The goal is to remove unneeded prescriptions from homes and medicine cabinets and prevent medication from being misused.
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The DEA is partnering with local and state law enforcement agencies to hold Drug Take Back events nationwide.
There are close to 5,000 local drop-off locations across the country where people can anonymously dispose of unneeded medications.
Old, unwanted or expired drugs can be a gateway to addiction, according to the DEA.
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"Properly disposing of unneeded medications is essential. It stops drug poisonings and minimizes the risk for misuse," said DEA Administrator Anne Milgram. "DEA is committed to protecting the safety and health of all Americans.
DEA's National Prescription Drug Take Back Day is a free and easy way to come together as a community to turn the tide on the drug poisoning epidemic."
Misuse of prescription medications includes taking someone else's prescription, taking drugs to get high or feel numb, or mixing them with illicit drugs or alcohol, the DEA said.
Opioids, such as oxycodone, hydrocodone, codeine, and morphine, are the most misused prescription pain medications, According to The Substance Abuse and Mental Health Services Administration.