Buprenorphine Treatment for Opioid Disorder Linked to Less Cannabis Use Than Naltrexone | Research

The takeaway

In a randomized trial of people with opioid use disorder, those receiving buprenorphine were 39% less likely to use cannabis than those receiving naltrexone.

addiction medicine clinicians, opioid use disorder researchers, medication-assisted treatment prescribers

What the researchers found

Participants receiving buprenorphine-naloxone were 39% less likely to use cannabis than those receiving extended-release naltrexone across all timepoints (p = 0.0499). No significant mediation was found between treatment assignment and opioid use on cannabis outcomes, or vice versa.

Why it matters

Cannabis use is highly prevalent among people with opioid use disorder, but it has been unclear whether the type of medication treatment affects cannabis use patterns. This finding suggests buprenorphine may have differential effects on cannabis use compared to naltrexone.

The numbers in context

570 total participants (283 naltrexone, 287 buprenorphine). Buprenorphine group 39% less likely to use cannabis (p = 0.0499). No significant mediation between opioid and cannabis use outcomes by treatment assignment.

How the study worked

Secondary analysis of the CTN-0051 X:BOT randomized clinical trial comparing extended-release naltrexone (n=283) versus buprenorphine-naloxone (n=287) for opioid use disorder. Mixed-effects logistic regression modeled cannabis use odds. Cross-lagged mediation models explored whether cannabis and opioid use mediated each other.

What this study cannot tell us

Secondary analysis of a trial not designed for this outcome. Borderline statistical significance. Cannabis use was self-reported. Mechanisms for the differential effect are unknown. May not generalize to all people with opioid use disorder.

How to read the evidence

Randomized trial design is strong, but this was a secondary analysis with borderline significance, limiting evidence to moderate.

When this study was published

Based on data from the CTN-0051 X:BOT trial.

The bigger picture

This is a secondary analysis, meaning the trial was not designed to test this question. The borderline significance (p = 0.0499) warrants cautious interpretation. However, the finding raises interesting questions about whether opioid receptor pharmacology differently modulates cannabis use behavior.

Questions still open

What mechanism explains why buprenorphine reduces cannabis use more than naltrexone?
Would a trial designed to test this question replicate the finding?

Common questions

Does buprenorphine reduce cannabis cravings?

The study did not measure cravings directly. It found that people on buprenorphine used cannabis less often than those on naltrexone, but the mechanism behind this difference is unknown.

Should people on buprenorphine also stop using cannabis?

This study examined cannabis use as an outcome, not whether cannabis use affected opioid treatment success. No mediation between cannabis and opioid outcomes was found.

Read the original research

Effects of randomization to buprenorphine or naltrexone for OUD on cannabis use outcomes: A secondary analysis of the X:BOT trial.

Drug and alcohol dependence, 268, 112550

View on PubMed ↗Publisher’s paper ↗

Citation

Shulman, Matisyahu; Choo, Tse-Hwei; Ohrtman, Kaitlyn; Pavlicova, Martina; Rotrosen, John; Nunes, Edward V. (2025). Effects of randomization to buprenorphine or naltrexone for OUD on cannabis use outcomes: A secondary analysis of the X:BOT trial.. Drug and alcohol dependence, 268, 112550. https://doi.org/10.1016/j.drugalcdep.2025.112550