The effects of acute Δ9-tetrahydrocannabinol on striatal glutamatergic function : A proton magnetic resonance spectroscopy study

Journal article

Bloomfield, Michael A. P., Petrilli, Katherine, Lees, Rachel, Hindocha, Chandni, Beck, Katherine, Turner, Ryan J., Onwordi, Ellis Chika, Rane, Neil, Lythgoe, David J., Stone, James M., Curran, H. Valerie, Howes, Oliver D. and Freeman, Tom 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), pp. 660-667. https://doi.org/10.1016/j.bpsc.2021.04.013
AuthorsBloomfield, Michael A. P., Petrilli, Katherine, Lees, Rachel, Hindocha, Chandni, Beck, Katherine, Turner, Ryan J., Onwordi, Ellis Chika, Rane, Neil, Lythgoe, David J., Stone, James M., Curran, H. Valerie, Howes, Oliver D. and Freeman, Tom P.
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.

Keywordscannabis; glutamate; MRS; psychosis; striatum; tetrahydrocannabinol
Year2021
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Journal citation6 (6), pp. 660-667
PublisherElsevier Inc.
ISSN2451-9022
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bpsc.2021.04.013
Scopus EID2-s2.0-85107377757
Research or scholarlyResearch
Page range660-667
Publisher's version
License
All rights reserved
File Access Level
Controlled
Output statusPublished
Publication dates
Online04 Jun 2021
Publication process dates
Accepted09 Apr 2021
Deposited05 Nov 2021
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Chandni Hindocha, Tom P. Freeman, Meryem Grabsk, Jack B. Stroud, Holly Crudgington, Alan C. Davies, Ravi K. Das, William Lawn, Celia Morgan and H. Valerie Curran. (2018). Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal. Addiction. 113(9), pp. 1696-1705. https://doi.org/10.1111/add.14243
Amisulpride for very late-onset schizophrenia-like psychosis: The ATLAS three-arm RCT
Howard, Robert, Cort, Elizabeth, Bradley, Rosie, Harper, Emma, Kelly, Linda, Bentham, Peter, Ritchie, Craig, Reeves, Suzanne, Fawzi, Waleed, Livingston, Gill, Sommerlad, Andrew, Oomman, Sabu, Nazir, Ejaz, Nilforooshan, Ramin, Barber, Robert, Fox, Chris, Macharouthu, Ajay, Ramachandra, Pranathi, Pattan, Vivek, ... Gray, Richard. (2018). Amisulpride for very late-onset schizophrenia-like psychosis: The ATLAS three-arm RCT. Health Technology Assessment. 22(67), pp. 1 - 60. https://doi.org/10.3310/hta22670
Ketamine treatment for depression : Opportunities for clinical innovation and ethical foresight
Singh, Ilina, Morgan, Celia, Curran, Valerie, Nutt, David, Schlag, Anne and McShane, Rupert. (2017). Ketamine treatment for depression : Opportunities for clinical innovation and ethical foresight. The Lancet Psychiatry. 4(5), pp. 419-426. https://doi.org/10.1016/S2215-0366(17)30102-5
Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration
Chandni Hindocha, Tom P. Freeman and H. Valerie Curran. (2017). Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration. Cannabis and Cannabinoid Research. 2(1), pp. 217-223. https://doi.org/10.1089/can.2017.0024
Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: A placebo-controlled trial
Hindocha, Chandni, Freeman, T. P., Xia, J. X., Shaban, Natacha D. C. and Curran, Helen V.. (2017). Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: A placebo-controlled trial. Psychological Medicine. 47(15), pp. 2708 - 2719. https://doi.org/10.1017/S0033291717001222
Editorial : Reporting guidelines for psychopharmacology
Steckler, Thomas, Curran, H. Valerie, de Wit, Harriet, Howes, Oliver, Hoyer, Daniel, Lucki, Irwin, Miczek, Klaus A., Morrow, A. Leslie, Price, Lawrence H. and Robbins, Trevor W.. (2016). Editorial : Reporting guidelines for psychopharmacology. Psychopharmacology. 233(7), pp. 1131-1134. https://doi.org/10.1007/s00213-016-4252-7
AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers
Morgan, Celia J. A., Freeman, T. P., Powell, J. and Curran, Helen V.. (2016). AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers. Translational Psychiatry. 6(2), pp. 1 - 6. https://doi.org/10.1038/tp.2015.219
Deconstructing the nature of episodic foresight deficits associated with chronic opiate use
Mercuri, Kimberly, Terrett, Gill, Bailey, Phoebe E., Henry, Julie D., Curran, Helen Valerie and Rendell, Peter G.. (2016). Deconstructing the nature of episodic foresight deficits associated with chronic opiate use. British Journal of Clinical Psychology. 55(4), pp. 401 - 413. https://doi.org/10.1111/bjc.12110
Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males
Mokrysz, Claire, Freeman, Tom P., Korkki, S., Griffiths, K. and Curran, Helen V.. (2016). Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males. Translational Psychiatry. 6(11), pp. 1 - 10. https://doi.org/10.1038/tp.2016.225
LSD enhances the emotional response to music
Kaelen, M., Barrett, F. S., Roseman, L., Lorenz, R., Family, N., Bolstridge, M., Curran, Helen V., Feilding, A., Nutt, David J. and Carhart-Harris, R. L.. (2015). LSD enhances the emotional response to music. Psychopharmacology. 232(19), pp. 3607 - 3614. https://doi.org/10.1007/s00213-015-4014-y
Effects of immediate-release opioid on memory functioning: A randomized-controlled study in patients receiving sustained-release opioids
Kamboj, S. K., Conroy, L., Tookman, A., Carroll, E., Jones, L. and Curran, H.. (2014). Effects of immediate-release opioid on memory functioning: A randomized-controlled study in patients receiving sustained-release opioids. European Journal of Pain. 18(10), pp. 1376 - 1384. https://doi.org/10.1002/j.1532-2149.2014.498.x
Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study
Stewart, L. H., Ferguson, B., Morgan, C. J. A., Swaboda, N., Jones, L., Fenton, R., Wall, M. B. and Curran, H.. (2014). Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study. Journal of Psychopharmacology. 28(11), pp. 1001 - 1008. https://doi.org/10.1177/0269881114544775
Prospective memory impairment in long-term opiate users
Terrett, Gillian, McLennan, Skye, Henry, Julie, Biernacki, Kathryn, Mercuri, Kimberly, Curran, Valerie and Rendell, Peter. (2014). Prospective memory impairment in long-term opiate users. Psychopharmacology. 231(13), pp. 2623 - 2632. https://doi.org/10.1007/s00213-014-3432-6
Benzodiazepines: Risks and benefits. A reconsideration
Baldwin, David S., Aitchison, Katherine, Bateson, Alan, Curran, H. Valerie, Davies, Simon, Leonard, Brian, Nutt, David J., Stephens, David N. and Wilson, Sue. (2013). Benzodiazepines: Risks and benefits. A reconsideration. Journal of Psychopharmacology. 27(11), pp. 967 - 971. https://doi.org/10.1177/0269881113503509
Prospective memory and future event simulation in individuals with alcohol dependence
Griffiths, Alison, Hill, Robert, Morgan, Celia, Rendell, Peter Gregory, Karimi, Khashayar, Wanagaratne, Shamil and Curran, Valerie. (2012). Prospective memory and future event simulation in individuals with alcohol dependence. Addiction. 107(10), pp. 1809 - 1816. https://doi.org/10.1111/j.1360-0443.2012.03941.x
Neurocognitive function and schizophrenia-proneness in individuals dependent on ketamine, on high potency cannabis (skunk) or on cocaine
Morgan, Celia, Duffin, S., Hunt, S., Monaghan, L., Mason, O. and Curran, Helen. (2012). Neurocognitive function and schizophrenia-proneness in individuals dependent on ketamine, on high potency cannabis (skunk) or on cocaine. Pharmacopsychiatry. 45(7), pp. 269 - 274. https://doi.org/10.1055/s-0032-1306310