Rachel Reeves has called on students not to smoke weed, warning that the drug ruins lives.
In an emotional outburst, the shadow work and pensions secretary also hit out at the Green party for seeking to decriminalise cannabis.
She was backed by shadow business secretary Chuka Umunna, who warned pupils of the dangers of "marijuana-induced psychosis".
The pair were on a panel answering questions at Park High School in Harrow, north-west London.
One student asked what they made of the Green party's pledge. Reeves replied: "When I was at school, lots of people did really well at GCSEs and then the next year it all started going wrong.
"And often things started to go wrong because people started smoking weed and using other drugs. And boys and girls who were getting good grades at GCSE suddenly started falling back when it came to A-levels, and I think that's a huge waste.
"Some people say, 'Oh, it's harmless.' It's not harmless. Some people have friends who have gone off the rails because they have taken drugs, and cannabis then leads to other drugs that are even more harmful.
"So my advice to all of you is to stay away from that stuff. You're all doing incredibly well, you're at a good school, you've got your whole lives ahead of you. Don't risk it by doing stupid things.
"The Green party, they can promise that if they want. But they're letting down young people, they're letting down our country if they legalise those sorts of drugs."
Her words were greeted with loud applause by the audience of almost 150 students aged between 15 and 18.
Umunna added: "Amen to what Rachel said on weed."
He told the pupils: "You need to make your own decisions about these things. Your parents, your teachers, even the police, they can't watch you every single minute of the day.
"But what Rach said is really, really important. I've got an ongoing case with a guy who's now 22 and he started smoking weed when he was about 14, 15 – mainly skunk, frankly. And he as a result got marijuana-induced psychosis and is in and out of mental health institutions and has been since he was 16.
"He had his whole life ahead of him and it's been ruined."
Both Labour and the Conservatives are completely opposed to the decriminalisation of drug use. But the Liberal Democrats want to effectively decriminalise the possession of all drugs and turn the policy into a health, not a criminal, matter.
The Green party want to decriminalise cannabis and abolish jail sentences for the possession of other drugs.