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Neuropsychopharmacology
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Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

Neuropsychopharmacologyvolume 40pages1343–1352 (2015)Cite this article

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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.

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Acknowledgements

We thank Glynis Ivin for help with the blinding procedure, storage and dispensing of the drugs. This work was supported by a Joint MRC/Priory Clinical research training fellowship award (G0501775) from the Medical Research Council (MRC), UK to SB and a grant from the Psychiatry Research Trust, UK to PM. SB has received support from the National Institute of health Research (NIHR) (NIHR Clinician Scientist Award; NIHR CS-11-001) and the MRC (MR/J012149/1). IF was supported by the GA Lienert Foundation, Adolf-Schmidtmann-Foundation, FAZIT-Foundation and the German Academic Exchange Service. JAC is the recipient of a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) Productivity fellowship. The authors acknowledge infrastructure support from the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. SB had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Author information

Authors and Affiliations

  1. Department of Psychosis Studies, King’s College London, Institute of Psychiatry, London, UK

    Sagnik Bhattacharyya, Irina Falkenberg, Zerrin Atakan & Philip McGuire

  2. Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany

    Irina Falkenberg

  3. Instituto de Investigaciones Biomedicas August Pi i Sunyer (IDIBAPS), and Centro de Investigación Biomedica en Red en Salud Mental (CIBERSAM), Barcelona, Spain

    Rocio Martin-Santos

  4. Department of Psychiatry and Psychology, Hospital Clinic, University of Barcelona, Barcelona, Spain

    Rocio Martin-Santos

  5. INCT Translational Medicine (CNPq), Rio de Janeiro, Brazil

    Rocio Martin-Santos & Jose A Crippa

  6. Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil

    Jose A Crippa

  7. Department of Neuroimaging, King’s College London, Institute of Psychiatry, London, UK

    Vincent Giampietro & Mick Brammer

Authors
  1. Sagnik Bhattacharyya
  2. Irina Falkenberg
  3. Rocio Martin-Santos
  4. Zerrin Atakan
  5. Jose A Crippa
  6. Vincent Giampietro
  7. Mick Brammer
  8. Philip McGuire

Corresponding author

Correspondence toSagnik Bhattacharyya.

Additional information

Supplementary Information accompanies the paper on the Neuropsychopharmacology website

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Bhattacharyya, S., Falkenberg, I., Martin-Santos, R.et al. Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience.Neuropsychopharmacol40, 1343–1352 (2015). https://doi.org/10.1038/npp.2014.258

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