The six victims, all young people, had smoked between two and four roll-up cigarettes offered by people they met on the street in the past few days in the central French town of Roanne.
Several were robbed of their smartphones and other personal items.
Investigators said the tobacco appeared to have been sprayed with a noxious substance that left the smokers delirious, lethargic or in a comatose state.
One of the victims was so disturbed he swallowed gravel and another reacted aggressively when the emergency services tried to help him.
Some were treated in hospital for their symptoms.
The public prosecutor for Roanne, Abdelkrim Grini, said while previous such attacks have been reported on the French Indian Ocean island of Reunion, these were the first known cases on the mainland.
The prosecutor's office said tests were being carried out on cigarette butts and the victims' blood samples to try to identify the toxic substance used in the cigarettes.
Investigators suspect local gangs of being behind the scam