You could imagine that certain unlucky genes create a set point in adaptive systems, set the thermostat in your brain so that you are more susceptible to the effects of certain drugs. We would like to know, because it might really help with both prevention and treatment efforts. The environment in which you grow up. That can be both good or bad. It can give you the strength to avoid drugs but it also may mean, when somebody becomes newly independent and has no real experience they literally go crazy.
Psychiatric illnesses are a predisposing factor.
When people get depressed or have other psychiatric illnesses, such as certain anxiety disorders, they may be predisposed to take drugs initially in a misguided attempt to self-medicate to feel better. Then they get caught. Chronic pain may actually be a predisposing factor. But also there is no doubt that social context really counts. A very dramatic example of the importance of social context is the Vietnam experience.