schizophreniabulletin.oxfordjournals.org
schizophreniabulletin.oxfordjournals.org
How Cannabis Causes Paranoia: Using the Intravenous Administration of ?9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia
Daniel Freeman *,1, Graham Dunn2, Robin M. Murray3, Nicole Evans1, Rachel Lister1, Angus Antley1, Mel Slater4,5, Beata Godlewska1, Robert Cornish6, Jonathan Williams7, Martina Di Simplicio8, Artemis Igoumenou9, Rudolf Brenneisen10, Elizabeth M. Tunbridge1, Paul J. Harrison1, Catherine J. Harmer1, Philip Cowen1 and Paul D. Morrison3 +Author Affiliations
1 Department of Psychiatry, University of Oxford, Oxford, UK;2 Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester, UK;3 Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, UK;4 Department of Computer Science, University College London, London, UK;5 Institució Catalana de Recerca i Estudis Avançats (ICREA), University of Barcelona, Barcelona, Spain;6 Oxford Health NHS Foundation Trust, Oxford, UK;7 Waikato Hospital, Hamilton, New Zealand;8 MRC Cognition and Brain Sciences Unit, Cambridge, UK;9 Queen Mary University of London, Violence Prevention Research Unit, Barts and the London School of Medicine and Dentistry, Wolfson Institute of Preventive Medicine, London, UK;10 Department Clinical Research, University of Bern, Bern, Switzerland ?*To whom correspondence should be addressed; Oxford Cognitive Approaches to Psychosis, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK; tel:+44 (0)1865 226590, fax: + 44 (0)1865 793101, e-mail: daniel.freeman@psych.ox.ac.uk
Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis—?9-tetrahydrocannabinol (THC)—causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences.
(emphasis mine) |
