Pupils are to be used as "influencers" in order to discourage their classmates from taking drugs in what is said to be the UK's biggest trial of a school-based drug-prevention programme.
The three-year scheme will involve classmates nominating the most influential pupils in their schools who will then be trained to hold discussions about drug use with their peers.
The Frank Friends programme will be run across 48 schools in the West of England and South Wales from September, and will involve 5,600 Year 9 students aged 13 to 14.
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Dr James White, of the Centre for Trials Research at Cardiff University, one of the leaders of the programme, said 37 per cent of 15-year-olds had tried an illicit drug and more than 13,000 11 to 18-year-olds accessed drug treatment in the UK.
He said: "Schools provide a systematic and efficient way of reaching a large number of people every year. This randomised controlled trial is the best way to determine if the Frank Friends intervention prevents drug use among young people."
Under the scheme, students in the top 17.5 per cent of nominations as the most influential in school will be asked to become peer supporters.
They will undergo two days of training and then be expected to have conversations about the potential harms of drug use with their peers over a 10-week period.
The scheme is also being led by researchers from Bristol University.