Background: Cardiovascular and metabolic problems combined with a bad lifestyle are a major cause of a shortened life expectancy in chronic psychotic disorders. While the incidence of cannabis use is twice as high in psychosis compared to the general population, use of cannabis has been associated with better outcomes on cardiometabolic risk factors. This study investigates whether this effect is mediated by the AKT1 gene, as activation of the related enzyme by cannabis may cause changes in metabolism. Methods: Patients with a recent onset psychosis (n=623) were included from a cohort study (GROUP). Cannabis use, based on self-report and urine screening, was related to Body Mass index (BMI). Next the mediating effects of six AKT1 polymorphisms (rs1130214, rs1130233, rs2494732, rs2498784, rs3730358 and rs3803300) were investigated. Results: There was a strong, negative association between BMI and cannabis use. Moreover, two SNP's (rs1130233 and rs2494732) showed an association with cannabis use, but did not mediate the effect of cannabis on BMI. Conclusion: In conclusion, cannabis use results in a lower body weight in patients with a psychosis. While AKT1 is related to cannabis use, it does not affect body mass via AKT1. Instead, AKT1 risk alleles may increase the incidence of cannabis use. Future studies may investigate whether other genes mediate the effect between cannabis and metabolic risk factors.