Cannabis Beyond Good and Evil. How genetic and epidemiological factors shape the relationship between cannabis and psychosis

Abstract

The studies presented in this thesis aimed to identify genetic and non-genetic (epidemiological) factors that shape the association between cannabis use and psychosis. We showed that the age of first use of cannabis is a determinant for the strength of the association between cannabis use and psychotic symptoms and general mental health, as is the amount of cannabis that is consumed. Moreover it is likely that the THC/CBD ratio in consumed cannabis products further shapes the relationship between cannabis and psychosis. In the second part we suggest that carriers of the “A” risk allele in a SNP of the P2RX7 gene might have an increased risk of experiencing psychosis symptoms if they are heavy cannabis users. Finally we showed that the expression of liprin-α-2 mRNA is increased in the blood of heavy cannabis users compared to cannabis-naïve individuals. The meaning of the latter two findings is still unclear. We are currently conducting additional functional analyses to test these hypotheses. In conclusion, the current thesis adds to the notion that exposure of the developing brain to THC increases the risk of developing psychosis. Several potential pathophysiological pathways are suggested, including interference with microglial function