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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)766-776
JournalEuropean Neuropsychopharmacology
Issue number6
Early online date8 Apr 2019
Publication statusPublished - Jun 2019


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

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    Bossong, M. G., van Hell, H. H., Schubart, C. D., van Saane, W., Iseger, T. A., Jager, G., van Osch, M. J. P., Jansma, J. M., Kahn, R. S., Boks, M. P., & Ramsey, N. F. (2019). Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype. European Neuropsychopharmacology, 29(6), 766-776.