title: Cannabinoid modulation of functional connectivity within regions processing attentional salience.
abstract: There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli.
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Sagnik
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: 1] Department of Psychosis Studies, King's College London, Institute of Psychiatry, London, UK [2] Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Falkenberg
authors.affiliation: 1] Instituto de Investigaciones Biomedicas August Pi i Sunyer (IDIBAPS), and Centro de Investigación Biomedica en Red en Salud Mental (CIBERSAM), Barcelona, Spain [2] Department of Psychiatry and Psychology, Hospital Clinic, University of Barcelona, Barcelona, Spain [3] INCT Translational Medicine (CNPq), Rio de Janeiro, Brazil.
authors.forename: Rocio
authors.initials: R
authors.lastname: Martin-Santos
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Zerrin
authors.initials: Z
authors.lastname: Atakan
authors.affiliation: 1] INCT Translational Medicine (CNPq), Rio de Janeiro, Brazil [2] Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Department of Neuroimaging, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Giampietro
authors.affiliation: Department of Neuroimaging, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Mick
authors.initials: M
authors.lastname: Brammer
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D002185:Cannabidiol / Q000494:pharmacology*; D002188:Cannabis; D013759:Dronabinol / Q000494:pharmacology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008385:Marijuana Smoking / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009483:Neuropsychological Tests; D011619:Psychotropic Drugs / Q000494:pharmacology*
chemical_list: D011619:Psychotropic Drugs; D002185:Cannabidiol; D013759:Dronabinol