The European Medicines Agency (EMA) supports the implementation of the 3Rs principle  – replace, reduce and refine – for the ethical use of animals in medicine testing across the European Union (EU) (Ethical use of animals in medicine testing | European Medicines Agency (europa.eu)). These principles encourage alternatives to the use of animals in the testing of medicines while safeguarding scientific quality and improving animal welfare where the use of animals cannot be avoided.

In line with the 3R principles, the environMENTAL project has focused on the implementation of human, stem-cell derived cellular as well as in silico brain models, such as the Virtual Brain Twin platform (https://www.ebrains.eu/projects/virtual-brain-twin-for-personalized-treatment-of-psychiatric-disorders). Combining in vitro human stem cell-derived model systems and in silico virtual brain models is a key and innovative approach to highlight novel molecular mechanisms mediating the effect of environmental factors on mental health.