The Senate is expected to vote late Thursday or Friday on an amendment introduced by Sens. Rand Paul (R., Ky.) and Cory Booker (D., N.J.) to block the Justice Department from interfering with state-approved medical marijuana laws.
The amendment, attached to a spending bill, would block the Drug Enforcement Administration (DEA) and federal prosecutors from investigating people complying with state marijuana laws.
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Sen. John Walsh (D., Mont.) is also sponsoring an amendment that would protect patients.
Marijuana legalization advocates hailed the amendment.
"It is time that we allowed our unique federalist system to work the way it was intended," the National Organization for the Reform of Marijuana Laws (NORML) wrote on its blog.
The legislation is similar to a House amendment that passed in May in a surprise vote.
The Obama administration has directed federal law enforcement agents and prosecutors to not prioritize cases involving medical marijuana patients and growers who are in compliance with state law, but those directives have not always been followed.
In one high-profile case this year, the DEA raided a home in rural Washington where a family of four was growing marijuana. The family and a friend now face lengthy federal prison sentences.
The text of the amendment is as follows:
At the appropriate place in title II of division A, insert the following: Sec. __. None of the funds made available under this Act to the Department of Justice may be used, with respect to the States of Alabama, Alaska, Arizona, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Hawaii, Illinois, Iowa, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nevada, New Hampshire, New Jersey, New Mexico, Oregon, Rhode Island, South Carolina, Tennessee, Utah, Vermont, Washington, and Wisconsin, to prevent such States from implementing their own State laws that authorize the use, distribution, possession, or cultivation of medical marijuana.