Substance use by adolescents can lead to mortality, physical and social morbidity, and a brain disorder called substance dependence if allowed to progress to chronic, repetitive self-administration. Substance abuse and dependence can begin in adolescence or adulthood, but many of the attitudes and behaviors that affect risk become established during adolescence. Genetic risk factors have been identified for at least two distinct disorders and more are under active study to determine the cause and pathophysiology of addictive disorders. Although much remains to be done, a complex interplay of numerous genetic and environmental risk factors clearly is involved. An understanding of the most important environmental risk factors has led to effective primary prevention approaches; knowledge of the genetic risk factors and neuropharmacology of drugs of abuse in the brain is beginning to influence secondary prevention efforts and treatment, including better medications for addictive disorders. A large proportion of adolescents carry a genetic vulnerability that can be expressed when they accept peer and societal influences that promote experimentation with substances of abuse. At that point, the genetic factors take over, maintaining the drug self-administration pattern. Decay of social status results from association with drug-using peers and shifts in priorities supportive of drug use rather than education and productivity. More research into the genetic risk factors and applications of current knowledge to treatment is needed.

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