title: Genetic moderation of the effects of cannabis: catechol-O-methyltransferase (COMT) affects the impact of Δ9-tetrahydrocannabinol (THC) on working memory performance but not on the occurrence of psychotic experiences.
abstract: Cannabis use can induce cognitive impairments and psychotic experiences. A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val(158)Met) appears to influence the immediate cognitive and psychotic effects of cannabis, or ∆(9)-tetrahydrocannabinol (THC), its primary psychoactive ingredient. This study investigated the moderation of the impact of experimentally administered THC by COMT. Cognitive performance and psychotic experiences were studied in participants without a psychiatric diagnosis, using a between-subjects design (THC vs. placebo). The effect of COMT Val(158)Met genotype on the cognitive and psychotic effects of THC, administered intravenously in a double-blind, placebo-controlled manner to 78 participants who were vulnerable to paranoia, was examined. The results showed interactive effects of genotype and drug group (THC or placebo) on working memory, assayed using the Digit Span Backwards task. Specifically, THC impaired performance in COMT Val/Val, but not Met, carriers. In contrast, the effect of THC on psychotic experiences, measured using the Community Assessment of Psychic Experiences (CAPE) positive dimension, was unaffected by COMT genotype. This study is the largest to date examining the impact of COMT genotype on response to experimentally administered THC, and the first using a purely non-clinical cohort. The data suggest that COMT genotype moderates the cognitive, but not the psychotic, effects of acutely administered THC.
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK elizabeth.tunbridge@psych.ox.ac.uk.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Tunbridge
authors.affiliation: Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Dunn
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Evans
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lister
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Katharina
authors.initials: K
authors.lastname: Stumpenhorst
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Harrison
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Morrison
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Freeman
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D011110:Polymorphism, Genetic / Q000235:genetics; D011605:Psychoses, Substance-Induced / Q000235:genetics* / Q000523:psychology*
chemical_list: D013759:Dronabinol; D002394:Catechol O-Methyltransferase
keywords: Cannabis; dopamine; psychosis