SECOND KEY QUESTION: Since withdrawal discomfort is now readily controlled with various medications, so that an addict can be brought without difficulty to an abstinent state, why doesn’t that solve the problem? Why is relapse so common? Is it because of innate deficiencies in the reward pathway, or because chronic exposure to an opiate has caused irreversible changes? In either case, there may be addicts who can not function normally on their own supply of endorphins but require some opiate (like methadone) to occupy the receptors.

We need to know what triggers relapse in an abstinent ex-addict. Relapse is preceded by craving — an irresistible urge to use, often provoked by an environmental cue related to previous use. A cue such as the sight of injection paraphernalia or of a place to buy heroin on the street can not only evoke craving, but can cause measurable physiologic changes like altered pulse, blood pressure, and galvanic skin responses.

A recent study, by researchers at the National Institute on Drug Abuse, concerns craving for cocaine in former cocaine abusers. The method was PET scan, an imaging procedure that shows which areas in the living human brain are activated by certain stimuli. There are two groups of subjects — people who had never used cocaine, and people who had been cocaine abusers in the past but had not used any in recent months. Two kinds of cue were presented on video tape — a neutral one (such as a pastoral scene), and a cocaine-related one (such as injection equipment). Subjects who had never used cocaine showed no unusual brain activity when exposed to either kind of cue. Subjects who had abused cocaine in the past were not affected at all by a neutral cue; but they responded very differently to a cocaine-related cue. Intense craving was provoked, and specific brain areas lit up on the PET scan — areas in parts of the brain (frontal cortex and amygdala) that are known to be associated with emotional memories and craving.

I tell you about this experiment because it shows clearly that in the subjects with previous heavy exposure to cocaine, certain brain regions had been altered by the chronic use of the addictive drug. And it also shows which brain areas are specifically involved in the craving that leads to relapse. Most important for us, it points the way to future similar research with heroin addicts, using brain imaging techniques — an exciting prospect that was only a dream just a few years ago.

Neurobiology of Heroin Addiction and of Methadone Treatment
By: Avram Goldstein, M.D.
Professor Emeritus of Pharmacology, Stanford University

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