Materials and Methods

Collection of evidence started through library search available under quick links of the university website. An advanced search was chosen to seek for online newspaper articles. Originally, the keywords such as cannabis and effects were used to understand the biology of how cannabis would induce its effects on the brain. There were at least two thousand results found for all databases. It was possible to view a full text of the article via external link, which showed the newspaper website where article was published. The archives of Elsevier, PubMed, Nature and Highwire Press were most commonly used. The articles were about psychological and physiological effects of cannabis. Further actions towards evidence search were based upon the hypothesis, which indicated the influences of cannabis on psychotic symptoms would be controlled by COMT polymorphism. The keywords, such as COMT polymorphism, cannabis, psychosis were used. There were found articles pointing to the effects of cannabis on psychosis via control of several gene mutations and polymorphisms. There were studies, which have investigated neurobiology of cannabis induced schizophrenia. The newspaper articles, which were chosen to be of central importance: “Interaction between COMT haplotypes and cannabis in schizophrenia: a case-only study in two samples from Spain” by Costas and colleagues; “Moderation of the effect of adolescent – onset cannabis use on adult psychosis by a functional polymorphism in the Catecol-o-methyltransferase: Longitudinal evidence of a gene X environment interaction” by Caspi and colleagues; “Cannabis, COMT and psychotic experiences” by Zammit and colleagues; “A highly significant association between a COMT haplotype and schizophrenia” by Shifman and colleagues; “Opposite effects of catechol-o-methyltransferase Val158Met on cortical function in healthy subjects and patients with schizophrenia” by Diana P Prata and colleagues. It was logical to focus on COMT polymorphism as a candidate gene to psychosis because of the known relationship between COMT activity and dopamine regulation.

Results The effect of adolescent cannabis use on adult psychosis is controlled by genetic variation in the comt gene.

Participants were members of Dunedin Multidisciplinary Health and Development study. DNA samples were obtained by phlebotomy at age 26 from 953 study members. The functional SNP polymorphism (Val158Met) genotyping was performed by Applied Biosystems.

Psychosis outcomes at age 26 were examined according to the diagnostic criteria from the DSM-IV (Diagnostic Interview Schedule) for the symptoms, such as hallucinations, delusions, disorganized speech, catatonic behaviour and negative symptoms, such as avolition and alogia. Cannabis use at ages 13, 15, 21 and 26 was examined according to the diagnostic criteria for cannabis dependence.

Adolescent cannabis exposure was associated with increased risk of developing schizophreniform disorder among homozygous for Val allele individuals and heterozygous individuals, who also have shown adolescent cannabis use may operate as a risk factor for this disorder. The effects of Met/Met genotype and adolescent cannabis use on schizophreniform disorder development were not significant (Figure 4A).

Figure 4B shows number of individuals (%) reported phenomena, such as hallucinations and delusions at age 26. The influences of adolescent cannabis use on psychosis at age 26 were associated with Val/Val and Val/Met genotype but not with Met/Met genotype.

Figure 4C shows number of patients (%) reported hallucinatory experiences at age 26. Homozygous for Val allele individuals had higher risk of hallucination experience, when exposed to adolescent cannabis use than homozygous for Met allele.

Figure 4D shows number of individuals (%) with reports of at least one delusion at age 26. The interaction between Val/Val genotype and adolescent cannabis use results in increase in risk of delusional beliefs in adulthood. Adolescent cannabis use was also associated with increased risk of delusional beliefs among Val/Met and Met/Met carriers.

Figure 4E shows number of individuals (%) with informant reports of psychosis at age 26. Adolescent cannabis use was associated with informant reports of psychotic symptoms among homozygous for Val allele individuals and heterozygous Val/Met individuals, but not among Met/Met individuals.

In addition, gene and environment interactions were tested whether the influences of gender may affect psychosis outcomes. Three way interactions did not show significant results; adolescent cannabis use was associated with psychosis among homozygous for Val allele both male and female (Caspi 2005).

Figure 4 Genetic variation in COMT influences the harmful effects of adolescent cannabis use (Caspi 2005).