Aims We sought to characterize adverse events and deaths associated with the use of psychoactive substances in children and adolescents. Methods Two French Addictovigilance databases were analysed: spontaneous reports and deaths over the period 2016–2021, in subjects aged 10–<18 years. An unsupervised classification was implemented on consumption data (medications or nondrug substances [NDS]) to identify subject clusters. Results A total of 1544 spontaneous reports were analysed, comprising mainly boys (65.6%), aged on average 16 ± 1 years. Four clusters were identified: The cannabinoids users cluster ( n = 597) was typified by the use of cannabis or/and synthetic cannabinoids (95.1%), with psychiatric (67.7%) and digestive disorders (16.7%). The medications/solvents/cannabidiol users cluster ( n = 699) was distinguished by the use of medications or NDS including nitrous oxide/cannabidiol, with mainly neurological disorders (46.5%). The polydrug users cluster ( n = 177) includes polyusers (98.3%) of NDS and medications. These users mainly have substance use disorders (63.8%). The psychotropic medications users cluster ( n = 71) was characterized by the use of psychotropic medications. This cluster appeared to be correlated with psychiatric and organic disorders. The death database recorded 44 deaths, mainly in boys (61.4%) aged over 15 years. The main substances involved in the deaths were NDS (70.5%) and methadone. In 68.2% of cases, a single substance was responsible for the death. Conclusion The adverse events related to the abuse of psychoactive substances identified in children and adolescents and the emerging signals show the need for increased surveillance and the implementation of prevention campaigns adapted to each group of consumers.