Evidence suggests that childhood trauma and cannabis use sinergistically impact on psychosis risk, although a non-replication of this environment-environment interaction was recently published. Gene-environment interaction mechanisms may partially account for this discrepancy. The aim of the current study was to test whether the association between childhood abuse, cannabis use and psychotic experiences (PEs) was moderated by the COMT gene. PEs, childhood abuse, cannabis use and COMT Val158Met genotypes were assessed in 533 individuals from the general population. Childhood abuse was shown to have a significant main effect on PEs (B=.08; SE=.04; p=.047). Furthermore, a significant three-way interaction among childhood abuse, cannabis use and the COMT gene was found (B=-.23; SE=.11; p=.006). This indicates that COMT genotypes and cannabis use only influenced PE scores among individuals exposed to childhood abuse. Exposure to childhood abuse and cannabis use increased PE scores in Val carriers. However, in individuals exposed to childhood abuse but who do not use cannabis, PEs increased as a function of the Met allele copies of the COMT gene. Our findings suggest that the psychosis-inducing effects of childhood abuse and cannabis use are moderated by the Val158Met polymorphism of the COMT gene, which supports a gene-environment-environment interaction. Cannabis use after exposure to childhood abuse may have opposite effects on the risk of PEs, depending on the COMT genotypes. Val carriers are vulnerable to the psychosis-inducing effects of cannabis.