The bidirectional causal relationship between psychotic disorders and cannabis phenotypes is also often debated. A common hypothesis is that cannabis is a risk factor in the development of psychotic disorders,14 whereas a reverse causality hypothesis posits that psychotic disorders lead to cannabis use as a potential way to alleviate symptoms.14,15 Both causation and reverse causation are not mutually exclusive and have been assessed using mendelian randomization (MR), a statistical framework to test causal associations using genetic liability to the phenotypes of interest.16 For example, a bidirectional causal relationship has been suggested between LCU and SCZ.7,9,17 The accumulation of larger genome-wide association study (GWAS) datasets provides opportunities to improve assessment of causal relationships using MR.
