Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype

Matthijs G. Bossong, Hendrika H. van Hell, Chris D. Schubart, Wesley van Saane, Tabitha A. Iseger, Gerry Jager, Matthias J.P. van Osch, J.M. Jansma, René S. Kahn, Marco P. Boks, Nick F. Ramsey

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Abstract

Cannabis produces a broad range of acute, dose-dependent psychotropic effects. Only a limited number of neuroimaging studies have mapped these effects by examining the impact of cannabis on resting state brain neurophysiology. Moreover, how genetic variation influences the acute effects of cannabis on resting state brain function is unknown. Here we investigated the acute effects of ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on resting state brain neurophysiology, and their modulation by catechol-methyl-transferase (COMT) Val158Met genotype. Thirty-nine healthy volunteers participated in a pharmacological MRI study, where we applied Arterial Spin Labelling (ASL) to measure perfusion and functional MRI to assess resting state connectivity. THC increased perfusion in bilateral insula, medial superior frontal cortex, and left middle orbital frontal gyrus. This latter brain area showed significantly decreased connectivity with the precuneus after THC administration. THC effects on perfusion in the left insula were significantly related to subjective changes in perception and relaxation. These findings indicate that THC enhances metabolism and thus neural activity in the salience network. Furthermore, results suggest that recruitment of brain areas within this network is involved in the acute effects of THC. Resting state perfusion was modulated by COMT genotype, indicated by a significant interaction effect between drug and genotype on perfusion in the executive network, with increased perfusion after THC in Val/Met heterozygotes only. This finding suggests that prefrontal dopamine levels are involved in the susceptibility to acute effects of cannabis.

LanguageEnglish
Pages766-776
JournalEuropean Neuropsychopharmacology
Volume29
Issue number6
Early online date8 Apr 2019
DOIs
Publication statusPublished - Jun 2019

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Guaiacol
Dronabinol
Transferases
Cannabis
Genotype
Perfusion
Brain
Neurophysiology
Parietal Lobe
Frontal Lobe
Heterozygote
Prefrontal Cortex
Neuroimaging
Dopamine
Healthy Volunteers
Magnetic Resonance Imaging
Pharmacology
Pharmaceutical Preparations

Keywords

  • Arterial spin labelling
  • Cannabis
  • Catechol-methyl-transferase (COMT)
  • Delta9-tetrahydrocannabinol (THC)
  • Resting state connectivity
  • Salience

Cite this

Bossong, Matthijs G. ; van Hell, Hendrika H. ; Schubart, Chris D. ; van Saane, Wesley ; Iseger, Tabitha A. ; Jager, Gerry ; van Osch, Matthias J.P. ; Jansma, J.M. ; Kahn, René S. ; Boks, Marco P. ; Ramsey, Nick F. / Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype. In: European Neuropsychopharmacology. 2019 ; Vol. 29, No. 6. pp. 766-776.
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abstract = "Cannabis produces a broad range of acute, dose-dependent psychotropic effects. Only a limited number of neuroimaging studies have mapped these effects by examining the impact of cannabis on resting state brain neurophysiology. Moreover, how genetic variation influences the acute effects of cannabis on resting state brain function is unknown. Here we investigated the acute effects of ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on resting state brain neurophysiology, and their modulation by catechol-methyl-transferase (COMT) Val158Met genotype. Thirty-nine healthy volunteers participated in a pharmacological MRI study, where we applied Arterial Spin Labelling (ASL) to measure perfusion and functional MRI to assess resting state connectivity. THC increased perfusion in bilateral insula, medial superior frontal cortex, and left middle orbital frontal gyrus. This latter brain area showed significantly decreased connectivity with the precuneus after THC administration. THC effects on perfusion in the left insula were significantly related to subjective changes in perception and relaxation. These findings indicate that THC enhances metabolism and thus neural activity in the salience network. Furthermore, results suggest that recruitment of brain areas within this network is involved in the acute effects of THC. Resting state perfusion was modulated by COMT genotype, indicated by a significant interaction effect between drug and genotype on perfusion in the executive network, with increased perfusion after THC in Val/Met heterozygotes only. This finding suggests that prefrontal dopamine levels are involved in the susceptibility to acute effects of cannabis.",
keywords = "Arterial spin labelling, Cannabis, Catechol-methyl-transferase (COMT), Delta9-tetrahydrocannabinol (THC), Resting state connectivity, Salience",
author = "Bossong, {Matthijs G.} and {van Hell}, {Hendrika H.} and Schubart, {Chris D.} and {van Saane}, Wesley and Iseger, {Tabitha A.} and Gerry Jager and {van Osch}, {Matthias J.P.} and J.M. Jansma and Kahn, {Ren{\'e} S.} and Boks, {Marco P.} and Ramsey, {Nick F.}",
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Bossong, MG, van Hell, HH, Schubart, CD, van Saane, W, Iseger, TA, Jager, G, van Osch, MJP, Jansma, JM, Kahn, RS, Boks, MP & Ramsey, NF 2019, 'Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype', European Neuropsychopharmacology, vol. 29, no. 6, pp. 766-776. https://doi.org/10.1016/j.euroneuro.2019.03.010

Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype. / Bossong, Matthijs G.; van Hell, Hendrika H.; Schubart, Chris D.; van Saane, Wesley; Iseger, Tabitha A.; Jager, Gerry; van Osch, Matthias J.P.; Jansma, J.M.; Kahn, René S.; Boks, Marco P.; Ramsey, Nick F.

In: European Neuropsychopharmacology, Vol. 29, No. 6, 06.2019, p. 766-776.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype

AU - Bossong, Matthijs G.

AU - van Hell, Hendrika H.

AU - Schubart, Chris D.

AU - van Saane, Wesley

AU - Iseger, Tabitha A.

AU - Jager, Gerry

AU - van Osch, Matthias J.P.

AU - Jansma, J.M.

AU - Kahn, René S.

AU - Boks, Marco P.

AU - Ramsey, Nick F.

PY - 2019/6

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N2 - Cannabis produces a broad range of acute, dose-dependent psychotropic effects. Only a limited number of neuroimaging studies have mapped these effects by examining the impact of cannabis on resting state brain neurophysiology. Moreover, how genetic variation influences the acute effects of cannabis on resting state brain function is unknown. Here we investigated the acute effects of ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on resting state brain neurophysiology, and their modulation by catechol-methyl-transferase (COMT) Val158Met genotype. Thirty-nine healthy volunteers participated in a pharmacological MRI study, where we applied Arterial Spin Labelling (ASL) to measure perfusion and functional MRI to assess resting state connectivity. THC increased perfusion in bilateral insula, medial superior frontal cortex, and left middle orbital frontal gyrus. This latter brain area showed significantly decreased connectivity with the precuneus after THC administration. THC effects on perfusion in the left insula were significantly related to subjective changes in perception and relaxation. These findings indicate that THC enhances metabolism and thus neural activity in the salience network. Furthermore, results suggest that recruitment of brain areas within this network is involved in the acute effects of THC. Resting state perfusion was modulated by COMT genotype, indicated by a significant interaction effect between drug and genotype on perfusion in the executive network, with increased perfusion after THC in Val/Met heterozygotes only. This finding suggests that prefrontal dopamine levels are involved in the susceptibility to acute effects of cannabis.

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KW - Arterial spin labelling

KW - Cannabis

KW - Catechol-methyl-transferase (COMT)

KW - Delta9-tetrahydrocannabinol (THC)

KW - Resting state connectivity

KW - Salience

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DO - 10.1016/j.euroneuro.2019.03.010

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