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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.
J Psychopharmacol. 2015 Nov; 29(11):1146-51.JP

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+Show Affiliations

Department of Psychiatry, University of Oxford, Oxford, UK elizabeth.tunbridge@psych.ox.ac.uk.Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester, UK.Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.Department of Psychiatry, University of Oxford, Oxford, UK.Department of Psychiatry, University of Oxford, Oxford, UK.Department of Psychiatry, University of Oxford, Oxford, UK.Department of Psychiatry, University of Oxford, Oxford, UK.Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.Department of Psychiatry, University of Oxford, Oxford, UK.

Pub Type(s)

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

Language

eng

PubMed ID

26464454

Citation

Tunbridge, Elizabeth M., et al. "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." Journal of Psychopharmacology (Oxford, England), vol. 29, no. 11, 2015, pp. 1146-51.
Tunbridge EM, Dunn G, Murray RM, et al. 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. J Psychopharmacol (Oxford). 2015;29(11):1146-51.
Tunbridge, E. M., Dunn, G., Murray, R. M., Evans, N., Lister, R., Stumpenhorst, K., Harrison, P. J., Morrison, P. D., & Freeman, D. (2015). 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. Journal of Psychopharmacology (Oxford, England), 29(11), 1146-51. https://doi.org/10.1177/0269881115609073
Tunbridge EM, et al. 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. J Psychopharmacol (Oxford). 2015;29(11):1146-51. PubMed PMID: 26464454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Tunbridge,Elizabeth M, AU - Dunn,Graham, AU - Murray,Robin M, AU - Evans,Nicole, AU - Lister,Rachel, AU - Stumpenhorst,Katharina, AU - Harrison,Paul J, AU - Morrison,Paul D, AU - Freeman,Daniel, Y1 - 2015/10/13/ PY - 2015/10/15/entrez PY - 2015/10/16/pubmed PY - 2016/8/27/medline KW - Cannabis KW - dopamine KW - psychosis SP - 1146 EP - 51 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 29 IS - 11 N2 - 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. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/26464454/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_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881115609073?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -