Cannabis use disorder (CUD) is a complex issue, even more so when it is comorbid with a severe mental disorder (SMD). Available interventions are at best slightly effective, and their effects are not maintained over time. Therefore, the integration of virtual reality (VR) may increase efficacy; however, it has not yet been investigated in the treatment of CUD. A novel approach, avatar intervention for CUD, uses existing therapeutic techniques from other recommended therapies (e.g., cognitive behavioral methods, motivational interviewing) and allows participants to practice them in real-time. During immersive sessions, participants are invited to interact with an avatar representing a significant person related to their drug use. This pilot clinical trial aimed to evaluate the short-term efficacity of avatar intervention for CUD on 19 participants with a dual diagnosis of SMD and CUD. Results showed a significant moderate reduction in the quantity of cannabis use (Cohen’s d = 0.611,p= 0.004), which was confirmed via urinary quantification of cannabis use. Overall, this unique intervention shows promising results. Longer-term results, as well as comparison with classical interventions in a larger sample, are warranted through a future single-blind randomized controlled trial.