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Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC

Published online by Cambridge University Press:  05 March 2018

Sagnik Bhattacharyya ,
Thomas Sainsbury ,
Paul Allen ,
Chiara Nosarti ,
Zerrin Atakan ,
Vincent Giampietro ,
Michael Brammer  and
P K McGuire
Sagnik Bhattacharyya*
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK
Thomas Sainsbury
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Paul Allen
Affiliation:
Department of Psychology, University of Roehampton, UK
Chiara Nosarti
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, London, UK
Zerrin Atakan
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK
Vincent Giampietro
Affiliation:
Department of Neuroimaging, King's College London, Institute of Psychiatry, PO Box 089, De Crespigny Park, London, SE5 8AF, UK
Michael Brammer
Affiliation:
Department of Neuroimaging, King's College London, Institute of Psychiatry, PO Box 089, De Crespigny Park, London, SE5 8AF, UK
P K McGuire
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK
*
Author for correspondence: Dr Sagnik Bhattacharyya, E-mail: sagnik.2.bhattacharyya@kcl.ac.uk
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Abstract

Background

Cannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.

Methods

We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22).

Results

Under placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC.

Conclusions

These results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.

Keywords

Cannabisδ-9-tetrahydrocannabinolfMRIhippocampuspsychosisverbal learning
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 16 , December 2018 , pp. 2748 - 2756
Copyright
Copyright © Cambridge University Press 2018 

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