ABSTRACT: BACKGROUND:Young Australians (16-25 years) have the highest rates of past-month cannabis use in the world. Cannabis use increases the risk of alcohol and other drug disorders and depressive disorders, and has a robust dose-response association with psychotic experiences (PEs) and disorders. PEs are subthreshold positive psychotic symptoms, including delusions and hallucinations, which increase the risk of substance use, depressive or anxiety disorders, and psychotic disorders. Access to effective web-based early interventions targeting both cannabis use and PEs could reduce such risk in young people. OBJECTIVE:The objective of this study is to determine the efficacy and cost-effectiveness of the Keep it Real web-based program compared to an information-only control website among young cannabis users (16-25 years) with PEs. METHODS:Participants are recruited online, and consenting individuals meeting inclusion criteria (aged 16-25 years, who have used cannabis in the past month and experienced PEs in the past 3 months) are automatically randomized to either the Keep it Real web-based program (n=249) or an information-only control website (n=249). Both websites are self-guided (fully automated). The baseline and follow-up assessments at 3, 6, 9, and 12 months are self-completed online. Primary outcome measures are weekly cannabis use, PEs, and the relative cost-effectiveness for quality-adjusted life years. Secondary outcomes include other substance use and related problems, PE-related distress, cannabis intoxication experiences, severity of cannabis dependence, depression/anxiety symptoms, suicidality, and mental well-being and functioning. RESULTS:Recruitment commenced in February 2019, and the results are expected to be submitted for publication in mid-2021. CONCLUSIONS:This study protocol describes a large randomized controlled trial of a new web-based program for young cannabis users experiencing PEs. If effective, the accessibility and scalability of Keep it Real could help reduce growing public health concerns about the significant social, economic, and health impacts of cannabis use. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry ACTRN12618001107213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374800. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/15803.