The girls, believed to be 13 years old, were first treated by school medical personnel for experiencing what the L.A. Fire Department described as "altered levels of consciousness after possible exposure or ingestion of an unknown substance."
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Paramedics went to the campus in the 4000 block of Johnnie Cochran Vista about 11:35 a.m., according to LAFD.
The students were transported to a hospital for further evaluation after first responders arrived at the scene.
The campus went into lockdown when police and ambulances arrived, a student said.
Parents were notified of the incident, according L.A. School police Lt. Nina Buranasombati.
"It's sad and it's hurtful because it could've been anyone of our kids that go to this school," parent Ebony Walker said.
One parent said that a school official told her that the students had overdosed and needed to be given Narcan.
Because of the ages of the patients, officials said they're unable to release information on their condition.
Los Angeles Unified School District Superintendent Alberto Carvalho said that the district is remaining hopeful for a full recovery of the students.
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Carvalho urged students to take advantage of the Los Angeles Schools Anonymous Reporting, or LASAR, app to report any suspicious activity on campus.
City News Service contributed to this report.