title: Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis.
abstract: Cannabis use can induce acute psychotic symptoms and increase the risk of schizophrenia. Impairments in inhibitory control and processing are known to occur both under the influence of cannabis and in schizophrenia. Whether cannabis-induced impairment in inhibitory processing is related to the acute induction of psychotic symptoms under its influence is unclear. We investigated the effects of acute oral administration of 10mg of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on inhibitory control and regional brain activation during inhibitory processing in humans and examined whether these effects are related to the induction of psychotic symptoms under its influence using a repeated-measures, placebo-controlled, double-blind, within-subject design. We studied thirty-six healthy, English-speaking, right-handed men with minimal previous exposure to cannabis and other illicit drugs twice using functional magnetic resonance imaging (fMRI) while they performed a response inhibition (Go/No-Go) task. Relative to placebo, delta-9-THC caused transient psychotic symptoms, anxiety, intoxication and sedation, inhibition errors and impaired inhibition efficiency. Severity of psychotic symptoms was directly correlated with inhibition error frequency and inversely with inhibition efficiency under the influence of delta-9-THC. Delta-9-THC attenuated left inferior frontal activation which was inversely correlated with the frequency of inhibition errors and severity of psychotic symptoms and positively with inhibition efficiency under its influence. These results provide experimental evidence that impairments in cognitive processes involved in the inhibitory control of thoughts and actions and inferior frontal function under the influence of cannabis may have a role in the emergence of transient psychotic symptoms under its influence.
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. Electronic address: sagnik.2.bhattacharyya@kcl.ac.uk.
authors.forename: Sagnik
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Atakan
authors.affiliation: Pharmacology Research Unit, IMIM-Hospital del Mar and Psychiatric Department, ICN, Hospital Clinico, Barcelona-08036, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Martin-Santos
authors.affiliation: Department of Neuro science and Behavior, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14048-900 Ribeirão Preto, Brazil.
authors.forename: J A
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK; Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Kambeitz
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
authors.forename: S
authors.initials: S
authors.lastname: Malhi
authors.affiliation: Department of Neuroimaging, Centre for Neuroimaging Sciences, PO Box 089, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
authors.forename: V
authors.initials: V
authors.lastname: Giampietro
authors.affiliation: Department of Neuroimaging, Centre for Neuroimaging Sciences, PO Box 089, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.affiliation: Department of Neuroimaging, Centre for Neuroimaging Sciences, PO Box 089, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
authors.forename: M
authors.initials: M
authors.lastname: Brammer
authors.affiliation: Department of Child and Adolescent Psychiatry, PO Box 046, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
authors.forename: K
authors.initials: K
authors.lastname: Rubia
authors.affiliation: Social, Genetic & Developmental Psychiatry Centre, PO Box 082, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
authors.forename: P K
authors.initials: PK
authors.lastname: McGuire
mesh_terms: D019540:Area Under Curve; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D016009:Chi-Square Distribution; D018592:Cross-Over Studies; D003657:Decision Making / Q000187:drug effects; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects*; D005260:Female; D006213:Hallucinogens / Q000009:adverse effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007266:Inhibition, Psychological; D007859:Learning Disabilities / Q000139:chemically induced*; D008297:Male; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D013223:Statistics as Topic; D013997:Time Factors; D064232:Visual Analog Scale
chemical_list: D006213:Hallucinogens; D013759:Dronabinol; D010100:Oxygen
keywords: Cannabis; Functional MRI; Inferior frontal gyrus; Psychotic symptoms; Response inhibition; THC