The fundamental issue with cannabis (marijuana) legalization lies with the current drug scheduling in the Controlled Substances Act. The path to decriminalization / legalization requires that the drug schedule recognizes cannabis as having therapeutic benefits and low risk.
Cannabis is currently considered to have no therapeutic benefit, despite mountains of evidence to the contrary. In fact, for its effectiveness in reducing nausea, it is the benchmark which drug manufacturers are trying to match with synthetic substances.
Beyond this, overdose is impossible and drug interactions are minimal.
It is time for the DEA and FDA to recognize the minimal risk and maximal benefits provided by this plant that has been a part of human society for 10,000 generations.