 |
|
Induction of Psychosis by  9-Tetrahydrocannabinol Reflects Modulation of Prefrontal and Striatal Function During Attentional Salience Processing
Sagnik Bhattacharyya, MBBS, MD, PhD;
José Alexandre Crippa, MD, PhD;
Paul Allen, PhD;
Rocio Martin-Santos, MD, PhD;
Stefan Borgwardt, PhD;
Paolo Fusar-Poli, MD;
Katya Rubia, PhD;
Joseph Kambeitz, MB;
Colin O’Carroll, PhD;
Marc L. Seal, PhD;
Vincent Giampietro, PhD;
Michael Brammer, PhD;
Antonio Waldo Zuardi, MD, PhD;
Zerrin Atakan, MD, FRCPsych;
Philip K. McGuire, MD, PhD
Arch Gen Psychiatry. 2012;69(1):27-36. doi:10.1001/archgenpsychiatry.2011.161
Context The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing.
Objective To examine the effects of  9-tetrahydrocannabinol (9-THC) and cannabidiol (CBD) on regional brain function during salience processing.
Design Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of 9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli.
Setting University center.
Participants Fifteen healthy men with minimal previous cannabis use.
Main Outcome Measures Symptom ratings, task performance, and regional brain activation.
Results During the processing of oddball stimuli, relative to placebo, 9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. 9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of 9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of 9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation.
Conclusions 9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.
Author Affiliations: Departments of Psychosis Studies (Drs Bhattacharyya, Allen, Martin-Santos, Borgwardt, Fusar-Poli, Kambeitz, Atakan, and McGuire), Child & Adolescent Psychiatry (Dr Rubia), and Neuroimaging (Drs Giampietro and Brammer), Institute of Psychiatry, King's College London, London, England; Department of Neurology, Psychiatry, and Medical Psychology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil (Drs Crippa and Zuardi); Psychiatric Department, Institute of Neuroscience, Hospital Clinico, Institut d’investigacions Biomediques August Pi i Sunyer (IDIBAPS), Centro de investigacion Biomedica En Red de Salud Mental (CIBERSAM), Barcelona, Spain (Dr Martin-Santos); Psychiatric Outpatient Department, University of Basel, Basel, Switzerland (Dr Borgwardt); Dart Neuroscience LLC, San Diego, California (Dr O’Carroll); and Murdoch Childrens Research Institute, Melbourne, Australia (Dr Seal).
 CiteULike  Connotea  Delicious  Digg  Facebook  Reddit  Technorati  Twitter
What's this?
|
