Original Article

Neuropsychopharmacology (2010) 35, 764–774; doi:10.1038/npp.2009.184; published online 18 November 2009

Opposite Effects of Δ-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology

Sagnik Bhattacharyya1, Paul D Morrison2, Paolo Fusar-Poli1,3, Rocio Martin-Santos1,4, Stefan Borgwardt1,5, Toby Winton-Brown1, Chiara Nosarti6, Colin M O' Carroll7, Marc Seal8, Paul Allen1, Mitul A Mehta9, James M Stone1, Nigel Tunstall2, Vincent Giampietro10, Shitij Kapur11, Robin M Murray2, Antonio W Zuardi12,13, José A Crippa12,13, Zerrin Atakan1 and Philip K McGuire1

  1. 1Section of Neuroimaging, Division of Psychological Medicine & Psychiatry, Institute of Psychiatry, King's College London, London, UK
  2. 2Division of Psychological Medicine & Psychiatry, Institute of Psychiatry, King’s College London, London, UK
  3. 3Section of Psychiatry, Department of Health Sciences, University of Pavia, Pavia, Italy
  4. 4Department of Psychiatry, Institut of Neurosciences, Hospital Clínic, Barcelona, Spain
  5. 5Psychiatric Outpatient Department, University Hospital Basel, Basel, Switzerland
  6. 6Cognition Schizophrenia and Imaging (CSI) Laboratory, Division of Psychological Medicine & Psychiatry, Institute of Psychiatry, King’s College London, London, UK
  7. 7Columbia University, Department of Neuroscience, New York, NY, USA
  8. 8Melbourne Neuropsychiatry Centre, The University of Melbourne, National Neuroscience Facility, Carlton South, VIC, Australia
  9. 9Centre for Neuroimaging Sciences, Institute of Psychiatry, KCL, London, UK
  10. 10Department of Biostatistics, Institute of Psychiatry, King’s College London, London, UK
  11. 11Section on Schizophrenia, Imaging and Therapeutics, Division of Psychological Medicine & Psychiatry, Institute of Psychiatry, King's College London, London, UK
  12. 12Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
  13. 13INCT Translational Medicine, Ribeirão Preto, Brazil

Correspondence: Dr S Bhattacharyya, Kings College London, Section of Neuroimaging, Box P067, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. Tel: +44 20 7848 0955, Fax: +44 20 7848 0976, E-mail: s.bhattacharyya@iop.kcl.ac.uk

Received 20 May 2009; Revised 30 September 2009; Accepted 30 September 2009; Published online 18 November 2009.

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Abstract

Δ-9-tetrahydrocannabinol (Δ-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Δ-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Δ-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Δ-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Δ-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Δ-9-THC. Δ-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Δ-9-tetrahydrocannabinol. Δ-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Δ-9-THC.

Keywords:

Δ-9-tetrahydrocannabinol, Cannabidiol, psychosis, anxiety, fMRI

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