The consumption of psychoactive pharmaceuticals has increased worldwide, and wastewater treatment plants are not able to eliminate them from the effluent. An extensive review was carried out to assess the environmental risk (ERA model) based on secondary data about potential impacts on non-target organisms of seven psychoactive drugs consumed worldwide (alprazolam, bromazepam, citalopram, clonazepam, diazepam, lorazepam, and oxazepam). Risk quotients (RQs) were calculated according to the European Medicines Agency (EMA) on ERA of Medicinal Products For Human Use based on (i) the predicted and measured environmental concentrations (PEC and MEC, respectively) of the psychoactive drug in surface water, groundwater, and wastewater effluent and (ii) the predicted no-effect concentration (PNEC) derived from ecotoxicological assays or ECOSAR software. Furthermore, this study reviews and discusses non-standardized ecotoxicity assays, such as sublethal and behavioral effects on different organisms. In total, 903 MEC entries of psychoactive drugs and 162 data on ecotoxicological assays were gathered from the literature survey addressing behavioral effects (115), acute/chronic effects (35), and sublethal effects (12). Citalopram and diazepam were the only substances that are likely to pose an environmental risk (RQ > 1) to surface waters. Even though there is considerable amount of data on behavioral effects of psychoactive drugs to aquatic species, results are currently not integrated into the EMA risk assessment framework. The large amount of data on psychoactive drug concentrations and effects on non-target organisms collected, interpreted, and discussed in the present study should be used as a baseline for future improvement of ERA strategies.