Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis

Sagnik Bhattacharyya; Z Atakan; R Martin-Santos; J A Crippa; J Kambeitz; S Malhi; V Giampietro; S Williams; M Brammer; K Rubia; D A Collier; P K McGuire

doi:10.1016/j.euroneuro.2014.11.018

Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis

Eur Neuropsychopharmacol. 2015 Jan;25(1):26-37. doi: 10.1016/j.euroneuro.2014.11.018. Epub 2014 Dec 4.

Authors

Sagnik Bhattacharyya¹, Z Atakan², R Martin-Santos³, J A Crippa⁴, J Kambeitz⁵, S Malhi², V Giampietro⁶, S Williams⁶, M Brammer⁶, K Rubia⁷, D A Collier⁸, P K McGuire²

Affiliations

¹ 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.
² Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
³ Pharmacology Research Unit, IMIM-Hospital del Mar and Psychiatric Department, ICN, Hospital Clinico, Barcelona-08036, Spain.
⁴ Department of Neuro science and Behavior, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14048-900 Ribeirão Preto, Brazil.
⁵ 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.
⁶ Department of Neuroimaging, Centre for Neuroimaging Sciences, PO Box 089, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
⁷ Department of Child and Adolescent Psychiatry, PO Box 046, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
⁸ Social, Genetic & Developmental Psychiatry Centre, PO Box 082, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.

PMID: 25532865
DOI: 10.1016/j.euroneuro.2014.11.018

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.

Keywords: Cannabis; Functional MRI; Inferior frontal gyrus; Psychotic symptoms; Response inhibition; THC.

Publication types

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

MeSH terms

Area Under Curve
Brain / blood supply
Brain / drug effects*
Chi-Square Distribution
Cross-Over Studies
Decision Making / drug effects
Double-Blind Method
Dronabinol / adverse effects*
Female
Hallucinogens / adverse effects*
Humans
Image Processing, Computer-Assisted
Inhibition, Psychological*
Learning Disabilities / chemically induced*
Male
Oxygen / blood
Psychiatric Status Rating Scales
Statistics as Topic
Time Factors
Visual Analog Scale

Substances

Hallucinogens
Dronabinol
Oxygen

Abstract

Publication types

MeSH terms

Substances

Grants and funding