rats), morphine (study based on 12 male rats) and also nicotine (34 rats). There were direct indications that the alteration consisted of lasting anatomical changes in the reward system of the brain. Because the reward system is anatomically, physiologically, and functionally almost identical across the class of mammals, the importance of the findings from animal studies for the reward system in the human brain in relation to the liability to the use of further drugs has been pointed out in several reviews. In mice, nicotine increased the probability of later consumption of cocaine, and the experiments permitted concrete conclusions on the underlying molecular biological alteration in the brain. The biological changes in mice correspond to the epidemiological observations in humans that nicotine consumption is coupled to an increased probability of later use of cannabis and cocaine, as well as other drugs. In rats, alcohol increased the probability of later addiction to cocaine and again relevant alterations in the reward system were identified. These observations thus correspond to the epidemiological findings that the consumption of alcohol in humans is coupled to a later increased risk of a transition from cocaine use to cocaine addiction. Controlled animal and human studies showed that caffeine (energy drinks) in combination with alcohol increased the craving for more alcohol more strongly than alcohol alone. These findings correspond to epidemiological data that people who consume energy drinks generally showed an increased tendency to take alcohol and other substances. Personal, social and genetic factors According to the concept of similar attitudes across different drugs (common liability to addiction), a number of personal, social, genetic and environmental factors can lead to a generally increased interest in various drugs. The sequence of first-time use would then depend on these factors. Violations of the typical sequence of first-time drug usage give credit to this theory. For example, in Japan, where cannabis use is uncommon, 83.2% of the people who used illicit substances did not use cannabis first. The concept received additional support from a large-scale genetic analysis that showed a genetic basis for the connection of the prevalence of cigarette smoking and cannabis use during the life of a person. The results of a twin study presented indications that familial genetic and familial environmental factors do not fully explain these associations, and are possibly only relevant for sequences of some drugs. In 219 same-sex Dutch identical and non-identical twin pairs, one