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Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers

Published online by Cambridge University Press:  01 October 2012

Z. Atakan*
Section of Neuroimaging, Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
S. Bhattacharyya
Section of Neuroimaging, Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
P. Allen
Section of Neuroimaging, Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
R. Martín-Santos
Institut Municipal Investigació Mèdica IMIM Hospital del Mar, Barcelona, Spain
J. A. Crippa
Departamento de Neuropsiquiatria e Psicologia Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil
S. J. Borgwardt
Psychiatric Outpatient Department, University Hospital Basel, Basel, Switzerland
P. Fusar-Poli
Section of Neuroimaging, Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
M. Seal
Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Australia
H. Sallis
Department of Biostatistics, Institute of Psychiatry, King's College London, London, UK
D. Stahl
Department of Biostatistics, Institute of Psychiatry, King's College London, London, UK
A. W. Zuardi
Departamento de Neuropsiquiatria e Psicologia Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil
K. Rubia
Section of Developmental Neuropsychology and Neuroimaging, Institute of Psychiatry, King's College London, London, UK
P. McGuire
Section of Neuroimaging, Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
*Address for correspondence: Z. Atakan, M.D., Department of Psychosis Studies, PO67, Section of Neuroimaging, Institute of Psychiatry, King's College London, DeCrespigny Park, London, SE5 8AF, UK. (Email:



Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms.


In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task.


The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC.


In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.

Original Articles
Copyright © Cambridge University Press 2012 

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