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To examine the effectiveness of a personality-targeted intervention program (Adventure trial) delivered by trained teachers to high-risk (HR) high-school students on reducing marijuana use and frequency of use.A cluster-randomized controlled trial.Secondary schools in London, UK.Twenty-one secondary schools were randomized to intervention (n = 12) or control (n = 9) conditions, encompassing a total of 1038 HR students in the ninth grade [mean (standard deviation) age = 13.7 (0.33) years].Brief personality-targeted interventions to students with one of four HR profiles: anxiety sensitivity, hopelessness, impulsivity and sensation-seeking.Primary outcome: marijuana use. Secondary outcome: frequency of use. Assessed using the Reckless Behaviour Questionnaire at intervals of 6 months for 2 years. Personality risk was measured with the Substance Use Risk Profile Scale.Logistic regression analysis revealed significant intervention effects on cannabis use rates at the 6-month follow-up in the intent-to-treat sample [odds ratio (OR) = 0.67, P = 0.05, 95% confidence interval (CI) = 0.45–1.0] and significant reductions in frequency of use at 12- and 18-month follow-up (β = –0.14, P ≤ 0.05, 95% CI = –0.6 to –0.01; β = –0.12, P ≤ 0.05, 95% CI = –0.54 to 0.0), but this was not supported in two-part latent growth models. Subgroup analyses (both logistic and two-part models) reveal that the sensation-seeking intervention delayed the onset of cannabis use among sensation seekers (OR = 0.25, β = –0.833, standard error = 0.342, P = 0.015).Personality-targeted interventions can be delivered effectively by trained school staff to delay marijuana use onset among a subset of high-risk teenagers: sensation-seekers.