Introduction: Cannabis is the most widely used psychoactive substance among adolescents worldwide, and the age at which consumption begins to decrease. Cannabis use in adolescents is associated with a wide range of adverse consequences in adulthood including increased vulnerability to psychosis and other mental disorders, as well as suicidal ideation and attempt. The aim of this study is to extend understanding of the link between cannabis use and mental illness by examining whether cannabis use at early ages predicts transdiagnostic variables that are precursors to severe clinical diagnoses. Methods: A descriptive cross-sectional study was conducted. The sample was made up of 605 adolescents from 7th to 9th grades, with a mean age of 13.2 years ( SD = 1.0, 47% girls). The variables evaluated were: anomalous perception of reality, intolerance of uncertainty, rumination, suicide attempt, hopelessness, and symptoms of depression and anxiety. The administration of the questionnaires was carried out in groups of 20 participants under the supervision of a researcher in a unique session of 1 hour. Results: Adolescent cannabis users scored higher on all variables assessed: anomalous perception of reality (Cohen’s d = .60), rumination ( d = .48), intolerance of uncertainty ( d = .11), suicidal attempt (affirmative answer: 25.9% of users vs 7.7% of non-users), hopelessness ( d = .85), symptoms of depression ( d = .80), and anxiety ( d = .39). A binary logistic regression showed that the only variable uniquely related to cannabis use was hopelessness (Wald = 4.560, OR: 1.159, p = .033). Conclusions: Among some mental health risk factors, hopelessness appears uniquely related to cannabis use. Adolescents may use cannabis as a coping strategy for negative thoughts and emotions, or it may be a consequence of cannabis use. Future prevention programs should focus on preventing/treating modifiable factors such as hopelessness, and delaying cannabis use in specific subgroups of adolescents who experience pathologies such as depression or suicide attempts.