An alarming 440,000 deaths in the U.S. were attributed to tobacco smoking in 2000 with tobacco consumption persisting as the single most avoidable correlate of cancer-related mortality worldwide. More than half of adolescents in the 12th grade who smoke cigarettes report past month use of cannabis, the most widely used illicit psychoactive substance in the U.S. These tobacco smokers who also use cannabis are more likely to develop nicotine dependence and report greater inability to quit smoking tobacco, thereby making the association between cannabis use and tobacco smoking a serious public health problem that has received insufficient attention. This new investigator R01 proposes to examine the relationship between cannabis use and tobacco smoking, both their lifetime association and their concurrent use, by performing secondary data analyses utilizing resources from three independent data sets of adolescent and adult twin pairs from the U.S. and Australia. The Principal Investigator requests support to perform complex genetic epidemiological analyses that will determine (i) the extent to which the association between comparable stages of cannabis and tobacco involvement is due to familial and individual-specific influences; will investigate (ii) whether, controlling for shared familial, mental health and personality factors, cannabis users are more susceptible to subsequently increased involvement with tobacco, including regular use, developing nicotine dependence and long-term smoking due to causal or common environmental influences on both cannabis and tobacco involvement; and will characterize (iii) concurrent cannabis-tobacco users i.e. those who typically use tobacco with cannabis on the same occasion. Such an extensive assessment of the role of genetic and environmental factors on both the lifetime association between, and the concurrent use of cannabis and tobacco smoking is a strength of this application, which also proposes to combine the strengths of three twin data sets, which will afford the ability of examining gender heterogeneity and cohort effects in Australian and U.S. populations. Findings will hopefully elucidate the potential role of cannabis use in escalation of tobacco use behaviors and this information, combined with a greater understanding of familial and life processes associated with both cannabis and tobacco may help interventions designed to prevent initiation of, and escalation in, both cannabis and tobacco involvement. [unreadable] [unreadable] [unreadable] [unreadable]