Background Subsequent to initial exposure to the use of a psychoactive substance, psychoactive substance use disorder (PSUD;) may or may not develop. Aims To investigate the relationship between the risk factors for initiation and the subsequent misuse of psychoactive substances. Method The lifetime history of illicit substance use and misuse was obtained by telephone interview with 1934 members of female-female twin pairs. We apply a novel model, which estimates the role of genetic and environmental risk factors that influence initiation and those specific to misuse, to three classes of illicit psychoactive substances. Results The individual-specific environment and family environment influenced the probability of initiation, but only individual-specific environment had an impact on the probability of subsequent misuse. Genetic factors which influence the risk of initiation and of misuse were identified. Conclusions Aetiological factors that influence drug initiation and subsequent misuse are correlated but not identical. Family environment is an important determinant of risk fdr drug experimentation. Two classes of genetic risk factors act on the liability to PSUD: those that influence the probability of initiation and those that influence the risk of misuse. Declaration of interest Supported by the US National Institutes of Drug Abuse and Mental Health.
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