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

Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Jun;6(6):660-667. doi: 10.1016/j.bpsc.2021.04.013.

Authors

Affiliations

¹ Translational Psychiatry Research Group, Research Department of Mental Health Neuroscience, Division of Psychiatry, Institute of Mental Health, Faculty of Brain Sciences, University College London, London, United Kingdom; Clinical Psychopharmacology Unit, Research Department of Clinical, Educational & Health Psychology, Division of Psychology, Faculty of Brain Sciences, University College London, London, United Kingdom; National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Service (NHS) Foundation Trust, London, United Kingdom; Psychiatric Imaging Group, Medical Research Council London Institute of Medical Sciences, London, United Kingdom; Traumatic Stress Clinic, Camden and Islington NHS Foundation Trust St. Pancras Hospital, London, United Kingdom. Electronic address: m.bloomfield@ucl.ac.uk.
² Translational Psychiatry Research Group, Research Department of Mental Health Neuroscience, Division of Psychiatry, Institute of Mental Health, Faculty of Brain Sciences, University College London, London, United Kingdom; Clinical Psychopharmacology Unit, Research Department of Clinical, Educational & Health Psychology, Division of Psychology, Faculty of Brain Sciences, University College London, London, United Kingdom; Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Addiction and Mental Health Group, Department of Psychology, University of Bath, Bath, United Kingdom.
³ Translational Psychiatry Research Group, Research Department of Mental Health Neuroscience, Division of Psychiatry, Institute of Mental Health, Faculty of Brain Sciences, University College London, London, United Kingdom; Clinical Psychopharmacology Unit, Research Department of Clinical, Educational & Health Psychology, Division of Psychology, Faculty of Brain Sciences, University College London, London, United Kingdom; National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom.
⁴ Psychiatric Imaging Group, Medical Research Council London Institute of Medical Sciences, London, United Kingdom; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
⁵ Translational Psychiatry Research Group, Research Department of Mental Health Neuroscience, Division of Psychiatry, Institute of Mental Health, Faculty of Brain Sciences, University College London, London, United Kingdom.
⁶ Psychiatric Imaging Group, Medical Research Council London Institute of Medical Sciences, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom; West London Mental Health NHS Foundation Trust, London, United Kingdom.
⁷ Department of Neuroradiology, Imperial College London Hospitals NHS Trust, London, United Kingdom.
⁸ Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
⁹ Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom.
¹⁰ Clinical Psychopharmacology Unit, Research Department of Clinical, Educational & Health Psychology, Division of Psychology, Faculty of Brain Sciences, University College London, London, United Kingdom; National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom.
¹¹ Psychiatric Imaging Group, Medical Research Council London Institute of Medical Sciences, London, United Kingdom; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom.
¹² Translational Psychiatry Research Group, Research Department of Mental Health Neuroscience, Division of Psychiatry, Institute of Mental Health, Faculty of Brain Sciences, University College London, London, United Kingdom; Clinical Psychopharmacology Unit, Research Department of Clinical, Educational & Health Psychology, Division of Psychology, Faculty of Brain Sciences, University College London, London, United Kingdom; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Addiction and Mental Health Group, Department of Psychology, University of Bath, Bath, United Kingdom.

PMID: 34099186
DOI: 10.1016/j.bpsc.2021.04.013

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.

Keywords: Cannabis; Glutamate; MRS; Psychosis; Striatum; Tetrahydrocannabinol.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Bayes Theorem
Corpus Striatum
Dronabinol* / pharmacology
Hallucinogens*
Humans
Proton Magnetic Resonance Spectroscopy

Substances

Hallucinogens
Dronabinol