President Obama pledged during his 2008 campaign to take a hands-off approach to medical marijuana, but four years later raids and other tactics have forced as many as 200 medical-marijuana growers and distributors to cease operations, resulting in sharp criticism from likely voters and fellow Democrats.
Medical marijuana supporters say the reason behind the apparent policy shift remains a mystery.
"It's really confusing," Kris Hermes of Americans for Safe Access said, Thursday. "The president's tactics are worse than those of his predecessor, George Bush."
Hermes and others involved in the issue point at two Justice Department memos: the first was issued in 2009 and seemed to suggest the hands-off approach, and the second, issued last year, restated the previous so-called "Ogden memo," but also made clear federal law still prohibits the growing, selling and possession of marijuana.
"People took the 2009 letter to heart," Hermes said. "Then the government realized what was in the letter and freaked out."
Federal officials maintains the policy has not changed.
"The Department of Justice is focusing its limited resources on significant drug traffickers, not seriously ill individuals who are in compliance with applicable state medical marijuana statues," Allison Price, an agency spokeswoman told Fox News.
However federal officials have acknowledged the 2009 letter was followed by a proliferation of large-scale medical marijuana operations – some with projected annual revenue exceeding $1 million – which appeared to be driven by profiteers and those who want to legalize all drugs, not advocates for the compassionate use.
A promise not to use Justice Department money to "circumvent state laws" was among the president's campaign pledges. 
He attempted to clarify his position this week in a "Rolling Stone" magazine interview. Obama said the government was not going to "prioritize prosecutions of persons who are using medical marijuana," but that he never committed to giving "carte blanche to large-scale producers and operators of marijuana."
"I can't ask the Justice Department to say, 'Ignore completely a federal law that's on the books,'" he added.
Though 16 states and the District of Columbia have enacted medical marijuana laws in the absence of federal legislation, most of the raids and warnings about prosecutions have occurred in California, Colorado and Montana.
Federal agents participated in more than 20 raids on Montana distribution centers in 2011 alone, according to a Justice Department report.
And more than 200 California dispensaries have been shuttered "as a result of threats to threats and owners" since U.S. Attorneys announced a crackdown in the state in October 2011, according to Americans for Safe Access.
The most high-profile raid occurred April 2 at Oaksterdam University in Oakland. Federal agents said the established medical-marijuana training facility was too close to schools, but they were really targeting founder Richard Lee, a leader in marijuana-legalization efforts, according to published reports.
The raid and the growing concern among medical-marijuana supporters resulted in a flurry of sharply-worded responses.
"I am concerned about recent federal actions targeting duly permitted medicinal cannabis dispensaries," San Francisco Mayor Edwin Lee, a Democrat, wrote. "Time and time again, the president of the United States has made it clear that the Justice Department has more important priorities than working to prevent patients from accessing this medicine."
Among the most powerful was one sent by General Assembly lawmakers representing five states with medical marijuana laws.
"Unfortunately, these laws face a mounting level of federal hostility and confusing mixed messages from the Obama administration, the Department of Justice, and the various United States attorneys," the Democratic and Republican lawmakers wrote. "We call on President Obama to recommit to the principles and policy on which he campaigned and asserted his first year in office."
The letter also referred to U.S. attorneys threatening more investigations and the use of other federal resources against those who grow and distribute medical marijuana, saying some threats have been time to influence pending state legislation or to encourage the abandonment of state and local regulatory programs.
More disturbing, the letter states, is that some of the attorneys have also warned that state employees who implement the laws and regulations are not exempt from criminal prosecution.
New Jersey GOP Gov. Chris Christie, a former U.S. attorney, decided state workers face no real threat of federal prosecution and moved forward with implementing a medical marijuana program.
However, the "chilling" effect of one such warning resulted in Delaware Gov. Jack Markell suspending the implementation of his state's regulatory program, the letter points out.