Abuse and Dependence

addiction is a complex phenomenon with important psychological and social causes and consequences. However, at its core, it involves a biological process: the effects of repeated exposure to a biological agent (a substance) on a biological substrate (the brain) over time (Nestler and Aghajanian, 1997).

Ultimately, adaptations that substance exposure elicits in individual neurons alter the functioning of those neurons, which in turn alters the functioning of the neural circuits in which those neurons operate. This eventually leads to the complex behaviors (e.g., dependence, tolerance, sensitization, craving) that characterize addiction (Koob, 1992; Kreek, 1996; Wise, 1996; Koob and LeMoal, 1997).

A general definition of substance abuse is the habitual use of a substance not needed for therapeutic purposes, such as solely to alter one's mood, affect, or state of consciousness. The continued abuse of the substance may lead to adverse physiological, behavioral, and social consequences. A substance-dependent individual will continue his use despite these adverse consequences. Moderate chronic use or severe short-term use of substances may lead to abuse, which may eventually lead to addiction components (Ellinwood, 1974; Hall et al., 1988; Kramer, 1969).

Chronic substance abuse results in a complex set of physiological and neurological adaptations. These adaptations are simply the body's attempt to adjust to or compensate for substance-induced impairments. Repeated exposure to a substance can also lead to adaptations in the reward circuitry that opposes and/or neutralizes a substance's effects (i.e., counteradaptation).

Substance addiction (or substance dependence) is manifested by (1) psychological craving (see the following section); (2) tolerance (the need for increasing amounts of the substance to reproduce the initial level of response, or sometimes to simply stave off the unpleasant effects of withdrawal); (3) sensitization (discussed in the section on the medical effects of stimulants); and (4) symptoms of withdrawal upon cessation of use, indicating physiological dependence.

Social and behavioral manifestations of dependence include the reduced ability to function at work or home and may include displays of erratic, moody, or anxious behavior.

Similar to other substances of abuse, moderate chronic use or severe short-term use of stimulants in any form may lead to abuse or dependence (Ellinwood, 1974; Hall et al., 1988; Kramer, 1969).

Clinical observations of abuse patterns for both cocaine and MA have noted that, in general, there is an estimated 2- to 5-year latency period between first use and full-blown addiction. However, clinical experience and anecdotal evidence suggest that the latency period may be shortened to less than 1 year by rapid routes of administration (e.g., injection, smoking) and increased stimulant purity (e.g., ice, crack).

With increasing use, the user may develop tolerance to the effects of stimulants and may need to keep increasing the amount taken to produce the desired psychological effects. As chronic abuse progresses, users prefer the stimulant over enjoyable activities and eventually may prefer it over food and sex (Hall et al., 1988). At that point, the individual will usually continue her use even when faced with continuing adverse consequences--the hallmark of substance dependence.

Abrupt discontinuation of the psychoactive substance following chronic use generally results in discomfort, dysphoria, and behaviors consistent with craving. The user is now motivated to use a substance in order to avoid discomfort and dysphoria.

This shift from substance use as positive reinforcement to negative reinforcement is, perhaps, one of the foremost characteristics of late-stage addiction.

Drug Craving and Memory

The degree to which learning and memory sustain the addictive process has only recently been addressed. Researchers believe that each time a neurotransmitter like dopamine floods across a synapse, circuits that trigger thoughts and memories and that motivate action become hardwired in the brain. The neurochemistry supporting addiction is so powerful that people, objects, and places associated with substance use are also imprinted on the brain.

Craving, a central aspect of addiction, is a very strong learned response with powerful motivational properties often associated with specific memories (i.e., conditioned cues and triggers).

Cues--any stimuli (substance-using friends, locations, paraphernalia, moods) repeatedly paired with substance use over the course of a client's addiction--can become so strongly associated with the substance's effects that the associated (conditioned) stimuli can later trigger arousal and an intense desire for the substance and lead to relapse.

High relapse rates are common in cocaine addiction even after physical withdrawal and abstinence have been achieved.

Brain-imaging studies have shown that cue-induced drug craving may be linked to distinct brain systems involved in memory (e.g., London et al., 1990; Stapleton et al., 1995). Brain structures involved in memory and learning, including the dorsolateral prefrontal cortex, amygdala, and cerebellum, have been linked to cue-induced craving (Grant et al., 1995).

