This publication provides an authoritative summary of existing knowledge of the biological basis of substance use behaviours, including their relationship with environmental factors. The study focuses on a wide range of psychoactive substances, including tobacco, alcohol and illicit drugs. Developments in neuroscience research are discussed (e.g. mechanisms governing craving, tolerance and neuroadaptation), immunotherapies and the concept of dependence, as well as the ethical implications of these developments. As the product of consultations with and contributions from many international experts and partners, evidence is provided from the various schools of thought and areas of research in the field of neuroscience. The report is targeted at individuals with more than a basic knowledge of neuroscience, including scientists from a number of disciplines. It is expected that the publication will be of interest to health care workers, clinicians, social workers, university students, science teachers and informed policy makers.