Harvard Mental Health Letter | July 2004

Neuroscientific research reveals new ways of understanding drug and alcohol dependence. Drug addiction has been a stubborn problem for thousands of years, but only in the last genera- tion have scientists come to understand one of the reasons: It causes lasting changes in brain function that are difficult to reverse. That means many altered brains - nearly 2 million heroin and cocaine addicts, perhaps 15 million alcoholics, and tens of millions of cigarette smokers in the United States alone.

Why does the brain prefer opium to broccoli? Steven Hyman, a former director of the National Institute of Mental Health, has put the question of addiction that way. The answer involves the nucleus accumbnens, a cluster of nerve cells that lies beneath the cerebral hemispheres. When a human being or other animal performs an action that satisfies a need or fulfills a desire, the neurotransmitter dopamine is released into the nucleus accumbens and produces pleasure. It serves as a signal that the action promotes survival or reproduction, directly or indirectly. This system is called the reward pathway. When we do something that provides this reward, the brain records the experience and we are likely to do it again. Damage to the nucleus accumbens and drugs that block dopamine release in the region make everything less rewarding.

Addictive drugs provide a shortcut. Each in its own way sets in motion a biological process that results in flooding the nucleus accumbens with dopamine. In a person who becomes addicted through repeated use of a drug, overwhelmed receptor cells call for a shutdown. The natural capacity to produce dopamine in the reward system is reduced, dopamine in the reward system is reduced, while the need persists and the drug seems to be the only way to fulfill it. They are victims of conditioned learning, which creates habitual responses.

Drug-induced changes in the links between the brain cells establish associations between the drug experience and the circumstances in which it occurs. These implicit memories can be retrieved when addicts are exposed to any reminder of those circumstances - moods, situations, people, places or the substance itself.

Any addict may resume the habit on falling into a mood in which he used to turn to the drug. A single small dose of the drug itself is one of the most powerful reminders - "It's the first drink that gets you drunk," as they say in Alcoholics Anonymous.

Internal or external stress is another cause of relapse. In the last few years, research has suggested that addiction involves many of the same brain pathways that govern learning and memory. Addiction alters the strength of connections at the synapses (junctions) of nerve cells, especially those that use the excitatory neurotransmitter glutamate. Underlying these changes are drug- induced activation and suppression of genes within nerve cells, another process scientists are beginning to explore.

For those who will accept it (usually patients who find that their worries are irrational but compelling), a treatment based on cognitive behavioral methods may be effective.