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An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition.
Neuropsychopharmacology 2006; 31(12):2748-57N

Abstract

Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n=30), relatives of patients with a psychotic disorder (n=12), and healthy controls (n=32) were exposed to Delta-9-tetrahydrocannabinol (Delta-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to Delta-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. Delta-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to Delta-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMT Val(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions.

Authors+Show Affiliations

Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16936704

Citation

Henquet, Cécile, et al. "An Experimental Study of Catechol-o-methyltransferase Val158Met Moderation of Delta-9-tetrahydrocannabinol-induced Effects On Psychosis and Cognition." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 31, no. 12, 2006, pp. 2748-57.
Henquet C, Rosa A, Krabbendam L, et al. An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology. 2006;31(12):2748-57.
Henquet, C., Rosa, A., Krabbendam, L., Papiol, S., Fananás, L., Drukker, M., ... van Os, J. (2006). An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 31(12), pp. 2748-57.
Henquet C, et al. An Experimental Study of Catechol-o-methyltransferase Val158Met Moderation of Delta-9-tetrahydrocannabinol-induced Effects On Psychosis and Cognition. Neuropsychopharmacology. 2006;31(12):2748-57. PubMed PMID: 16936704.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. AU - Henquet,Cécile, AU - Rosa,Araceli, AU - Krabbendam,Lydia, AU - Papiol,Sergi, AU - Fananás,Lourdes, AU - Drukker,Marjan, AU - Ramaekers,Johannes G, AU - van Os,Jim, Y1 - 2006/08/23/ PY - 2006/8/29/pubmed PY - 2007/1/6/medline PY - 2006/8/29/entrez SP - 2748 EP - 57 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 31 IS - 12 N2 - Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n=30), relatives of patients with a psychotic disorder (n=12), and healthy controls (n=32) were exposed to Delta-9-tetrahydrocannabinol (Delta-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to Delta-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. Delta-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to Delta-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMT Val(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/16936704/abstract/An_Experimental_Study_of_Ca L2 - http://dx.doi.org/10.1038/sj.npp.1301197 DB - PRIME DP - Unbound Medicine ER -