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This chapter explores the historical context of drug control in the United States, the ongoing regulation of the cannabis market at the State level and the role of the United States in the international negotiations related to the United Nations General Assembly Special Sessions (UNGASS) on drugs in 1998 and 2016. We continue by analysing the position, allies and activities of the United States before and during UNGASS 2016 to provide an understanding of possible scenarios related to the 2009 Political Declaration and Plan of Action review to take place via a High-level Ministerial Segment within the 2019 Commission on Narcotic Drugs meeting. While US drug policy is not expected to positively shift in the next few years, State-level regulation of cannabis is expected to continue and create pressure from below.