The main risk factors for mortality and morbidity worldwide are alcohol and tobacco consumption. While knowledge about individual factors that influence the initiation and maintenance of substance consums is increasing, there is still a lack of in-depth knowledge about modulatory factors and mechanisms that contribute to the loss and regaining of control over drug use. A better understanding of these factors and mechanisms will be critical to improving the treatment of substance use disorders (SUDs).The goal of our research consortium in TRR265 is to identify the trajectories of loss and regain of control over drug use, to investigate the underlying neurobiological and learning mechanisms, and to develop mechanism-based therapies. These goals should be achieved through 3 approaches: (I) the use of innovative mobile health tools to determine the influence of triggers, (II) in closely networked studies on humans and in animal models, the decisive mechanisms should be identified and mathematically modeled (III) based on this, interventions should be developed that specifically target these mechanisms in order to support regaining control over drug use.