Although many physicians are concerned about "creating addicts," relatively few individuals begin their drug addiction problems by misuse of prescription drugs. Confusion exists because the correct use of prescribed medications for pain, anxiety, and even hypertension commonly produces tolerance and physical dependence. These are normal physiological adaptations to repeated use of drugs from many different categories. Tolerance and physical dependence are explained in more detail later, but it must be emphasized that they do not imply abuse or addiction. This distinction 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 abruptly.
DEFINITIONS While tolerance and physical dependence are biological phenomena that can be defined precisely in the laboratory and diagnosed accurately in the clinic, there is an arbitrary aspect to the definitions of the overall behavioral syndromes of abuse and addiction. The most influential system of diagnosis for mental disorders is that published by the American Psychiatric Association (APA). The APA diagnostic system uses the term substance dependence instead of "addiction" for the overall behavioral syndrome. It also applies the same general criteria to all types of drugs regardless of their pharmacological class. Although accepted widely, this terminology can lead to confusion between physical dependence and psychological dependence. The term addiction, when used here, refers to compulsive drug use, the entire substance-dependence syndrome. This should not be confused with physical dependence alone. Addiction is not used as a pejorative term but rather for clarity of communication.
The APA defines substance dependence (addiction) as a cluster of symptoms indicating that the individual continues use of the substance despite significant substance-related problems. Evidence of tolerance and withdrawal symptoms are included in the list of symptoms, but neither tolerance nor withdrawal is necessary or sufficient for a diagnosis of substance dependence. Dependence (addiction) requires three or more of the symptoms, whereas abuse can be diagnosed when only one or two symptoms are present. The chronic, relapsing nature of dependence (addiction) fulfills criteria for a chronic disease, but because of the voluntary component at initiation, the disease concept is controversial.
ORIGINS OF SUBSTANCE DEPENDENCE Many variables operate simultaneously to influence the likelihood that a given person will become a drug abuser or an addict. These variables can be organized into three categories: agent (drug), host (user), and environment (Table 23-1).
Agent (Drug) Variables Drugs that reliably produce intensely pleasant feelings (euphoria) are more likely to be taken repeatedly. Reinforcement refers to the capacity of drugs to produce effects that make the user wish to take them again. The more strongly reinforcing a drug is, the greater is the likelihood that the drug will be abused.
Reinforcing properties of drugs are associated with their capacity to increase neuronal activity in critical brain areas (see Chapter 12). Cocaine, amphetamine, ethanol, opioids, cannabinoids, and nicotine all reliably increase extracellular fluid dopamine (DA) levels in the ventral striatum, specifically the nucleus accumbens region.
In contrast, drugs that block DA receptors generally produce bad feelings, i.e., dysphoric effects. Despite strong correlative findings, a causal relationship between DA and euphoria/dysphoria has not been established.
The abuse liability of a drug is enhanced by rapidity of onset because effects that occur soon after administration are more likely to initiate the chain of events that leads to loss of control over drug taking. The history of cocaine use illustrates the changes in abuse liability of the same compound, depending on the form and the route of administration (e.g., "crack" cocaine).
Although the drug variables are important, they do not fully explain the development of abuse and addiction. Most people who experiment with drugs that have a high risk of producing addiction (addiction liability) do not intensify their drug use and lose control. The risk for developing addiction among those who try nicotine is about twice that for those who try cocaine (Table 23-2), but this does not imply that the pharmacological addiction liability of nicotine is twice that of cocaine. Rather, there are other variables listed in the categories of host factors and environmental conditions that influence the development of addiction.
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