AIMS: Cannabis use is highly prevalent in patients seeking treatment for opioid use disorder. Studies have shown mixed results on the association between cannabis use and opioid use as well as the impact of MOUD on cannabis use. The current study aims to investigate the effects of buprenorphine versus naltrexone on cannabis use outcomes in treatment seeking individuals with Opioid Use Disorder (OUD). METHODS: The current study was based on data from the CTN-0051 X:BOT trial, which compared the time to return to significant opioid use survival outcomes of two treatment seeking groups, one receiving Extended-Release Naltrexone (XR-naltrexone) (N = 283) versus another receiving Buprenorphine-Naloxone (N = 287) for OUD. A mixed-effects logistic regression model including treatment assignment (buprenorphine-naloxone vs XR-naltrexone), time, and a time by treatment interaction was run on the sample with the odds of cannabis use as the outcome, as well as two cross-lagged mediation models to explore the prospective mediation of cannabis use on opioid use outcomes (and opioid use on cannabis use outcomes) by treatment assignment during the trial. RESULTS: There was a significant effect of buprenorphine treatment on reduced cannabis use. Participants receiving buprenorphine treatment were 39 % less likely to use cannabis than those receiving naltrexone over all the timepoints (p = .0499). No significant mediation was found between treatment assignment and opioid use on cannabis use outcomes or between treatment assignment and cannabis use on opioid use outcomes in this trial. CONCLUSION: Participants in this trial receiving buprenorphine treatment for OUD used less cannabis than those receiving naltrexone treatment.