Both Colorado and Washington have become magnets for patients seeking different forms of cannabis, such as pot in an edible form, that can be used to treat medical problems.
One of the latest is a toddler from New Jersey who suffers from severe epilepsy. Vivian Wilson's family is moving across the country to Colorado, frustrated by the Garden State's pot laws, which limit sales to smokable marijuana.
(Read more: Seattle throws birthday party for legal pot)
This coming year will witness dramatic growing pains of an industry coming out from the shadows, a rollout that many hope will create a tax windfall but that others fear will have unforeseen negative consequences.
Change begins Wednesday in Colorado, and the Justice Department will be watching. No state has done more to start a regulatory process from the ground up in an effort to make the system work and keep federal authorities at bay. An official with the state's Revenue Bureau told the Journal that Colorado is "blazing a new trail"—an interesting choice of words.
Rocky Mountain High is about to get down to business.
—By CNBC's Jane Wells; Follow her on Twitter: