ABSTRACT
Background Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown.
Methods Using a double-blind, parallel-group design, 33 CHR patients were randomised to a single oral 600mg dose of CBD or placebo. Nineteen healthy controls were studied under identical conditions but did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labelling. We examined differences relating to CHR status (controls vs placebo), effects of CBD in CHR (placebo vs CBD) and linear between-group relationships, such that placebo>CBD>controls or controls>CBD>placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.
Results Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<.01) compared to controls. There were no suprathreshold effects in the CBD vs placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE=.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo.
Conclusions These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalised by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
ISRCTN46322781
Funding Statement
This study was supported by grant MR/J012149/1 from the Medical Research Council (MRC). SB has also received support from the National Institute for Health Research (NIHR) (NIHR Clinician Scientist Award; NIHR CS-11-001), the NIHR Mental Health Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London. This study represents independent research supported by the NIHR/Wellcome Trust King's Clinical Research Facility and NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or the Department of Health and Social Care. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. No other disclosures or any competing financial interests were reported.
Author Declarations
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Ethics committee/IRB of Camberwell St Giles gave ethical approval for this work.
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Footnotes
Title, abstract and coverage of previous literature updated in introduction and discussion; some new supplemental analyses.
Data Availability
Data produced in the present study are not openly available.