In its Monitoring the Future survey for 2013, the National Institute on Drug Abuse said 39.5 percent of high school seniors view marijuana as harmful -- down from 44.1 percent just a year ago.
What's more, nearly 23 percent of seniors, typically 18-year-olds, said they had smoked marijuana in the month prior to taking part in the survey -- and 36 percent said they had done so in the preceding year.
Under federal law, marijuana is considered a highly addictive Schedule One drug alongside heroin, LSD and ecstasy.
But following referendums, the western states of Colorado and Washington are legalizing the sale of marijuana for recreational use from next year, while 19 states allow its sale for medicinal use.
In October, for the first time in a Gallup poll, a majority of Americans -- 58 percent -- said they favored the legalization of marijuana.
Responding to the shifting tide of public opinion, the Obama administration in August told federal prosecutors to stop targeting individual pot users in states where legalization is in place.
Instead they were asked to focus their efforts on criminal gangs and sales to minors.
Wednesday's findings alarmed White House drug czar Gil Kerlikowske, who called increased marijuana use "a serious setback in our nations efforts to raise a healthy generation of young people."
"Today's news demands that all of us recommit to bolstering the vital role prevention and involved parenting play in keeping young people safe, strong, and ready to succeed," he said in a statement.
Nora Volkow, director of the National Institute on Drug Abuse, expressed concern not only at the number of teenaged users in America, but also the kind of pot they are inhaling.
"It is important to remember that over the past two decades, levels of THC (the main psychoactive ingredient in marijuana) have gone up a great deal, from 3.75 percent in 1995 to an average of 15 percent in today's marijuana cigarettes," she said.
"Daily use today can have stronger effects on a developing teen brain than it did 10 or 20 years ago," she added.