IS THERE A DEFICIENT BRAIN CHEMISTRY IN ADDICTS?

IS THERE A DEFICIENT BRAIN CHEMISTRY IN ADDICTS?

If everyone with a brain can become an addict, why are there (relatively) so few addicts? Could there be a unique group of people whose pleasure circuits are abnormal in some way so that these drugs feel particularly good? Or could there be a group of people whose pleasure circuits don't work very well, so that they are inclined to drink alcohol, smoke, or take cocaine to feel normal? There are probably people in each of these catego­ries. In studying these questions in human addicts, there is a real "chicken and egg" problem. If brain function is abnormal, it is impossible to know whether the abnormality was caused by years of substance abuse or was present before. This is one challenge about the aforementioned dopamine receptor finding. Some scientists have tried to solve this problem by studying the children of alcoholics. There are certain EEG (brain wave) changes that have been noted in some alcoholics and in their sons. How­ever, we don't really understand the significance of this EEG anomaly yet. The only way to be sure is to study these children until they become adults to see if this difference predicted alcoholism. Such studies are underway, but they take a long time. We can do these experiments in animals, and we have found that even with free access to cocaine, only a certain per­centage of animals (about a fifth) progress to the stage of compulsive use. Are these differences due to a deficient gene that could simply be repaired? The mapping of the human genome has really speeded up the search for genes related to addiction as well as other diseases. Many candi­dates have been identified. Some are specific to specific addictions. A vari­ant of one gene for the receptor through which ethanol acts is associated with alcoholism, and a variant for a receptor that narcotics act upon is associated with narcotic addiction. Others, like the dopamine D2 receptor, are related to all addictions. Others have been surprises. One of the best

genetic "predictors' of nicotine dependence is a gene that controls the breakdown of nicotine in the liver—not anything related to brain function at all. Finally, there are genes that seem to protect people from addictions.

Two genes involved in alcohol degradation fit into this category (see the

chapter on alcohol). So, as many scientists predicted, drug addiction is a complicated disorder that can involve many genes. Can we fix the affected genes? Not yet. Do we want to? Because most or these genes affect normal brain activities, we are not even vaguely close to knowing if changing them would treat addiction without causing other troubles. And even if we

could, the ethical questions raised by such manipulations are huge. Finally, it is important to realize that biology is not destiny. People are more than bags of genes that produce behavior. They are influenced bytheir environment and can control their behavior voluntarily. Simply possessing a particular gene that has been found in the brains of some alco‑ holics does not mean that an individual must become an alcoholic. If he or she abstains from alcohol, for one thing, there will never be a problem.

Maybe these slightly abnormal genes provide some benefit to the person that we don't fully understand. On the other hand, people with no genetic predisposition may experience such traumatic life circumstances (being sexually abused during childhood, for example) that they develop com­pulsive use of alcohol or other substances in an attempt to self-medicate their psychological trauma. The bottom line is that everyone with a brain can become an addict. Given the diversity of human brains, it is likely that some people will find the experience more compelling than others, but we have not really defined exactly what brain chemistry leads to this vulnerability yet.