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Abstract: The number of accidents that can be attributed to driving under the influence of psychoactive substances (alcohol, drugs, and certain medicines) is constantly on a high level with drugs and medicines proportionally increasing over the years. The overall objective of the EU 6th Framework Programme project DRUID is to gain better knowledge of the various aspects of driving under the influence of drugs, alcohol and medicines. DRUID wants to offer scientific support to EU transport policy makers by suggesting guidelines and measures to combat impaired driving. To reach this ambitious aim a wide range of studies is conducted. The various studies are divided into seven work packages with complex interdependencies. There are experimental studies assessing the effects of single and combined psychoactive substances on driving performance (WP1) as well as epidemiological studies aiming to assess the situation in Europe regarding prevalence of alcohol and other psychoactive substances in drivers (WP2).The principal objective of these studies is to gain relative risk estimates for traffic accident involvement of drivers impaired by psychoactive substances and to recommend substance concentration thresholds. A theoretical framework which allows the integration of the experimental and epidemiological findings serves as a fundament for developing these recommendations. WP3 aims at improving the possibilities of detecting drug driving in Europe. Police forces evaluate practically (under realistic enforcement conditions) oral fluid screening devices. A scientific evaluation of oral fluid screening devices and other methods (i.e. roadside checklists of signs of impairment) is done as well. The outcome of the practical and scientific evaluations serves as input to cost-benefit analyses of enforcement.