The current findings suggest that heavy and early-onset cannabis users are more likely to report unusual cannabis-related experiences and that higher genetic vulnerability to schizophrenia may place regular cannabis users at even greater risk for these experiences, especially cognitive difficulties. Even accounting for aspects of cannabis involvement, including polygenic risk for CUD, the schizophrenia PRS was significantly associated with all cannabis-related experiences except for hallucinations. This suggests a role for genetic vulnerability to schizophrenia in cannabis-related experiences, even in those without psychotic disorders. Interestingly, we find that accounting for a PRS for CUD does not dampen the associations between the PRS for schizophrenia and cannabis-related experiences, suggesting that these cannabis-related experiences are more strongly related to genetic liability for schizophrenia in this sample. Despite nonsignificant effects in the replication models, the magnitude of association for the schizophrenia PRS was comparable (supplementary table 6), implying that the much smaller sample size for CATS is the primary factor behind the null results in this replication sample. Notably, these findings are from samples that were partly ascertained for AUD or opioid use disorder and generally had high levels of other substance use; therefore, these results may not generalize to the overall population.
