While intuitively appealing, the above genotype x environment interaction model has witnessed only limited replication. For instance, Zammit and colleagues (66), examined whether cannabis use at age 14 was associated with psychotic symptoms at age 16 in the Avon Longitudinal Study of Parents and Children (N=2630). There was no support for an interaction between cannabis exposure and COMT genotype and sensitivity analyses indicated a high degree of variability in the interaction findings based on the outcomes and exposure definition under study. However, in a smaller sample of patients with psychotic disorder (N=31) and healthy controls (N=25), carriers of the Val allele showed hallucinations after cannabis exposure (recorded via experience sampling) but only if they had reported a prior history of psychosis proneness (67). Similarly, in another psychiatric patient population (N=157), decreasing copies of the Val allele were associated with decreasing age at onset of psychotic disorder in lifetime cannabis users whereas the reverse was noted (decreasing age at onset with decreasing copies of Val allele) for lifetime nonusers (68). In addition, a recent study (N=533) posits that the predictive effect
