THC boosted brain activity in attention networks, and a common gene variant influenced the effect | Research

The takeaway

THC increased blood flow in brain areas involved in attention and salience processing, and the COMT gene variant modulated how the executive network responded, suggesting prefrontal dopamine levels affect cannabis susceptibility.

Neuroscientists, pharmacogeneticists, and researchers studying individual differences in cannabis response.

Gene variant modulates THC response

What the researchers found

THC increased perfusion in bilateral insula, medial superior frontal cortex, and left orbital frontal gyrus. The orbital frontal area showed decreased connectivity with the precuneus. THC effects on left insula perfusion correlated with subjective changes in perception and relaxation. COMT genotype significantly modulated THC effects, with Val/Met heterozygotes showing increased executive network perfusion after THC while other genotypes did not.

Why it matters

This study identifies a specific gene (COMT) that influences individual vulnerability to acute THC effects, providing a biological basis for why cannabis affects people differently. The COMT gene is already known to influence prefrontal dopamine levels.

The numbers in context

39 healthy volunteers. THC increased perfusion in bilateral insula, medial superior frontal cortex, left middle orbital frontal gyrus. Left insula perfusion correlated with subjective perception/relaxation changes. COMT Val/Met heterozygotes showed unique executive network response.

How the study worked

Pharmacological MRI study with 39 healthy volunteers. Used Arterial Spin Labelling for perfusion and fMRI for resting state connectivity. Examined THC effects and their modulation by COMT Val158Met genotype.

What this study cannot tell us

Sample size of 39 limits genetic subgroup analysis power. Single acute THC dose may not represent chronic use patterns. Only one genetic variant examined. Healthy volunteers may not represent clinical populations.

How to read the evidence

Rated moderate because this is a controlled pharmacological imaging study, though sample size limits genetic analysis power.

When this study was published

Published in 2019.

The bigger picture

Individual differences in cannabis response are clinically important but poorly understood. Linking a well-characterized gene (COMT) to specific brain responses to THC moves the field toward precision approaches to cannabis risk assessment.

Questions still open

Does COMT genotype predict long-term cannabis outcomes? Would other dopamine-related genes show similar modulation? Could COMT genotyping help identify who should avoid cannabis?

Common questions

Why does cannabis affect people differently?

This study found that the COMT gene, which influences dopamine levels in the prefrontal cortex, modulated how the brain responded to THC. People with different COMT variants showed different brain activation patterns.

What brain areas does THC activate?

THC increased activity in the salience network, particularly the insula and frontal areas. These regions are involved in attention, self-awareness, and processing the relevance of stimuli.

Read the original research

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

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 29(6), 766-776

View on PubMed ↗Publisher’s paper ↗

Citation

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 Martijn; Kahn, René S; Boks, Marco P; Ramsey, Nick F. (2019). Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype.. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 29(6), 766-776. https://doi.org/10.1016/j.euroneuro.2019.03.010