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Pathways of Addiction: Opportunities in Drug Abuse Research
limited its utility in humans. Other researchers, using monoclonal antibody techniques, recently reported the development of an artificial enzyme that inactivates cocaine by cleaving it into two inactive metabolites (Landry et al., 1993). This technique is effective in the test tube, but it must now be demonstrated in nonhumans before it proceeds to human trials; researchers are pursuing this work in conjunction with behavioral researchers experienced in drug self-administration research and medications development (J. Woods, University of Michigan, personal communication, 1995). Further evidence for the promising nature of immunopharmacotherapy is given in a recent report (Carrera et al., 1995) describing suppression of locomotor activity and stereotyped behavior in rats after active immunization with a cocaine immunogen. This response was specific to cocaine and was not seen after amphetamine administration.
Administration of antagonists or immunization against specific drugs, although clearly potentially important tools in our armamentarium against drug use (see discussion on behavioral economics, below), promises no more success than the available opiate antagonist naltrexone 3 for the treatment of heroin addiction. It is very clear that nonhumans, treated with naltrexone, will show extinction in their opiate responding (Koob et al., 1984), and humans, under residential laboratory conditions, also will stop using heroin after treatment with naltrexone (Mello et al., 1981). However, after leaving the structured setting of a residential laboratory individuals relapse to heroin use. Although laboratory studies on naltrexone, with nonhuman and human subjects, demonstrate the utility of the drug self-administration model in the initial assessment of the utility of a new medication, the model does not allow for an evaluation of the contextual (social and environmental) factors that could ultimately affect drugtaking behavior. Thus, there is a need for behavioral models that pattern complex behaviors (e.g., studies that give heroin users the choice of taking naltrexone and explore the range of conditions under which it is taken). Studies focused on compliance are becoming increasingly important because the most efficacious medications are useless if the patient does not take them.
The National Institute on Drug Abuse (NIDA) Medications Development Program relies on drug self-administration and drug discrimination models for its preclinical evaluation of new medications (IOM, 1995; Mello
Naltrexone acts to block or reverse the effects of mu opioids, such as heroin. Patients taking naltrexone cannot feel the effects of heroin if they take it; so heroin's positive reinforcing effects are reduced or eliminated (IOM, 1995). Naltrexone has proven most useful in highly motivated, dependent patients who have a great socioeconomic risk or other risk associated with relapse.