"The recent events in France and similar ones in some other Western countries have convinced me to directly talk to you about them," he wrote in reference to the January 7-9 jihadist attacks in Paris that left 17 dead.
"Many attempts have been made over the past two decades, almost since the disintegration of the Soviet Union, to place this great religion in the seat of a horrifying enemy," Khamenei said of Islam.
"Don't allow them to hypocritically introduce their own recruited terrorists as representatives of Islam," he said.
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"Receive knowledge of Islam from its primary and original sources," said the supreme guide of the Islamic republic.
Khamenei called for the youth of Europe and United States to "study and research the incentives behind this widespread tarnishing of the image of Islam".
Iran denounced the attack on the offices of French satirical magazine Charlie Hebdo but has also condemned as "insulting" and "provocative" its publication last week of a new cartoon of the Prophet Mohammed.