BACKGROUND: Little is known about psychoactive substance use in students, apart from tobacco, alcohol, and cannabis. OBJECTIVES: This study investigated the prevalence of substance use and overlap between various psychoactive substances in students. METHODS: This cross-sectional study was conducted in 10,066 students included in the i-Share cohort between 2015 January 1(st) and 2017 December 31(st) . The baseline questionnaire was the key source of information. Psychoactive substances of interest (PSI) were cannabis, cocaine, amphetamines, nitrous oxide, poppers and MDMA. Their patterns of use were categorized as lifetime, past year and current use. Use of other psychoactive substances including alcohol and tobacco was described in PSI users and non-users. RESULTS: Most participants were female (75%) and their average age was 21 years. Lifetime use of at least one PSI was reported by 65.5% of participants. Cannabis was the most frequently used substance both over lifetime (57% of students) and past year (35%), followed by poppers and nitrous oxide (28% and 26% of students over lifetime, respectively). Among polydrug users (n=1242), 65% used only nitrous oxide and poppers, showing a strong link between these two substances. Regular alcohol use, binge drinking and current tobacco use were higher in PSI users than in non-users. CONCLUSION: Substance use was higher than previously found in both French and European studies in young people. Nitrous oxide use was particularly high. Regular alcohol use, binge drinking and tobacco use could be used as markers to identify students at-risk of PSI use to be targeted by prevention programmes.< Réduire