Objective: Drug use is one of the most controversial issues affecting adolescents and the youth. Accordingly, the purpose of this study was to predict the tendency to drug abuse based on academic alienation, negative academic emotions, and general self-efficacy in male students. Method: This study was descriptive-correlational and the statistical population of the present study was all male senior high school students in Rasht in the academic year 2019-2020. Among them, 200 students were selected by multi-stage cluster sampling. In this study, the Addiction Tendency Questionnaire (Weed et al., 1992), the Educational Alienation Questionnaire (Dillon & Grout, 1976), the General Self-Efficacy Scale (Schwartzer and Jerusalem, 1979), and the Achievement Emotion Questionnaire (Pekrun et al., 2005) were used. Results: Tendency to drug abuse had positive and significant relationships with academic alienation and negative academic emotions, and negative and significant relationship with general self-efficacy in students. Academic alienation, negative academic emotions, and general self-efficacy predicted 62% of the variance of tendency to drug abuse in students. Conclusion: It can be stated that by measuring the three variables mentioned in this study, school principals can be aware of students' tendencies to use drugs and implement the necessary management and prevention programs.