Give Research a Push on Reversing Addiction

Stanley G. Korenman, MD, is a professor of medicine and associate dean for educational development at UCLA School of Medicine.

The war on drugs will not be won in the jungles of Colombia or along the borders of the United States. The drug crisis will come under control when biomedical research can relieve addicts of their compulsive need for a fix.

For the first time in history we possess the tools to understand the behavioral neurochemistry of addiction. Spectacular advances in molecular and cellular biology have made it possible to conceive of reversing the addictive process by restoring the affected brain cells to their pristine state.

Addictions are chronic diseases originating in adolescence and young adulthood. Although the decision to experiment with drugs may have been voluntary, what occurs thereafter, particularly with crack, is a physiological disorder, not a "failure of the will." Susceptibility to addiction is an inherent feature of animals and can be demonstrated in every species tested. For example, in humans, cocaine activates the brain's intrinsic reward system, initially producing an intense sense of pleasure, a high. It also acts as a reinforcer--a form of long-term memory--that creates a neurobehavioral demand for cocaine resulting in "drug-seeking behavior." The reinforcing properties of crack (smokable, quickly absorbed cocaine) are so powerful that a single dose may create an addiction and long drug-free periods will not extinguish the craving.

To scientists, the problem of addiction is analogous to the quesiton of how brain cells undergo long-term modification during learning and how tissues differentiate into their final form during development from the embryo. Molecular and cellular biologists are producing exciting progress in the neurosciences and the regulation of development. While there also have been advances in understanding addiction, the full force of contemporary science had not been applied to this problem. This is because of the persistence of beliefs that substance abuse is a behavioral disorder and that addicts are morally suspect and undeserving, and also because of low funding levels.

There has been no national mandate for biological research on addiction, and, unfortunately, none is proposed.

With 10 years of a well-funded commitment--$200 million annually--we could elucidate the detailed mechanisms underlying each of the principal addictions. Practical therapeutic results would come even sooner if sufficient funds were appropriated to examine promising approaches.

We are not starting from scratch. There are good animal models of addiction to study. The reward center has been identified in many species, as have many of the neurotransmitters and nerve pathways involved in addictive behavior. Chemical tools that mimic or inhibit various effects of neurotransmitters and addicting agents are available for experimentation. Research results on one substance of abuse may apply to others because of similarities of central nervous system responses among them.

Three groups of researchers have proposed promising candidates for inhibitors of drug-seeking behavior, including the anti-epileptic carbamazepine, the tranquilizer desipramine and the angalgesic buprenorphine. Others will follow.

New therapies require expensive clinical trials to validate their safety and efficacy. Large groups of patients eager to break their habit would be willing to participate, but pharmaceutical companies will not undertake clinical trials unless they foresee a large market for the developed product. Thus, a government commitment to pay for therapy would unleash a massive commercial development effort.

What must be done? Substantial new government funds should be appropriated for fundamental research on addiction, and outstanding scientists must be induced to participate in this effort. Additional applied reserach funds should be appropriated to permit large-scale clinical trials of promising addiction-reversing agents.

There is a great need for a private, nonprofit foundation for the biological study of addiction, to engage public interest and enthusiasm, supplement government funding, provide educational materials and lobby Congress for support.

Addiction reversal offers perhaps the best and most cost-effective approach to the epidemic of substance abuse. If successful, the hooked would regain the opportunity to live a fruitful life, and substance-abuse therapy would enter the medical mainstream and be widely available. As the market of substance abusers declined, so would the profitability of trading in drugs. Ultimately, society would be spared the vast expenditures for interdiction, law enforcement and health care.

In responding to the epidemic of crack we should lead from our strengths rather than those of the cocaine cartels. The laboratory must be a principal battleground for a successful war on drugs.

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