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Evidence is increasing for involvement of the endocannabinoid system in cognitive functions including attention and executive function, as well as in psychiatric disorders characterized by cognitive deficits, such as schizophrenia. Executive function appears to be associated with both modulation of active networks and inhibition of activity in the default mode network. In the present study, we examined the role of the endocannabinoid system in executive function, focusing on both the associated brain network and the default mode network. A pharmacological functional magnetic resonance imaging (fMRI) study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist Δ9-tetrahydrocannabinol (THC) on executive function in 20 healthy volunteers, using a continuous performance task with identical pairs. Task performance was impaired after THC administration, reflected in both an increase in false alarms and a reduction in detected targets. This was associated with reduced deactivation in a set of brain regions linked to the default mode network, including posterior cingulate cortex and angular gyrus. Less deactivation was significantly correlated with lower performance after THC. Regions that were activated by the continuous performance task, notably bilateral prefrontal and parietal cortex, did not show effects of THC. These findings suggest an important role for the endocannabinoid system in both default mode modulation and executive function. This may be relevant for psychiatric disorders associated with executive function deficits, such as schizophrenia and ADHD.
Pubmed ID: 23936144 RIS Download
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A not-for-profit organization that initiates and manages drug development consortia that involve the pharmaceutical industry, academia, and the Dutch Government. The aim of all their consortia is to conduct pre-competitive research while strengthening the Netherlands' international reputation for drug development. The consortia are focused on addressing therapeutic areas that are listed as priority areas by the World Health Organization including: autoimmune diseases, cardiovascular diseases, cancer, infectious diseases, and diseases of the brain. The consortia are also focused on enabling: therapeutic target discovery, validation, and animal models; lead selection and in-silico modeling; predictive drug disposition and toxicology; biomarkers and biosensors; drug formulation, delivery, and targeting; and, production technologies. TI Pharma consortia aim to improve the efficiency of the drug-development process, with a focus on advancing regulatory science. In addition to research, TI Pharma also has objectives to train and educate scientists in the Netherlands on the drug discovery and development processes, as well as on entrepreneurship. Participants include: all Dutch universities and academic medical centers, more than 30 industrial partners, small-to-medium sized companies, and representatives from the Dutch Medicines Evaluation Board (Netherlands regulatory body for drugs).
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