which when smoked, produces volatilized pure drug exposed to the lungs' massive surface area) is far more quickly addictive than powdered cocaine hydrochloride absorbed via the nasal mucosa, which is, in turn, far more quickly addictive than chewed coca leaves, where the cocaine is absorbed more slowly from the mouth and gastrointestinal tract (and partially destroyed by digestive enzymes) (Wilkinson et al., 1980). The form in which a drug is used, however, may also create barriers to use. For example, smoking is not initially natural and may cause coughing and other discomfort. Thus a certain amount of social pressure or support for smoking is needed to get young people over this initial barrier before they find tobacco smoking pleasurable and put themselves at risk for addiction. Taking alcohol or other drugs orally in liquid or tablet form does not present this type of barrier, so initial use may be easier to achieve.

People report that they take drugs to gain pleasure, to produce alterations in consciousness, to conform to the behavior of their peers, and to relieve stress and other negative emotions. However, the fact that certain drugs produce subjective euphoria or relieve dysphoria in humans and are reinforcing in animal models does not necessarily mean that they will produce addiction (i.e., inability to control use despite serious negative consequences; see Chapter 1). Indeed, over time, the addicted person's enjoyment of drug-taking is decreased because tolerance develops or medical complications ensue. Despite diminished enjoyment, the life of the addicted person revolves around the obtaining, using, and recovering from the effects of the drug despite problems at home and work and failure in life roles. The effects of the drug and circumstances of use are somehow so important that the addicted individual may go to great lengths to deny that its use is causing any difficulty. The denial, manipulation, and dishonesty that the addicted person frequently exhibits in the service of ongoing drug use may frustrate and anger family members, colleagues, and caregivers.

A key point in our current understanding of the neurobiology of drug abuse is that there is good evidence that use of a drug at an adequate dose with adequate frequency and chronicity produces long-lived changes in brain functioning. Many of these changes represent compensatory adaptations (homeostatic responses) to excessive bombardment by the drug. It is these drug-induced changes in brain function that produce addiction in some individuals.

The types of long-term changes that addictive drugs produce in the brain now can be divided conceptually into three categories. First, opioids and ethyl alcohol, but not cocaine, produce compensatory adaptations in brain regions that control somatic functions, thus producing physical dependence. As a result, discontinuation of opioids or alcohol can produce a physical withdrawal syndrome, such as the well-known alcohol withdrawal syndrome that includes hypertension, rapid heartbeat, tremor, nystagmus, insomnia, and grand mal seizures (O'Brien, 1996).

Second, all addictive drugs appear to produce adaptations within the brain reward circuitry itself. These are quite complex and far from fully understood. A subset of these adaptations contributes to tolerance, decreasing some of the reinforcing

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