Sanjay Gupta had a great piece on this on CNN. The origins of marijuana law were based on the lack of knowledge about the effect of THC on human physiology. The government then virtually banned anyone from discovering a benefit, thus self fulfilling it's own prophecy.
I suspect its intransigence is rooted in the profitability of interdiction policies on law enforcement agencies. Let's hear it of the states! I hope more follow on Colorado's lead.
The History Channel ran a documentary that claimed the impetus for Marijuana's prohibition in the first place came during the Depression. They claimed that it was used by a lot of Mexicans, and that the southwestern states were pushing for it because they didn't want them competing with U.S. citizens for jobs.