend), but also tried cocaine. This “recreational use” came to an abrupt halt when he married at age 27 and entered a professional training program that allowed him to obtain his current job, now jeopardized by his cocaine use. Is Mr V addicted, dependent, or both? What is the reason for the use of several different addictive drugs at the same time?

Drugs are abused (used in ways that are not medically approved) because they cause strong feelings of euphoria or alter perception. However, repetitive exposure induces widespread adaptive changes in the brain. As a consequence, drug use may become compulsive—the hallmark of addiction.



Recent neurobiologic research has led to the conceptual and mechanistic separation of “dependence” and “addiction.” The older term “physical dependence” is now denoted as dependence, whereas “psychological dependence” is more simply called addiction.

Every addictive drug causes its own characteristic spectrum of acute effects, but all have in common that they induce strong feelings of euphoria and reward. With repetitive exposure, addictive drugs induce adaptive changes such as tolerance (ie, escalation of dose to maintain effect). Once the abused drug is no longer available, signs of withdrawal become apparent. A combination of such signs, referred to as the withdrawal syndrome, defines dependence. Dependence is not always a correlate of drug abuse—it can also occur with many classes of nonpsychoactive drugs, eg, sympathomimetic vasoconstrictors and bronchodilators, and organic nitrate vasodilators. Addiction, on the other hand, consists of compulsive, relapsing drug use despite negative consequences, at times triggered by cravings that occur in response to contextual cues (see Box: Animal Models in Addiction Research). Although dependence invariably occurs with chronic exposure, only a small percentage of subjects develop a habit, lose control, and become addicted. For example, very few patients who receive opioids as analgesics desire the drug after withdrawal. And only one person out of six becomes addicted within 10 years of first use of cocaine. Conversely, relapse is very common in addicts after a successful withdrawal when, by definition, they are no longer dependent.


To understand the long-term changes induced by drugs ...

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