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Updated: Jan 26, 2026

Administration of Δ9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice
Published on: August 1, 2025
Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype
Matthijs G Bossong1, Hendrika H van Hell2, Chris D Schubart3
1Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, United Kingdom.
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.
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