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WASHINGTON — The Justice Department said Thursday that it would not sue to block laws legalizing marijuana in 20 states and the District of Columbia, a move that proponents hailed as an important step toward ending the prohibition of the drug.

In a memo to federal prosecutors nationwide Thursday, James M. Cole, the deputy attorney general, erased some uncertainty about how the government would respond to state laws making it legal to use marijuana for medical or recreational purposes.

Citing “limited prosecutorial resources,” Cole explained the change in economic terms. But the memo also made clear that the Justice Department expects states to put in place regulations aimed at preventing marijuana sales to minors, illegal cartel and gang activity, interstate trafficking of marijuana, and violence and accidents involving the drug. “A system adequate to that task must not only contain robust controls and procedures on paper; it must also be effective in practice,” he wrote.

Voters in Washington and Colorado recently approved measures decriminalizing the possession of small amounts of recreational marijuana, while 18 other states and the District of Columbia permit the use of marijuana for medical purposes.

In a phone call Thursday, Attorney General Eric H. Holder Jr. explained the government’s “trust but verify” approach to Gov. Jay Inslee of Washington and Gov. John W. Hickenlooper of Colorado, a Justice Department official said.

Marijuana advocates praised the decision as a potentially historic shift in the federal government’s attitude toward a drug it once viewed as a leafy menace to public health. By allowing states to legalize and regulate marijuana, advocates said, the federal government could reduce jail populations and legal backlogs, create thousands of jobs, and replenish state coffers with marijuana taxes.

“This is a historic day,” said Ean Seeb, a co-owner of a marijuana dispensary called Denver Relief. “This is the beginning of the end of marijuana prohibition.”

But the prospect that marijuana could be legalized after a ban of decades drew criticism from law enforcement and drug policy officials. They warned that the Justice Department’s decision would have unintended consequences, like more impaired driving and more criminal marijuana operations.

“This sends the wrong message,” said former Rep. Patrick J. Kennedy, a Rhode Island Democrat, who is a recovering prescription drug addict. “Are we going to send up the white flag altogether and surrender and say ‘have at it’? Or are we going to try to reduce the availability and accessibility of drugs and alcohol? That should be our mission.”

Under the new guidance, a large scale and a for-profit status would no longer make dispensaries and cultivation centers a potential target for criminal prosecution. However, prosecutors have broad discretion in determining, for instance, whether drug laws exacerbate “adverse public health consequences associated with marijuana use.”