Acute effects of Δ9-tetrahydrocannabinol (THC) on human cognitive brain function
Dr. Matthijs Bossong, University of Utrecht
The endocannabinoid (eCB) system, consisting of cannabinoid receptors and accompanying ligands,
has been implicated in cognitive functions which are also affected in various psychiatric disorders. In
addition, behavioural evidence from healthy subjects indicates that modulation of the eCB system by
administration of eCB agonists such as Δ9-tetrahydrocannabinol (THC) impairs performance on
cognitive paradigms. However, the neurophysiological mechanisms underlying these effects are
unknown. Here, I will present a series of functional MRI studies in which we investigated the acute
effects of THC on cognitive brain function of healthy volunteers. Results of these studies show that
the impact of THC administration depends on the difficulty of the task performed. Impaired
performance of cognitive paradigms is demonstrated on more challenging tasks, which is associated
with both activity deficits in temporal and prefrontal areas and a failure to deactivate regions of the
default mode network. Normal performance levels after THC administration demonstrated for less
demanding tasks are shown to be related to either increased neural effort in task-specific regions
(‘neurophysiological inefficiency’) or recruitment of alternative brain areas, which suggests a change
in strategy to meet cognitive demands. Together, these results provide compelling support for
endocannabinoid involvement in the control of higher cognitive functions.