For some, drug use becomes a way to medicate misery.

Why do some people survive drug and alcohol abuse, while others succumb to addiction? Scientists have only recently begun to find the answer. According to the 2008 National Survey of Drug Use and Health, 46 percent of Americans have tried an illicit drug. But only 8 percent have used one in the past month. By comparison, 51 percent have used alcohol in the past month.

Most people who experiment with drugs, then, do not become addicted. So who is at risk?

Clinicians know that patients with certain types of psychiatric illnesses - including mood, anxiety and personality disorders - are more likely to become addicts. According to the National Institute of Mental Health's Epidemiologic Catchment Area Study, patients with mental health problems are nearly three times as likely to have an addictive disorder as those without.

Conversely, 60 percent of people with a substance abuse disorder also suffer from another form of mental illness. Still, it's unclear whether addict ion predisposes someone to mental illness, or vice versa.

Scientists do know that having a mental illness also significantly raises the risk of dependence and addiction. Theconvent ional wisdom is the link represents a form of "self-medication" - that is, people are medicating theirmisery.

Alcohol and drugs affect mood and behavior by activating the same brain circuits that are disrupted in major psychiatric illnesses. No surprise, then, that depressed and anxious patients turn to alcohol and other sedatives. But these substances are terrible antidepressants that worsen the underlying problem, leading to a downward spiral of depression and addiction.

Certain personality disorders - narcissistic patients or people with borderline personality disorder - also raise the odds of drug and alcohol abuse. But emerging evidence suggests that drug abuse also can be a developmental brain disorder, and that people who become addicted are wired differently from those who do not.

Dr. Nora Volkow, director of the National Institute on Drug Abuse, has shown in several studies that drug addicts have fewer dopamine receptors in the brain's reward pathways than nonaddicts. Dopamine is critical to the experience of pleasure and desire. When she compared the responses of addicts and normal controls who were given a stimulant, she found that controls with high numbers of D2 receptors, a subtype of dopamine receptors, found it aversive, while addicts with low receptor levels found it pleasurable.

This suggests that addicts' brains may have blunted reward systems, and that everyday pleasures don't come close to the powerful reward of drugs. But people are influenced by their environments, too.

The singer Amy Winehouse, 27, whose highly publicized battle with addiction seems to have played a significant role in her death last month, traveled in a world that appears to have been awash in illicit drugs and alcohol.

Even people who aren't wired for addict ion can become dependent on drugs and alcohol with constant exposure, studies have found. Primates that aren't predisposed to addiction will become compulsive cocaine users as D2 receptors decline in their brains, Dr. Volkow noted. And one way to produce such a decline is to place the animals in stressful social situations in which there is ready access to drugs, trumping a low genetic risk of addiction in the animals. It seems humans too, regardless of genetic risk, can become an addict under the right circumstances.

That notion has profound implications for treatment. Long-term drug use usually begins in adolescence, when the brain is the most plastic. In those who are most vulnerable, substance abuse must be confronted early, before it has set the stage for a lifetime of addiction.

Who can experiment uneventfully with drugs and who will be undone by them results from a complex interplay  of genes, environment and psychology. And just plain chance.