Context The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing.
Objective To examine the effects ofΔ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing.
Design Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration ofΔ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli.
Setting University center.
Participants Fifteen healthy men with minimal previous cannabis use.
Main Outcome Measures Symptom ratings, task performance, and regional brain activation.
Results During the processing of oddball stimuli, relative to placebo,Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex.Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect ofΔ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those ofΔ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation.
Conclusions Δ9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.