Acute effects of Δ9-tetrahydrocannabinol (THC) on resting state connectivity networks and impact of COMT genotype: A multi-site pharmacological fMRI study
Teuntje A. D. Pelgrim, Johannes G. Ramaekers, Matthew B. Wall, Tom P. Freeman, Matthijs G. Bossong
Drug and Alcohol Dependence August 11, 2023 DOI: 10.1016/j.drugalcdep.2023.110925 via OpenAlex
Summary
AI-generated from the abstractTHC, the main psychoactive component of cannabis, reduces functional connectivity in the salience network—a brain system involved in processing awareness and salient information—specifically weakening connections from the right insula to the left insula and anterior cingulate cortex. A trend toward decreased connectivity was also observed in the hippocampus-midbrain-striatum network, which may relate to acute psychotic-like effects. The COMT Val158Met genotype modulated subjective responses: individuals with the Met/Met genotype experienced the strongest dysphoric reactions and showed reduced connectivity in the hippocampus-midbrain-striatum network after THC. These findings suggest that prefrontal dopamine levels influence the acute effects of cannabis.
Study at a glance
| Characteristics | Re-analysis of three double-blind, placebo-controlled, within-subject pharmacological functional magnetic resonance imaging studies Peer reviewed |
|---|---|
| Sample size | 87 |
| Population | Healthy occasional cannabis users |
| Intervention | Δ9-tetrahydrocannabinol (THC) |
| Topics | Default mode network |
| Keywords | Psychology Neuroscience Resting State FMRI Striatum Insula |
| Citations | 3 |
| Key finding | THC robustly decreases connectivity in the salience network, and COMT genotype modulates both subjective effects and connectivity changes in the hippocampus-midbrain-striatum network. |
Abstract
BACKGROUND: Cannabis produces various acute psychotropic effects, with marked individual differences. Cannabis use is a risk factor for developing psychotic disorders. The main component responsible for these effects is Δ9-tetrahydrocannabinol (THC). Here we investigated the neural basis of acute THC effects and its modulation by catechol-methyl-transferase (COMT) Val158Met genotype. METHODS: Resting state functional MRI data of healthy occasional cannabis users were combined and re-analyzed from three double-blind, placebo-controlled, within-subject pharmacological functional magnetic resonance imaging studies (total N=87). Functional connectivity after placebo and THC was compared in three functional networks (salience, executive and default mode network) and a network implicated in psychosis (the hippocampus-midbrain-striatum network). COMT genotype modulation of subjective effects and connectivity was examined. RESULTS: THC reduced connectivity in the salience network, specifically from the right insula to both the left insula and anterior cingulate cortex. We found a trend towards decreased connectivity in the hippocampus-midbrain-striatum network after THC. COMT genotype modulated subjective effects of THC, with strongest dysphoric reactions in Met/Met individuals. In addition, reduced connectivity after THC was demonstrated in the hippocampus-midbrain-striatum network of Met/Met individuals only. CONCLUSIONS: In this large multisite study we found that THC robustly decreases connectivity in the salience network, involved in processing awareness and salient information. Connectivity changes in the hippocampus-midbrain-striatum network may reflect the acute psychotic-like effects of THC. COMT genotype modulation of THC's impact on subjective effects and functional connectivity provides further evidence for involvement of prefrontal dopamine levels in the acute effects of cannabis.