A network of these brain regions integrates emotional and cognitive aspects of memory and triggers craving when it reacts to cues and memories. These cues and memories also play an important role in reinforcing substance use (Grant et al., 1995).

Most substance treatment programs recognize the power of these factors in triggering relapse and warn clients to avoid everything previously associated with their substance use--a tall order for a client in an urban environment saturated with the substance and its associated reminders.

Treatment approaches that address these learning and memory issues of addiction may prove effective. For example, Childress developed treatment strategies to help clients reduce craving and arousal during encounters with substance-related stimuli (Childress, 1994). In the laboratory, clients are given repeated, passive exposure to substance-reminding cues in a substance-free protected environment.

The research finds that initial arousal and strong craving produced by the cues eventually decrease (Childress, 1994). Better understanding of the relationship of learning and memory to the addiction process may lead to new treatment approaches.

Role of New Technologies

The recent development of noninvasive brain imaging has created a powerful new tool for demonstrating not only the short-term effects of substance use, but also the longer term consequences of chronic substance abuse and addiction.

These tools have allowed researchers to boldly go where they previously could not--literally into the depths of a living human brain. Such noninvasive techniques can depict normal and abnormal functioning of different brain areas by measuring metabolic activity (i.e., glucose utilization). They can identify substance-induced structural changes and physiological adaptations.

Through a combination of techniques, they can observe the altered "processing" of information in various circuits as the brain responds to substance use.

Using these techniques, investigators have been able to identify brain structures involved in craving, map the emotions of substance users, plot the neurobiological basis of substance-induced euphoria, and more.

For example, researchers have used magnetic resonance imaging (MRI) and spectroscopy to see how brain structures change as substances produce their effects. Others have used a functional imaging technique called phosphorus magnetic resonance spectroscopy (31P MRS) to show that chronic substance abuse is accompanied by abnormal metabolism in some areas of the brain that seems to return to normal when people stop using substances (Christensen et al., 1996).

Positron emission tomography (PET) has revealed subtle alterations in the dopamine receptors of stimulant users' brains (Iyo et al., 1993). More recent PET studies have demonstrated long-term vulnerability to chronic stimulant abuse (Melega et al., 1997a; Volkow et al., 1996, 1997b).

Another PET study has established a dose-response relationship between cocaine and the drug's subjective effects: The greater the amount of cocaine that is administered, the greater the high experienced by the user (Volkow et al., 1997a).

Other researchers combined electroencephalograms (EEGs) and MRI to produce a topographic brain map showing increased electrical activity (in the form of beta waves) during stimulant withdrawal (Herning et al., 1997). Mapping EEG activity during stimulant use and withdrawal may allow researchers to further document substance-induced neuropsychological impairments.

Although much is known about the effects of stimulants in animals, there is little such knowledge of these effects in humans (CSAT, 1997). The continuing development and application of new technologies such as noninvasive brain imaging will allow researchers to improve their understanding of how stimulants affect the human brain. Greater understanding of the underlying neuronal impairments of stimulant abuse will aid in the development of new, more effective treatment approaches.

General Effects Of Stimulants

Substances of abuse--and stimulants in particular--appear to increase the brain's levels of free dopamine in a dose-dependent manner; that is, more dopamine is available when higher doses of the substance are administered (Nash, 1997). The higher the substance dose, the greater the feelings of elation, euphoria, and satisfaction, and as the dopamine levels and pleasurable feeling subside, there is an intense desire to replicate the feelings of pleasure by administering another dose of the substance.

This tendency toward repeated administration is characteristic of stimulant abuse and underlies most of the other effects of stimulants, as well as most other addictive substances.

Continued use often leads to adverse consequences, which may include neuropsychological impairment and diminished physical health. Work performance and social and family relations can be adversely affected, and the risk of arrest and conviction on drug-related charges increases.

Even after a stimulant user discontinues use, impairments in cognition and functioning may persist, and there may even be persistent psychiatric symptoms (Wada and Fukui, 1990). Cravings for the stimulant's effects tend to linger, even after abstinence has been achieved, and the potential for relapse is high.