Introduction. It is assumed that the functional asymmetry of the brain must be taken into account in a complex of other predisposing factors that influence the tendency to various kinds of deviations in adolescents, in particular, the consumption of psychoactive substances.Purpose setting. The aim of the study was to study the relationship between functional asymmetry of the brain and the consumption of psychoactive substances (alcohol, nicotine) in adolescents of the South Siberian regions (Tuva, Altai).Methodology and methods of the study. 2 559 adolescents aged 14–17 years, students of educational institutions were examined. All students completed a specially designed questionnaire on their substance use. Motor, sensory and mental asymmetry have been studied. The test «Self-assessment of mental states of personality» was applied for adolescence by G. Aizenk in the interpretation of O. V. Zikeeva. The statistical analysis was carried out in the SPSS-26 program.Results. It has been shown that right-hemisphere adolescents have significantly more pronounced anxiety, frustration and rigidity, indicating a violation of social adaptation and predisposing to the consumption of psychoactive substances, which indirectly confirms the influence of functional asymmetry of the brain. Right- brain adolescents are more vulnerable to nicotine and alcohol. Conclusion. The results obtained allow us to substantiate prevention strategies that should take into account the functional asymmetry of the target audience’s brain.