Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol

Cathy Davies; Matthijs Bossong; Daniel Martins; Robin Wilson; Elizabeth Appiah-Kusi; Grace Blest Hopley; Fernando Zelaya; Paul Allen; Michael Brammer; Jesus Perez; Philip McGuire; Sagnik Bhattacharyya

doi:10.1017/S0033291723002775

Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol

Cathy Davies, Matthijs Bossong, Daniel Martins, Robin Wilson, Elizabeth Appiah-Kusi, Grace Blest Hopley, Fernando Zelaya, Paul Allen, Michael Brammer, Jesus Perez, Philip McGuire, Sagnik Bhattacharyya^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

56 Downloads (Pure)

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 randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. 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<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) 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 normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

Original language	English
Journal	Psychological Medicine
Early online date	17 Oct 2023
DOIs	https://doi.org/10.1017/S0033291723002775
Publication status	E-pub ahead of print - 17 Oct 2023

Keywords

Hippocampus
Psychosis Risk
Arterial Spin Labelling
Cerebral Perfusion
Cannabidiol

Access to Document

10.1017/S0033291723002775Licence: CC BY

Increased hippocampal blood flow_DAVIES_2023_GOLD VoR (CC BY)Final published version, 651 KBLicence: CC BY

Cite this

Davies, C., Bossong, M., Martins, D., Wilson, R., Appiah-Kusi, E., Blest Hopley, G., Zelaya, F., Allen, P., Brammer, M., Perez, J., McGuire, P., & Bhattacharyya, S. (2023). Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol. Psychological Medicine. Advance online publication. https://doi.org/10.1017/S0033291723002775

@article{bb65e0d00ed84914b1b73ef9de3f8abc,

title = "Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol",

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 randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. 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<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) 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 normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.",

keywords = "Hippocampus, Psychosis Risk, Arterial Spin Labelling, Cerebral Perfusion, Cannabidiol",

author = "Cathy Davies and Matthijs Bossong and Daniel Martins and Robin Wilson and Elizabeth Appiah-Kusi and {Blest Hopley}, Grace and Fernando Zelaya and Paul Allen and Michael Brammer and Jesus Perez and Philip McGuire and Sagnik Bhattacharyya",

note = "Funding Information: 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. Publisher Copyright: Copyright {\textcopyright} The Author(s), 2023. Published by Cambridge University Press.",

year = "2023",

month = oct,

day = "17",

doi = "10.1017/S0033291723002775",

language = "English",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

TY - JOUR

T1 - Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol

AU - Davies, Cathy

AU - Bossong, Matthijs

AU - Martins, Daniel

AU - Wilson, Robin

AU - Appiah-Kusi, Elizabeth

AU - Blest Hopley, Grace

AU - Zelaya, Fernando

AU - Allen, Paul

AU - Brammer, Michael

AU - Perez, Jesus

AU - McGuire, Philip

AU - Bhattacharyya, Sagnik

N1 - Funding Information: 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. Publisher Copyright: Copyright © The Author(s), 2023. Published by Cambridge University Press.

PY - 2023/10/17

Y1 - 2023/10/17

N2 - 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 randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. 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<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) 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 normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

AB - 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 randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. 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<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) 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 normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

KW - Hippocampus

KW - Psychosis Risk

KW - Arterial Spin Labelling

KW - Cerebral Perfusion

KW - Cannabidiol

UR - http://www.scopus.com/inward/record.url?scp=85175058167&partnerID=8YFLogxK

U2 - 10.1017/S0033291723002775

DO - 10.1017/S0033291723002775

M3 - Article

SN - 0033-2917

JO - Psychological Medicine

JF - Psychological Medicine

ER -

Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this