Risk for cannabis use and schizophrenia is influenced by genetic factors, and genome-wide association studies (GWASs) and polygenic risk score (PRS) studies have shown that cannabis use and schizophrenia share genetic overlap.11–13 There is also evidence that genetic factors contribute to risk for PLEs,14–16 and studies have found that cognitive symptoms of schizophrenia (eg, disorganized thought patterns) show the most robust associations with polygenic risk for schizophrenia.17–19 Furthermore, a recent study from Wainberg et al.20 showed that the relationship between cannabis use and PLEs in the UK Biobank was moderated by a schizophrenia PRS, with cannabis use having a larger influence on the risk of PLEs for individuals with a higher genetic vulnerability for schizophrenia. It is plausible that individuals with greater polygenic vulnerability to schizophrenia may be particularly sensitive to the psychotomimetic and mood-altering effects of THC and thus, are at greater likelihood of experiencing schizophrenia-related symptoms after cannabis use—including PLEs and cognitive difficulties. Empirical evidence on the association between genetic risk for schizophrenia and cannabis-related experiences, including paranoia, hallucinations, and cognitive difficulties, is scarce. Our study sought to understand whether genetic predisposition to schizophrenia, even in individuals without schizophrenia, could contribute to how individuals respond to cannabis.
