The aim of this study was to examine contribution of personality traits and motives for cannabis and new psychoactive substances use to the explanation cannabis and new psychoactive substances lifetime use, and also to examine differences in the cannabis and new psychoactive substances use regarding to various socio-demographic characteristics. The sample consisted of 555 participants, 160 male and 395 female students, of whom 128 students of technical, 210 of social, 62 of natural, 44 of biomedical sciences and 111 humanities. The participants completed IPIP-50 personality traits questionnaire, Frequency of Cannabis and New Psychoactive Substances Use Questionnaire, Marijuana Motives Questionnaire, New Psychoactive Substances Motives Questionnaire and Questionnaire about Socio-Demographic Characteristics. The study was conducted online. Of the total number of participants, 366 were cannabis users and 90 were new psychoactive substances users. The results have show that male students whose parents were divorced and students whose parents had a high and a higher level of education statistically more often abused cannabis than female students who lived in nuclear and single-parent families and students whose parents had a middle and low level of education. It has also been found that male students who studied and lived at home during college, students whose parents were divorced and had a high and a higher level of education, and those of middle family socio-economic status statistically more often abused new psychoactive substances than female students who were studying and living away from home during college, students who lived in nuclear and singleparent families, students whose parents had a middle and low level of education, and those of low and high family socio-economic status. It was found that after controlling for sociodemographic characteristics, intellect, enhancement motives, coping motives and expansion motives had the largest contribution to the explanation of lifetime cannabis use. Furthermore, after controlling for socio-demographic characteristics, enhancement motives had the most significant contribution to the explanation of lifetime use of new psychoactive substances.