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BackgroundDespite increasing demand for treatment among cannabis users in many countries, most users are not in treatment. Internet-based self-help offers an alternative for those hesitant to seek face-to-face therapy, though low effectiveness and adherence issues often arise. ObjectiveThrough adherence-focused guidance enhancement, we aimed to increase adherence to and the effectiveness of internet-based self-help among cannabis users. MethodsFrom July 2016 to May 2019, cannabis users (n=775; male: 406/575, 70.6%, female: 169/575, 29.4%; age: mean 28.3 years) not in treatment were recruited from the general population and were randomly assigned to (1) an adherence-focused guidance enhancement internet-based self-help intervention with social presence, (2) a similar intervention with an impersonal service team, and (3) access to internet as usual. Controls who were placed on a waiting list for the full intervention after 3 months underwent an assessment and had access to internet as usual. The primary outcome measurement was cannabis-use days over the preceding 30 days. Secondary outcomes included cannabis-dependence severity, changes in common mental disorder symptoms, and intervention adherence. Differences between the study arms in primary and secondary continuous outcome variables at baseline, posttreatment, and follow-up were tested using pooled linear models. ResultsAll groups exhibited reduced cannabis-use days after 3 months (social presence: –8.2 days; service team: –9.8 days; internet as usual: –4.2 days). The participants in the service team group (P=.01, d=.60) reported significantly fewer cannabis-use days than those in the internet as usual group; the reduction of cannabis use in the social presence group was not significant (P=.07, d=.40). There was no significant difference between the 2 intervention groups regarding cannabis-use reduction. The service team group also exhibited superior improvements in cannabis-use disorder, cannabis-dependence severity, and general anxiety symptoms after 3 months to those in the internet as usual group. ConclusionsThe adherence-focused guidance enhancement internet-based self-help intervention with an impersonal service team significantly reduced cannabis use, cannabis-use disorder, dependence severity, and general anxiety symptoms. Trial RegistrationISRCTN Registry ISRCTN11086185; http://www.isrctn.com/ISRCTN11086185