Cannabinoid modulation of functional connectivity within regions processing attentional salience

Area of Science:

• Neuroscience
• Psychopharmacology
• Brain Imaging

Background:

• Psychotic symptoms are linked to abnormal salience attribution, mediated by the prefrontal cortex, striatum, and hippocampus.
• Cannabis derivatives delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD) differentially activate these brain regions.
• Limited understanding exists regarding the impact of delta-9-THC and CBD on functional connectivity within these key brain areas.

Purpose of the Study:

• To investigate the effects of delta-9-THC and CBD on functional brain connectivity.
• To examine how these cannabinoids modulate connectivity between the prefrontal cortex, striatum, and hippocampus during salience processing.
• To correlate observed connectivity changes with task performance in healthy cannabis users.

Main Methods:

• Event-related functional magnetic resonance imaging (fMRI) was used in healthy occasional cannabis users.
• Participants received oral administration of delta-9-THC, CBD, or a placebo.
• Seed cluster-based functional connectivity analysis was employed during an oddball salience processing task.

Main Results:

• Delta-9-THC and CBD exhibited opposing effects on fronto-striatal connectivity.
• Delta-9-THC reduced fronto-striatal connectivity, correlating with task performance, while CBD enhanced it.
• Mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD.

Conclusions:

• Single doses of delta-9-THC and CBD differentially modulate functional integration in brain regions involved in salience processing.
• The observed changes in brain connectivity are related to the processing of salient stimuli.
• Cannabinoids exert distinct effects on neural networks underlying salience attribution.