title: Cannabis, COMT and psychotic experiences.
abstract: BACKGROUND
  A putative interaction between cannabis and variation at rs4680 within the catechol-methyl-transferase (COMT) gene on psychosis has been reported, but not adequately replicated.
  
  
  OBJECTIVE
  To examine whether the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT.
  
  
  METHODS
  A longitudinal study of 2630 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who completed questionnaire-based assessments for cannabis use at age 14 and incident psychotic experiences at age 16. Six SNPs within COMT were genotyped.
  
  
  RESULTS
  There was no evidence of an interaction under multiplicative models between cannabis use and COMT on the risk of developing psychotic experiences in our primary analyses. In sensitivity analyses we observed highly variable evidence of interaction, whereby psychotomimetic effects of cannabis were greater in methionine homozygotes under some scenarios, but in valine homozygotes under others.
  
  
  CONCLUSIONS
  Cannabis increases risk of psychosis irrespective of underlying COMT genotypes. These findings argue against the widely held belief that the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT. The public health message about the potential increase in risk of psychotic disorders following cannabis use should not be tempered by reports that this harm is subgroup specific in the absence of robust evidence of replication.
authors.affiliation: Department of Psychological Medicine & Neurology, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. zammits@cardiff.ac.uk
authors.forename: Stanley
authors.initials: S
authors.lastname: Zammit
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Evans
authors.forename: Jon
authors.initials: J
authors.lastname: Heron
authors.forename: Glyn
authors.initials: G
authors.lastname: Lewis
mesh_terms: D000293:Adolescent; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006212:Hallucinations / Q000453:epidemiology / Q000523:psychology; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D002189:Marijuana Abuse / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D008715:Methionine / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D012306:Risk; D057566:Self Report; D014633:Valine / Q000235:genetics
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine