This year is 10 years since the Drug Policy Modelling Program commenced. Using the three streams framework from the Drug Policy Modelling Program -generating evidence, translating evidence and studying policy processes -this paper reflects on some of the inherent challenges in conducting policy research. If making a difference is the key goal for policy research, then activities across all three streams are necessary. We need to generate new research that is policy relevant. Beyond this, we need to translate research into meaningful information for policy makers. The extent of research data and its translation however is not enough by itself.The actual processes by which policies get made need to be understood. The experiences of the Drug Policy Modelling Program suggest that there are many issues and challenges within each of these streams. In generating research an essential consideration is 'asking the right question'. The ways in which questions are posed sets up the kinds of research that will be generated. And in the case of commissioned research, the researcher does not necessarily get to decide the question. Appreciating one's own values and worldviews is also necessary in a politicised domain such as drug policy. In the translation area, using new tools and methods are required. Ethical dilemmas also abound in the translation space. One example is the delicate balance between simplification of results and misrepresentation of results. In studying policies processes, researchers need to be alert to sensitivities, secrets and different narratives. This paper explores these various challenges in undertaking policy research, with a view to making overt the complexities of conducting policy research that aims to make a difference.The battle has been fought and controlled drinking as an appropriate alternative to abstinence for certain problem drinkers has been accepted in many, although not all, quarters. However, much remains to be settled in the translation of this treatment goal to routine clinical practice: Who can successfully achieve moderation? What is a sensible limit in such cases and how should this be monitored? To address these questions Assoc Prof Simon Adamson will examine the literature, including his own research, and will draw on his clinical experience.Data from multiple sources have converged over the past several decades to support the idea that exposure to severe adversity, especially during childhood, can place an individual at increased risk for subsequently developing psychiatric and medical disorders, in particular substance use disorders (SUD). This presentation will focus on the interaction between stress, adversity and SUDs with a particular emphasis on neurobiological connections. Epidemiologic evidence for the connection between stress and SUDs, in particular the prevalence of co-occurring post-traumatic stress disorder and SUDs, will be reviewed. New treatments focused on addressing vulnerabilities at the interface between stress and SUDs will be explored.