The Effects of Acute Δ9-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study

Michael A.P. Bloomfield; Katherine Petrilli; Rachel Lees; Chandni Hindocha; Katherine Beck; Ryan J. Turner; Ellis Chika Onwordi; Neil Rane; David J. Lythgoe; James M. Stone; H. Valerie Curran; Oliver D. Howes; Tom P. Freeman

doi:10.1016/j.bpsc.2021.04.013

The Effects of Acute Δ⁹-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study

Michael A.P. Bloomfield, Katherine Petrilli, Rachel Lees, Chandni Hindocha, Katherine Beck, Ryan J. Turner, Ellis Chika Onwordi, Neil Rane, David J. Lythgoe, James M. Stone, H. Valerie Curran, Oliver D. Howes, Tom P. Freeman

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

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Abstract

Background: Cannabis and its main psychoactive component, Δ⁹-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. Methods: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. Results: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p =.58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. Conclusions: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate.

Original language	English
Pages (from-to)	660-667
Number of pages	8
Journal	Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Volume	6
Issue number	6
Early online date	4 Jun 2021
DOIs	https://doi.org/10.1016/j.bpsc.2021.04.013
Publication status	Published - 30 Jun 2021

Bibliographical note

Funding Information:
This work was supported by the British Medical Association Foundation for Medical Research (Margaret Temple grant [to MAPB]), Medical Research Council (Grant No. MC-A656-5QD30 [to ODH]), UCL Excellence Fellowship (to MAPB), National Institute for Health Research University College London Hospitals Biomedical Research Centre (to MAPB, CH, and HVC), and Society for the Study of Addiction (senior academic fellowship to TPF).

Publisher Copyright:
© 2021

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

Cannabis
Glutamate
MRS
Psychosis
Striatum
Tetrahydrocannabinol

ASJC Scopus subject areas

Biological Psychiatry
Cognitive Neuroscience
Clinical Neurology
Radiology Nuclear Medicine and imaging

Access to Document

10.1016/j.bpsc.2021.04.013

MRS THC_Revision_Submission_2Accepted author manuscript, 157 KBLicence: CC BY-NC-ND

Cite this

Bloomfield, M. A. P., Petrilli, K., Lees, R., Hindocha, C., Beck, K., Turner, R. J., Onwordi, E. C., Rane, N., Lythgoe, D. J., Stone, J. M., Curran, H. V., Howes, O. D., & Freeman, T. P. (2021). The Effects of Acute Δ⁹-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 6(6), 660-667. https://doi.org/10.1016/j.bpsc.2021.04.013

The Effects of Acute Δ⁹-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study. / Bloomfield, Michael A.P.; Petrilli, Katherine ; Lees, Rachel et al.
In: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Vol. 6, No. 6, 30.06.2021, p. 660-667.

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

Bloomfield, MAP, Petrilli, K , Lees, R, Hindocha, C, Beck, K, Turner, RJ, Onwordi, EC, Rane, N, Lythgoe, DJ, Stone, JM, Curran, HV, Howes, OD & Freeman, TP 2021, 'The Effects of Acute Δ⁹-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study', Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, vol. 6, no. 6, pp. 660-667. https://doi.org/10.1016/j.bpsc.2021.04.013

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title = "The Effects of Acute Δ9-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study",

abstract = "Background: Cannabis and its main psychoactive component, Δ9-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. Methods: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. Results: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p =.58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. Conclusions: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate.",

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note = "Funding Information: This work was supported by the British Medical Association Foundation for Medical Research (Margaret Temple grant [to MAPB]), Medical Research Council (Grant No. MC-A656-5QD30 [to ODH]), UCL Excellence Fellowship (to MAPB), National Institute for Health Research University College London Hospitals Biomedical Research Centre (to MAPB, CH, and HVC), and Society for the Study of Addiction (senior academic fellowship to TPF). Publisher Copyright: {\textcopyright} 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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T1 - The Effects of Acute Δ9-Tetrahydrocannabinol on Striatal Glutamatergic Function

T2 - A Proton Magnetic Resonance Spectroscopy Study

AU - Bloomfield, Michael A.P.

AU - Petrilli, Katherine

AU - Lees, Rachel

AU - Hindocha, Chandni

AU - Beck, Katherine

AU - Turner, Ryan J.

AU - Onwordi, Ellis Chika

AU - Rane, Neil

AU - Lythgoe, David J.

AU - Stone, James M.

AU - Curran, H. Valerie

AU - Howes, Oliver D.

AU - Freeman, Tom P.

N1 - Funding Information: This work was supported by the British Medical Association Foundation for Medical Research (Margaret Temple grant [to MAPB]), Medical Research Council (Grant No. MC-A656-5QD30 [to ODH]), UCL Excellence Fellowship (to MAPB), National Institute for Health Research University College London Hospitals Biomedical Research Centre (to MAPB, CH, and HVC), and Society for the Study of Addiction (senior academic fellowship to TPF). Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/6/30

Y1 - 2021/6/30

N2 - Background: Cannabis and its main psychoactive component, Δ9-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. Methods: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. Results: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p =.58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. Conclusions: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate.

AB - Background: Cannabis and its main psychoactive component, Δ9-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. Methods: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. Results: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p =.58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. Conclusions: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate.

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